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.

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.

Safety and efficacy of transcatheter closure of atrial septal defects guided by transthoracic echocardiography: a prospective study from two Chinese Medical Centers.

The purpose of this study was to evaluate the safety and efficacy of transcatheter atrial septal defect (ASD) closure guided by transthoracic echocardiography (TTE). A total of 191 patients with ASD were recruited from two Chinese medical centers and TTE was carefully performed in multiple views to observe ASD number, position, diameter and relation with adjacent cardiac structures. All patients were divided into three groups based on their largest ASD diameters: 66 subjects with ASD diameter 5-14 mm (group A); 60 subjects with ASD diameter 15-20 mm (group B); and 65 subjects with ASD diameter 21-38 mm (group C). Atrial septal occluders (ASOs) were successfully deployed in 188 patients (98.4%) and ASD was successfully closed at 6-mo follow-up in 185 patients (96.9%). The difference between diameters of ASO and ASD (ASO-ASD) in groups A, B and C were 3.9 +/- 2.4 (0-7) mm, 5.0 +/- 2.6 (3-8) mm and 6.2 +/- 3.8 (5-11) mm, respectively. In group A, no complications occurred. In group B, only four patients had mild complications such as sinus bradycardia, transient hematuria and migraine, all of which disappeared after treatment. In group C, one patient developed ASO migration into the right atrium and two patients had their ASO migrated into the right ventricular outflow tract. Immediately after the closure, 60 (90.9%), 53 (88.3%) and 53 (82.8%) patients had complete ASD closure; 2, 4 and 6 patients had trivial residual shunts; 4, 3 and 2 patients had small residual shunts; and 0, 0 and 2 patients had moderate residual shunts in groups A, B and C, respectively. Most of the residual shunts were persistent at 6-mo follow-up. No embolism or death at procedure and 6-mo follow-up occurred. In conclusion, TTE is a reliable technique for measurement of ASD diameter, guidance of transcatheter ASD closure and evaluation of residual shunts. Transcatheter ASD closure guided by TTE is safe and effective, especially in patients with ASD

Immune tolerance to cardiac myosin induced by anti-CD4 monoclonal antibody in autoimmune myocarditis rats.

Autoimmune myocarditis is a T-cell-mediated autoimmune disease. CD4-positive T cells are believed to be the most important for the initiation and mediation of the disease. This study was aimed at evaluating whether anti-CD4 monoclonal antibody could induce immune tolerance to porcine cardiac myosin and whether the immune tolerance could protect rats with autoimmune myocarditis from myocardial injury. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis. Immune tolerance was induced by injections of anti-CD4 monoclonal antibody on days -2, -1, 0, and 1. Results showed that cardiac function of antibody-treated rats was significantly increased compared with untreated rats 18 days postimmunization examined by transthoracic echocardiography. Typical cardiac histopathological changes were observed obviously in untreated group but not in antibody-treated group. Lymphocytes obtained from antibody-treated group had no proliferative response to porcine cardiac myosin examined by lymphocyte proliferation assay. Serological examination showed that rats immunized with cardiac myosin could produce high levels of anti-cardiac myosin antibody. The administration of anti-CD4 monoclonal antibody significantly prevented the increase of them. Serum levels of Th1 cytokines were significantly down-regulated by antibody administration, while the production of Th2 cytokines were up-regulated or unaffected evaluated by enzyme-linked immunosorbent assay. It concluded that immune tolerance to porcine cardiac myosin could be induced by anti-CD4 monoclonal antibody in vivo, and cardiac dysfunction and myocardial injury could be prevented by induction of immune tolerance.

Dynamic changes in myocardial matrix metalloproteinase activity in mice with viral myocarditis.

