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Background: Carbapenem-resistant gram-negative bacilli (CR-GNB) have been increasingly reported in China. However, dynamic monitoring data on molecular epidemiology of CR-GNB are limited in pediatric patients. Results: 300 CR-GNB isolates (200 Carbapenem-resistant K. pneumoniae (CRKP), 50 carbapenem-resistant A.baumannii (CRAB) and 50 carbapenem-resistant P. aeruginosa (CRPA)) were investigated. The predominant carbapenemase gene was blaNDM−1 (73%) and blaKPC−2 (65%) in neonates and non-neonates. Meanwhile, the predominant STs were ST11 (54%) in neonates and ST17 (27.0%) and ST278 (20.0%) in non-neonates. Notably, a shift in the dominant sequence type of CRKP infections from ST17 /ST278-NDM-1 to ST11-KPC-2 was observed during the years 2017–2021 and KPC-KP showed relatively higher resistance to aminoglycosides and quinolones than NDM-KP.BlaOXA−23 was isolated from all the CRAB isolates while only one isolate expressing blaBIC and 2 isolates expressing blaVIM−2 were found in CRPA isolates. ST195 (22.0%) and ST244 (24.0%) were the most common in CRAB and CRPA isolates and all the STs of CRAB belonged to CC92 while CRPA presents ST types with diversity distribution. Conclusion: CRKP showed different molecular phenotypes in neonates and non-neonates and was changing dynamically and high-risk clone of ST11 KPC-KP should be paid more attention. Most CRKP and CRAB strains shared the same CCs, suggesting that intrahospital transmission may occur, and large-scale screening and more effective measures are urgently needed. [ABSTRACT FROM AUTHOR]

Background: The concept of acute kidney injury (AKI) substages has been recommended to better phenotype AKI and identify high-risk patient groups and therefore improve the diagnostic accuracy of AKI. However, there remains a gap between the recommendation and the clinical application. The study aimed to explore the incidence of AKI substages based on a sensitive AKI biomarker of urinary cystatin C (uCysC), and to determine whether AKI substages were relevant with respect to outcome in critically ill children. Results: The multicenter cohort study enrolled 793 children in pediatric intensive care unit (PICU) of four tertiary hospitals in China. Children were classified as non-AKI, sub-AKI and AKI substages A and B according to uCysC level at PICU admission. Sub-AKI was defined by admission uCysC level ≥ 1.26 mg/g uCr in children not meeting the KDIGO criteria of AKI. In children who fulfilled KDIGO criteria, those with uCysC < 1.26 was defined as AKI substage A, and with ≥ 1.26 defined as AKI substage B. The associations of AKI substages with 30-day PICU mortality were assessed. 15.6% (124/793) of patients met the definition of sub-AKI. Of 180 (22.7%) patients with AKI, 90 (50%) had uCysC-positive AKI substage B and were more likely to have classical AKI stage 3, compared to substage A. Compared to non-AKI, sub-AKI and AKI substages A and B were risk factors significantly associated with mortality, and the association of sub-AKI (adjusted hazard ratio HR = 2.42) and AKI substage B (adjusted HR = 2.83) with mortality remained significant after adjustment for confounders. Moreover, AKI substage B had increased risks of death as compared with sub-AKI (HR = 3.10) and AKI substage A (HR = 3.19). Conclusions: Sub-AKI defined/based on uCysC occurred in 20.2% of patients without AKI and was associated with a risk of death close to patients with AKI substage A. Urinary CysC-positive AKI substage B occurred in 50% of AKI patients and was more likely to have classical AKI stage 3 and was associated with the highest risk of mortality. [ABSTRACT FROM AUTHOR]

The incidence and mortality of influenza in children had risen, but data are limited on children with severe influenza virus infection in China. We conducted a retrospective case–control study and collected the patients' clinical data. Clinical data including demography, clinical presentation, laboratory findings, radiologic findings, treatment and outcomes were collected. Children were clinically confirmed to have virus infection in Shanghai in three hospitals from June 2014 to June 2019. During the study, 36,047 children were enrolled. Among them, 118 met the criteria for severe flu. Clinical symptoms such as fever, cough, gastrointestinal symptoms, coma and epilepsy were higher in the severe group. Complications such as pneumorrhagia, heart failure, septic shock, acute renal failure and influenza-associated encephalitis were higher in the severe influenza group than the death group. The laboratory findings including decreased hemoglobin, high alanine aminotransferase, high urea nitrogen and high lactate levels were risk factors for death in children with influenza. Influenza-associated encephalopathy (IAE), acute respiratory distress syndrome (ARDS) were the common clinical manifestations and complications for the severe influenza, and delayed use of oseltamivir was found to be associated with fatality. [ABSTRACT FROM AUTHOR]

