Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored ATP synthesis. Among the transcriptome sequencing data, the difference of CXCL5 was the most significant. Both high copper and ADR exposure can cause up-regulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.

miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis.

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 µg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1ß, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.

MiR-539-5p inhibits the inflammatory injury in septic H9c2 cells by regulating IRAK3.

BACKGROUND: MicroRNAs (miRNAs) have been confirmed to play a potential role in sepsis, but little is known about their role in sepsis-induced cardiomyopathy (SIC). METHODS: The model of septic cardiomyopathy was constructed with H9c2 cells induced by lipopolysaccharide (LPS), and the expression of miR-539-5p was detected by qRT-PCR assay. ELISA, CCK-8, EdU TUNEL analysis were performed to evaluate the role of miR-539-5p in inflammation response, viability, proliferation and apoptosis of LPS-treated H9c2 cells. Moreover, miRWalk and TargetScan prediction, and dual-luciferase reporter gene assays were carried out to predict and confirm the target of miR-539-5p. Furthermore, the effects of target on inflammation response, proliferation and apoptosis of LPS-induced H9c2 cells mediated by miR-539-5p was further explored. RESULTS: The expression of miR-539-5p was obviously down-regulated in LPS-induced H9c2 cells. In addition, over-expression of miR-539-5p significantly inhibited the inflammation response, promoted viability and proliferation, and suppressed apoptosis of LPS-treated H9c2 cells. Moreover, interleukin-1 receptor-associated kinase 3 (IRAK3) was verified as a target of miR-539-5p by dual-luciferase reporter gene assay. Besides, IRAK3 was highly expressed in H9c2 cells transfected with miR-539-5p inhibitor detected with qRT-PCR and western blot assays. Furthermore, over-expression of IRAK3 partially weakened the effects of miR-539-5p mimic on the inflammation response, proliferation and apoptosis of LPS-induced H9c2 cells. CONCLUSIONS: MiR-539-5p potentially plays an important role in the pathogenesis of LPS-induced sepsis by targeting IRAK3, suggesting that miR-539-5p may be a potential new target for the treatment of LPS-induced sepsis.

Pediatric Reference Change Value Optimized for Acute Kidney Injury: Multicenter Retrospective Study in China.

OBJECTIVES: The standard definition of pediatric acute kidney injury (AKI) is evolving, especially for critically ill in the PICU. We sought to validate the application of the Pediatric Reference Change Value Optimized for Acute Kidney Injury in Children (pROCK) criteria in critically ill children. DESIGN: Multicenter retrospective study. SETTING: Six PICUs in mainland China. PATIENTS: One thousand six hundred seventy-eight hospitalized children admitted to the PICU with at least two creatinine values within 7 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKI was diagnosed and staged according to the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE), the Kidney Disease Improving Global Outcomes (KDIGO), and the pROCK criteria. Multiple clinical parameters were assessed and analyzed along with 90-day follow-up outcomes. According to the definitions of pRIFLE, KDIGO, and pROCK, the prevalence of AKI in our cohort of 1,678 cases was 52.8% (886), 39.0% (655), and 19.0% (318), respectively. The presence of AKI, as defined by pROCK, was associated with increased number of injured organs, occurrence of sepsis, use of mechanical ventilation, use of continuous renal replace therapy ( p < 0.05), higher Pediatric Risk of Mortality III score, and higher Pediatric Logistic Organ Dysfunction-2 score ( p < 0.001). The survival curve of 90-day outcomes showed that pROCK was associated with shorter survival time (LogRank p < 0.001), and pROCK definition was associated with better separation of the different stages of AKI from non-AKI ( p < 0.001). CONCLUSIONS: In this retrospective analysis of AKI criteria in PICU admissions in China, pROCK is better correlated with severity and outcome of AKI. Hence, the pROCK criteria for AKI may have better utility in critically ill children.

Update on recommendations for the diagnosis and treatment of SARS-CoV-2 infection in children.

