Plasma profiles of inflammatory cytokines in children with moderate to severe traumatic brain injury: a prospective cohort study.

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.

Functional connectivity, tissue microstructure and T2 at 11.1 Tesla distinguishes neuroadaptive differences in two traumatic brain injury models in rats: A Translational Outcomes Project in NeuroTrauma (TOP-NT) UG3 phase study.

The damage caused by contusive traumatic brain injuries (TBIs) is thought to involve breakdown in neuronal communication through focal and diffuse axonal injury along with alterations to the neuronal chemical environment, which adversely affects neuronal networks beyond the injury epicenter(s). In the present study, functional connectivity along with brain tissue microstructure coupled with T2 relaxometry were assessed in two experimental TBI models in rat, controlled cortical impact (CCI) and lateral fluid percussive injury (LFPI). Rats were scanned on an 11.1 Tesla scanner on days 2 and 30 following either CCI or LFPI. Naive controls were scanned once and used as a baseline comparison for both TBI groups. Scanning included functional magnetic resonance imaging (fMRI), diffusion weighted images (DWI), and multi-echo T2 images. fMRI scans were analyzed for functional connectivity across laterally and medially located region of interests (ROIs) across the cortical mantle, hippocampus, and dorsal striatum. DWI scans were processed to generate maps of fractional anisotropy, mean, axial, and radial diffusivities (FA, MD, AD, RD). The analyses focused on cortical and white matter (WM) regions at or near the TBI epicenter. Our results indicate that rats exposed to CCI and LFPI had significantly increased contralateral intra-cortical connectivity at 2 days post-injury. This was observed across similar areas of the cortex in both groups. The increased contralateral connectivity was still observed by day 30 in CCI, but not LFPI rats. Although both CCI and LFPI had changes in WM and cortical FA and diffusivities, WM changes were most predominant in CCI and cortical changes in LFPI. Our results provide support for the use of multimodal MR imaging for different types of contusive and skull-penetrating injury.

Risk factors for mortality in pseudomonas aeruginosa bacteremia in children.

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.

Effect of intravenous immunoglobulin on the outcome of children with septic shock in a PICU: a retrospective cohort study.

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.

Electrical bioimpedance measurement and near-infrared spectroscopy in pediatric postoperative neurocritical care: a prospective observational study.

Background: To investigate the clinical significance of the disturbance coefficient (DC) and regional cerebral oxygen saturation (rSO2) as obtained through the use of electrical bioimpedance and near-infrared spectroscopy (NIRS) in pediatric neurocritical care. Participants and methods: We enrolled 45 pediatric patients as the injury group and 70 healthy children as the control group. DC was derived from impedance analysis of 0.1 mA-50 kHz current via temporal electrodes. rSO2 was the percentage of oxyhemoglobin measured from reflected NIR light on the forehead. DC and rSO2 were obtained at 6, 12, 24, 48 and 72 h after surgery for the injury group and during the health screening clinic visit for the control group. We compared DC and rSO2 between the groups, their changes over time within the injury group and their correlation with intracranial pressure (ICP), cerebral perfusion pressure (CPP), Glasgow coma scale (GCS) score, Glasgow outcome scale (GOS) score, and their ability to diagnose postoperative cerebral edema and predict poor prognosis. Results: DC and rSO2 were significantly lower in the injury group than in the control group. In the injury group, ICP increased over the monitoring period, while DC, CPP and rSO2 decreased. DC was negatively correlated with ICP and positively correlated with GCS score and GOS score. Additionally, lower DC values were observed in patients with signs of cerebral edema, with a DC value of 86.5 or below suggesting the presence of brain edema in patients aged 6-16 years. On the other hand, rSO2 was positively correlated with CPP, GCS score, and GOS score, with a value of 64.4% or below indicating a poor prognosis. Decreased CPP is an independent risk factor for decreased rSO2. Conclusion: DC and rSO2 monitoring based on electrical bioimpedance and near-infrared spectroscopy not only reflect the degree of brain edema and oxygenation, but also reflect the severity of the disease and predict the prognosis of the patients. This approach offers a real-time, bedside, and accurate method for assessing brain function and detecting postoperative cerebral edema and poor prognosis.