Genome sequencing is used to make genetic diagnoses in critically ill infants with rapid turnaround time (TAT). Herein, to delineate the value of a genetic diagnosis, we provide the results from 130 pediatric patients in a large, comprehensive children's hospital in China. This study was performed using an optimized trio genome sequencing (OTGS) test. The sequencing depth for patients was 40–50 × and for their parents, it was 8–10 ×. Patients from the pediatric or neonatal intensive care unit (PICU/NICU) with complicated clinical features were enrolled between June 2018 and December 2018, each with a phenotype suggesting an underlying genetic disorder. OTGS testing identified pathogenic variants in 62 of 130 individuals, resulting in a diagnosis rate of 47.7%. The TAT varied from 72 to 120 h, with an average of 94 h and a median of 90 h. Of the 62 infants with diagnoses, 48 (77.4%) had pathogenic single-nucleotide variants (SNVs), 12 (19.4%) had pathogenic copy number variations (CNVs) or structure variants (SVs), and 2 (3.2%) had small deletions in one allele plus pathogenic variants in another allele of autosomal recessive genes. Therapeutic strategies for 48.4% (30/62) of the diagnosed patients were modified and included transplantation, dietary recommendations, or change of drugs, which avoided morbidity and improved prognosis. This study provided high-capacity OTGS testing in detecting SNVs and chromosomal abnormalities with fast response, higher diagnostic yield, and lower cost. OTGS demonstrates the potential to be the first-tier of genetic testing used in critically ill infants in developing countries. [ABSTRACT FROM AUTHOR]

Background Vancomycin is a first-line antibiotic used for the treatment of severe gram-positive bacterial infections. Clinical guidelines recommend that the vancomycin trough concentration be 10–15 mg/L for regular infections and 15–20 mg/L for severe infections. We investigated whether increasing the vancomycin concentration would result in better clinical outcomes with sustainable adverse effects (AEs) in the Chinese population. Methods A prospective, open, multicenter clinical observational study was performed in patients with gram-positive bacterial infections from 13 teaching hospitals. Patients received vancomycin therapeutic drug monitoring. Clinical, microbiological, and laboratory data were collected. Results In total, 510 patients were enrolled, and 470 were evaluable, of whom 370 were adults and 100 were children; 35.53% had methicillin-resistant Staphylococcus aureus infections (vancomycin 50% minimum inhibitory concentration [MIC50] = 1, 90% minimum inhibitory concentration [MIC90] = 1), and 23.19% had Enterococcus species infections (vancomycin MIC50= 1, MIC90= 2). The average trough concentration was 10.54 ± 8.08 mg/L in adults and 6.74 ± 8.93 mg/L in children. The infection was eradicated in 86.22% of adults and 96% of children. Thirty-six vancomycin-related nephrotoxicity cases were reported in the enrolled population. No severe AEs or deaths were related to vancomycin therapy. Logistic regression analysis showed that trough concentration had no relationship with clinical outcomes (adults P =.75, children P =.68) but was correlated with adult nephrotoxicity (P <.0001). Vancomycin trough concentration had an applicable cut point at 13 mg/L. Conclusions Our study shows that vancomycin trough concentration has no statistical correlation with clinical outcomes, and is an indicator of nephrotoxicity in the observed population. We found no evidence that increasing vancomycin trough concentration to 15-20 mg/L can benefit Chinese patients with complicated infections. Clinical Trials Registration ChiCTR-OPC-16007920. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Nursing-sensitive indicators are considered effective tools for improving the quality of care in hospitals. However, these have not been used in paediatric intensive care units ( PICUs) in China. Aim To develop nursing-sensitive indicators for PICUs and to assess the quality of nursing in PICUs in China based on the nursing-sensitive indicators. Design Multi-centre, cross-sectional study. Methods Structure, process and outcome indicators were developed and measured from 1 January to 31 March 2014 in seven PICUs in China. Results The structure indicators showed that one nurse cared for an average of 2·8 patients in a PICU, and 44% of nurses had a bachelor's degree. The process indicators revealed that hand-washing compliance varied across PICUs, whereas pain management and physical restraint have not been adequately addressed in China. The outcome indicators revealed that the incidence rates of ventilator-associated pneumonia and central-line-associated blood stream infections were 2·96 and 0·7, respectively, per 1000 device days. Patients were intubated for a total of 4392 mechanical ventilator days, and 32 patients (7·29‰) had an unplanned extubation. Nurses were moderately satisfied in their jobs (3·1 ± 0·3), and parents reported that nurses provide high quality of care. Conclusions This study developed and used nursing-sensitive indicators to assess the quality of nursing in PICUs in China, which provided a reference for national and international comparisons of nursing quality in PICUs. Nursing staffing levels and education should be improved. Pain management and physical restraints should be regulated in China's PICUs. Nurse managers need to explore staff attitudes towards implementation of family-centred care. The development of a national database of nursing quality indicators can contribute to quality and safety improvement. Relevance to clinical practice This study developed a set of nursing-sensitive indicators, and these indicators were used to assess and improve the quality of nursing in PICUs. [ABSTRACT FROM AUTHOR]

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The article presents the authors' comments on Chinese contribution to global health as of August 30, 2014. Topics include China's global health development, China's rural and urban health-care network, and health-care technologies' use. Attention is paid to the China-Association of Southeast Asian Nations (ASEAN) Public Health Fund, the Asia-Pacific Economic Cooperation (APEC), and the first Brazil, Russia, India, China, and South Africa (BRICS) Health Ministers' meeting in Beijing, China.

