[Prognostic factors of extracorporeal membrane oxygenation in the treatment of severe pediatric acute respiratory distress syndrome].

Objective: To explore the factors affecting the prognosis of severe pediatric acute respiratory distress syndrome (ARDS) after receiving extracorporeal membrane oxygenation (ECMO) support. Methods: It was a multicenter prospective observational study. A total of 95 children with severe ARDS who were treated with ECMO salvage therapy from January 2018 to December 2022 in 9 pediatric ECMO centers in China were enrolled in the study. The general data, disease severity, organ function, comprehensive treatment and prognosis were recorded, and they were divided into survival group and death group according to the outcome at discharge. T test, chi-square test, multivariate Logistic regression and mixed linear model were used to analyze the relationship among baseline before ECMO treatment, some important indicators (pediatric critical scores, platelet count, albumin, fibrinogen, etc) during ECMO treatment and prognosis. Results: Among the 95 children with severe ARDS who received ECMO, 55 (58%) were males and 40 (42%) were females, aged 36.9 (0.5, 72.0) months. Twelve children (13%) were immunodeficient. Sixty-eight (72%) children were treated with venous artery (VA) mode and 27 (28%) with venous vein (VV) mode. The discharge survival rates of overall, VA, and VV mode children were 51% (48/95), 47% (32/68), and 59% (16/27), respectively. The number of immunodeficient children in the death group was higher, and there were lower pediatric critical scores, platelet count, albumin, fibrinogen and arterial oxygen partial pressure/fraction of inspired oxygen (PaO2/FiO2), higher ventilator driving pressure (ΔP), oxygenaion index (OI), and longer ARDS duration before ECMO (all P<0.05). There were no statistically significant differences in other indicators, including age, gender, weight, and ECMO mode among different prognostic groups (all P>0.05). High ΔP, high OI, low P/F, and low albumin were high-risk factors affecting prognosis(all P<0.05). After further grouping, it was found that ΔP≥25 cmH2O (1 cmH2O=0.098 kPa), P/F≤67 mmHg (1 mmHg=0.133 kPa) and OI≥35 were the thresholds for predicting poor prognosis (P<0.05). From 24 h after ECMO, there were significant differences in ΔP, P/F and OI between the dead group and the survival group (all P<0.05), and the differences gradually increased with the ECMO process. The platelet level was significant from 7 days after ECMO (P<0.05) and gradually expanded. Blood lactate levels showed a significant difference between the 2 groups on before and after ECMO (P<0.05) and gradually increased from 24 h after ECMO. Conclusions: The risk factors affecting the prognosis of severe ARDS in ECMO include high ΔP, high OI, low P/F and low albumin purification therapy before ECMO. The gradual decrease of ΔP, OI and increase of P/F from 24 h of ECMO predicted a good prognosis, while the gradual increase of lactate after ECMO application showed a poor prognosis.

The role of bacterial colonization of ventilator circuit in development of ventilator-associated pneumonia: a prospective observational cohort study.

OBJECTIVES: Ventilator-associated pneumonia (VAP) is a significant cause of prolonged hospital stay and increased mortality in mechanically ventilated children. Studies of the relationship between bacterial colonization of ventilator circuits (VCs) and VAP are lacking. This study aimed to investigate the role of bacterial colonization of VCs in the development of VAP, and to provide evidence for preventing VAP. METHODS: Mechanically ventilated patients admitted to the paediatric intensive care unit of a teaching hospital in China from October 2018 to November 2019 were enrolled. Specimens were collected from the VC and the patient's lower respiratory tract (LRT) for bacterial culture. Paired bacteria isolated from the VC and the patient's LRT, where colonization of the VC preceded that of the LRT, were evaluated for relatedness using pulsed field gel electrophoresis (PFGE). RESULTS: A total of 114 patients were included; the incidence rate of VAP was 28.1% (32/114). A total of 1368 samples were collected from VCs; 16% had positive bacterial culture. There was no significant difference in bacterial colonization of VCs between VAP and non-VAP. In 13 patients, the LRT and VC were concurrently colonized with the same bacteria, where colonization of the VC occurred before colonization of the patient's LRT. PFGE results demonstrated high correlation between bacteria from the LRT and VC in 11 patients. Among 114 mechanically ventilated children, VAP caused by bacteria from the VC occurred in six patients, accounting for 18.8% (6/32) of the overall VAP rate in this study. DISCUSSION: Bacterial colonization of the VC is a significant cause of VAP development in mechanically ventilated children. Preventive strategies for early identification and decontamination measures for contaminated VC may play a key role in preventing VAP.

