Elevated total bile acid levels as an independent predictor of mortality in pediatric sepsis.

BACKGROUND: The close relationship between bile acid (BA) metabolism and sepsis has been investigated in recent years, as knowledge of the role of the gut microbiome and metabolomics in sepsis has grown and become more comprehensive. METHODS: Patients with sepsis who were admitted to the PICU of the Children's Hospital, Zhejiang University School of Medicine from January 2016 to December 2021 were enrolled in this study. Preoperative non-infectious pediatric patients undergoing elective surgeries in our hospital's department of surgery were recruited as controls during the same period. Clinical data were collected and analyzed. RESULTS: 702 children were enrolled, comprising 538 sepsis survivors, 164 sepsis fatalities, and 269 non-infected controls. Statistical analysis revealed that total BA (TBA) increased in both the early and severe stages of pediatric sepsis. In the severe stage, TBA (OR = 2.898, 95% CI 1.946-4.315, p < 0.05) was identified as a risk factor for sepsis. A clinical model identified TBA (the cut-off value is >17.95 µmol/L) as an independent predictor of sepsis mortality with an AUC of 0.842 (95% CI 0.800-0.883), sensitivity of 54.9%, specificity of 96.6%, and HR = 7.658 (95% CI 5.575-10.520). CONCLUSIONS: The study showed that elevated TBA was associated with a heightened risk of mortality in pediatric sepsis. IMPACT: Many clinical indicators show differences between children with sepsis and the control group, among which the difference in serum total bile acid levels is the most significant. During the hospitalization of the patients, the overall bile acid levels in the sepsis death group were higher and exhibited greater fluctuations compared to the survival group, with significant differences. Serum total bile acid levels can serve as effective biomarker for predicting the prognosis of children with sepsis.

The epidemiological characteristics of pediatric head injury in Hangzhou, China: a retrospective study based on cranial CT examinations.

PRIMARY OBJECTIVE: This study aims to create a pediatric head injury database based on cranial CT examinations and explore their epidemiologic characteristics. METHODS: Data related to cranial CT examinations of pediatric head injuries from March 2014 to March 2021 were collected at outpatient and emergency department of a pediatric medical center. The causes of injury, observable post-injury symptoms, and cranial injury findings were extracted with the assistance of natural language processing techniques. RESULTS: Reviewing the data from records on 52,821 children with head injuries over a period of 7 years, the most common causes of pediatric head injury were falls (58.3%), traffic accidents (26.0%), smash/crush/strike (13.9%), violence (1.5%) and sports-related incidents (0.3%). Overall, most of those injured were boys which accounting for 62.2% of all cases. Skull fractures most commonly occur in the parietal bone (9.0%), followed by the occipital (5.2%), frontal (3.3%) and temporal bones (3.0%). Most intracranial hemorrhages occurred in epidural (5.8%), followed by subdural (5.1%), subarachnoid (0.9%), intraparenchymal (0.5%) and intraventricular (0.2%) hemorrhages. Spring and autumn showed more events than any other season. CONCLUSIONS: To the best of our knowledge, this is the largest sample of epidemiological study of head injury in the Chinese pediatric population to date.

Well-defined and biocompatible hydrogels with toughening and reversible photoresponsive properties.

In the present study, novel hydrogels with extremely high strength, reversible photoresponsive and excellent biocompatible properties were prepared. The functional hydrogels were synthesized from a well-defined poly (ethylene glycol) polymer with spiropyran groups at a given position (PEG-SP) via a Cu(i)-catalyst Azide-Alkyne Cycloaddition (CuAAC) reaction. The molecular structures of the sequential intermediates for PEG-SP hydrogel preparation were verified by (1)HNMR and FT-IR. The mechanical property, swelling ratio, compression strength, surface hydrophilicity, and biocompatibility of the resulting hydrogel were characterized. Since spiropyran is pivotal to the switch in hydrophilicity on the hydrogel surface, the swelling ratio of PEG-SP hydrogel under Vis irradiation has a major decrease (155%). Before and after UV light irradiation, the contact angle of the hydrogel has a change of 13.8°. The photoresponsive property of this hydrogel was thus demonstrated, and such a property was also shown to be reversible. The well-defined PEG-SP hydrogel can also sustain a compressive stress of 49.8 MPa without any macro- or micro-damage, indicating its outstanding mechanical performance. Furthermore, it possessed excellent biocompatibility as demonstrated by its performance in an in vivo porcine subcutaneous implantation environment. No inflammation was observed and it got along well with the adjacent tissue. The above features indicate that PEG-SP hydrogels are promising as an implantable matrix for potential applications in biomaterial.

