Bioelectrical impedance phase angle and the mortality in critically ill children.

Background: Phase angle (PhA) is a variable obtained from bioelectrical impedance analysis (BIA). It is highly sensitive and specific and is commonly used in clinical nutrition assessment. Recently, PhA has shown promise in predicting clinical outcomes, especially as a new indicator of mortality, but its use in pediatric research is limited. This study aims to investigate the association between PhA measured at admission using BIA and PICU length of stay (LOS) and 60-day mortality in critically ill children and adolescents. Methods: A consecutive series of pediatric patients in the PICU underwent BIA measurements within 72 h of admission. All patients met the inclusion and exclusion criteria. Patient demographics, anthropometric measurements, pediatric index of mortality 2 score (PIM-2), and laboratory exams were recorded. Kaplan-Meier (K-M) survival curves were constructed based on the critical PhA value to assess differences in survival status within the 60-day window. Multivariate cox regression model was employed to illustrate the relationship between PhA and 60-day mortality rates. The Youden's index method was used to identify the critical cut-off value for PhA in relation to mortality rates. ROC curves provided the area under the curve (AUC) and a 95% confidence interval (CI). Results: A total of 205 pediatric patients (118 boys) were included, with a mean age of 9.2 years (±6.0). Survival curves indicated a cutoff value of 3.1°, with higher survival in patients with PhA ≥3.1° compared to those with PhA <3.1° (F = 10.51, p < 0.0001). The area under the ROC curve was 0.70, with a sensitivity of 0.65 and specificity of 0.72. Total hospital LOS was longer in the PhA <3.1° group compared to the PhA ≥3.1° group (p = 0.000). The PhA <3.1° group had a longer PICU LOS (adjusted for age and sex, HR 1.871, p = 0.000, log-rank test, p = 0.000). PhA and PIM-2 were two independently significant correlated variables (p < 0.05) for the 60-day mortality rate in this study. Conclusion: Low PhA in patients is associated with longer PICU LOS and an increased risk of PICU patient mortality. PhA not only serves as an indicator for monitoring pediatric nutrition but also as a prognostic indicator for PICU patients.

Cfhr1 gene deficiency exacerbates Staphylococcus aureus-induced sepsis and acute lung injury through complement alternative pathway hyperactivation.

OBJECTIVE: To explore the role of excessive activation of the complement alternative pathway (AP) in acute lung injury (ALI) and sepsis induced by Staphylococcus aureus. Subsequently, we aimed to define the effects of Cfhr gene deletion on Factor H expression, AP activation, and the development of sepsis-induced ALI. METHODS: A sepsis-induced ALI model was established in Cfhr1-knockout mice by tail vein injection of S. aureus. Sepsis scores, bacterial load in lungs, and cytokine and complement factor levels in blood and lung tissues were evaluated at 6, 12, and 24 h after model establishment. Real-time quantitative PCR and RNA sequencing (RNA-seq) were employed to assess the expression of complement pathway-associated molecules and identify differentially expressed genes (DEGs) related to immune responses. RESULTS: Compared to wild-type mice, Cfhr1-knockout mice exhibited significantly increased C3a formation in lung tissues following S. aureus infection, indicating enhanced terminal complement pathway activation. Notably, these mice also had higher bacterial colony counts in the lungs, suggesting impaired S. aureus clearance. Transcriptome analysis provided further insights into the impact of Cfhr1 deletion on biological processes and signalling pathways involved in immune response regulation. CONCLUSION: Cfhr1 deletion leads to excessive AP activation, exacerbating S. aureus-induced sepsis and ALI.

Quality improvement programmes in paediatric sepsis from a global perspective.

Sepsis is a major contributor to poor child health outcomes around the world. The high morbidity, mortality, and societal cost associated with paediatric sepsis render it a global health priority, as summarised in Paper 1 of this Series. Sepsis is characterised by a dysregulated host response to infection that manifests as organ failure, and children are uniquely susceptible to sepsis, as discussed in Paper 2. The focus of this third Series paper is quality improvement in paediatric sepsis. The 2017 WHO resolution on sepsis outlined key aims to reduce the burden of sepsis. As of 2024, only a small number of countries have implemented systematic, paediatric-focused quality improvement programmes to raise sepsis awareness, enhance recognition of sepsis, promote timely treatment, and provide long-term support for paediatric sepsis survivors. We examine programme successes and systematic barriers to quality improvement targeting paediatric sepsis. We highlight the need for programme design to consider the entire patient journey, starting with prevention, caregiver awareness, recognition at home, education of the health-care workforce, development of health-care systems, and establishment of long-term family and survivor support extending beyond the intensive care unit. Building on lessons learnt from existing quality improvement programmes, we outline implementation strategies and measures to enable benchmarking. Ultimately, quality improvement on a global scale can only be accelerated through a global learning platform focusing on paediatric sepsis.

