Clinical and genetic characteristics of Chinese patients with Shwachman Diamond syndrome: a literature review of Chinese publication.

Shwachman Diamond syndrome (SDS) is a rare autosomal recessive genetic disorder and due to its complex and varied clinical manifestations, diagnosis is often delayed. The purpose of this study was to investigate the clinical manifestations and genetic characteristics of SDS in Chinese patients, in order to increase pediatricians' awareness of SDS and to allow early diagnosis. We conducted a search to identify patients presenting SBDS gene pathogenic variant in two Chinese academic databases. We analyzed and summarized the epidemiology, clinical features, gene pathogenic variants, and key points in the diagnosis and treatment of SDS. We reviewed the clinical data of 39 children with SDS from previously published articles. The interval from the onset of the first symptoms to diagnosis was very long for most of our patients. The age of presentation ranged from 1 day to 10 years (median: 3 months). However, the age of diagnosis was significantly delayed, ranging from 1 month to 14 years (median: 14 months). Hematological abnormalities were the most common presentation, 89.7% (35/39) at the beginning and 94.9% (37/39) at diagnosis of SDS. Diarrhea was the second most common clinical abnormality at the time of diagnosis. 59% (23/39) of patients had a typical history of persistent chronic diarrhea. Furthermore, hepatic enlargement or elevation of transaminase occurred in 15 cases (38.5%). 56.4% patients (22/39) had a short stature, and 17.9% (7/39) patients showed developmental delay. Additionally, twenty patients had compound heterozygous pathogenic variants of c.258 + 2T > C and c.183_ 184TA > CT. Children with SDS in China had high incidence rates of chronic diarrhea, cytopenia, short stature, and liver damage. Furthermore, SBDS c.258 + 2T > C and c.183_ 184TA > CT were the most common pathogenic variants in patients with SDS. The diagnosis of SDS can be delayed if the clinical phenotype is not recognized by the health care provider.

Brain magnetic resonance imaging findings in children with neurological complications of coronavirus disease 2019 (Omicron variant): a multicenter retrospective observational study.

BACKGROUND: An increasing rate of encephalopathy associated with coronavirus disease 2019 (COVID-19) has been observed among children. However, the literature on neuroimaging data in children with COVID-19 is limited. OBJECTIVE: To analyze brain magnetic resonance imaging (MRI) of pediatric COVID-19 patients with neurological complications. MATERIALS AND METHODS: This multicenter retrospective observational study analyzed clinical (n=102, 100%) and neuroimaging (n=93, 91.2%) data of 102 children with COVID-19 infections and comorbid acute neurological symptoms. These children were hospitalized at five pediatric intensive care units (PICUs) in China between December 1, 2022, and January 31, 2023. RESULTS: All patients were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as detected via reverse transcriptase polymerase chain reaction. About 75.7% of the children were infected with the Omicron variant BF.7 strain. Brain MRI was performed 1-12 days following the onset of neurological symptoms, which revealed acute neuroimaging findings in 74.2% (69/93) of cases, including evidence of acute necrotizing encephalopathy (33/69, 47.8%), encephalitis (31/69, 44.9%), reversible splenial lesion syndrome (3/69, 4.3%), reversible posterior leukoencephalopathy (1/69, 1.4%), and hippocampal atrophy (1/69, 1.4%). CONCLUSIONS: Overall, these data highlighted five neuroimaging patterns associated with the outbreak of the SARS-CoV-2 Omicron variant, with acute necrotizing encephalopathy being the most common of these neuroimaging findings. Rarely, the brain MRI of these pediatric COVID-19 patients also demonstrate hippocampal atrophy.

Pathogens in PICU before and during the SARS-CoV-2 pandemic in China: a multicenter retrospective study.

