Asthma is the most common chronic respiratory disease seriously endangering the health of children. But disease awareness and self-management skills are relatively poor in children; parents play an ...important role in the control of childhood asthma.
To investigate the status of asthma control and severity of asthma in children and to identify impact factors.
We studied 1 tertiary hospital in each of the 29 provinces. A total of 2,960 parents with children with asthma who visited those hospitals were selected for the knowledge, attitude, and practice (KAP) questionnaire survey, and separated into the controlled asthma group and uncontrolled asthma group according to children's asthma conditions in the past 12 months. Multivariate analysis was carried out based on the answers to 28 tested factors.
In the past 12 months, 66.0% of children with asthma had asthma attacks, 26.8% visited an emergency room, and 16.2% were hospitalized. The total cost for asthma was significantly higher in the uncontrolled group than controlled group (χ(2) = 23.14, P < .01). Twelve protective factors of asthma control were founded, such as older age of children, long disease course, high KAP scores of parents, compliance with using nasal steroids, and knowledge of "3 or more times recurrent wheezing suggesting asthma." The risk factors were eczema and family history of asthma.
Children's asthma is poorly controlled. The cost of asthma is significantly higher in uncontrolled asthma than in controlled. The age of children, course of asthma, personal history of allergy, family history of asthma, parents' education level, and parents' KAP are factors that affect asthma control.
Pulmonary hypertension (PH) is a common entity in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI), but its role on clinical outcomes remains ...undetermined. We evaluated the impact of baseline and postprocedural PH on clinical outcomes and changes in pulmonary artery systolic pressure after TAVI by performing a meta-analysis of 16 studies enrolling 9,204 patients with AS who underwent TAVI. In patients with baseline PH, all-cause mortality was significantly increased, as shown by pooled odds ratio (ORs) for overall 30-day (OR 1.52, 95% confidence interval CI 1.28 to 1.80), 1-year (OR 1.39, 95% CI 1.27 to 1.51), and 2-year all-cause mortality (OR 2.00, 95% CI 1.49 to 2.69), compared with those without PH, independent of different methods of PH assessment. The presence of post-TAVI PH was associated with a significant increase in 2-year all-cause mortality (OR 2.32, 95% CI 1.43 to 3.74). Nevertheless, pulmonary artery systolic pressure decreased at 3-month to 1-year follow-up (standardized mean difference −1.12, 95% CI −1.46 to −0.78). Baseline PH was associated with higher 30-day and 1-year cardiovascular mortality. Patients with baseline PH had higher risk of stroke at 1 year and acute kidney injury at 30 days. But the risk of major vascular complications was significantly lower in patients with baseline PH. In conclusion, the presence of PH is associated with increased short- and long-term mortality, also higher risk of stroke and acute kidney injury after TAVI. A significant decrease in PSAP is detected in patients with AS in midterm follow-up after TAVI.
Background Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-α, an important autocrine stimulator of dendritic cells and macrophages in the airways. Objective We ...sought to study the mechanisms by which TNF-α and SP-D can affect cellular components of the pulmonary innate immune system. Methods Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow–derived dendritic cells was investigated in vitro. Results TNF-α, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro , and the SP-D response to allergen challenge was impaired in IL-13–deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-α release and cell influx. SP-D–deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-α, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow–derived dendritic cell cultures. Conclusions TNF-α can contribute to enhanced SP-D production in the lung indirectly through inducing IL-13. SP-D, on the other hand, can antagonize the proinflammatory effects of TNF-α on macrophages and dendritic cells, at least partly, by inhibiting production of this cytokine.
Abstract Severe bleeding (SB) in patients undergoing transcatheter aortic valve implantation (TAVI) could be fatal. Though multiple independent predictors of bleeding post-TAVI have been identified, ...the definitions of bleeding and predictors vary across studies. This study aimed to provide summary effect estimates for predictors of SB within 30 days post-TAVI. A systematic review of studies that reported the incidence of bleeding post-TAVI with raw data for predictors of interest was performed. Data on characteristics of study, patient and procedure were extracted. Crude risk ratios (RRs) and 95% confidence intervals were calculated using random effect model. Fifteen predictors on 65,209 patients from 47 studies were analyzed. The median rate of SB was 11% across studies. Seven factors (3 patient-related and 4 procedure-related) were recognized as predictors of early SB post-TAVI. Age ≥ 90 (RR: 1.17; p = 0.008), female (RR: 1.13; p = 0.01) and sheath diameter > 19 French (RR: 1.19; p = 0.04) were weak predictors. Chronic kidney disease (CKD) (RR: 1.94; p < 0.001) and transapical access (TA) (RR: 1.82; p < 0.001) were moderate predictors that were almost associated with twofold risk. Vascular complication (VC) (RR: 2.97; p < 0.001) and circulatory support (CS) (RR: 3.39; p < 0.001) were strong predictors that were nearly associated with threefold risk. In conclusion, age, sex, CKD, TA, sheath diameter, VC, CS were all predictors of early SB post-TAVI in this meta-analysis, which provided possible guidance for prevention and management of SB related to TAVI.