Fecal Microbiota Transplantation for Severe Infant Botulism, China.

Infant botulism in a 4-month-old boy in China who continued to excrete toxins for over a month despite antitoxin therapy was further treated with fecal microbiota transplantation. After treatment, we noted increased gut microbial diversity and altered fecal metabolites, which may help reduce intestinal pH and enhance anti-inflammatory capabilities.

Pyogenic liver abscess in pediatric populations in beijing (2008-2023).

BACKGROUND: Data on pyogenic liver abscess (PLA) of children in China have been limited. We aimed to summarize the clinical feather, microbiological characteristics, management, and outcome of PLA in children. METHOD: We retrospectively reviewed PLA cases from January 2008 to June 2023 at Beijing Children's Hospital. Clinical characteristics, pathogens and management were analyzed. RESULTS: We diagnosed 57 PLA patients in our center. The median onset age was 4.5 years and the male-to-female ratio was 1.6:1. The median diagnostic time was nine days and the median length of stay was 22 days. Twenty-eight patients (49.1%) had predisposing factors, around 71.4% of the patients had malignant hematology and primary immunodeficiency disease. Patients with underlying factors were more likely to have extrahepatic organ involvement (p = 0.024), anemia (p < 0.001), single abscess (p = 0.042), unilateral involvement (p = 0.039), and small size of the abscess (p = 0.008). Twenty-four patients (42.1%) had extrahepatic organ involvement. Pathogens were identified in 17 patients (29.8%), the most common pathogens were Klebsiella pneumoniae and Staphylococcus aureus. The positive rate of metagenomic next-generation sequencing (mNGS) was 87.5% (7/8). On multivariable analysis, the extrahepatic organ involved (p = 0.029) and hepatomegaly (p = 0.025) were two independent factors associated with poor outcomes. CONCLUSIONS: PLA is usually seen in children with predisposing factors. Malignant hematology and primary immunodeficiency disease were the most common underlying diseases. Extrahepatic organ involvement and hepatomegaly are associated with poor prognosis. Increased use of mNGS could be beneficial for identifying pathogens.

Clinical characteristics and prognosis of paediatric respiratory syncytial virus-related encephalopathy.

BACKGROUND: To understand the clinical characteristics and prognosis of respiratory syncytial virus (RSV)-related encephalopathy in children. METHODS: A retrospective analysis of the data of children who were diagnosed with RSV-related encephalopathy and admitted to the paediatric intensive care unit (PICU) of Beijing Children's Hospital between November 2016 and November 2023 was performed. RESULTS: Four hundred and sixty-four children with RSV infection were treated in the PICU, and eight of these patients (1.7%) were diagnosed with RSV-related encephalopathy. The mean age of the patients was 24.89 (5.92 ∼ 36.86) months. Two patients had underlying diseases. The time from the onset of illness to impaired consciousness was 3 (1.88-3.75) days. Five patients had convulsions, and three patients had an epileptic status. The serum procalcitonin (PCT) level was 1.63 (0.24, 39.85) ng/ml for the eight patients, and the cerebrospinal fluid (CSF) protein level was 232 (163 ∼ 848) g/L. Among the 8 patients, four patients underwent electroencephalogram (EEG) monitoring or examination. One patient showed continuous low-voltage, nonresponsive activity, and another patient displayed persistent slow waves, the remaining two patients had negative results. One patient had a combination of acute necrotizing encephalopathy (ANE) and acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Additionally, one patient had ANE, and another had acute brain swelling (ABS). One patient died in the hospital, and the other seven patients were discharged with improvement. Routine follow-up was conducted for 4.58(0.5 ∼ 6.50) years, and all patients fully recovered. CONCLUSIONS: RSV-related encephalopathy could have varying clinical manifestations, and some types, such as ANE and ABS, are dangerous and can lead to death.

Enhancing Diagnosis and Treatment Adjustments for Travelers Infected with Burkholderia pseudomallei: A Case Report - Beijing Municipality, China, June 2023.