Since the outbreak of novel coronavirus infection pneumonia in Wuhan City, China, in late 2019, such cases have been gradually reported in other parts of China and abroad. Children have become susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their immature immune function. As the outbreak has progressed, more cases of novel coronavirus infection/pneumonia in children have been reported. Compared with adults, the impact of SARS-CoV-2 infection in children is less severe, with a lower incidence and susceptibility in children, which results in fewer children being tested, thereby underestimating the actual number of infections. Therefore, strengthening the diagnosis of the disease is particularly important for children, and early and clear diagnosis can determine treatment strategies and reduce the harm caused by the disease to children. According to the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (trial version 7) issued by National Health Committee and the latest diagnosis and treatment strategies for novel coronavirus infection pneumonia in children, this review summarizes current strategies on diagnosis and treatment of SARS-CoV-2 infection in children.

Circulating plasma circular RNAs as novel diagnostic biomarkers for congenital heart disease in children.

OBJECTIVE: The diagnostic value of circulating circular RNAs (circRNAs) has received more and more attention. However, little has been reported about their potential in the diagnosis of congenital heart diseases (CHD). In this study, we explored differential expression of circRNAs from children with CHD to evaluate their potential as clinical biomarkers. METHODS: We established a discovery cohort (four CHD cases; four matched healthy controls) and a validation cohort (40 CHD cases; 40 matched healthy controls). Microarray expression analysis was performed on the discovery set to identify candidate circRNAs. Candidates were further validated in the validation set. The diagnostic accuracy of circRNAs was determined by receiver operating characteristic (ROC) analysis. Gene ontology (GO), pathway, and network analysis were performed to predict a network of circRNA/miRNA and target mRNAs related to CHD. RESULTS: The top seven significantly differentially expressed CHD-associated circRNAs were validated by RT-PCR as follows: hsa_circRNA_004183, hsa_circRNA_079265, hsa_circRNA_105039, hsa_circRNA_404686, hsa_circRNA_101050, hsa_circRNA_100787, and hsa_circRNA_101328. Three significantly down-regulated circRNAs (hsa_circRNA_004183, hsa_circRNA_079265, and hsa_circRNA_105039) were identified with area under curve (AUC) values of 0.758, 0.809, and 0.907, respectively; the combination had an AUC of 0.965. An interaction network was constructed by 43 circRNAs, 9 miRNAs, and 29 mRNAs, which involved in heart development. CONCLUSIONS: We identified three circRNAs under-expressed in plasma from children with CHD. These circRNAs may be crucial in the development of CHD and may serve as novel non-invasive biomarkers for the diagnosis of CHD in children.

MiR-107 induces TNF-α secretion in endothelial cells causing tubular cell injury in patients with septic acute kidney injury.

Activation of endothelial cells plays a key role in septic acute kidney injury (AKI). This study investigated the role of miRNA in endothelial-induced tubular cell injury in sepsis. Circulating endothelial cells (CECs) from septic AKI, non-septic AKI, septic non-AKI patients and healthy volunteers were isolated and cultured, and HK2 cells were exposed to CEC-conditioned medium. CEC-conditioned medium prepared from septic AKI patients led to cell shrinkage, decreased E-cadherin, the release of NAG and cell apoptosis in HK2 cells. TNF-α mediated the tubular cell injury induced by CEC-conditioned medium prepared from septic AKI patients. PCR array analysis detected that miR-107 was significantly increased in the CECs of septic AKI patients. MiR-107 was verified to target the 3'UTR of Dual-specificity phosphatase 7(DUSP7). Transfection of miR-107 ASO recovered the expression of DUSP7, suppressed the phosphorylation of ERK, and decreased the secretion of TNF-α in the CECs of septic AKI patients and in the peritubular endothelial cells of septic AKI mice. The inhibition of miR-107 prevented the decrease of E-cadherin, the release of NAG and cell apoptosis in HK2 cells exposed to CEC-conditioned medium prepared from septic AKI patients, and preserved the normal renal morphology and decreased the serum creatinine level in septic AKI mice. In conclusion, our study suggests that the increased miR-107 induces TNF-α secretion by targeting DUSP7 in endothelial cells, which may directly cause tubular cell injury in septic AKI.