Abstract Background The authors previously reported that the c-kit–positive (c-kitPOS ) cells isolated from slowly adhering (SA) but not from rapidly adhering (RA) fractions of cardiac mesenchymal ...cells (CMCs) are effective in preserving left ventricular (LV) function after myocardial infarction (MI). Objectives This study evaluated whether adherence to plastic alone, without c-kit sorting, was sufficient to isolate reparative CMCs. Methods RA and SA CMCs were isolated from mouse hearts, expanded in vitro, characterized, and evaluated for therapeutic efficacy in mice subjected to MI. Results Morphological and phenotypic analysis revealed that murine RA and SA CMCs are indistinguishable; nevertheless, transcriptome analysis showed that they possess fundamentally different gene expression profiles related to factors that regulate post-MI LV remodeling and repair. A similar population of SA CMCs was isolated from porcine endomyocardial biopsy samples. In mice given CMCs 2 days after MI, LV ejection fraction 28 days later was significantly increased in the SA CMC group (31.2 ± 1.0% vs. 24.7 ± 2.2% in vehicle-treated mice; p < 0.05) but not in the RA CMC group (24.1 ± 1.2%). Histological analysis showed reduced collagen deposition in the noninfarcted region in mice given SA CMCs (7.6 ± 1.5% vs. 14.5 ± 2.8% in vehicle-treated mice; p < 0.05) but not RA CMCs (11.7 ± 1.7%), which was associated with reduced infiltration of inflammatory cells (14.1 ± 1.6% vs. 21.3 ± 1.5% of total cells in vehicle and 19.3 ± 1.8% in RA CMCs; p < 0.05). Engraftment of SA CMCs was negligible, which implies a paracrine mechanism of action. Conclusions We identified a novel population of c-kit–negative reparative cardiac cells (SA CMCs) that can be isolated with a simple method based on adherence to plastic. SA CMCs exhibited robust reparative properties and offered numerous advantages, appearing to be more suitable than c-kitPOS cardiac progenitor cells for widespread clinical therapeutic application.
Summary Background The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) ...in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population. Methods In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m2 on days 1 and 8, intravenously) plus platinum (carboplatin 5 × area under the curve or cisplatin 75 mg/m2 on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15–28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks. With the exception of an independent group responsible for monitoring data and safety monitoring board, everyone outside the interactive internet response system company was masked to treatment allocation. Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death, and all patients in the placebo group were offered second-line erlotinib at the time of progression. The primary endpoint was PFS in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT00883779. Findings From April 29, 2009, to Sept 9, 2010, 451 patients were randomly assigned to chemotherapy plus erlotinib (n=226) or chemotherapy plus placebo (n=225). PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo (median PFS 7·6 months 95% CI 7·2–8·3, vs 6·0 months 5·6–7·1, hazard ratio HR 0·57 0·47–0·69; p<0·0001). Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months (16·3–20·8) and 15·2 months (12·7–17·5), respectively (HR 0·79 0·64–0·99; p=0·0420). Treatment benefit was noted only in patients with an activating EGFR gene mutation (median PFS 16·8 months 12·9–20·4 vs 6·9 months 5·3–7·6, HR 0·25 0·16–0·39; p<0·0001; median overall survival 31·4 months 22·2–undefined, vs 20·6 months 14·2–26·9, HR 0·48 0·27–0·84; p=0·0092). Serious adverse events were reported by 76 (34%) of 222 patients in the chemotherapy plus placebo group and 69 (31%) of 226 in the chemotherapy plus erlotinib group. The most common grade 3 or greater adverse events were neutropenia (65 29% patients and 55 25%, respectively), thrombocytopenia (32 14% and 31 14%, respectively), and anaemia (26 12% and 21 9%, respectively). Interpretation Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status. Funding F Hoffmann-La Roche.