BACKGROUND: Nonpharmacological interventions for COVID-19 could reduce the incidence of children hospitalized in pediatric intensive care units (PICU) and the incidence of children with bacterial infections. This study aimed to evaluate changes in the bacterial profile of children in PICU before and during the COVID-19 pandemics. METHODS: This is a retrospective study, involving clinical data of children with positive bacterial cultures admitted to the PICU respectively in 2019 and 2021. RESULTS: In total 652 children were included in this study. The total number of hospitalized patients and the incidence of bacteria-positive children in 2021 were lower than those in 2019. There were no significant differences in the ratio of Gram-positive bacterial infection, Gram-negative bacteria infection or fungi infection between the two years. The rate of Streptococcus pneumoniae in 2021 was higher than that in 2019(p = 0.127). The incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend(p = 0.002). The distribution of previous underlying diseases in children admitted to PICU with different outcomes of bacterial infection between the two years were homogeneous (p > 0.05). CONCLUSION: After the implementation of COVID-19 isolation, prevention and control measures, the number of hospitalizations and bacterial infections in PICU decreased, which may be due to changes in population's behavior patterns. Meanwhile, the incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend.

Dexmedetomidine improves the outcomes for pediatric severe sepsis with mechanical ventilation.

BACKGROUND: The sedative dexmedetomidine has been shown to reduce mortality in adult patients with severe sepsis, but it is not known whether children benefit. This study explored the effects of dexmedetomidine on the outcomes of children with severe sepsis with mechanical ventilation. METHODS: In this retrospective cohort study, children with severe sepsis requiring mechanical ventilation from 2016 to 2020 were categorized as dexmedetomidine and non-dexmedetomidine group. The propensity score matching was performed to match cases in both groups. The primary outcome was 28-day mortality, and the secondary outcomes were acute kidney injury, ventilator-free days, lengths of PICU and hospital stays. The Kaplan-Meier method and was the log-rank test used to estimate the 28-day mortality rate and assess between-group differences. RESULTS: In total, 250 patients were eligible patients: 138 in the dexmedetomidine group and 112 in the non-dexmedetomidine group. After 1:1 propensity score matching, 61 children in each group. dexmedetomidine group showed more lower 28-day mortality (9.84% vs. 26.23%, P = 0.008). During the 7-day observation period after PICU admission, the dexmedetomidine group showed significantly lower neurological and renal sub-scores at day 7 and serum creatinine level at day 3 and day 7. There were no statistical differences in the incidence of acute kidney injury, ventilator-free days, lengths of PICU and hospital stays between the two groups. CONCLUSIONS: dexmedetomidine treatment in children with severe sepsis is associated with better outcomes and should therefore be considered for the sedation strategy.

Combination of Plasma Exchange and Adsorption Versus Plasma Exchange in Pediatric Acute Liver Failure: A Multicenter Cohort Study.

OBJECTIVES: This study aimed to compare the efficacy of double plasma molecular adsorption system (DPMAS) with half-dose plasma exchange (PE) to that of full-dose PE in pediatric acute liver failure (PALF). METHODS: This multicenter, retrospective cohort study was conducted in 13 pediatric intensive care units in Shandong Province, China. DPMAS+PE and single PE therapies were performed in 28 and 50 cases, respectively. The patients' clinical information and biochemical data were obtained from the patients' medical records. RESULTS: The severity of illness did not differ between the 2 groups. At 72 hours after treatment, comparing with PE group, the rates of decline of Pediatric model for End-stage Liver Disease and Pediatric Sequential Organ Failure Assessment scores as well as total bilirubin blood ammonia and interleukin-6 were significantly higher, while the short-term effective rate (75.0% vs 44.0%, P = 0.008) was significantly higher in the DPMAS+PE group. The volume of plasma consumption (26.5 vs 51.0 mL/kg, P = 0.000) and the rate of adverse events (3.6% vs 24.0%, P = 0.026) were lower in the DPMAS+PE group than in the PE group, respectively. However, there was no statistical difference in the 28-day mortality between the 2 groups (21.4% vs 40.0%, P > 0.05). CONCLUSIONS: For PALF patients, both DPMAS + half-dose PE and full-dose PE could improve the liver function, while DPMAS + half-dose PE could significantly reduce plasma consumption without obvious adverse effects in contrast with full-dose PE. Thus, DPMAS + half-dose PE may be a suitable alternative method for PALF in the context of the increasingly tight blood supply situation.