The aim of this study was to establish the population pharmacokinetics (PK) model of Vancomycin for Chinese pediatric patients which can extrapolate to whole age periods by bridging the published adult population PK model and the established pediatric population PK model. The final consolidated population PK model was used to explore the correlation of pharmacokinetics/pharmacodynamics (PK/PD) indices and efficacy of vancomycin and to provide evidence for the optimized regimen of vancomycin in Chinese pediatric patients with Gram-positive bacterial infection. 108 pediatric patients with Gram-positive infections from 2 pediatric hospitals in China in the first period of the prospective multi-center vancomycin clinical observational study were enrolled to establish the population PK model. A one-compartment population PK model was established and validated. The correlation between vancomycin PK/PD indices [trough concentration (Cmin), peak concentration (Cmax), 0–24 h area under the curve (AUC0–24) and the area under the curve to minimum inhibitory concentration ratio (AUC0–24/MIC)] and the overall clinical outcomes (clinical efficacy and microbiological efficacy) in Chinese pediatric patients were evaluated. There is no significant correlation between PK/PD indices and clinical efficacy or microbiological efficacy. Considering the high clinical effective rate (>90%) and median AUC0–24/MIC values of 200–300, Chinese pediatric patients with Gram-positive bacterial infection may be suitable for lower AUC0–24/MIC target value compared to the target value of 400–600 recommended by IDSA guideline. Different optimal dose regimen of vancomycin for Chinese pediatric patients should be considered. Further evaluation in more prospective studies will be needed. [ABSTRACT FROM AUTHOR]

Objectives: Continuous renal replacement therapy becomes available utilization for pediatric critically ill, but the impact of mortality rate in severe sepsis remains no consistent conclusion. The aim of the study is to assess the effect of continuous renal replacement therapy in pediatric patients with severe sepsis and the impact this therapy may have on their mortality.Design: Propensity score-matched cohort study analyzing data prospectively collected by the PICUs over 2 years (2016-2018).Setting: Four PICUs of tertiary university children's hospital in China.Patients: The consecutive patients with severe sepsis admitted to study PICUs were enrolled from July 2016 to June 2018.Interventions: The patients were divided into the continuous renal replacement therapy group and the conventional (noncontinuous renal replacement therapy) group.Measurements and Main Results: A total of 324 patients with severe sepsis were enrolled. The hospital mortality rate was 35.6% (64/180) in the continuous renal replacement therapy group and 47.9% (69/144) in the noncontinuous renal replacement therapy group. After propensity score adjustment, the hospital mortality rate was 21.3% (29/136) in the continuous renal replacement therapy group and 32.4% (44/136) in the noncontinuous renal replacement therapy group. In subgroup analysis, the relative risk of dying was 0.447 (95% CI, 0.208-0.961) only in patients complicated by acute respiratory distress syndrome (p = 0.037), but not in patients with shock, acute kidney injury, acute liver dysfunction, encephalopathy, and fluid overload greater than 10%. The mean duration of continuous renal replacement therapy was 45 hours (26-83 hr) with an ultrafiltration rate of 50 mL/kg/hr. The level of interleukin-6 was decreased, and the percent of natural killer cells (%) was improved in the continuous renal replacement therapy group compared with the noncontinuous renal replacement therapy group. Furthermore, continuous renal replacement therapy was an independently significant risk factor for hospital mortality in pediatric patients with severe sepsis, and the interval between continuous renal replacement therapy initiation and PICU admission was an independent risk factor for hospital mortality in patients receiving continuous renal replacement therapy.Conclusions: Continuous renal replacement therapy with an ultrafiltration rate of 50 mL/kg/hr decreases hospital mortality rate in pediatric severe sepsis, especially in patients with acute respiratory distress syndrome. [ABSTRACT FROM AUTHOR]

We developed a clay pore water (CPW) isotopic method for tracing paleoenvironments characterized by sporopollens. The thick clayey layers have the advantage of preserving pore water regardless of whether the water is inherent in the clayey layers or not. Therefore, the clayey layers are a suitable target from which paleoenvironmental information can be extracted. Sediment sporopollens as well as CPW deuterium and oxygen isotopes were investigated in drilling cores obtained from a 130-m borehole at a field site in Hengshui in the North China Plain. Our interpretation of δ 18 O in CPW was consistent with sporopollens climate indices, indicating that CPW was an effective proxy for obtaining paleoenvironmental information. Sporopollens species were abundant in the cores, but the quantity of each species was low. Furthermore, mean annual temperature and precipitation curves were established using a pollen–climatic response surface model. The results indicated two warm-humid periods (5.2–0 m, 22.6–11 m) and one cold-dry period (8.8–6.4 m) in the Holocene as well as two warm-humid periods (90.6–83 m, 110.6–108.2 m) and three cold-dry periods (approximately 40 m, 66.4–56.8 m, approximately 100 m) in the Late Pleistocene. Data derived from the sporopollens and CPW cumulatively elucidate the environmental change in Northern China. [ABSTRACT FROM AUTHOR]