[Interfacility transport with extracorporeal membrane oxygenation in pediatric patients: a multicenter study in China].

Objective: To investigate application and safety of pediatric interfacility-transport with extracorporeal membrane oxygenation (ECMO) in China. Methods: The data of 48 patients transported inter-hospital from February 2016 to May 2018 were collected from the following 4 centers: pediatric intensive care unit (PICU) of Bayi Children's Hospital Affiliated to the 7th Medical Center of PLA General Hospital, Pediatric Hospital of Fudan University, Henan Provincial People's Hospital and Children's Hospital of Zhejiang University School of Medicine. The data of patients' characteristics, ECMO mode and wean rate, and mortality were reviewed, which was further compared with the data of 57 compatible inner-hospital ECMO cases with t test, Rank sum test or chi-square test. Results: All the 48 interfacility-transports were accomplished by ambulance on land, with an average transfer distance of (435±422) km. The incidence of ECMO complications was 13% (6 case), without death. There were no significant differences in lactic acid, PaO(2) or SaO(2) before and after transport (4.0 (2.0, 7.5) vs. 3.0 (1.5, 6.0) mmol/L, Z=-1.579, P>0.05; 112(47, 405) vs. 166(122, 240) mmHg (1 mmHg=0.133 kPa), Z=-0.104, P>0.05; 0.97±0.02 vs. 0.96±0.03, t=1.570, P>0.05). Instead, PaCO(2) and pH were significantly different ((47±8) vs. (42±5) mmHg, t=2.687, P<0.05; 7.3±0.2 vs. 7.5±0.2, t=3.379, P<0.05). The total ECMO weaned rate was 73% (35/48) and the survival rate was 67% (32/48). No significant differences in demographic characteristics, ECMO mode or duration, transport distance or duration, or complications existed between the survival group and the death group (7/25 vs. 2/14, χ(2)=0.615, P>0.05; 4/28 vs. 2/14, χ(2)=0, P>0.05; (405±404) vs. (493±465) km, t=0.525, P>0.05; (5±4) vs. (5±5) h, t=0.388, P>0.05; 166 (128, 239) vs. 187(52, 405) h, Z=-0.104, P>0.05; 3/32 vs. 3/16, χ(2)=0.734, P>0.05). The lowest lactate value in survival group before ECMO transport was significantly lower than that in the death group ((5±5) vs. (8±6) mmol/L, t=2.151, P<0.05). There were neither significant differences in age, ECMO mode or support pattern (9/39 vs. 15/42, χ(2)=0.845, P>0.05; 6/42 vs. 7/50, χ(2)=0.001, P>0.05; 29/19 vs. 38/19, χ(2)=0.441, P>0.05), nor in ECMO weaned rate, survival rate or complications between interfacility-transport group and inner-hospital group (35/48 vs. 37/57, χ(2)=0.775, P>0.05; 32/48 vs. 35/57, χ(2)=0.313, P>0.05; 20/48 vs. 22/57, χ(2)=0.102, P>0.05). Conclusion: With appropriate transport equipment and mature teams who handle problems timely during the transport, critically ill children could be safely transported to the destination with ECMO.

[A modified mouse model of instable carotid atherosclerotic plaque].

Objective: To explore a modified method for constructing a mouse model of instable carotid plaque and provide the mouse model for simulating the development of human instable carotid plaque. Methods: Twenty-four low density lipoprotein receptor deficiency (LDLr-/-), C57BL/6, male mice were randomized into two groups according to computer-generated table, tandem constriction of carotid artery+ high cholesterol diet (tandem surgery group, n=12); sham surgery+ high cholesterol diet(sham surgery group, n=12). After 12 weeks of consecutive feeding, murine carotid artery were collected and analyzed by carotid ultrasound, pathological examination to assess the formation and stability of atherosclerotic plaque. Results: No statistical difference in body weight and blood lipid level between the two groups was observed (all P>0.05). After surgery, through ultrasound biomicroscopy, obvious stenosis at the two sites of tandem constriction and atherosclerotic plaque between the two sites were observed in tandem surgery group. By pathological examination, no plaque was formed in carotid artery in sham surgery group. The lipid area in the stable plaque of innominate artery in sham surgery group and the plaque of carotid artery in tandem surgery group were (4.8±0.6) ×10(4),(10.2±1.1)×10(4) µm(2), respectively. The difference was statistically significant between the two groups (t=12.023,P<0.001). In addition, the thickness of fibrous cap in the above groups were (122.4±17.8), (41.3±20.2) µm, respectively. The difference was statistically significant either (t=9.224, P<0.001). The region of necrotic core were (3.3±0.4)×10(4),(8.1±0.9)×10(4) µm(2).The difference was statistically significant as well (t=13.456, P<0.001). The percentage of macrophages in innominate artery of sham surgery group and in carotid artery of tandem surgery group were (20.8±5.2)%, (38.6±6.4)%, respectively.The percentage of vascular smooth muscle cells were (32.5±7.3)%,(21.2±5.1)%, respectively (t=6.114,3.585, all P<0.05). The results indicated that the plaque in tandem surgery group had severer inflammatory response. Conclusion: Through tandem constriction surgery upon carotid artery in LDL-/-mouse, instable carotid atherosclerotic plaque can be induced, which is less time-consuming, replicable and effective.

