The influence of statin-fibrate combination therapy on lipids profile and apolipoprotein A5 in patients with acute coronary syndrome.

BACKGROUND: Statin-fibrate combination therapy has been used to treat patients with acute coronary syndrome (ACS) complicated by elevated triglycerides (TG) and decreased high density lipoprotein cholesterol (HDL-C). The purpose of this study was to evaluate the influence of the combination therapy on lipids profile and apolipoprotein A5 (apoA5) level in patients with ACS. METHODS: One hundred and four patients with ACS were recruited and randomly assigned into two groups: one was statin group (n = 52), given atorvastatin (20 mg QN) or other statins with equivalent dosages; the other was combination group (n = 52), given the same dose of statin plus bezafibrate (200 mg BID). Follow-up visits were scheduled at the end of 6 and 12 weeks post treatment. Serum apoA5 levels were determined using a commercial available ELISA kit. RESULTS: (1) Compared with that of statin monotherapy, statin-bezafibrate combination treatment not only resulted in a significant reduction of TG, TC and LDL-C levels, (all p < 0.05), but also led to increases in HDL-C and apoA5 levels (p < 0.05).(2) The percentage changes of TC, TG, LDL-C and apoA5 levels in both groups were even bigger at 12 weeks after treatment than that at 6 weeks (all p < 0.05). Similarly, the rates of achieving lipid-control target were higher in statin-bezafibrate combination treatment group than those in statin monotherapy group (all p < 0.05).(3) Spearman rank correlation analysis showed that the pre-treatment apoA5 level was positively correlated with TG (r = 0.359, p = 0.009). However, a negative correlation was observed between apoA5 and TG (r = -0.329, p = 0.017) after 12 weeks treatment. CONCLUSIONS: Statin and fibrate combination therapy is more effective than statin alone in achieving a comprehensive lipid control for ACS patients. Serum apoA5 elevation after statin and fibrate combination treatment could be due to the synergistic effect of both drugs on hypertriglyceridemia control.

[The lipid-regulating effect and safety of combined statin and bezafibrate therapy in acute coronary syndrome patients complicating with dyslipidemia].

OBJECTIVE: To investigate the lipid-regulating effect and safety of combined statin and bezafibrate therapy in acute coronary syndrome(ACS) patients complicating with dyslipedemia. METHODS: One hundred and four hospitalized patients with established ACS and increased serum triglycerides (TG) levels and/or low serum levels of high density lipoprotein cholesterol (HDL-C) were selected. Except for conventional therapy, the patients were randomly divided into 2 groups: control group (n = 52), treated with atorvastatin 20 mg qn or other statin equivalent to 20 mg atorvastatin; treatment group (n = 52), treated with the same dose statin plus bezafibrate 200 mg bid. The serum levels of total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C) and HDL-C were assessed before and after 6 and 12 weeks treatment, side effects and adverse events were recorded. RESULTS: After 6 weeks treatment, the serum levels of TC, TG and LDL-C in two groups were significantly reduced compared to baseline (all P < 0.05), which were further declined after 12 weeks treatment, and the reduction was more significant in treatment group(29.8%, 38.0% and 36.1%, respectively) than in control group(14.7%, 9.8% and 26.7%, respectively) (all P < 0.05). After treatment, the serum levels of HDL-C in the two groups were significantly higher than the baseline levels, especially after 12 weeks treatment (all P < 0.05), and the elevations of HDL-C levels in control group and in treatment group were 19.3% and 24.2%, respectively, but there were no significant difference between the two groups (P > 0.05). After 12 weeks, the rates reaching to target goals of LDL-C, TG, HDL-C, and non-HDL-C levels in the treatment group (69.2%, 88.5%, 92.3%, 46.2% and 65.4%, respectively) were significantly higher than those in the control group (34.6%, 65.4%, 46.2%, 7.7% and 42.3%, respectively, all P < 0.05). No serious side effects were observed in the two groups during the treatment period. CONCLUSION: The combined statin and bezafibrate treatment is safe and could increase the ratios of reaching target lipid levels in ACS patients complicating with increased TG and (or) decreased HDL-C.

[Change of serum myeloperoxidase and lipoxin A4 level in coronary heart disease patients with anxiety and/or depression].