What is already known about this topic?: Burkholderia pseudomallei (BP) infection leads to melioidosis, a tropical disease endemic to coastal provinces of southern China. Physicians in non-endemic areas, do not commonly consider this disease as a primary differential diagnosis for febrile patients. What is added by this report?: This article discusses a case of melioidosis in Northern China. The patient, who had recently visited a Southeast Asian region with high melioidosis prevalence, fell ill after exposure to contaminated water. The disease progressed quickly and with severity. What are the implications for public health practice?: Healthcare workers need to remain vigilant regarding travel-related diseases for accurate differential diagnosis and to provide timely and effective treatment, especially for patients with recent travel history or symptoms during travel.

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OBJECTIVES: To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation (PMV) due to different primary diseases. METHODS: A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022. According to the primary disease, they were divided into respiratory disease (RD) group, central nervous system (CNS) group, neuromuscular disease (NMD) group, and other disease group. The four groups were compared in terms of general information, treatment, and outcome. RESULTS: There were significant differences among the four groups in age, body weight, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, Pediatric Risk of Mortality III (PRISM Ⅲ) score, analgesic and sedative treatment, nutrition supply, rehabilitation treatment, tracheotomy, successful ventilator weaning, and outcomes (P<0.05). Compared with the RD group, the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment, and the CNS group had a significantly higher proportion of children receiving tracheotomy (P<0.008). Compared with the other disease group, the CNS group and the NMD group had significantly lower PELOD-2 and PRISM III scores, and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged (P<0.008). CONCLUSIONS: There are differences in clinical characteristics among children receiving PMV due to different etiologies. Most children in the RD group have a younger age, and children in the CNS group have a relatively good prognosis.

Current situation and prospect for the diagnosis and treatment of pediatric critical rare diseases in China.

The onset of critical rare diseases (RDs) in children is rapid and dangerous, accompanied by a high mortality rate, which brings a heavy burden to both families and society. Multiple malformations, neuromuscular diseases, metabolic diseases, and heart diseases are the most common types of RDs in children of China, often manifesting with multiple organ dysfunction. At present, the diagnosis and treatment of critical RDs in children face challenges such as prolonged diagnosis time, a high misdiagnosis rate, limited treatment modalities, and a significant disease burden. However, with the progress in genetic testing technology, the establishment of multidisciplinary diagnosis and treatment platforms, and the implementation of relevant RD policies in China, children with critical RDs will received enhanced medical services, experience improved prognoses, and reintegrate into social life.

Incidence of coronary artery lesions in children with recurrent Kawasaki disease.

OBJECTIVE: Coronary artery lesions (CALs) are a major complication of Kawasaki disease (KD); however, data on CAL incidence and risk factors in recurrent KD are limited. METHODS: Ninety-seven children with recurrent KD were retrospectively enrolled from 2013 to 2022, and CAL incidence was tracked during admission, discharge, and during follow-up. RESULTS: Initially, 27.8% had CAL at admission and discharge, declining to 7.2% at 12 months post-discharge. Most patients (66 of 97, 68.0%) did not exhibit CAL at any of the time points, 7 cases presented CAL at all time points, indicating a persistent CAL. The remaining 20 cases presented CAL at admission but recovered at discharge or during follow-up. Notably, transient CALs had presented at discharge, or during the follow-up, but finally resolved at 12 months after discharge. Notably, prior IVIG resistance and increased prothrombin time seemed associated with CAL in recurrent KD, suggesting they could help identify patients needing close monitoring. CONCLUSION: The study highlights decreasing CAL incidence over time in recurrent KD but with diverse patterns, emphasizing the importance of monitoring and further investigations to confirm these findings.

Dynamics of platelet parameters in children with severe community-acquired pneumonia between viral and bacterial infections.

Background: Changes in platelet parameters may vary according to the different pathogens. However, little is known about the differences in platelet parameters in children with severe community-acquired pneumonia (CAP) children of viral and bacterial infections. Methods: This was a single-center retrospective study that included 156 children with severe CAP. Dynamic changes in platelet parameters, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT), were recorded at 24 h, 48 h, 72 h, and day 7 of admission, as well as at discharge. Results: At 72 h of admission, PLT in the viral infection group was significantly lower than that in the bacterial infection and bacterial and viral coinfections group. Meanwhile, the curve of changes in PLT (ΔPLT) in the viral infection group was clearly separated from the other two groups at this time point. Receiver operating characteristic (ROC) analysis showed that PLT at 72 h of admission could assist in distinguishing bacterial and viral infections in severe pneumonia children with the area under curve (AUC) value of 0.683 [95% confidence interval (CI): 0.561-0.805, P=0.007]. However, its sensitivity and specificity were not high, at 68% and 65%, respectively. Conclusions: Although the diagnostic value of platelet parameters in bacterial and viral infection in children with severe CAP is limited, they are still expected to be combined with other indicators to provide a reference for timely treatment.