[Multicenter investigation of extracorporeal membrane oxygenation application in pediatric intensive care unit in China].

Objective: To survey the conduction and evaluate the effectiveness of extracorporeal membrane oxygenation (ECMO) therapy in pediatric intensive care unit (PICU) in China mainland. Methods: In a questionnaire-based survey, we retrospectively reviewed the application of ECMO in children's hospital and general hospital in China mainland to summarize and analyze the categories of diseases and prognosis of children treated with ECMO therapy. Results: By December 31, 2017, a total of 23 hospitals using ECMO, including 22 tertiary referral hospitals and 1 secondary hospital, among which 16 were children's hospitals and 7 were general hospitals. Thirty-seven ECMO equipment was available. A total of 518 patients treated with ECMO, within whom 323 (62.4%) successfully weaned from ECMO and 262 (50.6%) survived to discharge. Among 375 pediatric patients, 233 (62.1%) were successfully weaned from ECMO and 186 (49.6%) survived to discharge. Among 143 newborn patients, 90 (62.9%) successfully weaned from ECMO, 76 (53.1%) survived to discharge. ECMO was applied in veno-arterial (VA) mode to 501 (96.7%) patients, veno-venous (VV) mode to 14 (2.7%) patients, and VV-VA conversion mode to 3 (0.6%) patients. Sixty-nine patients required extracorporeal cardiopulmonary resuscitation (ECPR), including 20 newborn patients (29.0%) and 38 pediatric patients (71.0%), who were all with cardiovascular disease. Neonatal respiratory distress syndrome (26/61), persistent pulmonary hypertension of the newborn (PPHN) (12/61), and meconium aspiration syndrome (MAS) (11/61) are the most common pulmonary diseases in newborn patients; among whom, infants with PPHN had highest survival rate (10/12), followed by MAS (9/11). Among newborn patients with cardiovascular diseases, those who admitted were after surgery for congenital cardiac disease were the most common (54/82), while those with septic shock had the highest survival rate (2/3). In pediatric pulmonary diseases, acute respiratory distress syndrome was the most common (42/93), while plastic bronchitis was with the highest survival rate (4/4), followed by viral pneumonia (13/16). Among pediatric cardiovascular diseases, congenital cardiac defect was the most common (124/282), while fulminant myocarditis had the highest survival rate (54/77). Conclusion: The application of ECMO as a rescue therapy for children with severe cardiopulmonary failure has dramatically developed in China mainland.

[Effects and mechanisms of high-volume hemofiltration on endotoxin-induced acute lung injury of piglets].