Association between Cerebrospinal Fluid and Serum Biomarker Levels and Diagnosis, Injury Severity, and Short-Term Outcomes in Patients with Acute Traumatic Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) is recognized as a global problem that can lead to a range of acute and secondary complications impacting morbidity and mortality. There is still a lack of reliable diagnostic and prognostic biomarkers in patients with SCI that could help guide clinical care and identify novel therapeutic targets for future drug discovery. The aim of this prospective controlled study was to determine the cerebral spinal fluid (CSF) and serum profiles of 10 biomarkers as indicators of SCI diagnosis, severity, and prognosis to aid in assessing appropriate treatment modalities. CSF and serum samples of 15 SCI and ten healthy participants were included in the study. The neurological assessments were scored on admission and at discharge from the hospital using the American Spinal Injury Association Impairment Score (AIS) grades. The CSF and serum concentrations of SBDP150, S100B, GFAP, NF-L, UCHL-1, Tau, and IL-6 were significantly higher in SCI patients when compared with the control group. The CSF GBDP 38/44K, UCHL-L1, S100B, GFAP, and Tau levels were significantly higher in the AIS A patients. This study demonstrated a strong correlation between biomarker levels in the diagnosis and injury severity of SCI but no association with short-term outcomes. Future prospective controlled studies need to be done to support the results of this study.

Infantile orbital abscess caused by methicillin-resistant Staphylococcus aureus: a case report and literature review.

Objective: To report and review infantile orbital abscess caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: We report a case of MRSA-induced infantile orbital abscess accompanied by sepsis, pneumonia, and purulent meningitis. We systematically review cases of MRSA-induced infantile orbital abscess published in PubMed, Web of Science and ScienceDirect until April 2023. Results: We reviewed 14 patients [our patient + 13 patients (10 papers) identified via literature searches]. There were nine boys and five girls; nine neonates and five older infants; and 8 full-term births and 1 preterm birth. The gestational age at birth was unknown for five infants. The right and left orbits were affected in 10 and 4 patients, respectively. The clinical presentation included periorbital soft-tissue edema or redness (11 patients), fever (7 patients), exophthalmos (10 patients), limited eye movement (4 patients), purulent eye secretions (2 patients), and skin abscess and convulsion (1 patient each). The source of infection was sinusitis (8 patients), vertical transmission, gingivitis, dacryocystitis, upper respiratory tract infection (1 patient each), and unknown (2 patients). MRSA was detected in blood (6 patients) or pus culture (8 patients). Vancomycin or linezolid were used for 11 patients; corticosteroids were administered to only 1 patient. Surgical drainage was performed for 13 infants (external drainage, 11 patients; endoscopic drainage, 2 patients). Two patients initially had pulmonary and intracranial infections. Except for one patient with neurological dysfunction at discharge, all other infants had no sequelae or complications. Conclusion: Early aggressive anti-infective treatment and timely drainage are essential for managing MRSA-induced infantile orbital abscess.

Safety and efficacy of corticosteroids in ARDS patients: a systematic review and meta-analysis of RCT data.

