The Protective Role and Mechanism of Mild Therapeutic Hypothermia Protection on Brain Cells.

Background: Moderate therapeutic hypothermia is protective against several cellular stressors. However, the mechanisms behind this protection are not entirely known. In the current investigation, we investigated that therapeutic hypothermia at 33°C administered following peroxide-induced oxidative stress might protect human oligodendroglioma cells using an in vitro model. Methods and Results: Tert-butyl peroxide treatment for one hour significantly increased cell apoptosis and suppressed cell viability. In the range of 50-1000 M tert-butyl peroxide, this cell death was dose-dependent. MTT assay and cell apoptosis assay were applied to analyze cell viability/death at 24 hours after peroxide-induced stress. Therapeutic hypothermia at 33°C delivered for two hours after peroxide exposure significantly increased cell viability and suppressed cell death. Even 15 minutes after peroxide washout when delayed hypothermia was used, this protection was still apparent. Three FDA-approved antioxidants (Tempol, EUK134, and Edaravone at 100 M) were added immediately after tert-butyl peroxide, followed by hypothermia treatment. These three antioxidants greatly increased cell viability and cell apoptosis. RT-qPCR was applied to determine the effects of hypothermia treatment on the expression of caspase-3 and -8 as well as tumor necrosis factor-alpha (TNF-α). Therapeutic hypothermia significantly downregulated these three factors. Conclusion: Overall, these findings confirmed that hypothermia and antioxidants quenching reactive oxygen species may lower mitochondrial oxidative stress and/or apoptotic pathways. Further investigation are needed to investigate the role of hypothermia in other cell models.

Case report: Epigastric heteropagus twins and literature review.

Epigastric heteropagus twins are an extremely rare congenital anomaly of conjoined twins. We present a case of epigastric heteropagus twins who were diagnosed via prenatal ultrasound imaging: the fetus (or host) was connected to the abdominal wall of the parasite (the dependent portion), and an omphalocele was present. The male infant was delivered by cesarean section at 35 + 5 weeks gestation. The parasite lacked a head and heart and presented long bones of the limbs. After abdominal computed tomography, omphalocele repair, and parasite removal were surgically performed under general anesthesia. After discharge (follow-up, 3 months), the infant is currently growing well and is healing satisfactorily. Forty-one cases of epigastric heteropagus twins were retrieved from database searches: 38 good postoperative outcomes, 2 perioperative deaths, and 1 termination. The case highlights that even when parasites are massive in size, births can present good outcomes with suitable surgical treatment.

Inhibition of Microglial Activation by Delayed Mild Hypothermia Reduced Preoligodendrocyte Injury in a Neonatal Rat Brain Slice Model.

Periventricular leukomalacia (PVL), characterized by distinctive form of white matter injury, often arises after neonatal cardiac surgery. Proven therapies for PVL are absent. In this study, we designed to quest therapeutic effects of delayed mild hypothermia on PVL and its mechanism in a neonatal rat brain slice model. With the increase of delayed mild hypothermia-treating time, the reduced expression of myelin basic protein and loss of preoligodendrocytes were significantly attenuated after oxygen-glucose deprivation. In addition, the proportion of ionized calcium binding adapter molecule 1 (Iba-1)-positive cells and the expression of Iba-1 were apparently reduced with the increased duration of mild hypothermia treatment. Furthermore, the levels of tumor necrosis factor alpha and interleukin-6 reduced after the mild hypothermia treatment relative to the control. Inhibition of microglial activation with prolonged mild hypothermia may be a potential strategy for white matter protection during cardiopulmonary bypass and hypothermic circulatory arrest.

Effect of perioperative amplitude-integrated electroencephalography on neurodevelopmental outcomes following infant heart surgery.

The purpose of the current study was to determine the effect of perioperative amplitude-integrated electroencephalography (aEEG) on neurodevelopmental outcomes in infants with congenital heart disease (CHD). A total of 93 children with CHD were included in the current study. All patients enrolled in the present study had undergone cardiac surgery prior to 3 months of age and pre- or postoperative aEEG was monitored. Participants were assessed after 1 year using the Bayley Scales of Infant Test. A total of 82.2% of infants exhibited continuous normal voltage preoperatively (CNV) and 93.7% exhibited CNV postoperatively. Seizures were indicated in 2 infants preoperatively and 3 infants postoperatively. Compared with infants with PDI, infants with cyanotic CHD (ß=17.218) exhibited a significantly lower MDI, an increased length of intensive care stay, and lower PDI scores (ß=-0.577). Infants that underwent surgery with CPB exhibited higher PDI scores (ß=11.956). Infants that exhibited behavioral problems also had lower PDI scores (ß=-10.605). An abnormal preoperative background pattern and an absent postoperative SWC independently predicted poorer motor (P=0.014) and cognitive (P=0.049) outcomes at 1 year. The current study demonstrated that infants with CHD who underwent cardiac surgery prior to 3 months of age exhibited delayed neurodevelopmental outcomes, and that an aEEG assessment can aid in predicting these outcomes following surgery.