Objective: To compare the effects of high-volume hemofiltration (HVHF) and continuous veno-venous hemofiltration (CVVH) on cardiopulmonary functions, lung fluid balance, lung damage and cytokine expression in endotoxin-induced acute lung injury piglet model, and to further evaluate the value of high-volume hemofiltration in acute lung injury. Method: Eighteen piglets were randomly divided into the control group (6 piglets), the CVVH group (6 piglets) and the HVHF group (6 piglets). By general anesthesia, the intravenous infusion of 0.15 mg/kg endotoxin were received in all the animals and induced acute lung injury.High-volume hemofiltration and continuous veno-venous hemofiltration were addressed to different groups.Subsequently, hemodynamic parameters (heart rate, mean arterial blood pressure, central venous pressure, pulse contour cardiac index, systemic venous resistance index and extravascular lung water index) as well as gas exchange and lung mechanics parameters (respiratory rate, partial pressure of carbon dioxide, partial pressure of oxygen/fraction of inspired oxygen, dynamic lung compliance and airway resistance) were intermittently measured.Lung tissues were collected for further analysis (the lung wet-to-dry weight ratio, lung injury scoring). The plasma protein levels of cytokines (interleukin(IL) -6, 10 and tumor necrosis factors alpha(TNF-α)) were also assessed.Two-way analysis of variance (ANOVA) and Bonferroni post-test were conducted to identify significant differences among the control, CVVH and HVHF group. Result: Compared with CVVH, HVHF had the capacity to improve significantly the index of Cdyn(HVHF (2.3±0.5) vs. CVVH (1.5±0.5) ml/(cmH(2)O·kg), 1 cmH(2)O=0.098 kPa, P<0.05)and Rrs(HVHF (22.0±1.9) vs.CVVH (29.5±1.5) cmH(2)O/(L·s), P<0.05)at the time of 6 h, and decreased lung water accumulation(index of EVLWI in HVHF (22.7±2.1) vs.CVVH (39.5±2.6) ml/m(2,) P<0.01) at the time of 6 h, and the plasma concentration of cytokines(IL-6, IL-10, TNF-α)in the HVHF group had an obvious decline compared with those in the CVVH group at the time of 6 h( (200±55) vs. (280±61), (74±17) vs. (102±21), (54±13) vs. (73±21) pg/ml, all P<0.05). The lung injury scoring of HVHF group was significantly lower than those of CVVH group((7.8±1.9) vs. (11.3±2.2) scores, P<0.05). Although the plasma concentration of cytokines(IL-6, IL-10, TNF-α) in the CVVH group were lower than those in the control group at the time of 6 h((374±55), (137±25), (98±17) pg/ml, all P<0.05), the indexes of respiratory function were not improved (all P<0.05). Conclusion: Different doses hemofiltration can reduce plasma inflammatory mediators indicators in piglets.Early high volume hemofiltration can improve respiratory function of piglets with endotoxin-induced acute lung injury and reduce lung injury pathological score.

[Follow-up of survived children supported by extracorporeal membrane oxygenation].

Objective: To summarize the follow-up of children treated with venoarterial extracorporeal membrane oxygenation (ECMO) by incision of internal carotid artery-vein. Method: This was a retrospective study, 10 children in whom the conventional therapy failed, but survived after treatment with ECMO technique through right internal jugular artery-venous incision and ligation after ECMO in pediatric intensive care unit (PICU) of Fudan University were followed up from December 2011 to December 2015. Primary disease situation, neurological development, growth and development, quality of life and personality development were included. All children were followed up once every six months after discharge, and once a year after 2 years. The longest follow-up period was 2 years. Result: Of the 10 children 6 were boys and 4 girls, and ranged in age of onset from 1 day to 12 years . Five children had neurological problems, including abnormal brain CT (n=3), abnormal electroence phalogram (EEG) (n=3), and mental retardation (n=2). Three of those children had a history of hypoxia, 2 of whom accepted cardiopulmonary resuscitation. Eight children had normal brainstem evoked potential (BEAP) examinations. Primary diseases were all well controlled except for 6 children who had different degrees of sequelae, including mild arrhythmia (n=1), heart structure abnormality (n=2) and abnormal pulmonary function (n=3). The sequelae caused by the primary diseases were just embodied in examination. Their head circumference measurement and physical examination showed no obvious abnormalities, and blood biochemical tests, hemoglobin and blood gas analysis were also normal. One child's height was less than P3. The one who accepted cardiopulmonary resuscitation (CPR) at early stage of primary disease had trouble in daily life, presenting uncoordinated and unstable walking. One child was slightly bad tempered and asocial, and the rest were normal. Conclusion: The rest could take care of themselves. The ECMO sequelae of those survived children were mostly caused by primary diseases. ECMO treatment is safe and has less adverse consequences.

[Investigation on extracorporeal membrane oxygenation application in pediatric intensive care unit in China].