[Effects of ω-3 polyunsaturated fatty acids on lymphocyte apoptosis rate in rats with sepsis].

OBJECTIVE: To investigate the effects of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on the apoptosis of thymic and splenic lymphocytes in rats with sepsis. METHODS: A total of 80 female Sprague-Dawley rats aged 7-8 weeks were randomly divided into model group, conventional lipid emulsion group (0.1 g/kg daily), low-dose ω-3 PUFAs group (0.1 g/kg daily), middle-dose ω-3 PUFAs group (0.2 g/kg daily), and high-dose ω-3 PUFAs group (0.3 g/kg daily). Cecal ligation and puncture were used to establish a rat model of sepsis. The treatment groups were then given tail vein injection of lipid emulsion or glucose diluents of ω-3 PUFAs at different doses, and the model group was given glucose injection via the tail vein at the same dose. According to the time of sacrifice, each group was further divided into 24-hour and 72-hour subgroups, with 8 rats in each subgroup. Hematoxylin and eosin staining was used to observe the pathological changes in the thymus and spleen. TUNEL was used to measure the apoptosis rates of thymic and splenic lymphocytes. RESULTS: In the three ω-3 PUFAs groups, the rats had a complete thymic lobular structure and clear structures of the cortex and medulla. In the model and the conventional lipid emulsion groups, the boundaries of the cortex and medulla were unclear and the number of lymphocytes was significantly reduced. In the ω-3 PUFAs groups, the structure of the red and white pulp of the spleen was maintained with the presence of splenic follicles, while in the model and the conventional lipid emulsion groups, the structure of the red and white pulp of the spleen was disordered and splenic follicles were significantly reduced or disappeared. Compared with the model and the conventional lipid emulsion groups, the ω-3 PUFAs groups showed significant reductions in the apoptosis rates of thymic and splenic lymphocytes at 24 and 72 hours (P<0.01). Compared with the low-dose ω-3 PUFAs group, the high-dose ω-3 PUFAs group had significantly reduced apoptosis rates of splenic lymphocytes at 24 and 72 hours (P<0.05). CONCLUSIONS: ω-3 PUFAs can reduce the apoptosis of thymic and splenic lymphocytes in rats with sepsis in a dose-dependent manner.

Interaction Between IGF1 Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Chinese Children.

BACKGROUND/AIMS: IGF1 is a key regulator in cell proliferation and apoptosis, and the 3' un-translated region (3'UTR) of the gene plays an important role in gene expression. For the first time, we explored the relationship between polymorphisms in the IGF1 3'UTR region and the risk of childhood acute lymphoblastic leukemia (ALL). METHODS: Questionnaires were applied to collect epidemiological data. The genotypes of IGF1 polymorphisms were tested in a population of 744 ALL patients and 1088 cancer-free controls utilizing Taqman. Cell functional studies included real-time PCR, cell culture and transfection and luciferase assays. RESULTS: We found that rs6214 homozygous AA genotype and rs6218 homozygous CC genotype were significantly associated with increased risk of childhood ALL. In addition, rs6218 CC genotype was associated with increased level of IGF1 mRNA in bone marrow, and the mutation in rs6218 led to aberrant binding capacity of hsa-miR-603 and hsa-miR-3941 in the 3'UTR of IGF1. CONCLUSION: Polymorphisms of rs6214 and rs6218 in the 3'UTR of IGF1 are associated with childhood ALL susceptibility, and the polymorphism of rs6218 is related with IGF1 expression at mRNA level.

Incidence, outcome, and prognostic factors of prolonged mechanical ventilation among children in Chinese mainland: a multi-center survey.