Effect of Antimicrobial Stewardship 2018 on severe pneumonia with bacterial infection in paediatric intensive care units.

OBJECTIVES: Antimicrobial Stewardship 2018 (ASP 18) in China emphasizes the hierarchical control of antimicrobial drugs and the management of physicians' prescribing authority, especially in children. The purpose of this study was to assess the effect of implementation of ASP 2018 on antibiotic consumption, resistance, and treatment outcomes in children with severe pneumonia from bacterial infections. METHODS: A single center, retrospective study was conducted on 287 children with severe bacterial pneumonia, including 165 patients before intervention (May 2016-April 2018) and 122 patients after intervention (May 2018-April 2020). The antimicrobial resistance rates, antibiotic consumption, and clinical outcomes of the two periods were compared. RESULTS: After the implementation of ASP 2018, Staphylococcus aureus (17.9%) became the predominant Gram-positive bacterium. The resistance of Streptococcus pneumoniae to clindamycin, erythromycin, and tetracycline was significantly reduced (P < 0.001), and Staphylococcus aureus to tetracycline also decreased (P = 0.034). In addition, Klebsiella pneumoniae (18.4%) replaced Pseudomonas aeruginosa (9.5%) as the most common Gram-negative bacterium. The resistance rates of Klebsiella pneumoniae to amoxicillin/clavulanic acid (AMC) and trimethoprim/sulfamethoxazole (SXT), and Acinetobacter baumannii to cefotaxime and SXT decreased significantly (P < 0.02). Total consumption (DDD/100 patient-days) of five antibiotics (cephalosporins, carbapenems, macrolides, antifungal agents, and linezolid) showed a decreasing trend, and the decrease in antifungal agents and linezolid was the most significant (27.4% and 25.6%, P < 0.001). The isolation rate of multidrug-resistant (MDR) strains decreased significantly from the highest, 16.8%, before intervention to 6.7% after intervention (P < 0.001). CONCLUSION: Our data indicate that the implementation of antimicrobial management strategies has significantly reduced the consumption of antibiotics and the occurrence of antimicrobial resistance in children with severe bacterial pneumonia in PICU.

Multilevel omics for the discovery of biomarkers in pediatric sepsis.

Severe sepsis causes organ dysfunction and continues to be the leading reason for pediatric death worldwide. Early recognition of sepsis could substantially promote precision treatment and reduce the risk of pediatric death. The host cellular response to infection during sepsis between adults and pediatrics could be significantly different. A growing body of studies focused on finding markers in pediatric sepsis in recent years using multi-omics approaches. This narrative review summarized the progress in studying pediatric sepsis biomarkers from genome, transcript, protein, and metabolite levels according to the omics technique that has been applied for biomarker screening. It is most likely not a single biomarker could work for precision diagnosis of sepsis, but a panel of markers and probably a combination of markers detected at multi-levels. Importantly, we emphasize the importance of group distinction of infectious agents in sepsis patients for biomarker identification, because the host response to infection of bacteria, virus, or fungus could be substantially different and thus the results of biomarker screening. Further studies on the investigation of sepsis biomarkers that were caused by a specific group of infectious agents should be encouraged in the future, which will better improve the clinical execution of personalized medicine for pediatric sepsis.

Cryptosporidiosis diagnosed using metagenomic next-generation sequencing in a healthy child admitted to pediatric intensive care unit: a case report.

Background: Cryptosporidium infections in humans typically result in symptoms such as abdominal pain and diarrhea. When the diarrhea is severe, it can cause serious complications and even be life-threatening, especially in patients with compromised immune systems. Case presentation: Here, we reported the use of metagenomic next-generation sequencing (mNGS) to assist in the diagnosis and treatment of a 10-year-old boy with severe Cryptosporidium infection. Despite the absence of any history of immunocompromise, the infection still resulted in severe symptoms, including shock, as well as damage to his pancreas and kidneys. The mNGS tests detected the presence of Cryptosporidium parvum when conventional methods failed. The patient received anti-parasite treatment along with supportive care to manage the condition. With disease surveillance based on regular clinical tests and sequential mNGS tests, the child recovered from the severe conditions. Conclusion: Our study emphasized the importance of recognizing the potential severity of Cryptosporidium infection, even among individuals with normal immune systems. Timely diagnosis and ongoing monitoring are essential for patient prognosis.