Management of descending necrotizing mediastinitis with severe thoracic empyema using minimally invasive video-assisted thoracoscopic surgery: a case report.

Background: Descending necrotizing mediastinitis (DNM) is a rare but serious complication of odontogenic or pharyngeal infection spreading into the mediastinum. Very few childhood cases of DNM have been described. Case Description: We report a case of DNM complicated with severe thoracic empyema in a previously healthy 6-year-old girl who was successfully treated using minimally invasive video-assisted thoracoscopic surgery (VATS). The patient presented with odynophagia and dental pain, followed by rapid clinical deterioration including high fever, tachypnea, and left chest pain. As chest computed tomography (CT) revealed features of DNM, she was transferred from the local hospital to our hospital for intensive care. Empirical treatment was started with meropenem and linezolid. However, her tachypnea and dyspnea progressed rapidly. An ultrasound-guided left-sided thoracentesis drained 80 mL of brown sticky pus and the pus culture yielded Streptococcus constellatus. A contrast-enhanced CT scan demonstrated large mediastinal abscess and severe thoracic empyema. We performed debridement and drainage of the mediastinum and pleura using VATS. She recovered and was discharged on hospital day 18. Conclusions: Early diagnosis by cervicothoracic CT and multidisciplinary approaches including intensive care, broad-spectrum antibiotics, and aggressive surgical intervention are crucial to reducing morbidity and mortality. VATS is a minimally invasive and appropriate treatment strategy for children with DNM, especially complicated with thoracic empyema.

Identification of two novel ACAT1 variant associated with beta-ketothiolase deficiency in a 9-month-old boy.

OBJECTIVES: Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase, T2) is necessary for the catabolism of ketone bodies andisoleucine. T2 deficiency is an autosomal recessive metabolic disorder caused by variant in the ACAT1 gene. In this report, we describe two novel ACAT1 variant identified in a Chinese family. CASE PRESENTATION: The 9-month-old male proband was admitted to the pediatric intensive care unit for altered consciousness. At the time of admission, the patient had acidosis, drowsiness, and respiratory failure. Both urine organic acid analyses and LC-MS/MS suggested T2 deficiency. Novel compound heterozygous variant (c.871G>C and c.1016_1017del) in the ACAT1 gene were detected in the proband by WES and verified through direct sequencing. Family analysis demonstrated that the first variant was transmitted from his father and the second variant was from his mother, indicating autosomal recessive inheritance. This report is the first to describe the association of these variant with T2 deficiency based on genetic testing. Although these variant were identified in the patient's elder sister and elder brother, they continue to be asymptomatic. CONCLUSIONS: We identified two novel ACAT1 variants associated with T2 deficiency. The identification expands the spectrum of known variant linked to the disorder.

Comparing the precision of the pSOFA and SIRS scores in predicting sepsis-related deaths among hospitalized children: a multi-center retrospective cohort study.