OBJECTIVE: To investigate the change of serum myeloperoxidase (MPO) and lipoxin A4 (LXA4) in coronary heart disease (CHD) patients with anxiety and depression and its clinical significance. METHODS: From December 2010 to February 2011, 143 CHD patients and 44 non-CHD patients (the control group) hospitalized in the Department of Cardiology at the Second Xiangya Hospital were enrolled. The hospital anxiety and depression scale (HADS) was used to evaluate the psychological state of all patients and the CHD patients were assigned to an anxiety and depression group (n=57) or a non-depression and anxiety group (n=86). The serum levels of high sensitive C-reactive protein (Hs-CRP), MPO, and LXA4 were examined, and the ratio of MPO and LXA4 (M/L) was calculated. RESULTS: The levels of Hs-CRP, MPO, and LXA4 as well as M/L ratios in both CHD groups were significantly higher than those in the control group (all P<0.01). Compared with the non-anxiety and depression group, the levels of MPO and LXA4, and M/L ratios in the anxiety and depression group increased (all P<0.05). Correlation analysis showed that MPO was positively correlated with the score of HADS-total (HADS-t), HADS-anxiety (HADS-a), or HADS-depression (HADS-d), while LXA4 was negatively correlated with HADS-t or HADS-d. Multiple ordinal logistic regression analysis revealed that higher HADS-t score, stable angina, unstable angina, and acute myocardial infarction were the independent impact factors for the elevation of M/L ratio. CONCLUSION: Anxiety and depression may aggravate the inflammatory response in CHD patients. The imbalance between inflammation and anti-inflammation may be part of the mechanism.

Perioperative parameters-based prediction model for acute kidney injury in Chinese population following valvular surgery.

Background: Acute kidney injury (AKI) is a relevant complication after cardiac surgery and is associated with significant morbidity and mortality. Existing risk prediction tools have certain limitations and perform poorly in the Chinese population. We aimed to develop prediction models for AKI after valvular cardiac surgery in the Chinese population. Methods: Models were developed from a retrospective cohort of patients undergoing valve surgery from December 2013 to November 2018. Three models were developed to predict all-stage, or moderate to severe AKI, as diagnosed according to Kidney Disease: Improving Global Outcomes (KDIGO) based on patient characteristics and perioperative variables. Models were developed based on lasso logistics regression (LLR), random forest (RF), and extreme gradient boosting (XGboost). The accuracy was compared among three models and against the previously published reference AKICS score. Results: A total of 3,392 patients (mean [SD] age, 50.1 [11.3] years; 1787 [52.7%] male) were identified during the study period. The development of AKI was recorded in 50.5% of patients undergoing valve surgery. In the internal validation testing set, the LLR model marginally improved discrimination (C statistic, 0.7; 95% CI, 0.66-0.73) compared with two machine learning models, RF (C statistic, 0.69; 95% CI, 0.65-0.72) and XGBoost (C statistic, 0.66; 95% CI, 0.63-0.70). A better calibration was also found in the LLR, with a greater net benefit, especially for the higher probabilities as indicated in the decision curve analysis. All three newly developed models outperformed the reference AKICS score. Conclusion: Among the Chinese population undergoing CPB-assisted valvular cardiac surgery, prediction models based on perioperative variables were developed. The LLR model demonstrated the best predictive performance was selected for predicting all-stage AKI after surgery. Clinical trial registration: Trial registration: Clinicaltrials.gov, NCT04237636.

BMMSC-derived Exosomes Attenuate Cardiopulmonary Bypass-related Acute Lung Injury by Reducing Inflammatory Response and Oxidative Stress.

BACKGROUND: Acute lung injury (ALI), which is characterized by inflammation and oxidative stress, is a common complication after cardiopulmonary bypass (CPB). Exosomes from bone marrow mesenchymal stem cells (BMMSC-Exo) have recently been identified as promising treatments for ALI. However, the effects of BMMSC-Exo on inflammation and oxidative stress in CPB-related ALI remain unclear. OBJECTIVE: We aim to evaluate the effects of BMMSC-Exo on post-CPB ALI and explore their potential mechanisms. METHODS: We randomly divided rats into three groups: sham, ALI, and ALI+BMMSC-Exo groups. Histological changes were evaluated by lung histo-pathology and bronchoalveolar lavage fluid (BALF). ELISA assay was used to determine inflammatory cytokine levels and oxidative stress. RESULTS AND DISCUSSION: BMMSC-Exo attenuated histological changes (including the invasion of inflammatory cells), reduced the wet/dry (W/D) weight ratio, and downregulated inflammatory cytokine levels, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1ß. BMMSC-Exo also alleviated oxidative stress. In vitro, we further administered lipopolysaccharide (LPS) to alveolar macrophages (AMs) to mimic the pathological changes of ALI and found that BMMSC-Exo suppressed reactive oxygen species (ROS) production and downregulated the levels of inflammatory cytokines. Mechanistically, BMMSC-Exo inhibited the phosphorylation of nuclear factor-κB (NF-κB), the nuclear translocation of p65, also facilitated the phosphorylation of Akt and the nuclear translocation of Nrf2, while upregulating the expression of HO-1. CONCLUSION: In summary, we indicate that BMMSC-Exo reduces CPB-related ALI by alleviating inflammation and oxidative stress. The underlying mechanism may involve the NF-κB p65 and Akt/Nrf2/HO-1 signaling pathways.