Peri- and Post-operative Amplitude-integrated Electroencephalography in Infants with Congenital Heart Disease.

OBJECTIVE: To identify the factors influencing brain injury in infants with congenital heart disease (CHD) after cardiac surgery. METHODS: This retrospective study investigated 103 infants with CHD undergoing cardiac surgery between January 2013 and February 2016. Pre- and postoperative amplitude-integrated electroencephalography (aEEG) recordings were assessed for background pattern, sleep-wake cycle pattern and seizure activity. Logistic regression model was used to determine the influencing factors of brain injury. RESULTS: Pre-operatively, most infants in our study exhibited a normal background pattern, with 16.5% showing discontinuous normal voltage, whereas this pattern was observed in only 7.8% of infants postoperatively. The improvement in background pattern after surgery was significant (P<0.05) in infants at no more than 39 weeks of gestational age. Infants with postoperative sepsis or severe postoperative infection were prone to show a worse sleep-wake cycle pattern after heart surgery. CONCLUSIONS: The improvement in brain function of infants with CHD after cardiac surgery was associated with the gestational age and postoperative infection.

Identification of risk factors affecting catch-up growth after infant congenital heart disease surgery: rationale and design of a multicentre prospective cohort study in China.

INTRODUCTION: Successful surgical treatment of congenital heart disease improves neonates' long-term survival and leads to catch-up growth, which however does not occur in part of the patient population for largely undetermined reasons. METHODS AND ANALYSIS: A multicentre, prospective cohort study is being conducted in four paediatric medical institutions in China to collect detailed nutritional, anthropometric and clinical data at perioperative phases and during a 1-year period of follow-up after surgery. The study is expected to recruit approximately 5000 patients by the year of 2023 when the cohort is fully established. The primary endpoint of this study is the occurrence of postoperative catch-up growth, which will be determined in both absolute and relative terms (ie, reduced anthropometric deficits from the reference measures and improved z-scores that have passed the -2 SD cut-offs). Multivariable regression analyses will be performed to identify factors that are statistically significantly associated with the absence of postoperative catch-up growth. ETHICS AND DISSEMINATION: The protocol of this study has been approved by the individual ethics committees of the participating centres (Guangzhou Women and Children's Medical Centre (2008071601), the Children's Hospital of Zhejiang University School of Medicine (2018-IRB-094), Gansu Provincial Maternity and Child-Care Hospital (2019-IRB-01) and Zhengzhou Cardiovascular Hospital (2019012001)). Written informed consent from parents will be obtained before study entry. Findings of this study will be disseminated through publications in international peer-reviewed journals and will be presented in academic conferences.

The Screening Performance of Serum 1,3-Beta-D-Glucan in Patients with Invasive Fungal Diseases: A Meta-Analysis of Prospective Cohort Studies.

The serum 1,3-beta-D-glucan (BG) assay aids in the early diagnosis of invasive fungal diseases (IFDs) and has been approved for their diagnosis. However, reports on the screening performance of BG are scarce. We performed a meta-analysis of data extracted from only prospective cohort studies to evaluate the screening performance of the BG assay in the diagnosis of IFDs. We specifically searched 4 databases (the PubMed, Web of Science, Elsevier, and Cochrane Collaboration databases) according to EORTC-MSG criteria. A total of 1068 patients in 11 studies were analyzed. Deeks' funnel plot asymmetry test suggested a low likelihood of publication bias for the included studies (p = 0.055). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve, with 95% confidence intervals, were 0.75(0.63,0.84), 0.87(0.81,0.92), 5.85(3.96,8.63), 0.30(0.20,0.45), 19.53(11.16,34.18), and 0.89(0.86,0.91), respectively. The findings of this meta-analysis suggest that the BG assay is a useful screening tool with high sensitivity and specificity for discriminating between patients with and without IFDs. In clinical practice, BG assay results should be evaluated together with clinical and microbiological findings.

[Airway obstruction caused by large blood vessel anomalies: assessment by flexible bronchoscopy].