BACKGROUND: The latest sepsis definition includes both infection and organ failure, as evidenced by the sequential organ failure assessment (SOFA) score. However, the applicability of the pediatric SOFA score (pSOFA) is not yet determined. This study evaluated the effectiveness of both pSOFA and system inflammatory reaction syndrome (SIRS) scores in predicting sepsis-related pediatric deaths. METHODS: This is a retrospective multi-center cohort study including hospitalized patients <18 years old with diagnosed or not-yet-diagnosed infections. Multivariate analyses were carried out to evaluate risk factors for in-hospital mortality. According to Youden index (YI), three sub-categories of pSOFA were screened out and a new simplified pSOFA score (spSOFA) was formed. The effectiveness and accuracy of prediction of pSOFA, SIRS and spSOFA was retrieved from the area under the receiver operating characteristic curve (AUROC) and Delong's test. RESULTS: A total of 1,092 participants were eligible for this study, and carried a 23.4% in-hospital mortality rate. The 24-h elevated pSOFA score (24 h-pSOFA), bloodstream infection, and mechanical ventilation (MV) requirement were major risk factors associated with sepsis-related deaths. The AUROC analysis confirmed that the spSOFA provided good predictive capability in sepsis-related pediatric deaths, relative to the 24 h-pSOFA and SIRS. CONCLUSIONS: The pSOFA score performed better than SIRS in diagnosing infected children with high mortality risk. However, it is both costly and cumbersome. We, therefore, proposed spSOFA to accurately predict patient outcome, without the disadvantages. Nevertheless, additional investigations, involving a large sample population, are warranted to confirm the conclusion of this study.

Neuropsychological development in school-aged children after surgery or transcatheter closure for ventricular septal defect.

OBJECTIVES: We aimed to assess neuropsychological development in school-aged children with ventricular septal defect (VSD) after surgery or transcatheter closure. METHODS: We included 31 children with VSD who underwent surgery and 35 who underwent transcatheter closure and their age- and sex-matched best friends as normal controls and parents. The Halstead-Reitan Battery was used to measure psychological and behavioral functions of children. RESULTS: The mean finger-tapping time (left hand) was significantly lower for children with than without VSD (P < 0.05). For non-handedness tactual performance, the mean time was significantly longer for surgery than interventional therapy groups and controls (P < 0.05). The number of remembered locations was significantly lower for surgery than interventional therapy groups and controls (P < 0.05). The correct number of music rhythms was significantly lower for the surgery than control group (P < 0.05). Children with and without VSD did not differ in the correct number of first-group music rhythms. Nevertheless, for second- and third-group music rhythms, the correct number was significantly lower for the surgery than interventional therapy groups and controls (P < 0.05). The correct number of third-group music rhythms was significantly lower for only the interventional therapy than control group. CONCLUSION: School-aged children with VSD had normal IQ levels after surgery or interventional therapy but decreased fine-motor and auditory discrimination abilities as well as visual spatial disorder. Children with and without VSD did not differ in general tasks, but abilities on more complex and difficult tasks were lower for children with VSD. Impairments were greater after surgery than interventional therapy.

MKP-1 is a target of miR-210 and mediate the negative regulation of miR-210 inhibitor on hypoxic hPASMC proliferation.

Chonic hypoxia, smooth muscle cell (SMC) proliferation and vascular remodeling are hallmark features of pathogenic pulmonary artery hypertension. MicroRNAs (miRNAs), endogenously expressed small noncoding RNAs, regulate gene expression at the post-transcriptional level. MiR-210 is considered a "master miRNA" in the control of diverse functions in hypoxic cells and tissues and has a cytoprotective function in pulmonary artery SMCs during hypoxic stress. MiR-210 is also upregulated in lung tissue of chonically hypoxic mice suffering from pulmonary hypertension. Jin et al. () showed that mice deficient in mitogen-activated protein kinase phosphatase 1 (MKP-1) had severe hypoxia-induced pulmonary hypertension, so MKP-1 may be important in the progression of hypoxic pulmonary artery hypertension. We investigated the possible interactions between miR-210 and MKP-1 and the effect on cell proliferation in hypoxic human pulmonary artery SMCs (hPASMCs). miR-210 was significantly increased in cultured hPASMCs exposed to 1% O2 hypoxia for 48 h, as was MKP-1 mRNA and protein expression. Furthermore, inhibiting miR-210 expression increased MKP-1 mRNA and protein expression in hPASMCs and decreased cell proliferation under hypoxia. Conversely, overexpressing miR-210 prevented hypoxia-induced MKP-1 expression with no effect on cell proliferation. siRNA knockdown of MKP-1 abolished the miR-210-inhibition prevention of cell proliferation under hypoxia. MKP-1 is a target of miR-210 and could mediate the negative regulation of miR-210 inhibition on hypoxic hPASMCs.