Summary Background Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic ...diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis. Methods In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids were enrolled at 161 hospitals, clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a central interactive voice/web response system, stratified by severity and global region. All three groups were given concomitant topical corticosteroids with or without topical calcineurin inhibitors where inadvisable for topical corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted on the basis of disease activity. Coprimary endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-point or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses included all randomised patients; week 52 efficacy included patients who completed treatment by US regulatory submission cutoff. This study is registered with ClinicalTrials.gov , NCT02260986. Findings Between Oct 3, 2014, and July 31, 2015, 740 patients were enrolled: 319 were randomly assigned to dupilumab qw plus topical corticosteroids, 106 to dupilumab q2w plus topical corticosteroids, and 315 to placebo plus topical corticosteroids. 623 (270, 89, and 264, respectively) were evaluable for week 52 efficacy. At week 16, more patients who received dupilumab plus topical corticosteroids achieved the coprimary endpoints of IGA 0/1 (39% 125 patients who received dupilumab plus topical corticosteroids qw and 39% 41 patients who received dupilumab q2w plus topical corticosteroids vs 12% 39 patients who received placebo plus topical corticosteroids; p<0·0001) and EASI-75 (64% 204 and 69% 73 vs 23% 73; p<0·0001). Week 52 results were similar. Adverse events were reported in 261 (83%) patients who received dupilumab qw plus topical corticosteroids, 97 (88%) patients who received dupilumab q2w, and 266 (84%) patients who received placebo, and serious adverse events in nine (3%), four (4%), and 16 (5%) patients, respectively. No significant dupilumab-induced laboratory abnormalities were noted. Injection-site reactions and conjunctivitis were more common in patients treated with dupilumab plus topical corticosteroids-treated patients than in patients treated with placebo plus topical corticosteroids. Interpretation Dupilumab added to standard topical corticosteroid treatment for 1 year improved atopic dermatitis signs and symptoms, with acceptable safety. Funding Sanofi and Regeneron Pharmaceuticals Inc.
Abstract To date, the impact of diabetes mellitus (DM) on prognosis after Transcatheter Aortic Valve Implantation (TAVI) is still contradictory and thus merits further investigation. The purpose of ...this meta-analysis was to evaluate the impact of DM on outcomes after TAVI. A systematic search of the Pubmed database was performed. Primary endpoints were 30-day and 1-year all-cause mortality after TAVI. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effect or fixed effect model, depending on heterogeneity between studies, and p values <0.05 was considered significant. A total of 16 studies involving 13,253 patients were included in our meta-analysis. There was no significant difference between the groups with DM and without DM regarding 30-day (RR 1.07, 95% CI 0.90 to 1.27, p=0.45) or 1-year (RR 1.04, 95% CI 0.94 to 1.15, p=0.42) all-cause mortality. The risks of 30-day complications, including myocardial infarction, stroke, major vascular complications, major bleeding and acute kidney injury, were similar between patients with and without DM. In conclusion, DM neither affected short-term or midterm all-cause mortality nor short-term complications after TAVI.
Objective The PDLIM5 gene is known to interact specifically with the N-type calcium channel α-1B subunit and protein kinase Cε and is critical for rapid, efficient potentiation of the calcium channel ...activation by protein kinase C in neurons. Increasing amounts of data suggested that PDLIM5 might be involved in the pathophysiology of major depressive disorder (MDD). The aim of this study was to examine whether genetic variations in the human PDLIM5 gene might contribute to the liability to develop MDD. Method We undertook a gene-based association analysis of single nucleotide polymorphisms (SNPs). Three SNPs (rs10008257, rs2433320 and rs2452600) were identified in the PDLIM5 gene and genotyped in patients diagnosed with recurrent MDD and in matched control subjects. Results We observed significant allele ( p = 0.007) and genotype ( p = 0.007) association with rs2433320, and the G allele of rs2433320 was significantly overrepresented in control subjects in comparison with MDD patients. Conclusion These results support the hypothesis of a protective effect for the G allele of rs2433320 in the PDLIM5 gene in recurrent MDD.
We recently reported that an S140G mutation in human KCNQ1, an alpha subunit of potassium channels, was involved in the pathogenesis of familial atrial fibrillation (AF), but it is not clear whether ...the mutation is associated with other cardiac arrhythmias.
The purpose of this study was to further explore the association of the KCNQ1 S140G mutation with cardiac arrhythmias.
We produced a transgenic mouse model with myocardium-specific expression of the human KCNQ1 S140G mutation under the control of an alpha-cardiac myosin heavy chain promoter by standard transgenic procedure and evaluated the relationship between the KCNQ1 mutation and its phenotypes in a human family.
Four lines of transgenic mice were established with a high level of human KCNQ1 S140G expression in the heart. Frequent episodes of first-, second-, advanced-, or third-degree atrioventricular block (AVB) occurred in at least 65% of transgenic descendants from the four lines. However, none of the five wild-type transgenic lines presented with AVBs. HMR1556, a KCNQ1-specific blocker, can terminate the AVBs. With the exception of at most three AF individuals, at least 13 AF patients were found to show obviously slow ventricular response, which may be one manifestation of AVBs. Interestingly, AF was not detected in these transgenic mice.
The results suggest that human KCNQ1 S140G is also likely to be a causative mutation responsible for AVBs. The transgenic mouse model is a potential tool to explore mechanisms of AVBs.
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