Objective: To evaluate the incidence, outcome, and prognostic factors of prolonged mechanical ventilation (PMV) in children in Mainland China. Methods: A prospective study was conducted in 11 pediatric intensive care units (PICUs) from May 1, 2021, to April 30, 2022. All pediatric patients on mechanical ventilation meeting the criteria for PMV were included in the study. Results: Out of 5,292 patients receiving mechanical ventilation, 278 children met the criteria for PMV (5.3%). After excluding case with incomplete data or lost to follow-up, the study included 250 patients. Among them, 115 were successfully weaned from mechanical ventilation, 90 died, and 45 were still on mechanical ventilation. The 6-month survival rate was 64%. The primary associated conditions of PMV were lower airway diseases (36%), central nervous system diseases (32%), and neuromuscular diseases (14%). The stepwise multiple logistic regression analysis indicated that the utilization of vasoactive agents and an elevated pediatric logistic organ dysfunction-2 (PELOD-2) score on the day of PMV diagnosis were significantly associated with an increased of PMV death. Specifically, the odds ratio (OR) for vasoactive agent use was 2.86; (95% CI: 0.15-0.84; P = 0.018), and for the PELOD-2 score, it was 1.37; 95% CI: 1.17-1.61; P < .001). Conversely, early rehabilitation intervention was negatively associated with the risk of PMV death (OR = 0.45; 95% CI: 0.22-0.93; P = .032). Furthermore, the tracheotomy timing emerged as an independent predictor of failure to wean from PMV, with an OR of 1.08, (95% CI: 1.01-1.16; P = .030). Conclusions: The study revealed a 5.3% incidence of PMV in children requiring mechanical ventilation in China. The use of vasoactive agents and a higher PELOD-2 score at PMV diagnosis were significantly associated with an increased risk of PMV death, whereas early rehabilitation intervention was identified as crucial for improving patient outcomes. The timing of tracheostomy was identified as a high-risk factor for failure to wean from mechanical ventilation.

[Risk factors for progression to severe pneumonia in children visiting the emergency department with pneumonia].

OBJECTIVE: To determine the risk factors for developing severe pneumonia in children under 5 years old with pneumonia. METHODS: A case-control study was conducted 246 children with pneumonia between 2 and 59 months old who were admitted to the department of emergency of the Children's Hospital of Nanjing Medical University from May 2019 to May 2021 were enrolled. The children with pneumonia were screened according to the diagnostic criteria of the World Health Organization (WHO). Case information of the children was reviewed to obtain relevant socio-demographic, nutritional status and potential risk factors. The independent risk factors for severe pneumonia were analyzed by univariate analysis and multivariate Logistic regression respectively. RESULTS: Among the 246 patients with pneumonia, 125 were male and 121 were female. The average age was (21.0±2.9) months, 184 children with severe pneumonia. The results of population epidemiological characteristics showed that there were no significant differences in gender, age and place of residence between the severe pneumonia group and the pneumonia group. Prematurity, low birth weight, congenital malformation, anemia, length of intensive care unit (ICU) stay, nutritional support, treatment delay, malnutrition, invasive treatment, history of respiratory infection were all related factors affecting the occurrence of severe pneumonia (severe pneumonia group vs. pneumonia group: the proportion of premature infants was 9.52% vs. 1.23%, low birth weight was 19.05% vs. 6.79%, congenital malformation was 22.62% vs. 9.26%, anemia was 27.38% vs. 16.05%, length of ICU stay < 48 hours was 63.10% vs. 38.89%, enteral nutritional support was 34.52% vs. 20.99%, treatment delay was 42.86% vs. 29.63%, malnutrition was 27.38% vs. 8.64%, invasive treatment was 9.52% vs. 1.85%, respiratory tract infection history was 67.86% vs. 40.74%, all P > 0.05). However, breastfeeding, type of infection, nebulization, use of hormones, use of antibiotics, etc. were not risk factors affecting severe pneumonia. Multivariate Logistic regression analysis showed that history of premature birth, low birth weight, congenital malformation, treatment delay, malnutrition, invasive treatment, and history of respiratory infection were independent risk factors for severe pneumonia [history of premature birth: odds ratio (OR) = 2.346, 95% confidence interval (95%CI) was 1.452-3.785; low birth weight: OR = 15.784, 95%CI was 5.201-47.946; congenital malformation: OR = 7.135, 95%CI was 1.519-33.681; treatment delay: OR = 11.541, 95%CI was 2.734-48.742; malnutrition: OR = 14.453, 95%CI was 4.264-49.018; invasive treatment: OR = 6.373, 95%CI was 1.542-26.343; history of respiratory infection: OR = 5.512, 95%CI was 1.891-16.101, all P < 0.05]. CONCLUSIONS: Premature birth history, low birth weight, congenital malformation, delayed treatment, malnutrition, invasive treatment, and history of respiratory infection are independent risk factors for severe pneumonia in children under 5 years old.