Arginase II is a target of miR-17-5p and regulates miR-17-5p expression in human pulmonary artery smooth muscle cells.

Vascular remodeling and smooth muscle cell proliferation are hallmark pathogenic features of pulmonary artery hypertension. MicroRNAs, endogenously expressed small noncoding RNAs, regulate gene expression at the posttranscriptional level. It has previously been shown that miR-17 overexpression in cultured human pulmonary artery smooth muscle cell (hPASMC) resulted in increased viable cell number. Previously, we have found that arginase II promotes hypoxia-induced proliferation in hPASMC. Therefore, we hypothesized that miR-17 would be upregulated by hypoxia in hPASMC and would result in greater arginase II expression. We found that levels of miR-17-5p and arginase II were significantly greater in cultured hPASMC exposed to 1% O2 for 48 h than in hPASMC exposed to 21% O2 for 48 h. Furthermore, inhibiting miR-17-5p expression decreased hypoxia-induced arginase II protein levels in hPASMC. Conversely, overexpressing miR-17-5p resulted in greater arginase II protein levels. Somewhat surprisingly, arginase II inhibition was associated with lower miR-17-5p expression in both normoxic and hypoxic hPASMC, whereas overexpressing arginase II resulted in greater miR-17-5p expression in hPASMC. These findings suggest that hypoxia-induced arginase II expression is not only regulated by miR-17-5p but also that there is a feedback loop between arginase II and miR-17-5p in hPASMC. We also found that the arginase II-mediated regulation of miR-17-5p was independent of either p53 or c-myc. We also found that l-arginine, the substrate for arginase II, and l-ornithine, the amino acid product of arginase II, were not involved in the regulation of miR-17-5p expression.

Behavioural and emotional outcomes in school-aged children after surgery or transcatheter closure treatment for ventricular septal defect.

OBJECTION: We aimed to assess and compare the behavioural and emotional outcomes of school-aged children after surgery or transcatheter closure for ventricular septal defect and investigate the risk factors for developing abnormal behavioural problems with the condition. METHODS: In this study, we included 29 children, including 20 boys, with ventricular septal defect who underwent surgery and 35 children, including 21 boys, who underwent transcatheter closure (6-13 years old) and their age- and sex-matched best friends (n = 56) and their parents. The Child Behavior Checklist was used to obtain standardised parents' reports of behavioural and emotional problems in children. The 28-item version of the General Health Questionnaire was used to assess parents' psychological distress. Pearson correlation and logistic regression were used to analyse risk factors for developing behaviour problems. RESULTS: Behavioural problems were greater for boys and girls undergoing surgery or transcatheter closure than controls. The behavioural problems were mainly depression, somatic complaints, and social withdrawal for boys and thought problems, depression, somatic complaints, and social withdrawal for girls. Depression and somatic complaints were greater for boys undergoing surgery than for boys undergoing transcatheter closure. Behavioural problems did not differ between treatment groups for girls. Risk factors for developing behavioural problems were age at the time of ventricular septal defect repair (p = 0.03; odds ratio = 2.35), skin scar (p = 0.04; odds ratio = 3.12), post-operative atrioventricular block (p = 0.03; odds ratio = 2.81), and maternal anxiety (p < 0.01; odds ratio = 4.5). CONCLUSION: School-aged children who underwent repair of ventricular septal defect regardless of the type of treatment (surgery or transcatheter closure) exhibit internalising behavioural problems. Risk factors for developing problems are young age, scarring, post-operative atrioventricular block, and maternal anxiety. In particular, maternal anxiety is the most important risk factor.