The role of plasma gelsolin in cardiopulmonary bypass induced acute lung injury in infants and young children: a pilot study.

BACKGROUND: Acute lung injury (ALI) induced by cardiopulmonary bypass (CPB, CPB-ALI) is a common and serious complication after cardiac surgery. And infants and young children are more prone to CPB-ALI. The purpose of this study was to investigate the perioperative changes of plasma gelsolin (pGSN) in patients below 3 years of age with cardiac surgeries and CPB, and determine whether pGSN are associated with the occurrence and severity of CPB-ALI. METHODS: Seventy-seven consecutive patients ≤3 years of age with congenital heart diseases (CHD) performed on open heart surgery with CPB were finally enrolled, and assigned to ALI and non-ALI groups according to the American-European Consensus Criteria. Plasma concentrations of gelsolin and total protein were measured at following 8 time points: before CPB (a), after CPB (b), 2 hours after CPB (c), 6 hours after CPB (d), 12 hours after CPB (e), 24 hours after CPB (f), 48 hours after CPB (g) and 72 hours after CPB (h). RESULTS: Twenty-seven (35.1%) patients developed CPB-ALI in the study, including eleven (14.3%) patients with ARDS. The earliest significant drop of pGSN and normalized pGSN (pGSNN) of ALI group both occurred at 6 hours after CPB (p = 0.04 and p < 0.01), which was much earlier than those of non-ALI group (48 hours, p = 0.03 and 24 hours, p < 0.01); PGSN of ALI group before CPB and 6 hours after CPB were both significantly lower than those of non-ALI group (p < 0.01); PGSNN of ALI group before CPB and 6 hours after CPB were both significantly lower than those of non-ALI group (p < 0.01, p = 0.04); PGSN before CPB was the only independent risk factor predicting the occurrence of CPB-ALI (OR, 1.023; 95% CI, 1.007-1.039; p < 0.01) with an AUC of 0.753 (95% CI, 0.626-0.880); The optimal cutoff value of pGSN before CPB was 264.2 mg/L, with a sensitivity of 58.3% and a specificity 94.7%. And lower pGSN before CPB was significantly associated with the severity of CS-AKI (r = -0.45, p < 0.01). CONCLUSIONS: Patients developing CPB-ALI had lower plasma gelsolin reservoir and a much more amount and rapid consumption of plasma gelsolin early after operation. PGSN before CPB was an early and sensitive predictor of CPB-ALI in infants and young children undergoing cardiac surgery, and was negatively correlated with the severity of CPB-ALI.

Repair of ventricular septal defect with Eisenmenger syndrome after bosentan treatment.

We report a patient with ventricular septal defect (VSD) and Eisenmenger syndrome. The patient was treated with bosentan for 12 weeks, with a decrease in pulmonary vascular resistance index (PRVi) from 18.84 to 9.63 Wood unit (WU) m2 , and underwent successful corrective repair of the VSD after 12 weeks of bosentan therapy.

Epidemiological analysis of a 10-year retrospective study of pediatric trauma in intensive care.