OBJECTIVE: To evaluate the diagnostic value and safety of flexible bronchoscopy in congenital great vessel diseases complicated with airway compression. METHOD: The medical records of patients with great vessels abnormalities who were admitted to the neonatal intensive care unit (NICU) from October 2005 to June 2009 were retrospectively reviewed; 34 cases were diagnosed as airway compression by flexible bronchoscopy, 10 cases as vascular ring, 24 cases as aortal arch obstruction. The age of the patients was 6 d - 11 m, body weight 2.2 - 8.7 kg [(4.6 +/- 1.4) kg]. Recorded airway abnormalities detected by bronchoscopy and CT, cardiac vascular defects and airway compression were consistent with the findings on operation. The relation between the airway compression and cardiac vascular abnormalities, treatment of the airway compression and outcome were analysed. RESULT: Bronchoscopic assessment was successfully performed in NICU or operating room for all the patients. (1) Initial presentation of the 34 cases were tachypnea, stridor, refractory lung infection and prolonged mechanical ventilation. (2) Extrinsic compression was found in all the 10 cases with vascular ring by bronchoscopy initially which indicated vascular ring, airway compression was mainly of lower part of trachea. Diagnosis of 9 cases was consistent with CT diagnosis and in 1 case the diagnosis was confirmed by surgery; among these cases, 7 had congenital tracheal stenosis. (3) In the 24 cases with aortic obstructive lesion, 5 were detected to have tracheal stenosis by CT before correction of vascular abnormality, among whom one case was indicated to have tracheal stenosis by bronchoscopy, the other 19 cases were found with airway compression by bronchoscopy during or after vascular correction. Among the 24 cases, 21 had left main bronchial stenosis, 2 had congenital tracheal stenosis. Airway compression diagnosed by bronchoscopy agreed with the findings of CT. Two cases developed transient decrease of oxygen saturation, 5 cases developed transient tachycardia. CONCLUSION: Flexible bronchoscopy plays an important role in assessment of the airway compression complicated with great vessel abnormalities. Bronchoscopy is an accurate, convenient, safe and rapid way for airway assessment, but further examination of the peripheral structure and vascular malformation need combined examination with CT.

[Screening analysis of retinopathy of prematurity and treatment of threshold retinopathy of prematurity].

OBJECTIVE: To investigate the incidence and the risk factors associated with the development of retinopathy of prematurity (ROP) by ROP screening in the premature infants and to evaluate the treatment effect of threshold ROP. METHODS: From March 2000 to December 2004, 108 premature infants with birth weight less than 2.0 kg or gestational age less than 37 weeks admitted to the Neonatal Intensive Care Unit at Guangdong Provincial People's Hospital were enrolled in the present study. They were examined with binocular indirect ophthalmoscope. The perinatal variables of the premature infants were analyzed to evaluate their correlation with the development of ROP. The infants with threshold ROP were treated with retinal photocoagulation or cryotherapy. RESULTS: The overall incidence of ROP was 21.3% (23 of 108). Among 23 premature infants with ROP, 56.5% (13 of 23) were in stage 1, 13.0% (3 of 23) in stage 2 and 30.4% (7 of 23) in stage 3. All infants with ROP stage 3 fulfilled the criteria of threshold ROP. As compared with non-ROP group, ROP infants had lower birth weight [(1.43 +/- 0.25) kg; t = 4.059, P < 0.001], shorter gestation age [(31.0 +/- 2.3) W; t = 2.637, P = 0.013], longer median time of oxygen supplementation (17 d; Z = -3.630, P < 0.001) and more demand of mechanical ventilation (chi(2) = 12.009, P = 0.001). Cases with multiple gestational births in ROP group were not significantly different from that in non-ROP group (chi(2) = 1.013, P = 0.314). Multivariate logistic regression analysis showed that low birth weight (beta = -2.542, OR = 0.079, P = 0.032) and mechanical ventilation (beta = 1.341, OR = 3.823, P = 0.025) were significantly associated with the development of ROP. In a total of seven cases with threshold ROP, six cases were treated with retinal laser photocoagulation or transscleral cryotherapy timely. After followed up for two months to two years, all treated eyes had normal pupil response to the light. The optic disk, macula and posterior retina appeared normal. No abnormal retinal vessels and proliferative vitreoretinopathy were found. One premature infant with threshold ROP, not treated by laser photocoagulation or transscleral cryotherapy, developed retinal detachment in both eyes. CONCLUSIONS: Premature infants with low birth weigh, shorter gestational age, longer history of oxygen supplemental and the using of mechanical ventilation have more chance of developing ROP. The analysis of risk factors will be helpful in understanding and prediction of development of ROP. ROP screening and timely treatment for threshold ROP are very important for preventing the development of advanced ROP in premature infants.