Inhibition of hedgehog signaling by GANT58 induces apoptosis and shows synergistic antitumor activity with AKT inhibitor in acute T cell leukemia cells.

The hedgehog (Hh) signaling pathways have a crucial role in cell proliferation and survival, and the de-regulation of these pathways can lead to tumorigenesis. Here we investigated the expression and function of these pathways in acute T lymphocytic leukemia cells (T-ALL). Profiling of Hh pathway members revealed common expression of key Hh signaling effectors in all T-ALL cells. We found that T-ALL cells were insensitive to specific Smoothened (SMO) inhibition following the use of low concentrations of the SMO antagonist cyclopamine. In contrast, treatment with the novel GLI antagonist GANT58 reduced expression of the target gene Patched 1 as well as GLI family zinc finger 1 (GLI1) and preferentially decreased the viability of T-ALL cells. We also found perifosine, a novel AKT inhibitor, down-regulated GLI1 protein by dephosphorylation of AKT and GSK3ß dose-dependently and that pre-treatment with PD98059, a MEK/ERK pathway inhibitor, enhanced this down-regulation by 20%-30%. Then we questioned whether use of both GANT58 and AKT inhibitor together could confer a synergistic effect to decrease T-ALL cell viability. By applying the Chou-Talalay method, low concentration of GANT58 induced T-ALL cell death in a synergism fashion with perifosine or GSK690693 when used simultaneously. These findings indicate that the combined use of GANT58 and AKT inhibitor could help treat a broad range of malignant tumors in conjunction with existing cancer treatments.

Postimplant complications with transcatheter closure of congenital perimembranous ventricular septal defects: a single-center, longitudinal study from 2002 to 2011.

BACKGROUND: Whether or not to close perimembranous VSDs (pmVSDs) by transcatheter techniques is controversial because of a high rate of complications as compared with surgical alternatives. OBJECTIVE: We report the short- and long-term follow-up results of the use of several kinds of devices to close pmVSDs and the annual incidence of postimplant complications in our center. METHODS: From June 2002 to June 2011, 232 patients with pmVSD underwent attempted transcatheter closure; closure was successful in 209 cases (90.1%). Six types of occlusive devices were used. Patient age, defect size, device type, device size and its relation to defect size, and transcatheter and fluoroscopy time were analyzed for correlation with annual incidence of postimplant complications. RESULTS: There were no deaths during the follow-up period. Within 1 month after transcatheter closure, we found 91 adverse events (43.5%), but only 32 cases showed a trace amount of residual shunting. From 2002 to 2011, the annual incidence of postimplant complications gradually decreased, from 50% in 2002 to 17.6% in 2011. The use of Amplatzer occluder devices (r = 0.71, P = 0.033), double-disc symmetrical occluder devices (r = -0.68, P = 0.045), and transcatheter (r = 0.87, P = 0.003), and fluoroscopy time (r = 0.78, P = 0.02) were significantly correlated with the incidence of post-implant complications. CONCLUSIONS: Results of transcatheter closure of pmVSD in terms of postimplant complications are encouraging in our center. It seemed that eccentric Amplatzer and domestic occluder may be at rather higher risk for postimplant complications. The incidence of postimplant complications may be minimized by skilled maneuvers, excluding rather small patients, and selecting the appropriate kind of occlusive device.

Natural history of prenatal ventricular septal defects and their association with foetal echocardiographic features.