PURPOSE: Acute respiratory distress syndrome (ARDS) is an acute and critical disease among children and adults, and previous studies have shown that the administration of corticosteroids remains controversial. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to evaluate the safety and efficacy of corticosteroids. METHODS: The RCTs investigating the safety and efficacy of corticosteroids in ARDS were searched from electronic databases (Embase, Medline, and the Cochrane Central Register of Controlled Trials). The primary outcome was 28-day mortality. Heterogeneity was assessed using the Chi square test and I2 with the inspection level of 0.1 and 50%, respectively. RESULTS: Fourteen RCTs (n = 1607) were included for analysis. Corticosteroids were found to reduce the risk of death in patients with ARDS (relative risk (RR) = 0.78, 95% confidence interval (CI): 0.70-0.87; P < 0.01). Moreover, no significant adverse events were observed, compared to placebo or standard support therapy. Further subgroup analysis showed that variables, such as adults (RR = 0.78; 95% CI: 0.70-0.88; P < 0.01), non-COVID-19 (RR = 0.71; 95% CI: 0.62-0.83; P < 0.01), methylprednisolone (RR = 0.70; 95% CI: 0.56-0.88; P < 0.01), and hydrocortisone (RR = 0.79; 95% CI: 0.63-0.98; P = 0.03) were associated with 28-day mortality among patients who used corticosteroids. However, no association was found, regarding children (RR = 0.21; 95% CI: 0.01-4.10; P = 0.30). CONCLUSION: The use of corticosteroids is an effective approach to reduce the risk of death in ARDS patients. However, this effect is associated with age, non-COVID-19 diseases, and methylprednisolone and hydrocortisone use. Therefore, evidence suggests patients with age ≥ 18 years and non-COVID-19 should be encouraged during the corticosteroid treatment. However, due to substantial differences in the use of corticosteroids among these studies, questions still remain regarding the dosage, optimal corticosteroid agent, and treatment duration in patients with ARDS.

Analysis of predictors of mortality and clinical outcomes of different subphenotypes for moderate-to-severe pediatric acute respiratory distress syndrome: A prospective single-center study.

Background: This study aimed to observe the prognosis of patients with moderate-to-severe pediatric acute respiratory distress syndrome (PARDS) admitted to the Pediatric Intensive Care Unit (PICU) as a function of underlying conditions and available treatment strategies, and to investigate the risk factors for death and the outcomes of different clinical subphenotypes. Methods: Patients were divided into non-survivors and survivors according to the prognosis 28 days after the diagnosis. The risk factors for death and the predictive value of relevant factors for mortality were analyzed. Latent class analysis was used to identify different clinical subphenotypes. Results: A total of 213 patients with moderate-to-severe PARDS were enrolled, of which 98 (46.0%) died. Higher PELOD2 scores (OR = 1.082, 95% CI 1.004-1.166, p < 0.05), greater organ failure (OR = 1.617, 95% CI 1.130-2.313, p < 0.05), sepsis (OR = 4.234, 95% CI 1.773-10.111, p < 0.05), any comorbidity (OR = 3.437, 95% CI 1.489-7.936, p < 0.05), and higher infiltration area grade (IAG) (OR = 1.980, 95% CI 1.028-3.813, p < 0.05) were associated with higher mortality. The combination of these five indicators had the largest area under the curve (sensitivity 89.79%, specificity 94.78%). Patients were classified into higher-risk and lower-risk phenotype group according to the latent class analysis. Compared to the lower-risk phenotype, more patients with higher-risk phenotype suffered from sepsis (24.40% vs. 12.20%, p < 0.05), inherited metabolic diseases (45.80% vs. 25.60%, p < 0.05), positive respiratory pathogens (48.10% vs. 26.80%, p < 0.05), and higher IAG (p < 0.05); they also had significantly higher PIM3 and PELOD2 scores (p < 0.05), with an extremely high mortality rate (61.1% vs. 22.0%, p < 0.05). Conclusions: Moderate-to-severe PARDS has high morbidity and mortality in PICU; a higher PELOD2 score, greater organ failure, sepsis, any comorbidity, and higher IAG were risk factors for death, and the combination of these five indicators had the greatest value in predicting prognosis. More patients with sepsis, positive respiratory pathogens, higher PIM3 and PELOD2 scores, and higher IAG were in higher-risk phenotype group, which had worse outcomes. Clear classification facilitates targeted treatment and prognosis determination.

Comparing outcomes between culture-positive and culture-negative septic shock in a PICU: A retrospective cohort study.