Pediatric trauma plays a crucial role in pediatric mortality, with traffic injuries and falls frequently cited as leading causes of significant injuries among children. A comprehensive investigation, including geographical factors, is essential for developing effective strategies to prevent injuries and alleviate the burden of pediatric trauma. This study involved a retrospective analysis of clinical data from pediatric patients admitted to our hospital's intensive care unit (ICU) due to trauma over a 10-year period. Comprehensive analyses were conducted to elucidate trends, demographics, injury patterns, and risk factors associated with these admissions. This retrospective study included 951 pediatric patients (mean age: 4.79 ± 3.24 years; mean weight: 18.45 ± 9.02 kg; median time to ICU admission post-injury: 10.86 ± 14.95 h). Among these patients, 422 (44.4%) underwent emergency surgery, and 466 (49%) required mechanical ventilation support, with a mean duration of 70.19 ± 146.62 h. The mean duration of ICU stay was 6.24 ± 8.01 days, and the overall mean hospitalization duration was 16.08 ± 15.56 days. The predominant cause of unintentional injury was traffic accidents (47.9%), followed by falls (42.5%) and burns/scalds (5.3%). Most incidents involved children aged 0-6 years (70.7%), with males comprising 60.0% of patients. Injury incidents predominantly occurred between 12 and 6 PM (44.5%) and on non-workdays (37.6%). The most common locations where injuries occurred were roadsides (49%) and rural areas (64.35%). Single-site injuries (58.78%) were more prevalent than multiple-site injuries (41.22%), and head injuries were the most common among single-site injuries (81.57%). At ICU admission, the mean injury severity score was 18.49 ± 8.86. Following active intervention, 871 patients (91.59%) showed improvement, while 80 (8.41%) succumbed to their injuries. Traffic injuries remain the primary cause of pediatric trauma leading to ICU admission, underscoring the importance of using appropriate child restraint systems and protective gear as fundamental preventive measures. The increased incidence of injuries among children aged < 6 years and those residing in rural areas highlights the need for targeted preventive strategies, necessitating tailored interventions and public policy formulations that address these high-risk populations.

A nomogram for predicting hemorrhagic shock in pediatric patients with multiple trauma.

The timely detection and management of hemorrhagic shock hold paramount importance in clinical practice. This study was designed to establish a nomogram that may facilitate early identification of hemorrhagic shock in pediatric patients with multiple-trauma. A retrospective study was conducted utilizing a cohort comprising 325 pediatric patients diagnosed with multiple-trauma, who received treatment at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. For external validation, an additional cohort of 144 patients from a children's hospital in Taizhou was included. The model's predictor selection was optimized through the application of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Subsequently, a prediction nomogram was constructed using multivariable logistic regression analysis. The performance and clinical utility of the developed model were comprehensively assessed utilizing various statistical metrics, including Harrell's Concordance Index (C-index), receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Multivariate logistic regression analysis identified systolic blood pressure (ΔSBP), platelet count, activated partial thromboplastin time (APTT), and injury severity score (ISS) as independent predictors for hemorrhagic shock. The nomogram constructed using these predictors demonstrated robust predictive capabilities, as evidenced by an impressive area under the curve (AUC) value of 0.963. The model's goodness-of-fit was assessed using the Hosmer-Lemeshow test (χ2 = 10.023, P = 0.209). Furthermore, decision curve analysis revealed significantly improved net benefits with the model. External validation further confirmed the reliability of the proposed predictive nomogram. This study successfully developed a nomogram for predicting the occurrence of hemorrhagic shock in pediatric patients with multiple trauma. This nomogram may serve as an accurate and effective tool for timely and efficient management of children with multiple trauma.

RDmaster: A novel phenotype-oriented dialogue system supporting differential diagnosis of rare disease.

BACKGROUND: Clinicians often lack the necessary expertise to differentially diagnose multiple underlying rare diseases (RDs) due to their complex and overlapping clinical features, leading to misdiagnoses and delayed treatments. The aim of this study is to develop a novel electronic differential diagnostic support system for RDs. METHOD: Through integrating two Bayesian diagnostic methods, a candidate list was generated with enhance clinical interpretability for the further Q&A based differential diagnosis (DDX). To achieve an efficient Q&A dialogue strategy, we introduce a novel metric named the adaptive information gain and Gini index (AIGGI) to evaluate the expected gain of interrogated phenotypes within real-time diagnostic states. RESULTS: This DDX tool called RDmaster has been implemented as a web-based platform (http://rdmaster.nbscn.org/). A diagnostic trial involving 238 published RD patients revealed that RDmaster outperformed existing RD diagnostic tools, as well as ChatGPT, and was shown to enhance the diagnostic accuracy through its Q&A system. CONCLUSIONS: The RDmaster offers an effective multi-omics differential diagnostic technique and outperforms existing tools and popular large language models, particularly enhancing differential diagnosis in collecting diagnostically beneficial phenotypes.

Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives.

BACKGROUND: Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood. DATA SOURCES: A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included "COVID-19 in children", "severe pediatric COVID-19", and "critical illness in children with COVID-19". RESULTS: Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines. CONCLUSIONS: Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

A Patient Similarity Network (CHDmap) to Predict Outcomes After Congenital Heart Surgery: Development and Validation Study.

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

Use of extracorporeal membrane oxygenation in children with burn injury: Case report and literature review.

RATIONALE: Burns are one of the most debilitating injuries in the world and one of the major causes of accidental disability and death among children. Severe burns can result in irreversible brain damage, placing patients at high risk of brain failure and high mortality. Therefore, timely diagnosis and treatment of burn encephalopathy are crucial for improving prognosis. In recent years, extracorporeal membrane oxygenation (ECMO) has been increasingly used to improve the prognosis of patients with burns. Here, we report a case of ECMO treatment in a child with burns and review the relevant literature. PATIENT CONCERNS: A 7-year-old boy with a modified Baux score of 24 presented with asphyxia, loss of consciousness, refractory hypoxemia, and malignant arrhythmia after smoke inhalation for 1 day. Fiberoptic bronchoscopy revealed a large amount of black carbon-like substances aspirated from the trachea. DIAGNOSES: Considering that the boy inhaled a large amount of smoke, the clinical manifestation was unclear consciousness, laboratory examination revealed continuous low blood oxygen saturation, and bronchoscopy revealed a large amount of black carbon-like substances in the trachea, thereby leading to the diagnosis of asphyxia, inhalation pneumonia, burn encephalopathy, multiple organ dysfunction syndrome, and malignant arrhythmia. In addition, pulmonary edema and carbon monoxide poisoning are caused by chemical agents, gas fumes, and vapors. INTERVENTIONS: The boy's blood oxygen saturation and blood circulation remained unstable despite various ventilation methods and medications, thus we decided to use ECMO. After 8 days of ECMO support, the patient was successfully weaned from the machine. OUTCOMES: Under the application of ECMO, the respiratory and circulatory systems significantly improved. Nevertheless, due to the progressive brain injury caused by burns and the poor prognosis, the parents ceased all treatment and the boy passed away. LESSONS: This case report demonstrates that brain edema and herniation can arise as phenotypes of burn encephalopathy, which is a challenge to treat in children. Children with confirmed or suspected burn encephalopathy should undergo diagnostic tests completed as soon as possible to confirm the diagnosis. After receiving ECMO treatment, the respiratory and circulatory systems of the burn victims reported significantly improved. Hence, ECMO is a viable alternative for supporting patients with burns.

Mechanosensitive channel MscL induces non-apoptotic cell death and its suppression of tumor growth by ultrasound.

Mechanosensitive channel of large conductance (MscL) is the most thoroughly studied mechanosensitive channel in prokaryotes. Owing to its small molecular weight, clear mechanical gating mechanism, and nanopore forming ability upon opening, accumulating studies are implemented in regulating cell function by activating mechanosensitive channel of large conductance in mammalian cells. This study aimed to investigate the potentials of mechanosensitive channel of large conductance as a nanomedicine and a mechano-inducer in non-small cell lung cancer (NSCLC) A549 cells from the view of molecular pathways and acoustics. The stable cytoplasmic vacuolization model about NSCLC A549 cells was established via the targeted expression of modified mechanosensitive channel of large conductance channels in different subcellular organelles. Subsequent morphological changes in cellular component and expression levels of cell death markers are analyzed by confocal imaging and western blots. The permeability of mitochondrial inner membrane (MIM) exhibited a vital role in cytoplasmic vacuolization formation. Furthermore, mechanosensitive channel of large conductance channel can be activated by low intensity focused ultrasound (LIFU) in A549 cells, and the suppression of A549 tumors in vivo was achieved by LIFU with sound pressure as low as 0.053 MPa. These findings provide insights into the mechanisms underlying non-apoptotic cell death, and validate the nanochannel-based non-invasive ultrasonic strategy for cancer therapy.

Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children.

INTRODUCTION: Acute lung injury (ALI) after cardiac surgery is associated with a high postoperative morbidity and mortality, but few predictors are known for the occurrence of the complication. This study evaluated whether elevated plasma levels of soluble receptor for advanced glycation end products (sRAGE) and S100A12 reflected impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB). METHODS: Consecutive children younger than 3 years after cardiac surgery were prospectively enrolled and assigned to ALI and non-ALI groups, according to the American-European Consensus Criteria. Plasma concentrations of sRAGE and S100A12 were measured at baseline, before, and immediately after CPB, as well as 1 hour, 12 hours, and 24 hours after operation. RESULTS: Fifty-eight patients were enrolled and 16 (27.6%) developed postoperative ALI. Plasma sRAGE and S100A12 levels increased immediately after CPB and remained significantly higher in the ALI group even 24 hour after operation (P < 0.01). In addition, a one-way MANOVA revealed that the overall sRAGE and S100A12 levels were higher in the ALI group than in the non-ALI group immediately after CPB (P < 0.001). The multivariate logistic regression analysis showed that the plasma sRAGE level immediately after CPB was an independent predictor for postoperative ALI (OR, 1.088; 95% CI, 1.011 to 1.171; P = 0.025). Increased sRAGE and S100A12 levels immediately after CPB were significantly correlated with a lower PaO2/FiO2 ratio (P < 0.01) and higher radiographic lung-injury score (P < 0.01), as well as longer mechanical ventilation time (sRAGEN: r = 0.405; P = 0.002; S100A12N: r = 0.322; P = 0.014), longer surgical intensive care unit stay (sRAGEN: r = 0.421; P = 0.001; S100A12N: r = 0.365; P = 0.005) and hospital stay (sRAGEN: r = 0.329; P = 0.012; S100A12N: r = 0.471; P = 0.001). CONCLUSIONS: Elevated sRAGE and S100A12 levels correlate with impaired lung function, and sRAGE is a useful early biomarker of ALI in infants and young children undergoing cardiac surgery.

Factors associated with prolonged recovery after the arterial switch operation for transposition of the great arteries in infants.

This study aimed specifically to identify the predictors of prolonged recovery after the arterial switch operation for transposition of the great arteries in infants. The clinical records of all infants admitted to the surgical intensive care unit (SICU) between January 2000 and March 2011 after an arterial switch operation were retrospectively reviewed. The cohort was divided into a prolonged recovery group that included all patients who exceeded the 75th percentile for duration of SICU stay and a standard recovery group that included all the remaining patients. Of the 102 patients in the final analysis, 31 experienced prolonged recovery. The median SICU stay was 18 days (range, 14-58 days) for the patients in the prolonged recovery group and only 8 days (range, 5-13 days) for the patients in the standard recovery group. After univariate analysis, a stepwise logistic regression model analysis was used to compare the demographic data as well as the pre-, intra-, and postoperative variables between the two groups. Of all the variables analyzed, high postbypass serum lactate level [odds ratio (OR), 2.610; 95 % confidence interval (CI), 1.464-4.653; p = 0.039], need for larger volume of resuscitation fluid (OR, 3.154; 95 % CI, 1.751-5.682; p = 0.018), and noninfectious pulmonary complication (OR, 2.844; 95 % CI, 1.508-5.363; p = 0.025) were identified as independent risk factors for prolonged recovery among infants undergoing an arterial switch operation for transposition of the great arteries.