Development of a core dataset for child injury surveillance: a modified Delphi study in China.

Background: Understanding the occurrence and severity of child injuries is the cornerstone of preventing child injuries. Currently, there is no standardized child injury surveillance dataset in China. Methods: Multistage consultation by a panel of Chinese experts in child injury to determine items to include in the core dataset (CDS) was performed. The experts participated in two rounds of the modified Delphi method comprising a consultation questionnaire investigation (Round 1) and a face-to-face panel discussion (Round 2). Final consensus was established based on the opinions of the experts regarding the modified CDS information collection items. Enthusiasm and authority exhibited by the experts were evaluated by the response rate and using the expert authority coefficient, respectively. Results: The expert panel included 16 experts in Round 1 and 15 experts in Round 2. The experts during both rounds had a high degree of authority, with an average authority coefficient of 0.86. The enthusiasm of the experts was 94.12%, and the proportion of suggestions reached 81.25% in Round 1 of the modified Delphi method. The draft CDS evaluated in Round 1 included 24 items, and expert panelists could submit recommendations to add items. Based on findings in Round 1, four additional items, including nationality, residence, type of family residence, and primary caregiver were added to the draft of the CDS for Round 2. After Round 2, consensus was reached on 32 items arranged into four domains-general demographic information, injury characteristics, clinical diagnosis and treatment, and injury outcome-to include in the final CDS. Conclusion: The development of a child injury surveillance CDS could contribute to standardized data collection, collation, and analysis. The CDS developed here could be used to identify actionable characteristics of child injury to assist health policymakers in designing evidence-based injury prevention interventions.

Causes and Characteristics of Children Unintentional Injuries in Emergency Department and Its Implications for Prevention.

Background: Child unintentional injuries have become a hot topic worldwide, and substantial regional disparities existed in causes and characteristics. To date, limited data are available to investigate the causes and characteristics of child unintentional injuries from hospitals for children in China. Methods: A cross-sectional study was conducted between January 2017 and December 2018 in Shanghai, China. Patients aged <18 years with an unintentional injury presented to the emergency department were enrolled. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were retrieved from electronic health records (EHRs). Frequencies and proportions of categorical variables and means and SDs of continuous variables are presented. Chi-square test and Student's t-test were used for the comparison between groups, as appropriate. Logistic regression analysis was used to estimate potential risk factors for admission to the hospital. Results: A total of 29,597 cases with unintentional injuries were identified between January 2017 and December 2018, with boys vs. girls ratio of 1.75. Preschool children account for approximately two-thirds of unintentional injuries in the emergency department. A distinctive pattern of mechanisms of unintentional injuries between gender was documented, and sports injury was significantly higher in boys than in girls (10.2 vs. 7.8%). Compared with Canadian Emergency Department Triage and Acuity Scale (CTAS) Grade 3 patients, Grade 2 [odds ratio (OR) = 2.99, 95% CI = 1.93-4.63, P < 0.001] and Grade 1 (OR = 74.85, 95% CI = 12.93-433.14, P < 0.001) patients had higher risk of inhospital admission. For causes of injuries, compared with falling, foreign body and poison had a lower risk of inhospital admission, while transport injury (OR = 1.31, 95% CI = 1.07-1.59, P = 0.008) and high fall injury (OR = 2.58. 95% CI =1.48-4.49, P < 0.001) had a significantly higher risk of admission. Conclusions: There was a significant relationship between age-groups and unintentional injuries between gender, with decreased injuries among girls growing up older. Preventive measures should be taken to reduce transport injury and high fall injury, which had a significantly higher risk of admission.

Clinical features and risk factors for severe influenza in children: A study from multiple hospitals in Shanghai.

BACKGROUND: The incidence and mortality of influenza in children had risen, but data are limited on children with severe influenza virus infection in China. METHODS: We conducted a retrospective case-control study and collected the patients' clinical data. Clinical data including demography, clinical presentation, laboratory findings, radiologic findings, treatment and outcomes were collected. Children were clinically confirmed to have virus infection in Shanghai in three hospitals from June 2014 to June 2019. RESULTS: During the study, 36,047 children were enrolled. Among them, 118 met the criteria for severe flu. Clinical symptoms such as fever, cough, gastrointestinal symptoms, coma and epilepsy were higher in the severe group. Complications such as pneumorrhagia, heart failure, septic shock, acute renal failure and influenza-associated encephalitis were higher in the severe influenza group than the death group. The laboratory findings including decreased hemoglobin, high alanine aminotransferase, high urea nitrogen and high lactate levels were risk factors for death in children with influenza. CONCLUSION: Influenza-associated encephalopathy (IAE), acute respiratory distress syndrome (ARDS) were the common clinical manifestations and complications for the severe influenza, and delayed use of oseltamivir was found to be associated with fatality.

