A worldwide charter for all children with asthma

Childhood asthma is a huge global health burden. The spectrum of disease, diagnosis, and management vary depending on where children live in the world and how their community can care for them. Global improvement in diagnosis and management has been unsatisfactory, despite ever more evidence‐based guidelines. Guidelines alone are insufficient and need supplementing by government support, changes in policy, access to diagnosis and effective therapy for all children, with research to improve implementation. We propose a worldwide charter for all children with asthma, a roadmap to better education and training which can be adapted for local use. It includes access to effective basic asthma medications. It is not about new expensive medications and biologics as much can be achieved without these. If implemented carefully, the overall cost of care is likely to fall and the global future health and life chance of children with asthma will greatly improve. The key to success will be community involvement together with the local and national development of asthma champions. We call on governments, institutions, and healthcare services to support its implementation.     

Diagnosis and management of hepatic artery in-stent restenosis after liver transplantation by optical coherence tomography:A case report

BACKGROUND Percutaneous transluminal angioplasty and stenting represent an effective treatment for hepatic artery stenosis after liver transplantation. In the first year after stenting, approximately 22% of patients experience in-stent restenosis, increasing the risk of artery thrombosis and related complications, and 50% experience liver failure. Although angiography is an important tool for diagnosis and the planning of therapeutic interventions, it may raise doubts, especially in small-diameter arteries, and it provides low resolution rates compared with newer intravascular imaging methods, such as optical coherence tomography(OCT).CASE SUMMARY A 64-year-old male developed hepatic artery stenosis one year after orthotropic liver transplantation and was successfully treated with percutaneous transluminal angioplasty with stenting. Five months later, the Doppler ultrasound results indicated restenosis. Visceral arteriography confirmed hepatic artery tortuosity but was doubtful for significant in-stent restenosis(ISR) and intrahepatic flow reduction. To confirm ISR, identify the etiology and guide treatment, OCT was performed. OCT showed severe stenosis due to four mechanisms: Focal and partial stent fracture, late stent malapposition, in-stent neointimal hyperplasia, and neoatherosclerosis.CONCLUSION Intravascular diagnostic methods can be useful in evaluating cases in which initial angiography results are not sufficient to provide a proper diagnosis of significant stenosis, especially with regard to ISR. A wide range of diagnoses are provided by OCT, resulting in different treatment options. Interventional radiologists should consider intravascular diagnostic methods as additional tools for evaluating patients when visceral angiography results are unclear.     

Protective role of DDAH2 (rs805304) gene polymorphism in patients with myocardial infarction

The purpose of the present study was to establish the role of DDAH gene polymorphisms in the risk of developing myocardial infarction (MI) in a clinical cohort of Mexican patients. One polymorphism (rs1498373) in the DDAH1 and three in the DDAH2 (rs805304, rs3131383, and rs805305) genes were performed by TaqMan genotyping assays in 473 patients with MI and 447 healthy unrelated controls. Similar distribution of DDAH1 and DDAH2 polymorphisms was observed in MI patients and healthy controls. Under a recessive model adjusted for age, gender, and obesity, the rs805304 C allele was associated with decreased risk of MI (OR = 0.70, 95% CI = 0.51–0.96, P = 0.030). The effect of the polymorphisms on various cardiovascular risk factors was analyzed. Under a recessive model adjusted for age and gender, the DDAH2 rs805304 C allele was associated with decreased risk of obesity (OR = 0.35, 95% CI = 0.22–0.57, P = 0.001). The three DDAH2 polymorphisms were in strong linkage disequilibrium. Our results suggest that the rs805304 C allele was associated with decreased risk of MI and decreased risk of obesity.     

Cyclodextrin Reduces Intravenous Toxicity of a Model Compound

Solubilization of new chemical entities for toxicity assessment must use excipients that do not negatively impact drug pharmacokinetics and toxicology. In this study, we investigated the tolerability of a model freebase compound, GDC-0152, solubilized by pH adjustment with succinic acid and complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) to enable intravenous use. Solubility, critical micelle concentration, and association constant with HP-β-CD were determined. Blood compatibility and potential for hemolysis were assessed in vitro. Local tolerability was assessed after intravenous and subcutaneous injections in rats. A pharmacokinetic study was conducted in rats after intravenous bolus administration.GDC-0152 exhibited pH-dependent solubility that was influenced by self-association. The presence of succinic acid increased solubility in a concentration-dependent manner. HP-β-CD alone also increased solubility, but the extent of solubility enhancement was significantly lower than succinic acid alone. Inclusion of HP-β-CD in the solution of GDC-0152 improved blood compatibility, reduced hemolytic potential by ～20-fold in vitro, and increased the maximum tolerated dose to 80 mg/kg.     