Successful weaning from the invasive respiratory support after nusinersen treatment in a child with SMA type 1: A case report.

Background: Spinal muscular atrophy (SMA) is an autosomal recessive disease, which can be classified into 4 types according to the symptom onset age and the highest physical developmental milestone. Among them, type 1 SMA is the most severe form that affects infants younger than 6 months. Permanent assisted ventilation is usually needed for infants with type 1 SMA before the age of 2 years due to the rapid progression of disease. Nusinersen can improve the motor function of SMA patients, but its effect on respiratory function varies. In the present study, we reported a case of child with type 1 SMA who was successfully weaned from the invasive respiratory support after nusinersen treatment. Case presentation: A girl aged 6 years and 5 months was admitted for SMA in the Children's Hospital of Nanjing Medical University for 18 times. She received the first administration of nusinersen in November 2020 at the age of 5 years and 1 month. At the age of 6 years and 1 month following 6 loading doses, we tried to wean the child from the invasive ventilation for non-invasive respiratory support using a nasal mask. At present, the patient shows oxygen saturation (SpO2) above 95% without ventilator support during the daytime, and no signs of dyspnea. A non-invasive home ventilator was used at nighttime for the sake of safety. The CHOP INTEND score increased by 11 points from the first loading dose to the sixth. She can now move her limbs against gravity, take in food orally and perform partial vocal function. Conclusions: We reported a child with type 1 SMA who was successfully weaned from the 2-years invasive ventilation after 6 loading doses, and now only need non-invasive ventilation 12 h per day. It is suggested that even a late nusinersen treatment can improve respiratory and motor function in SMA patients, and wean them from mechanical ventilation, thus improve the quality of life and reduce the medical cost.

Association of SH2 domain-containing protein 1A, immunoglobulins and T lymphocyte subsets with Epstein- Barr virus infections.

BACKGROUND: We aimed to analyze the levels and associations of SH2 domain-containing protein 1A (SH2D1A), immunoglobulins and T lymphocyte (TL) subsets in children with Epstein-Barr virus (EBV) infections. METHODS: Sixty children with EBV infections admitted from January 2019 to January 2022 were selected, including 29 cases of infectious mononucleosis (IM group) and 31 cases of chronic active EBV infections (CAEBV group). Another 42 healthy children undergoing physical examination in the same period were selected as a control group. Their changes in SH2D1A, immunoglobulins and TL subsets (CD3+, CD4+ and CD8+) were compared. RESULTS: The levels of CD3+, CD4+ and CD8+ in the IM group were higher than those of the control group (P < 0.05), while they were lower in the CAEBV group than those of the control and IM groups (P < 0.05). The levels of SH2D1A, signaling lymphocyte activation molecule (SLAM) and SLAM-associated protein (SAP) were significantly higher in the IM group than those in the control and CAEBV groups (P < 0.05). The CAEBV group had decreased protein expressions of SLAM and SAP compared with those of the IM group. SH2D1A was positively correlated with immunoglobulin A, immunoglobulin G and TL subsets (CD3+, CD4+ and CD8+) (P < 0.05). CONCLUSIONS: Detecting SH2D1A, immunoglobulins and TLs contributes to the diagnosis and differentiation of IM and CAEBV.

Clinical observation of glucocorticoid therapy for critically ill patients with COVID-19 pneumonia.