Diagnosing Balamuthia mandrillaris encephalitis via next-generation sequencing in a 13-year-old girl.

Balamuthia amoebic encephalitis has a subacute-to-chronic course and is almost invariably fatal owing to delayed diagnosis and a lack of effective therapy. Here, we report a 13-year-old girl with cutaneous lesions and multifocal granulomatous encephalitis. The patient underwent a series of tests and was suspected as having tuberculosis. She was treated with various empiric therapies without improvement. She was finally correctly diagnosed via next-generation sequencing of the cerebrospinal fluid. The patient deteriorated rapidly and died 2 months after being diagnosed with Balamuthia mandrillaris encephalitis. This study highlights the important clinical significance of next-generation sequencing, which provides better diagnostic testing for unexplained paediatric encephalitis, especially that caused by rare or emerging pathogens.

A novel HAND2 loss-of-function mutation responsible for tetralogy of Fallot.

Congenital heart disease (CHD), the most common type of developmental abnormality, is associated with substantial morbidity and mortality in humans worldwide. The basic helix-loop-helix transcription factor, heart and neural crest derivatives expressed 2 (HAND2), has been demonstrated to be crucial for normal cardiovascular development in animal models. However, whether a genetically defective HAND2 contributes to congenital heart disease (CHD) in humans remains to be explored. In this study, the entire coding region and splicing boundaries of the HAND2 gene were sequenced in a cohort of 145 unrelated patients with CHD. A total of 200 unrelated, ethnically-matched healthy individuals used as controls were also genotyped for HAND2. The functional effect of the mutant HAND2 was characterized in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. As a result, a novel heterozygous HAND2 mutation, p.L47P, was identified in a patient with tetralogy of Fallot (TOF). The misense mutation, which altered the amino acid conserved evolutionarily among species, was absent in 400 control chromosomes. Functional analyses unveiled that the mutant HAND2 had a significantly decreased transcriptional activity. Furthermore, the mutation markedly reduced the synergistic activation between HAND2 and GATA4 or NKX2.5, other two cardiac key transcription factors involved in the pathogenesis of CHD. To the best of our knowledge, this study is the first to report the association of a HAND2 loss-of-function mutation with an increased vulnerability to TOF in humans, which provides novel insight into the molecular mechanism underpinning CHD, suggesting potential implications for the genetic counseling of families with CHD.

[A multicenter prospective clinical study on continuous blood purification in treating childhood severe sepsis].

OBJECTIVE: To evaluate efficacy of continuous blood purification (CBP) in childhood severe sepsis through the analysis of organ function, inflammatory mediators and prognosis. METHOD: Forty-seven children with severe sepsis aged 29 days -16 years who were treated in PICU of Shanghai and Zhejiang five hospitals during October 1, 2011 and September 30, 2012 were enrolled; 30 cases treated with CBP were recorded as logged group , 17 cases without CBP as unlogged group. Changes in the cardiovascular, respiratory function, renal function, inflammatory markers, PRISM score III, PCIS and survival were observed and compared between the two groups at baseline (d0), first days (d1), second days (d2), third days (d3), fifth days (d5). RESULT: (1) Cardiovascular function: In d3 and d5, heart rate (HR) and mean arterial pressure (MAP) were improved as compared to unlogged group (121, 119 vs. 138, 137; 71, 80 mmHg vs. 63, 62 mmHg, P < 0.05), with no statistical significance in arterial blood lactate concentration. (2) Oxygenation index (PaO2/FiO2) and arterial oxygen saturation (SaO2) increased as compared to unlogged group, but did not reach statistical significance. (3) Blood urea nitrogen (BUN) and creatinine (Cr) were improved as compared with unlogged group from d1 (P < 0.05). (4) Inflammatory mediators did not show significant differences. (5) Twenty-eight days survival rate: logged group was 70.0%, unlogged group was 52.9%, but the difference was not statistically significant (P = 0.242). CONCLUSION: CBP can improve circulatory function, oxygenation, and renal function in children with severe sepsis. No evidence was found that CBP could decrease the level of inflammatory mediators, improve critical score and 28 days survival rate.