BACKGROUND: Matrix metalloproteinases (MMPs) are the major regulators of collagen degradation involved in the pathogenesis of several diseases of the heart. The purpose of this study was to investigate the dynamic changes in myocardial MMP activity in mice with viral myocarditis (VM), the relationship between MMP activity and both cardiac function and the quantity of myocardial collagen, and the role MMPs playing in the pathological lesions of VM. METHODS: Sixty-five six-week-old male DBA/2 mice were divided into two groups. Mice in the infected group (n = 50) were inoculated intraperitoneally with 0.14 ml of Coxsackievirus B3 (CVB3, Nancy strain). Control mice (n = 15) were inoculated intraperitoneally with 0.14 ml of Eagle's medium. Eight infected mice and three control mice were sacrificed on each of days 3, 7, 10, 21 and 30 after inoculation. MMP activity was measured on an SDS-PAGE substrate gel embedded with type I gelatin (zymography). Echocardiographic studies were performed under anesthesia with 3% chloralhydrate administered intraperitoneally (0.01 ml/g - 0.015 ml/g). Cardiac systolic function indices, such as peak velocity of the aorta (Vp), flow velocity integral of the aorta (Vi), ejection fraction (EF), and fractional shortening (FS) were determined by echocardiography. Histological cross sections of the hearts were stained with hematoxylin-eosin and myocardial histopathological scores were determined under an optical microscope. The amount of myocardial collagen was measured by means of hydroxyproline quantification. RESULTS: In virus-infected mice, both MMP-2 and MMP-9 activities were significantly higher than in control mice, reaching a peak on day 10 (P < 0.01). On day 10, cardiac systolic function indices (EF, FS, Vp, and Vi) were all significantly lower compared both to other stages following viral inoculation and to the control group (P < 0.05). In the acute stage, the amount of myocardial collagen in mice with VM was not significantly different from normal control mice (P > 0.05). However, the amount of myocardial collagen in infected mice at the recovery stage (on days 21 and 30) was significantly greater than those of the control mice. MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores (r = 0.801, 0.821, P < 0.01) and negatively correlated with Vp (r = -0.649, -0.683, P < 0.01) and Vi (r = -0.711, -0.755, P < 0.01). However, Vp negatively correlated with myocardial histopathological scores (r = -0.756, P < 0.01). CONCLUSIONS: In mice with VM, the activities of myocardial MMP-2 and MMP-9 increase significantly during the acute stage, and the total quantity of myocardial collagen increases by the time of recovery. These changes are associated with myocardial interstition remodeling and cardiac dysfunction. MMP activity is an important reference marker for myocardial pathological lesions and can be used to evaluate the severity of myocardial interstitial damage and cardiac dysfunction.

[Myocardial matrix metalloproteinases activities in mice with viral myocarditis and their relationship with cardiac function and myocardial collagen amount].

OBJECTIVE: To investigate the dynamic changes of myocardial matrix metalloproteinases (MMPs) activities in mice with viral myocarditis (VM) and their relationships with cardiac function and myocardial collagen amount and to explore the role of MMPs in the pathologic lesion of VM. METHODS: Sixty-five six-week-old male DBA/2 mice were obtained from the Chinese Academy of Medical Sciences. They were divided into two groups randomly. Mice in infected group (n=50) were inoculated intraperitoneally with 0.14 ml of coxsackievirus B3 (CVB3, Nancy strain). Control mice (n=15) were inoculated intraperitoneally with 0.14 ml of Eagle's solution. Eight infected mice were sacrificed on day 3, 7, 10, 21 and 30, respectively and fifteen control mice were killed on day 30 after inoculation. Total protein concentration was determined according to the method of Bradford, while MMPs activities were measured with SDS-PAGE type substrate gels embedded with type I gelatin (zymography). Echocardiographic studies were performed under anesthesia with 3% chloralhydrate intraperitoneally (0.01-0.015 ml/g). Cardiac systolic function indexes, such as peak velocity of aorta (Vp) and flow velocity integral of aorta (Vi) were determined by echocardiography. Histological cross sections of hearts were stained with hematoxylin-eosin and myocardial histopathologic scores were counted under optical microscope. Myocardial collagen amount was measured by determination of hydroxyproline quantification. RESULTS: In virus-infected mice, both MMP-2 and MMP-9 activities were increased significantly compared with those in controls and reached the peak on day 10 (P < 0.01). On day 10, cardiac systolic function indexes (Vp and Vi) were all significantly lower than those at other stages after virus inoculation and in control group (P < 0.05). There was no obvious elevation in myocardial collagen amount in mice with VM at acute stage (P > 0.05). While the myocardial collagen amount in infected group at recovery stage (on day 21 and 30) increased significantly compared with controls. MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores, respectively (r =0.801, 0.821 P < 0.01), while they negatively correlated with Vp (r = -0.649, -0.683, P < 0.01) and Vi, respectively (r = -0.711, -0.755, P < 0.01). However, Vp and Vi negatively correlated with myocardial histopathological scores (r = -0.756, -0.584, P < 0.01). CONCLUSIONS: In mice with VM, the activities of myocardial MMP-2 and MMP-9 at acute stage increased significantly, then myocardial collagen amount elevated in recovery stage. These changes were associated with myocardial remodeling and cardiac dysfunction. Myocardial MMP activities are important markers of myocardial pathologic lesion. They are of value in the evaluation of the severity of myocardial damage and cardiac dysfunction in mice with VM.