Safety study of moxifloxacin in children with severe refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: With the increase in macrolide-resistant M. pneumoniae infections, off-label use is difficult to avoid. This study assessed the safety of moxifloxacin in pediatric patients with severe refractory M. pneumoniae pneumonia (SRMPP). METHODS: We retrospectively reviewed the medical records of children with SRMPP between January 2017 and November 2020 at Beijing Children's Hospital. They were divided into the moxifloxacin group and azithromycin group according to whether or not moxifloxacin was used. The clinical symptoms, radiographs of both knees, and cardiac ultrasounds of the children were collected after drug withdrawal for at least 1 year. A multidisciplinary team reviewed all adverse events and determined their relationship with moxifloxacin. RESULTS: A total of 52 children with SRMPP were included in this study (31 in the moxifloxacin group and 21 in the azithromycin group). In the moxifloxacin group, four patients had arthralgia, one had joint effusion, and seven had heart valve regurgitation. In the azithromycin group, three patients had arthralgia, one had claudication, and one had heart valve regurgitation; no obvious knee abnormalities were observed in the radiographs. No statistically significant differences in clinical symptoms or imaging findings were found between the groups. As for the adverse events, 11 patients in moxifloxacin group were deemed to be doubtfully related and one possibly related to moxifloxacin; in the azithromycin group, four patients were regarded to be doubtfully related to azithromycin and one not related. CONCLUSION: Moxifloxacin was well tolerated and safe for treating SRMPP in children.

The value of next-generation metagenomic sequencing in pathogen detection of pleural effusions and ascites from children with sepsis.

Objective: To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) using pleural effusion and ascites from children with sepsis. Methods: In this study, children with sepsis or severe sepsis and appeared pleural or peritoneal effusions were enrolled, of whom the pleural effusions or ascites and blood samples were conducted pathogen detection using both conventional and mNGS methods. The samples were divided into pathogen-consistent and pathogen-inconsistent groups based on the consistency of mNGS results from different sample types, and into exudate and transudate groups based on their pleural effusion and ascites properties. The pathogen positive rates, pathogen spectrum, consistency between different sample types, and clinical diagnosis consistency were compared between mNGS and conventional pathogen tests. Results: A total of 42 pleural effusions or ascites and 50 other type samples were collected from 32 children. The pathogen positive rate of the mNGS test was significantly higher than that of traditional methods (78.57% vs. 14.29%, P < 0.001) in pleural effusion and ascites samples, with a consistent rate of 66.67% between the two methods. Nearly 78.79% (26/33) of mNGS positive results of the pleural effusions and ascites samples were consistent with clinical evaluation, and 81.82% (27/33) of these positive samples reported 1-3 pathogens. The pathogen-consistent group outperformed the pathogen-inconsistent group in terms of consistency with respect to clinical evaluation (88.46% vs. 57.14%, P = 0.093), while there was no significant difference between the exudate and transudate groups (66.67% vs. 50.00%, P = 0.483). Conclusion: Compared to conventional methods, mNGS has great advantages in pathogen detection of pleural effusion and ascites samples. Moreover, consistent results of mNGS tests with different sample types provide more reference values in clinical diagnosis.

Fish oil fat emulsion alleviates traumatic brain injury in mice by regulation of microglia polarization.

Microglia activation, a hallmark of brain neuroinflammation, contributes to the secondary damage following traumatic brain injury (TBI). To explore the potential roles of different fat emulsions-long chain triglyceride (LCT) / medium chain triglyceride (MCT) and fish oil (FO) fat emulsion in neuroprotection and neuroinflammation in TBI, in this study, we first generated the controlled cortical impact (CCI) model of TBI mice. Then either LCT/MCT or FO fat emulsion treated mice were studied by Nissl staining to assess the lesion volume. Sham and TBI mice treated with 0.9% saline were used as controls. The fatty acid composition in different TBI mouse brains was further evaluated by gas chromatography. Immunofluorescent staining and quantitative RT-PCR both demonstrated the suppression of pro-inflammatory microglia and upregulated anti-inflammatory microglia in FO fat emulsion treated TBI brain or primary microglia induced by lipopolysaccharide (LPS) in vitro. Furthermore, motor and cognitive behavioral tests showed FO fat emulsion could partially improve the motor function in TBI mice. Together, our results indicate that FO fat emulsion significantly alleviates the TBI injury and neuroinflammation probably by regulating microglia polarization.