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 (8.89 ng/ml vs. 28.39 ng/ml, P = 0.001) and C-reactive protein (28 mg/L vs. 58 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 (137 mmol/L vs. 132 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.

Clinical Application Value of Pharmacokinetic Parameters of Vancomycin in Children Treated in the Pediatric Intensive Care Unit.

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.

Characteristics and Risk Factors of Children Requiring Prolonged Mechanical Ventilation vs. Non-prolonged Mechanical Ventilation in the PICU: A Prospective Single-Center Study.

BACKGROUND: Prolonged mechanical ventilation (PMV) has become an enormous challenge in intensive care units (ICUs) around the world. Patients treated with PMV are generally in poor health. These patients represent a select cohort with significant morbidity, mortality, and resource utilization. The status of children who have undergone PMV in China is unknown. Our goal is to investigate the prevalence and characteristics of pediatric patients with PMV, as well as the risk factors of PMV in the pediatric intensive care unit (PICU). METHODS: The subjects were divided into two groups. The PMV group(MV ≥ 14 days) and the non-PMV group(2 days < MV <14 days). The baseline characteristics, treatments, mortality and other results between the two groups were compared. The risk factors associated with PMV were evaluated using univariate and multivariable analyses. RESULTS: Of the 382 children enrolled, 127 (33.2%) received prolonged mechanical ventilation. The most common cause of MV in the PMV group was acute lung disease (48.0%), followed by acute circulatory system disease (26.0%), acute neurological disease (15.0%), postoperative monitoring (10.2%), and others (0.8%). Comorbidities were more prevalent among the PMV group (P = 0.004). The patients with PMV had a higher rate of premature birth (24.4 vs. 14.1%, P = 0.013) and higher PIM3 score at admission [5.6(3.0-9.9) vs. 4.1(1.7-5.5), P < 0.001]. The use of inotropes/vasopressors (63.8 vs. 43.1%, P < 0.001) was more common in patients with PMV compared with those in the non-PMV group. In the PMV group, the rate of extubation failure (39.4 vs. 6.7%, P < 0.001) was higher than the non-PMV group. The median hospital stay [35(23.0-50.0)d vs. 20(14.0-31.0)d, P < 0.001], PICU stay [22(15.0-33.0)d vs. 9(6.0-12.0)d, P < 0.001], hospitalization costs [¥391,925(263,259-614,471) vs. ¥239,497(158,723-350,620), P < 0.001], and mortality after 1-month discharge (22.0 vs. 1.6%, P < 0.001) were higher in the PMV group. Multivariate analysis revealed that age <1 year old, a higher PIM3 score at admission, prematurity, the use of inotropes or vasopressors, extubation failure, and ventilator mode on the first day of MV were associated with PMV. CONCLUSIONS: The incidence and mortality of PMV in pediatric patients is surprisingly high. Premature infants or patients with severe disease or extubation failure are at higher risk of PMV. Patients with PMV exhibit a greater burden with regard to medical costs than those on non-PMV. It is important to establish specialized weaning units for mechanically ventilated patients with stable conditions.

Compensatory functional connectome changes in a rat model of traumatic brain injury.

Penetrating cortical impact injuries alter neuronal communication beyond the injury epicentre, across regions involved in affective, sensorimotor and cognitive processing. Understanding how traumatic brain injury reorganizes local and brain wide nodal interactions may provide valuable quantitative parameters for monitoring pathological progression and recovery. To this end, we investigated spontaneous fluctuations in the functional MRI signal obtained at 11.1 T in rats sustaining controlled cortical impact and imaged at 2- and 30-days post-injury. Graph theory-based calculations were applied to weighted undirected matrices constructed from 12 879 pairwise correlations between functional MRI signals from 162 regions. Our data indicate that on Days 2 and 30 post-controlled cortical impact there is a significant increase in connectivity strength in nodes located in contralesional cortical, thalamic and basal forebrain areas. Rats imaged on Day 2 post-injury had significantly greater network modularity than controls, with influential nodes (with high eigenvector centrality) contained within the contralesional module and participating less in cross-modular interactions. By Day 30, modularity and cross-modular interactions recover, although a cluster of nodes with low strength and low eigenvector centrality remain in the ipsilateral cortex. Our results suggest that changes in node strength, modularity, eigenvector centrality and participation coefficient track early and late traumatic brain injury effects on brain functional connectivity. We propose that the observed compensatory functional connectivity reorganization in response to controlled cortical impact may be unfavourable to brain wide communication in the early post-injury period.