OBJECTIVE: We aimed to investigate the clinical effects of intravenous glucocorticoid (GC) therapy for severe COVID-19 pneumonia. METHODS: Seventy-two patients hospitalized with severe COVID-19 pneumonia who were discharged or died between 5 January 2020 and 3 March 2020 at Huangshi Infectious Disease Hospital were included. Patients were divided into a treatment group (GC group) and non-treatment group (non-GC group) according to whether they had received GCs within 7 days of hospital admission. RESULTS: There was no significant difference between groups for Acute Physiology and Chronic Health Evaluation (APACHE) II score and 28-day survival rate. The rate of invasive mechanical ventilation was higher in the GC group than in the non-GC group. On day 7 after admission, the GC group had shorter fever duration and higher white blood cell count than the non-GC group. In subgroup analysis by age and severity, there was no significant difference in 28-day survival rate and other indicators. Compared with those in the non-GC group, patients in the GC group more frequently required admission to the intensive care unit. CONCLUSION: In the present study, we found no significant improvement in patients with severe COVID-19 pneumonia treated with GCs within 7 days of admission.

A Systematic Review of Linezolid Pharmacokinetics/Pharmacodynamics in Patients Undergoing Continuous Renal Replacement Therapy: Does One Size Fit All?

BACKGROUND: Selection of the optimal antimicrobial posology in critically ill patients remains a challenge, especially in patients with sepsis who undergo continuous renal replacement therapy (CRRT). This systematic review aimed to analyze factors that influence the extracorporeal removal of linezolid. METHODS: A comprehensive search was performed to identify studies published up to March 2022 in PubMed, MEDLINE and EMBASE databases. Studies involving adults receiving CRRT and treatment with linezolid were considered eligible if the CRRT setting and linezolid's pharmacokinetic parameters were clearly mentioned. RESULTS: Six out of 110 potentially relevant studies were included. A total of 101 treatments were identified among 97 enrolled patients. Our analysis showed that continuous veno-venous hemodiafiltration (CVVHDF) was the most frequential used modality (52 cases). Despite distribution volume, the clearance (CL) of linezolid in these studies had large variability. Extracorporeal linezolid removal may be markedly impacted by CRRT dose. There is significant between-subject variability in the probability of pharmacokinetics-pharmacodynamics (PK-PD) target attainment of patients treated with CRRT. CONCLUSION: Dose adjustment, shortening the dosing interval, and continuous infusion were proposed as regimen optimization. Therapeutic drug monitoring is recommended due to the high variability of linezolid exposure among patients with CRRT, specifically for those whose bodyweight is high, renal function is preserved, and the MIC of infection bacteria is above 2 µg/mL.

Clinical characteristics and outcomes of children with prolonged mechanical ventilation in PICUs in mainland China: A national survey.

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.

Clinical Characteristics and Death Risk Factors of Severe Sepsis in Children.

Sepsis is a systemic inflammatory response syndrome caused by viral infection. The circulatory dysfunction caused by sepsis is also called septic shock or septic shock. The main characteristics are rapid onset, rapid changes, and involvement. Multiple organs in the body make diagnosis difficult, which seriously threatens the survival of patients. As many as one million people worldwide die every year because of SIRS, it is also the leading cause of death among children in hospital ICUs. This article is aimed at studying the clinical characteristics of severe sepsis in children and the risk factors for death. Based on the analysis of the pathogenesis of sepsis and the treatment of septic shock, 65 cases of children with PICU sepsis admitted to a hospital were selected. Data, to study its clinical characteristics and risk factors for death. The results of the study showed that despite the interaction among the removal factors of the three indexes of serum lactic acid value, PCIS level, and the number of organs involved in MODS, they are still related to the mortality of children with severe sepsis.

Epidemiology of Cardiopulmonary Arrest and Outcome of Resuscitation in PICU Across China: A Prospective Multicenter Cohort Study.