Epidemiology of unintentional injury in children admitted to ICU in China mainland: a multi-center cross-sectional study.

Background: To investigate the epidemiology of unintentional injury in children admitted to Intensive Care Unit (ICU) in China mainland. Methods: A total of 39 hospitals in 19 provinces contributed to the 1-day point prevalence study of serious unintentional injury in children aged 0-16 years admitted to ICU. Results: A total of 1,017 patients from the 39 participating ICUs on the study day were included. Among them, 56 pediatric patients were identified to be suffered from unintentional injury from 18 participating ICUs, accounting for 5.5% (56/1,017) of all the ICU patients. The percentage of boys was more than twice the percentage of girls. Most patients had an age of less than 6 years old (n=42, 75%). The leading cause of unintentional injury was fall (n=17, 30.4%). The patterns of unintentional injury in children were age-related. There were no urban-rural differences in our cohort. The injury happened on 12:00-18:00 PM in 27 cases (48.2%), and 28 patients (50%) had injuries happened at working day. 35 patients (62.5%) received primary treatment at local hospitals. Thirty-five patients (62.5%) needed resuscitation in the emergency department, 15 patients (26.8%) still needed resuscitation in ICU. These 56 children suffered from a total of 106 lesions corresponding to 1.89 lesions per patient. Respiratory failure was most commonly seen (n=18, 32.1%). There was no death in our cohort during the study. After effective treatment during their ICU stay, 45 (80.4%) patients showed improvement, with Glasgow Coma Scale (GCS), Pediatric Trauma Score (PTS) and Pediatric Risk of Mortality III (PRISM III) score significantly better than those before treatment (P<0.05). Conclusions: Higher injury rates among children under 6 years old of age illustrate the need for preventive measures, especially programs and public policies targeting this high-risk group.

A time-aware attention model for prediction of acute kidney injury after pediatric cardiac surgery.

OBJECTIVE: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery, and the early detection of AKI may allow for timely preventive or therapeutic measures. However, current AKI prediction researches pay less attention to time information among time-series clinical data and model building strategies that meet complex clinical application scenario. This study aims to develop and validate a model for predicting postoperative AKI that operates sequentially over individual time-series clinical data. MATERIALS AND METHODS: A retrospective cohort of 3386 pediatric patients extracted from PIC database was used for training, calibrating, and testing purposes. A time-aware deep learning model was developed and evaluated from 3 clinical perspectives that use different data collection windows and prediction windows to answer different AKI prediction questions encountered in clinical practice. We compared our model with existing state-of-the-art models from 3 clinical perspectives using the area under the receiver operating characteristic curve (ROC AUC) and the area under the precision-recall curve (PR AUC). RESULTS: Our proposed model significantly outperformed the existing state-of-the-art models with an improved average performance for any AKI prediction from the 3 evaluation perspectives. This model predicted 91% of all AKI episodes using data collected at 24 h after surgery, resulting in a ROC AUC of 0.908 and a PR AUC of 0.898. On average, our model predicted 83% of all AKI episodes that occurred within the different time windows in the 3 evaluation perspectives. The calibration performance of the proposed model was substantially higher than the existing state-of-the-art models. CONCLUSIONS: This study showed that a deep learning model can accurately predict postoperative AKI using perioperative time-series data. It has the potential to be integrated into real-time clinical decision support systems to support postoperative care planning.

Altered T-Cell Receptor ß-Chain and Lactate Dehydrogenase Are Associated With the Immune Pathogenesis of Biliary Atresia.