Talaromyces Marneffei Infection in an HIV-Negative Child with a CARD9 Mutation in China: A Case Report and Review of the Literature.

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.

Relationship between admission coagulopathy and prognosis in children with traumatic brain injury: a retrospective study.

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.

Characteristics of coagulation alteration in patients with COVID-19.

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.

Ecthyma gangrenosum due to Pseudomonas aeruginosa sepsis as initial manifestation of X-linked agammaglobulinemia: a case report.

BACKGROUND: X-linked agammaglobulinemia (XLA, OMIM#300,300), caused by mutations in the Bruton tyrosine kinase (BTK) gene, is a rare monogenic inheritable immunodeficiency disorder. Ecthyma gangrenosum is a cutaneous lesion caused by Pseudomonas aeruginosa that typically occurs in patients with XLA and other immunodeficiencies. CASE PRESENTATION: We report the case of a 20-month-old boy who presented with fever, vomiting, diarrhea, and ecthyma gangrenosum. Blood, stool, and skin lesion culture samples were positive for P. aeruginosa. A diagnosis of XLA was established, and the c.262G > T mutation in exon 4 of BTK was identified with Sanger sequencing. Symptoms improved following treatment with antibiotics and immunoglobulin infusion. CONCLUSIONS: Primary immunodeficiency (i.e., XLA) should be suspected in male infants with P. aeruginosa sepsis, highlighting the importance of genetic and immune testing in these patients.

Effect of blood analysis and immune function on the prognosis of patients with COVID-19.

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.

Intrahepatic T helper 17 cells recruited by hepatitis B virus X antigen-activated hepatic stellate cells exacerbate the progression of chronic hepatitis B virus infection.

Immunopathological injury induced by persistent hepatitis B virus (HBV) infection contributes to the progression from chronic hepatitis B (CHB) to hepatic cirrhosis and hepatocellular carcinoma (HCC). Regulatory T cells (Tregs), CD4+ T helper (Th) cells, and hepatic stellate cells (HSCs) are considered to be the pivotal factors during this progression. In this study, our aim was to investigate the molecular mechanisms of liver immunopathological injury associated with Tregs, CD4+ Th cells, and HSCs. Liver tissues were collected to assay the cytokines and distribution and frequencies of CD4+ Th cells and Tregs. The chemotaxis of Th17 cells towards the liver and the interactions between IL-22, IL-17A, and HSCs were explored. The data showed the frequencies of Th17 cells, and their effector molecules IL-22 and IL-17A were increased along with the severity of chronic liver diseases. However, the frequencies of Tregs were decreased in HBV-associated cirrhotic tissues compared with those in CHB tissues and HCC tissues. hepatitis B virus X antigen (HBxAg)-activated HSCs recruited more Th17 cells into the liver and conduced to the secretion of IL-17A and IL-22 that could in turn stimulate the proliferation and fibrotic marker secretion of the HSCs. Therefore, we suggest that the interactions between Th17 cells, IL-17A, IL-22, and HSCs form a positive feedback loop that aggravated the progression of chronic liver disease with HBV infection through the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) signalling pathway. Our findings indicated the IL-17A/IL-22 pathway might become a new treatment target for liver cirrhosis and HCC.

Clinical Analysis of 25 COVID-19 Infections in Children.

BACKGROUND: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiologic history of these patients were retrospectively collected and analyzed. RESULTS: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.