Prevalence of Metabolic Syndrome in Elderly and Agreement among Four Diagnostic Criteria

Background

Metabolic syndrome (MS) is an aggregation of risk factors that increase the incidence of cardiovascular events and diabetes mellitus (DM). Population aging is accompanied by higher prevalence of MS, which varies depending on the population studied and the diagnostic criteria used.

Objective

To determine prevalence of MS in the elderly using four diagnostic criteria and agreement between them.

Methods

Cross-sectional study on 243 patients older than 60 years (180 women) in Niterói, RJ. They were evaluated by clinical examination, fasting glucose, fasting insulin, lipid profile and anthropometric measurements - weight, height, waist circumference and waist/hip ratio. Prevalence of MS was estimated by World Health Organization (WHO) modified, National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III), International Diabetes Federation (IDF) and Joint Interim Statement (JIS) criteria.

Results

Prevalence was high with the four criteria WHO (51.9%), NCEP-ATPIII (45.2%), IDF (64.1%) and JIS (69.1%), and agreement between criteria by kappa was moderate in almost all comparisons WHO vs. IDF (k = 0.47;95% confidence interval (CI), 0.35 to 0.58); WHO vs. NCEP-ATPIII (k = 0.51; 95% CI, 0.40 to 0.61); WHO vs. JIS (k = 0.45; 95% CI, 0.33 to 0.56); IDF vs. NCEP-ATPIII (k = 0.55; 95% CI, 0.45 to 0.65) and NCEP-ATPIII vs. JIS (k = 0.53; 95% CI, 0.43-0.64), except between IDF vs. JIS (K = 0.89;95% CI, 0.83 to 0.95), which was considered good.

Conclusion

Prevalence of MS was high with the four diagnostic criteria, mainly by JIS. There was good agreement between JIS and IDF criteria and moderate among the others.     

BRAF Mutation in Papillary Thyroid Cancer and Its Value in Tailoring Initial Treatment: A Systematic Review and Meta-Analysis

ABSTRACT: Clinicians have long sought to characterize biological markers of neoplasia as objective indicators of tumor presence, pathogenicity, and prognosis. Armed with data that correlate biomarker activity with disease presence and progression, clinicians can develop treatment strategies that address risks of disease recurrence or persistence and progression. The B-type Raf kinase (BRAF V600E) mutation in exon 15 of the BRAF gene has been noted to be a putative prognostic marker of the most prevalent form of thyroid cancer, papillary thyroid cancer (PTC)-a tumor type with high proclivity for recurrence or persistence. There has been a remarkable interest in determining the association of BRAF mutation with PTC recurrence or persistence. Using many new studies that have been published recently, we performed a meta-analysis to investigate correlations of BRAF mutation status with PTC prognosis, focusing on the recurrence or persistence of the disease after initial treatment.The study was based on published studies included in the PubMed and Embase databases addressing the BRAF mutation and the frequency of recurrence of PTC. We selected studies with data that enabled measurement of the risk ratio for recurrent disease. We also analyzed the factors that are classically known to be associated with recurrence. These factors included lymph node metastasis, extrathyroidal extension, distant metastasis, and American Joint Committee on Cancer (AJCC) stages III/IV.We used 14 articles that included an analysis of these factors as well as PTC recurrence data, with a total of 2470 patients from 9 different countries. The overall prevalence of the BRAF mutation was 45%. The risk ratios in BRAF mutation-positive patients were 1.93 (95% confidence interval [CI], 1.61-2.32; Z = 7.01; p < 0.00001) for PTC recurrence, 1.32 (95% CI, 1.20-1.45; Z = 5.73; p < 0.00001) for lymph node metastasis, 1.71 (95% CI, 1.50-1.94; Z = 8.09; p < 0.00001) for extrathyroidal extension, 0.95 (95% CI, 0.63-1.44; Z = 0.23; p = 0.82) for distant metastasis, and 1.70 (95% CI, 1.45-1.99; Z = 6.46; p < 0.00001) for advanced stage AJCC III/IV.Thus, in this meta-analysis, the BRAF mutation in PTC was significantly associated with PTC recurrence, lymph node metastasis, extrathyroidal extension, and advanced stage AJCC III/IV. Patients with PTC harboring mutated BRAF are likely to demonstrate factors that are associated with an increased risk for recurrence of the disease, offering new prospects for optimizing and tailoring initial treatment strategies to prevent recurrence.     

Inhibition of Aurora kinases enhances chemosensitivity to temozolomide and causes radiosensitization in glioblastoma cells

Background  

Glioblastoma remains one of the most devastating human malignancies, and despite therapeutic advances, there are no drugs that significantly improve the patient survival. Altered expression of the Aurora kinases was found in different malignancies, and their inhibition has been studied in cancer therapy. In this study, we analyzed the expression of Aurora A and Aurora B in glioblastoma samples and also analyzed whether the effects of Aurora kinase inhibition were associated with temozolomide or not on cell lines and primary cultures of glioblastoma.