Objective: To investigate the epidemiology and the effectiveness of resuscitation from cardiopulmonary arrest (CPA) among critically ill children and adolescents during pediatric intensive care unit (PICU) stay across China. Methods: A prospective multicenter study was conducted in 11 PICUs in tertiary hospitals. Consecutively hospitalized critically ill children, from 29-day old to 18-year old, who had suffered from CPA and required cardiopulmonary resuscitation (CPR) in the PICU were enrolled (December 2017-October 2018). Data were collected and analyzed using the "in-hospital Utstein style." Neurological outcome was assessed with the Pediatric Cerebral Performance Category (PCPC) scale among children who had survived. Factors associated with the return of spontaneous circulation (ROSC) and survival at discharge were evaluated using multivariate logistic regression. Results: Among 11,599 admissions to PICU, 372 children (3.2%) had CPA during their stay; 281 (75.5%) received CPR, and 91 (24.5%) did not (due to an order of "Do Not Resuscitate" requested by their guardians). Cardiopulmonary disease was the most common reason for CPA (28.1% respiratory and 19.6% circulatory). The most frequent initial dysrhythmia was bradycardia (79%). In total, 170 (60.3%) of the total children had an ROSC, 91 had (37.4%) survived till hospital discharge, 28 (11.5%) had survived 6 months, and 19 (7.8%) had survived for 1 year after discharge. Among the 91 children who were viable at discharge, 47.2% (43/91) received a good PCPC score (1-3). The regression analysis results revealed that the duration of CPR and the dose of epinephrine were significantly associated with ROSC, while the duration of CPR, number of CPR attempts, ventricular tachycardia/ventricular fibrillation (VT/VF), and the dose of epinephrine were significantly associated with survival at discharge. Conclusion: The prevalence of CPA in critically ill children and adolescents is relatively high in China. The duration of CPR and the dose of epinephrine are associated with ROSC. The long-term prognosis of children who had survived after CPR needs further improvement.

A Novel Mutation c.841C>T in COPA Syndrome of an 11-Year-Old Boy: A Case Report and Short Literature Review.

COPA syndrome is a rare autosomal dominant disorder with auto-immune and auto-inflammatory abnormalities. This disease is caused by mutations of COPα, a protein that functions in the retrograde transport from the Golgi to the ER. Here we report the first COPA case of an 11-year-old boy with c.841C>T, p.R281W mutation. The arginine at position 281 was located in a highly evolutionary-conserved region. Immunosuppressive drugs and corticosteroids might not improve the long-term outcome of COPA patients. For patients with pulmonary disease, polyarthritis and/or kidney disorder, and suspected of COPA, genetic analysis should be conducted promptly for early diagnosis.

Study on the Clinical Significance of ACE2 and Its Age-Related Expression.

BACKGROUND: ACE2 plays a particular role in the changes in multiple organ functions. However, whether ACE2 expression differs at different ages and whether it plays a role in infection-related organ dysfunction remains unclear. METHODS: Female and male C57BL/6 mice in four different age groups were included in this study. Immunohistochemical and Western blot analyses were performed to evaluate ACE2 expression characteristics in lung tissues. At the same time, we detected the changes of ACE2 in human blood of different ages and evaluated its clinical significance in sepsis-associated organ dysfunction (SAOD). RESULTS: This study indicated that ACE2 is expressed differently in mouse lung tissues at four different ages (P < 0.05). The peak expression distribution of ACE2 in lung tissues was in the newborn and middle-aged cohorts (P < 0.05). Infants younger than one year had a significantly higher concentration of ACE2 in serum and enhanced susceptibility compared with other ages (P < 0.05). Serum APTT, D-dimer, LDH, and PCT, as well as ACE2 in sepsis and SAOD groups, were statistically significant (P < 0.05) and were related to an increased risk of SAOD. There was a positive correlation between ACE2 and D-dimer (P < 0.05). CONCLUSION: The levels of ACE2 expression varied in different age groups. It tends to be higher in infants and young children. This result suggests that young children are more susceptible to infection. Moreover, a cutoff value for the ACE2 level >1551.15 pg/mL and D-dimer >984.5 U/L should be considered a warning sign of infection-associated organ dysfunction and guide the clinician in evaluating the patient's multiple organ function.