• Macrolides-resistant Bordetella pertussis (MRBP) threatens global public health. • Pertussis frequently occurs in infants aged 0-6 months and children aged 6-10 years. • The spread of MT28 ptxP3-MRBP was first reported in China. • Continuous surveillance on ptxP3-MRBP is thus required. To reveal the clinical and molecular characteristics of Bordetella pertussis (BP) prevalent in Shanghai, China. A total of 9430 children with suspected pertussis from 2021 to 2022 were included, and nasopharyngeal swab samples were collected for polymerase chain reaction detection, culture, antimicrobial susceptibility testing, and 23S rRNA gene A2047G detection. BP strains were typed using multilocus variable-number tandem-repeat analysis and virulence genotyping. Of 9430 cases, 5.1% and 1.6% were confirmed by polymerase chain reaction and culture, respectively. Infants (aged <1 year) accounted for 24.7% and presented much more severe symptoms than noninfants. Pertussis was most frequently detected in infants aged 0-6 months (11.3∼14.0%) and children aged >6-10 years (10.8∼21.7%). Macrolide-resistant BP (MRBP) accounted for 89.3%, and all carried the A2047G mutation. There were six multilocus variable-number tandem-repeat analysis types (MTs), including MT28 (62.0%), MT195 (20%), MT27 (10.0%), MT104 (4.7%), MT55 (2.7%), and MT32 (0.7%). BP strains with pertussis toxin (ptx) P3/ (pertactin) prn2/ptxC2/ptxA1/ (fimbrial proteins) fim2-1/fim3-1, including MT27, MT28, and MT32, accounted for 72.7%, among which MT27 and MT32 were macrolide-sensitive BP, whereas most (94.6∼100%) of MT28 were MRBP. Strains harboring ptxP1/prn1/ptxC1/ptxA1/fim2-1/fim3-1, including MT55, MT104, and MT195, belonged to macrolide-sensitive BP. The emergence and spread of MT28 ptxP3 -MRBP was first reported in China, highlighting the importance of continuous surveillance of ptxP3 -MRBP to prevent its potential circulation. [ABSTRACT FROM AUTHOR]

• SE in children was a cost intensive disease in China. • The median inpatient medical cost of children with SE was $1175.5 (665.1–2320.6). • Cost-driving factors including LOS, etiology and examinations, and treatments. • PFS and idiopathic/cryptogenic epilepsy were associated with a lower cost. To describe the inpatient medical cost during hospitalization in children with status epilepticus (SE) and identify factors associated with the cost by a nationwide, multicenter study in China. We retrospectively identified pediatric inpatients with SE form Hospital Information System (HIS) of 44 hospitals in 27 provinces in China between 2013 and 2015. Inpatient medical cost and factors associated with the cost were analyzed. A total of 4041 children diagnosed with SE with inpatient medical cost were enrolled in the present study. The median age at admission was 2.9 (range 0.1–18) years, and 2271 patients were male (56.2%). The median inpatient medical cost of children with SE was $1175.5 (665.1–2320.6). The median inpatient medical cost was $3865.6 (1837.4–8210.4) in children with SRSE and $1048.6 (619.8–1865.4) in those with N-SRSE (p < 0.0001). Children with length of hospital stay (LOS) > 7 showed a much higher inpatient medical cost than those with LOS ≤ 7 day ($2300.7 vs. $767.2, p < 0.0001). Regarding different etiologies, children with acute symptomatic etiology showed the highest median inpatient medical cost of $1681.1 (901.0–3699.6), in which children with central nervous system (CNS) infection reported $2606.0 (1380.0–5016.1) and prolonged febrile seizures (PFS) reported $909.8 (649.3–1322.0). Additionally, children with idiopathic/cryptogenic etiology reported a medical cost of $923.2 (548.9–1534.5). Multiple linear regression analysis of cost-driving factors revealed LOS > 7, examinations, treatment equipment and procedures, and treatment medicines were independently associated with a higher inpatient medical cost (R 2 = 60.91). In addition, PFS and idiopathic/cryptogenic epilepsy etiology were independently associated with a lower cost. SE in children was a cost intensive disease in China with a median inpatient medical cost of $1175.5. LOS, etiology and examinations, treatment equipment and procedures, and treatment medicines were significantly associated with inpatient medical cost. [ABSTRACT FROM AUTHOR]