OBJECTIVE: To describe the evolution of ventricular septal defects in infants from intra-uterine diagnosis to the age of 3 years or until documented echocardiographic closure of the defect, as well as any relationship between closure rate, time and foetal echocardiographic features. METHODS: Between January, 2004 and December, 2006, 268 cases of congenital cardiac defect were detected in 14,993 pregnancies referred to our hospital for routine foetal echocardiography; of these cases, 125 had isolated ventricular septal defect. The mothers were scheduled for regular ultrasonography every 2 weeks from diagnosis until the ventricular septal defect closed or 3 years postnatally. RESULTS: Of the 125 cases of ventricular septal defects, the pregnancy was terminated in 25, four resulted in death, two defects closed spontaneously in utero, 55 closed at a mean age of 13.7 months postnatally, 17 were treated with surgery, nine remained unclosed, and 13 cases were lost to follow-up. Only 7.7% of muscular ventricular septal defects remained patent as compared with 35.7% of perimembranous ventricular septal defects (p is less than 0.01). Muscular ventricular septal defects closed earlier than perimembranous ventricular septal defects. All the ventricular septal defects less than or equal to 3 millimetres closed, whereas only 79.5% of the defects greater than 3 millimetres closed before the age of 3 years; 60.9% of the defects less than or equal to 3 millimetres closed before the age of 1 year as compared with 41.7% of the defects greater than 3 millimetres. The velocity of right-to-left flow was negatively correlated with closure rate but not related to closure period. CONCLUSION: Ventricular septal defects can close in utero or during the postnatal period, and both the size and site play a role in the natural history, with small and muscular ventricular septal defects having a high closure rate and early closure.

Cognitive P300-evoked potentials in school-age children after surgical or transcatheter intervention for ventricular septal defect.

BACKGROUND: Some studies have suggested that neurological development may be adversely affected in children with severe coronary heart disease who have undergone long periods of deep hypothermic cardiopulmonary bypass (CPB). Reports of cognitive function in VSD patients in whom surgical repair required only a relatively brief period of CPB are rare. Also, CPB is unnecessary for VSD patients undergoing transcatheter closure. The aim of this study was to assess the cognitive function in patients with ventricular septal defect. METHODS: A total of 29 patients treated with surgery, and 35 treated with transcatheter closure and their age- and sex-matched best friends completed the cognitive P300 auditory-evoked potentials test and the intelligence test. RESULTS: The patients and their best friends had normal intelligence quotient; however, the patients had longer P300 peak latencies in cranial frontal lobe and cranial vertex leads (329.2 ± 24.8 and 335.1 ± 20.0 ms) than the healthy controls did (319.1 ± 20.6 and 313 ± 18.2 ms) (P < 0.05). Patients who underwent surgery had longer P300 peak latency in the cranial frontal lobe and cranial vertex leads than did those with transcatheter closure and controls. When cardiopulmonary bypass and aortic clamping were used, the duration was associated with P300 peak latency for patients (P < 0.05). CONCLUSION: VSD patients, especially those undergoing surgery, showed poor cognitive function, which may be associated with duration of cardiopulmonary bypass or aortic-clamping.

Dexamethasone attenuates development of monocrotaline-induced pulmonary arterial hypertension.

Immunity and inflammation are well established factors in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether dexamethasone (Dex), a potent immunosuppressant, could prevent the development of monocrotaline (MCT)-induced PAH in rats as compared with pyrrolidine dithiocarbamate (PDTC) and its effect on the immune mechanism. PAH in rats (n = 66) was induced by MCT (50 mg/kg) injected intraperitoneally. Two days after MCT treatment, Dex (1.0 mg/kg) and PDTC (100 mg/kg) were administered once daily for 21 days. Samples were collected at 7, 14, and 21 days. Dex effectively inhibited MCT-induced PAH and reduced the T-helper (Th) 1 dominant cytokine response (interferon-γ) but up-regulated the Th2 one (interleukin 4). It increased the number of CD4+ T cells and decreased the number of CD8+ T cells around pulmonary arteries, upregulated the mRNA expression of fractalkine and downregulated that of CX3CR1 in the lung. Serum levels of interferon γ and interleukin 4 did not significantly differ from that of controls. Dex attenuated the process of MCT-induced PAH through its immunomodulatory property. Dex could be an appropriate therapy for PAH, although more studies are needed to define the appropriate treatment regimen.