Background: Biliary atresia (BA) is considered to be an autoimmune-mediating inflammatory injury. The pathogenesis of BA has been proposed with the clonal transformation of T cells expressing analogous T-cell receptor ß-chain variable regions (TRBVs). Methods: The TRBV profile of the peripheral blood mononuclear cells (PBMCs) in infants with BA and control infants (healthy donors, HDs), respectively, were characterized by using high-throughput sequencing (HTS). The diversity of T cells was analyzed based on the frequency of complementarity-determining region 3 (CDR3) or V(CDR3)J. Moreover, the correlation between absolute lymphocyte count (ALC) and lactate dehydrogenase (LDH) or diversity (clonality) indices, respectively, were analyzed for subjects with BA and HD. Results: The diversity indices of CDR3, V(CDR3)J in BA are lower than those in subjects with HD, in addition, there are significantly different levels of neutrophile, neutrophile/lymphocyte ratio (NLR), and LDH between groups of BA and HD. The correlation between ALC and diversity index is significant in subjects with HD but is not for subjects with BA. Conversely, the relationship between ALC and LDH is significant in subjects with BA but is not for subjects with HD. Moreover, 12 CDR3 motifs are deficient or lower expression in BA compared with that in the HD group. Conclusion: Our results demonstrate that the profile of TRBV repertoire is significantly different between subjects with BA and HD, and suggest that the immune imbalance and elevated LDH level are associated with the pathogenesis of BA. Moreover, the values of neutrophile, NLR, and LDH could be used for the differential diagnosis of BA.

Increased nitrosoglutathione reductase activity in hypoxic pulmonary hypertension in mice.

Altered S-nitrosothiols (RSNO) signaling is linked to pulmonary hypertension. Recent studies have shown that S-nitrosoglutathione (GSNO) reductase (GSNOR) catalyzes the degradation of GSNO and indirectly regulates the level of RSNO in vivo. Our present study tested the hypothesis that chronic hypoxia causes pulmonary hypertension, in part, by the change of GSNOR activity that contributes to the depletion of RSNO. Male mice were exposed to normobaric hypoxia in a ventilated chamber for 1 to 21 days or normoxia for 21 days. Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels increased significantly after 21 days of hypoxic exposure. Hypoxia induced the overexpression of endothelial nitric oxide synthase and inducible nitric oxide synthase. The mRNA expression of GSNOR decreased on day 1 of hypoxic exposure, but increased significantly on day 7 compared with the normoxic group. The protein expression of GSNOR increased significantly in the lung tissue after 7 days of hypoxic exposure and its enzymatic activities also increased. Both the ratios of glutathione to glutathione disulfide and nitrate to nitrite were significantly lower in the hypoxic groups than in the normoxic controls. The results suggest an increased GSNOR activity interfered with the metabolism of RSNO in mice with hypoxic pulmonary hypertension. An imbalanced of redox status is associated with the pathogenesis of hypoxic pulmonary hypertension.

Performance of Pediatric Risk of Mortality, Pediatric Index of Mortality and PIM2 in term Chinese neonates.

Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality (PIM) and PIM2 could be applicable to the subset of term neonates has not been well investigated. The purpose of this study is to access and compare the performance of these scoring systems in predicting mortality probability in term Chinese neonates with critical illness. PRISM, PIM and PIM2 scores were calculated prospectively during a 1-year period on 243 neonates admitted to the neonatal intensive care unit (NICU) in the Children's Hospital of Zhejiang University in China. Of these, 36 neonates (14.81%) died in the NICU, while the mortality rates estimated by PRISM, PIM and PIM2 were 16.19, 14.58 and 11.12%, respectively. The area under the receiver-operating characteristic (ROC) curve [95% confidence intervals (CIs)] were 0.834 (0.767-0.902), 0.851 (0.786-0.916) and 0.854 (0.790-0.918) for PRISM, PIM and PIM2, respectively. The Hosmer-Lemeshow test gave a chi-square of 1.35 (p = 0.930) for PRISM, 1.03 (p = 0.960) for PIM and 4.58 (p = 0.469) for PIM2. The standardized mortality rates (SMRs) (95% CI) using PRISM, PIM and PIM2 were 0.92 (0.79-1.08), 1.02 (0.88-1.20) and 1.33 (1.13-1.62), respectively. Although PRISM, PIM and PIM2 have displayed good discrimination and calibration in the present setting, PIM is considered as the most accurate and appropriate tool for predicting mortality in the studied NICU.