Abundant geothermal springs occur along the Moxi fault located in western Sichuan Province (the eastern edge of the Qinghai-Tibet plateau), highlighted by geothermal water outflow with an unusually high temperature of 218 °C at 21.5 MPa from a 2010-m borehole in Laoyulin, Kangding. Earthquake activity occurs relatively more frequently in the region and is considered to be related to the strong hydrothermal activity. Geothermal waters hosted by a deep fault may provide evidence regarding the deep underground; their aqueous chemistry and isotopic information can indicate the mechanism of thermal springs. Cyclical variations of geothermal water outflows are thought to work under the effect of solid earth tides and can contribute to understanding conditions and processes in underground geo-environments. This paper studies the origin and variations of the geothermal spring group controlled by the Moxi fault and discusses conditions in the deep ground. Flow variation monitoring of a series of parameters was performed to study the geothermal responses to solid tides. Geothermal reservoir temperatures are evaluated with Na-K-Mg data. The abundant sulfite content, dissolved oxygen (DO) and oxidation-reduction potential (ORP) data are discussed to study the oxidation-reduction states. Strontium isotopes are used to trace the water source. The results demonstrate that geothermal water could flow quickly through the Moxi fault the depth of the geothermal reservoir influences the thermal reservoir temperature, where supercritical hot water is mixed with circulating groundwater and can reach 380 °C. To the southward along the fault, the circulation of geothermal waters becomes shallower, and the waters may have reacted with metamorphic rock to some extent. Our results provide a conceptual deep heat source model for geothermal flow and the reservoir characteristics of the Moxi fault and indicate that the faulting may well connect the deep heat source to shallower depths. The approach of hot spring variation research also has potential benefits for earthquake monitoring and prediction. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the clinical characteristics and molecular epidemiology of CRKP infection in neonatal patients in a children's hospital in China from 2017 to 2021., Methods: Species identification and antibiotic susceptibilities were tested with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 systems. The clinical data were collected from medical records. Carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were investigated by antimicrobial susceptibility testing, carbapenemase genes and multilocus sequence typing., Results: Six kinds of resistant genes and 23 STs were detected. Bla NDM-1 (n=83, 55.3%) was the predominant carbapenemase gene, followed by bla KPC-2 (n=45, 30.0%), bla NDM-5 (n=7, 4.7%), bla IMP-38 (n=6, 4.0%). Bla NDM-1 was predominant in 2017 and 2018, whereas bla KPC-2 increased in 2019 and became the predominant gene from 2020 to 2021. ST11 accounted for most infections (n=35, 23.3%), followed by ST278 (n=23, 15.3%), ST17 (n=17, 11. 3%) and ST2735 (n=16, 10.7%). ST278 and ST17 were predominant in 2017 and 2018, whereas ST11 increased in 2019 and became the predominant sequence type from 2020 to 2021. Compared with bla NDM-1 , the CRKP strains producing bla KPC-2 were characterized by high resistance to gentamicin, amikacin and levofloxacin and the change trend of drug resistance rate before and after COVID-19 was consistent with that of bla NDM-1 and bla KPC-2 ., Conclusions: The main sequence type of CRKP infection changed dynamically from ST278-NDM-1 to ST11-KPC-2 during the years 2017-2021 in the newborns. Antibiotic exposure and the prevalence of COVID-19 since 2020 may have led to changes in hospital population and lead to the changes., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