OBJECTIVE: To review the use of non-open chest extracorporeal membrane oxygenation (ECMO) in pediatric intensive care unit (PICU) in China. METHOD: The survey was conducted in 28 tertiary hospitals in China mainland from March to October 2015. All children <18 years of age have been supported with non-open chest ECMO in PICU were reviewed.Patient demographics, diagnosis, indication for ECMO, details of ECMO support, complications, and patient survival were analyzed. All the patients were divided according to age into pediatric patients (age>28 d) and neonatal patients (age 0-28 d). For non-normally distributed measurement data, two groups were compared using independent samples of the Mann Whitney U test and for categorical data constitute ratio were compared by χ(2) test or Fisher's exact test. RESULT: A total of 63 patients received non-open chest ECMO support during this study, including 51 pediatric patients and 12 neonates. For 51 pediatric patients, their mean age was 55.5 (15.0-117.0) months, and mean weight was 17.5 (10.0-32.9) kg. Cardiac failure was the primary indication in 28 patients, respiratory failure in 21 patients, and both cardiac and respiratory in 2 patients. Patients with cardiac disease had a lower mortality rate compared with cases with respiratory disease (21%(6/28) vs. 67% (14/21), χ(2)=9.145, P=0.002). The average length of ECMO run was 112.0 (74.5-175.2) h, and 96.7(76.2-139.5)h for cardiac patients, 149.0(78.9-241.0)h for patients with respiratory disease. There were no significant difference between patients with cardiac disease and patients with respiratory disease in ECMO support time (Z=1.476, P=0.140). Forty-two patients (82%) were decanulated from ECMO successfully, and thirty-one (61%) patients survived to hospital discharge. The most common complications during ECMO run were bleeding, hemolysis and disfunction of oxygenation. Of the 25 (49%) survivors whom we followed up, 8 (17%) experienced obvious sequelae, and 5 (10%) had neurologic problems. Of twelve neonates, their mean weight was(3.2±0.5)kg. The primary cause of ECMO was neonatal respiratory distress syndrome(7 cases). All of the neonatal patients were treated with veno-arterial (VA)-ECMO. The mean duration of ECMO support was 88.4 (45.50-110.25) h. Seven patients were decanulated from ECMO successfully, five survived to hospital discharge. CONCLUSION: ECMO support can significantly improve the prognosis of pediatric and neonatal patients with refractory respiratory and cardiac failure. More efforts are needed on patient selection, experienced team establishment and ECMO therapy technology improvement need further improvement in China in the future.

[Complications of critically ill children supported by venoarterial extracorporeal membrane oxygenation].

OBJECTIVE: To study the complications occurred in the process of venoarterial extracorporeal membrane oxygenation (VA-EMCO) in critically ill children. METHOD: To analyze retrospectively 25 children who were admitted to PICU of Children's Hospital of Fudan University from December 2011 to December 2015. They were all treated with VA-ECMO with incision and catheterization in right internal carotid artery and jugular vein. Complications were recorded during ECMO process. RESULT: The duration of ECMO treatment was 14 to 567 h (153 (112, 204) h). Seventeen cases (68%) withdrew from ECMO successfully and 15 cases (60%) survived to discharge. Thirty-three complications occurred during ECMO treatment. Of which, mechanical complications occurred 9 times, including oxygenator leakage (n=3), hemolysis (n=2), water tank failure (n=2), pump head rupture (n=1) and piping thrombosis (n=1). Somatic complications appeared 24 times, including neurological complications (n=8) which included cerebral infarction (n=2), convulsions (n=2), intracranial hemorrhage (n=2), thrombosis after ligation of internal jugular vein (n=1) and cerebral atrophy (n=1); bleeding complications (n=8) which included bleeding at puncture sites (n=4), ECMO canalized site bleeding (n=3), and spontaneous (n=1), intracranial hemorrhage or hematoma cases(n=2) in mechanical complications; acute kidney injury (n=5) and microcirculation thrombosis (n=3). CONCLUSION: ECMO technique may cause complications, which mainly include neurological, mechanical and clotting complications. Advanced equipments and materials and well-managed teamwork are helpful in decreasing complications.

Interferometric fiber-optic bending/nano-displacement sensor using plastic dual-core fiber.

We demonstrate an interferometric fiber-optic bending/nano-displacement sensor based on a plastic dual-core fiber. The light coupled into the two fiber cores is first guided along the fiber, and then reflected by the mirror coated at the fiber end. Reflected light coming out of the fiber produces interference that shifts as the fiber bends. The interference shift is interrogated using a slit and a photodetector. The resolution of our sensor is ∼3×10(-4) m(-1) for sensing the bending curvature, and ∼70 nm for sensing the displacement.

Inhibitory effects of phenolic carboxylic acid analogues on xanthine oxidase.

Nineteen phenolic carboxylic acid analogues were tested for the effects on xanthine oxidase inhibition. 2,2',4,'4'-Tetrahydroxybenzophenone and 2,3,4-trihydroxybenzoic acid displayed the strongest activities (IC50 = 38.70 microM, IC50 = 90.16 microM respectively). Their apparent inhibition constants (Ki) were 7.052 and 0.535 microM respectively, and induced mixed type and competitive type inhibitions respectively with respect to the substrate xanthine.