We retrospectively investigated CRKP isolates among 92 pediatric patients (32 neonates and 60 non‑neonates) in 2019 and 2020 (59 and 33 isolates, respectively) to investigate the molecular characteristics and virulence factors of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from pediatric patients,. All the CRKP isolates were subjected to antimicrobial susceptibility testing, string testing, molecular typing of virulence and carbapenemase genes, and multilocus sequence typing. Hypervirulent K. pneumoniae (Hvkp) was defined based on the detection of the regulator of mucoid phenotype A (rmpA).Sequence type 11 (ST11) accounted for the majority of infections in both neonates (37.5%) and non‑neonates (43.3%) (P > 0.05), whereas it increased from 30.5% (18/59) in 2019 to 60.6% (20/33) in 2020 (P < 0.05). Carbapenemase gene KPC-2 was predominant in both neonates and non‑neonates (46.9% vs. 51.7%, respectively), followed by New Delhi metallo-beta-lactamase 1 (NDM-1) (34.4% vs. 28.3%, respectively) (all P > 0.05). Compared to 2019, the proportion of bla NDM-1 decreased (44.1% vs. 6.1%) (P < 0.001), while that of bla KPC-2 increased (40.7% vs. 66.7%) (P = 0.017) in 2020. ybtS and iutA had a higher positivity rate in KPC-2 and ST11 producers (all P < 0.05); the KPC-2-, ybtS-, and iutA-positive isolates showed relatively higher resistance to fluoroquinolones and aminoglycosides, nitrofurantoin, and piperacillin/tazobactam, respectively. Furthermore, the combined expression (95.7%, 88/92) of carbapenemase and virulence-associated genes was detected, with the carbapenemase genes bla KPC-2 and bla TEM-1 combined with virulence-associated genes entB, mrkD, and ybtS accounting for the highest percentage (20.7%).Carbapenemase gene mutations in the CRKP strain from 2019 to 2020 highlight the importance of dynamic monitoring. The spread of hypervirulence-associated genes in CRKP strains and the high positivity rates of ybtS and iutA in KPC-2- and ST11-producing ones signify their high virulence potential in pediatric patients., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The number of children on prolonged mechanical ventilation (PMV) in pediatric intensive care units (PICU) has increased markedly, but little is known about the situation in mainland China. We carried out a multicenter retrospective investigation to describe the clinical characteristics and prognosis of Chinese children receiving long-term ventilation in the PICU., Methods: A retrospective study was performed in 11 PICUs. All participating patients with prolonged mechanical ventilation in the study were retrospectively identified and included from cases admitted to PICUs between January 1, 2017 and December 31, 2019., Results: A total of 346 children diagnosed with prolonged mechanical ventilation were included in the study. Overall, 240 survived and were discharged from PICU, 55 died in hospital, and 51 withdrew from mechanical ventilation support with 41 died after discharge. Lower airway diseases were the most common underlying causes (41.6%), followed by central nervous system diseases (29.5%), and neuromuscular diseases (13.3%). Most children (327, 94.5%) received invasive mechanical ventilation (IMV) and only 19 (5.5%) children received noninvasive ventilation (NIV). The median time of tracheostomy after ventilation was 21 days (15-35). Children with tracheostomy had lower mortality with longer PICU stay compared with patients without tracheostomy. Children who underwent tracheostomy were more likely to have central nervous system diseases and neuromuscular diseases., Conclusion: This study showed a steady increase in the number of children receiving prolonged mechanical ventilation during the study period in Chinese PICUs with distinct clinical characteristics and outcomes. A better community-based care for PMV children is needed in mainland China., (© 2023 Wiley Periodicals LLC.)

Resurgence and spread of macrolide-resistant Bordetella pertussis (MRBP) threaten global public health. We collected 283 B. pertussis isolates during 2016-2022 in Shanghai, China, and conducted 23S rRNA gene A2047G mutation detection, multilocus variable-number tandem-repeat analysis, and virulence genotyping analysis. We performed whole-genome sequencing on representative strains. We detected pertussis primarily in infants (0-1 years of age) before 2020 and older children (>5-10 years of age) after 2020. The major genotypes were ptxP1/prn1/fhaB3/ptxA1/ptxC1/fim2-1/fim3-1 (48.7%) and ptxP3/prn2/fhaB1/ptxA1/ptxC2/fim2-1/fim3-1 (47.7%). MRBP increased remarkably from 2016 (36.4%) to 2022 (97.2%). All MRBPs before 2020 harbored ptxP1, and 51.4% belonged to multilocus variable-number tandem-repeat analysis type (MT) 195, whereas ptxP3-MRBP increased from 0% before 2020 to 66.7% after 2020, and all belonged to MT28. MT28 ptxP3-MRBP emerged only after 2020 and replaced the resident MT195 ptxP1-MRBP, revealing that 2020 was a watershed in the transformation of MRBP.

The role of oral microbiota in viral encephalitis and/or viral meningitis (VEVM) remains unclear. In this hospital-based, frequency-matched study, children with clinically diagnosed VEVM (n = 68) and those with other diseases (controls, n = 68) were recruited. Their oral swab samples were collected and the oral microbiota was profiled using 16S rRNA gene sequencing. The oral microbiota of children with VEVM exhibited different beta diversity metrics (unweighted UniFrac distance: P < 0.001, R 2 = 0.025, Bray-curtis dissimilarity: P = 0.045, R 2 = 0.011, and Jaccard dissimilarity: P < 0.001, R 2 = 0.017) and higher relative abundances of taxa identified by Linear discriminant analysis (LDA) with effect size (Enterococcus, Pedobacter, Massilia, Prevotella&#95;9, Psychrobacter, Butyricimonas, Bradyrhizobium, etc., LDA scores > 2.0) when compared with the control group. The higher pathway abundance of steroid hormone biosynthesis predicted by oral microbiota was suggested to be linked to VEVM (q = 0.020). Further, a model based on oral microbial traits showed good predictive performance for VEVM with an area under the receiver operating characteristic curve of 0.920 (95% confidence interval: 0.834-1.000). Similar results were also obtained between children with etiologically diagnosed VEVM (n = 43) and controls (n = 68). Our preliminary study identified VEVM-specific oral microbial traits among children, which can be effective in the diagnosis of VEVM., (© 2022. The Microbiological Society of Korea.)

Objectives: To determine the diagnostic and clinical utility of trio-rapid genome sequencing in critically ill infants., Design: In this prospective study, samples from critically ill infants were analyzed using both proband-only clinical exome sequencing and trio-rapid genome sequencing (proband and biological parents). The study occurred between April 2019 and December 2019., Setting: Thirteen member hospitals of the China Neonatal Genomes Project spanning 10 provinces were involved., Participants: Critically ill infants (n = 202), from birth up until 13 months of life were enrolled based on eligibility criteria (e.g., CNS anomaly, complex congenital heart disease, evidence of metabolic disease, recurrent severe infection, suspected immune deficiency, and multiple malformations)., Interventions: None., Measurements and Main Results: Of the 202 participants, neuromuscular (45%), respiratory (22%), and immunologic/infectious (18%) were the most commonly observed phenotypes. The diagnostic yield of trio-rapid genome sequencing was higher than that of proband-only clinical exome sequencing (36.6% [95% CI, 30.1-43.7%] vs 20.3% [95% CI, 15.1-26.6%], respectively; p = 0.0004), and the average turnaround time for trio-rapid genome sequencing (median: 7 d) was faster than that of proband-only clinical exome sequencing (median: 20 d) (p < 2.2 × 10-16). The metagenomic analysis identified pathogenic or likely pathogenic microbes in six infants with symptoms of sepsis, and these results guided the antibiotic treatment strategy. Sixteen infants (21.6%) experienced a change in clinical management following trio-rapid genome sequencing diagnosis, and 24 infants (32.4%) were referred to a new subspecialist., Conclusions: Trio-rapid genome sequencing provided higher diagnostic yield in a shorter period of time in this cohort of critically ill infants compared with proband-only clinical exome sequencing. Precise and fast molecular diagnosis can alter medical management and positively impact patient outcomes., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Child unintentional injuries have become a hot topic worldwide, and substantial regional disparities existed in causes and characteristics. To date, limited data are available to investigate the causes and characteristics of child unintentional injuries from hospitals for children in China. Methods: A cross-sectional study was conducted between January 2017 and December 2018 in Shanghai, China. Patients aged <18 years with an unintentional injury presented to the emergency department were enrolled. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were retrieved from electronic health records (EHRs). Frequencies and proportions of categorical variables and means and SDs of continuous variables are presented. Chi-square test and Student's t -test were used for the comparison between groups, as appropriate. Logistic regression analysis was used to estimate potential risk factors for admission to the hospital. Results: A total of 29,597 cases with unintentional injuries were identified between January 2017 and December 2018, with boys vs. girls ratio of 1.75. Preschool children account for approximately two-thirds of unintentional injuries in the emergency department. A distinctive pattern of mechanisms of unintentional injuries between gender was documented, and sports injury was significantly higher in boys than in girls (10.2 vs. 7.8%). Compared with Canadian Emergency Department Triage and Acuity Scale (CTAS) Grade 3 patients, Grade 2 [odds ratio (OR) = 2.99, 95% CI = 1.93-4.63, P < 0.001] and Grade 1 (OR = 74.85, 95% CI = 12.93-433.14, P < 0.001) patients had higher risk of inhospital admission. For causes of injuries, compared with falling, foreign body and poison had a lower risk of inhospital admission, while transport injury (OR = 1.31, 95% CI = 1.07-1.59, P = 0.008) and high fall injury (OR = 2.58. 95% CI =1.48-4.49, P < 0.001) had a significantly higher risk of admission. Conclusions: There was a significant relationship between age-groups and unintentional injuries between gender, with decreased injuries among girls growing up older. Preventive measures should be taken to reduce transport injury and high fall injury, which had a significantly higher risk of admission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gong, Lu, Ma, Zheng, Hu, Liu, Song, Hu, Sun, Chen, Xie, Zhang, Duan and Xu.)

Purpose: This study aimed to investigate the genetic aetiology in Chinese children diagnosed with status epilepticus (SE)., Methods: Next-generation sequencing, copy number variation (CNV) analysis, and other genetic testing methods were conducted for children with SE lacking an identifiable non-genetic aetiology. Furthermore, the phenotype and molecular data of patients with SE were retrospectively analysed., Results: Among children with SE lacking an identifiable non-genetic aetiology, 73 out of 163 children (44.8 %) were found to have causative variants associated with SE including 66 monogenic mutations in 22 genes and 7 CNVs. Based on the American College of Medical Genetics and Genomics scoring system, the monogenic variants included 64 pathogenic/likely pathogenic and 2 uncertain significance variants. SCN1A gene mutations (n = 32) were the most common cause, followed by TSC2 (n = 5), CACNA1A (n = 5), SCN2A (n = 4), SCN9A (n = 2) and DEPDC5 (n = 2) gene mutations. Sixteen mutations were identified in single genes. Furthermore, 51 (77.3 %) monogenic mutations were de novo. Age at SE onset < 1 year (odds ratio [OR] = 2.70, 95 % confidence interval [CI]: 1.25-5.83, p = 0.012) and co-morbidity of intellectual disability (OR = 3.36, 95 %CI: 1.61-6.99, p = 0.001) were independently associated with pathogenic genetic variants., Conclusion: This study identified genetic aetiology in 44.8 % of patients with SE, which indicates a high burden of genetic aetiology among children with SE in China. Our findings highlight the importance for genetic testing of children with SE that lacks an identifiable non-genetic aetiology., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To describe the aetiology, clinical features, and short-term outcomes of children with status epilepticus (SE), in particular super-refractory SE (SRSE), by a nationwide multicentre study in China., Methods: In this retrospective study, inpatient children with SE were identified from neurology departments and paediatric intensive care units from 44 hospitals in 27 provinces of China between 2013 and 2015. Clinical data were exported from the Hospital Information System., Results: Clinical records from children with SE (n = 4255) aged 1 month to 18 years were enrolled; 13.1 % were diagnosed with SRSE. The most common known SE aetiology was acute symptomatic aetiology (42.8 %) and 50.2 % of SE was caused by epilepsy of unknown aetiology. Acute central nervous system (CNS) infections (38.8 %) were associated with SRSE (P < 0.001). The overall SE in-hospital mortality rate was 3.0 %, which was significantly higher in the children with SRSE than in those with non-SRSE (15.2 % versus 1.4 %, respectively; P < 0.001). Fourteen percent of the children with SE had various levels of neurological dysfunction at discharge. SRSE was a risk factor for in-hospital mortality (hazard ratio = 4.14; 95 % confidence interval [CI]: 2.34-7.32; P < 0.001) and neurological dysfunction at discharge (odds ratio = 2.85; 95 % CI: 1.90-4.27; P < 0.001)., Conclusion: Acute symptomatic aetiology was the most common known cause of paediatric SE. Aetiology was associated with progression to SRSE and short-term neurological dysfunction at discharge. Furthermore, SRSE was considered a risk factor for in-hospital mortality and short-term neurological dysfunction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Xuezhikang (XZK) is an extract of fermented red yeast rice that has lipid-lowering properties., Objective: To evaluate the effects of XZK on lipids in subjects with dyslipidemia but no coronary heart disease., Methods: A total of 116 adults with baseline non-high-density lipoprotein cholesterol (non-HDL-C) levels of approximately 208 mg/dL and low-density lipoprotein cholesterol (LDL-C) levels of approximately 175 mg/dL were randomized to either placebo or XZK 1200 or 2400 mg daily and treated for 12 weeks., Results: A majority of the patients were white (53.4%) or Asian (37.1%). Daily XZK 1200 mg and 2400 mg for 4 to 12 weeks resulted in statistically significant (P < .001) and clinically meaningful decreases in non-HDL-C (∼24% reduction) and LDL-C (∼27% reduction) compared with placebo. XZK treatment at either dose enabled approximately 50% of subjects to reduce their LDL-C levels by ≥ 30%. Doubling the XZK daily dose from 1200 to 2400 mg at treatment week 8 caused an additional 4.6% reduction in LDL-C. Significant benefits were also observed across secondary efficacy variables, including total cholesterol (TC), apolipoprotein B (Apo B), triglycerides, HDL-C, the TC/HDL-C ratio, and the Apo B/Apo A-I ratio, at treatment week 8 or 12. XZK was safe and well tolerated. Safety and tolerability profiles were similar across treatment groups. Most adverse events were gastrointestinal. No subject experienced myopathy or markedly elevated liver transaminases or creatine kinase., Conclusion: Xuezhikang significantly reduced non-HDL-C and LDL-C, and was well tolerated. Further, longer-term studies in more diverse patient populations are needed to corroborate these findings., (Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Objective: To learn application status of continuous blood purification (CBP) in pediatric intensive care unit (PICU), to provide reference to promote the development of CBP technology., Method: The survey of CBP application was conducted using questionnaire in 40 hospitals providing intensive care, which included children's hospitals and the pediatric sections of general hospitals from 28 provinces/municipalities/autonomous regions in China during March to July of 2012., Result: Totally 38 hospital replied, 25 hospitals carried out CBP technology, first carried out in 1997, the median year was 2008, 21 hospitals' PICU could independently carry out CBP device, 18 hospitals had the nurses who could professionally operate, routinely maintain the device. Continuous veno-venous hemodiafiltration was the largest implementation mode of CBP, accounting for 51.9%. Twenty-three hospitals used ordinary heparin, and 2 hospitals used low molecular weight heparin; 21 hospitals chose activated partial thromboplastin time as the coagulation testing, due to lack of equipment, only four hospitals chose activated clotting time as coagulation testing. Only 3 hospitals could apply before and after dilution joint technology. Kidney failure is still the disease accounting for the highest proportion of diseases requiring CBP application, accounting for 38.1%, followed by sepsis, 19.1%, drug poisoning 16.7%., Conclusion: CBP started 10 years ago, and got attention and promotion nearly five years ago in China, but the associated personnel, equipment were inadequate, anticoagulation, before and after dilution and other technical applications were not complete enough, high volume hemofiltration mode was seldom used.