Efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy for advanced EGFR-mutated non-small cell lung cancer: systematic review and meta-analysis.

OBJECTIVE: It is controversial whether there is efficacy or safety benefit of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in advanced EGFR-mutated non-small cell lung cancer (NSCLC) compared to standard chemotherapy. We aim to assess the efficacy and safety of EGFR-TKIs compared to other chemotherapeutics in EGFR-mutated NSCLC. MATERIALS AND METHODS: Up to April 27th, 2020, PubMed, Embase, Medline, Scopus, Cochrane library, and ClinicalTrials.gov were searched for articles or trials meeting the inclusion criteria. After filtering, 230 eligible studies were initially identified. Data extraction followed PRISMA and included outcomes were progression-free survival (PFS), overall survival (OS), and severe adverse events (SAEs). Direct and indirect meta-analyses were generated in the context of log-linear mixed-effects models, with fixed effects for each relative comparison and random effects for each study. RESULTS: The results showed that EGFR-TKI therapy had improved PFS with a hazard ratio (HR) of 0.40 (95% CI: 0.36-0.44, p<0.001) compared to standard chemotherapy. Nevertheless, the EGFR-TKIs showed no benefit on OS (HR: 0.96, 95% CI: 0.83-1.10, p=0.556). In the analysis of adverse events, EGFR-TKIs had fewer SAEs than standard chemotherapy (HR: 0.29, 95% CI: 0.26-0.33, p<0.001). CONCLUSIONS: Our systemic review indicates that EGFR-TKI therapy has improved PFS, and reduced SAEs compared to standard chemotherapy in advanced EGFR-mutated NSCLC.

The effect of statins on all-cause and cardiovascular mortality in patients with non-dialysis chronic kidney disease, patients on dialysis, and kidney transplanted recipients: an umbrella review of meta-analyses.

OBJECTIVE: Although some previous meta-analyses have demonstrated a relationship between statin therapy and all-cause mortality in patients with chronic kidney disease (CKD), conflicting results have been reported. Thus, we performed an umbrella review to understand the strength of evidence and validity of the claimed associations between statin use and all cause and cardiovascular mortality in CKD patients, including patients on dialysis (CKD stage 5D) and transplant recipients. MATERIALS AND METHODS: We comprehensively re-analyzed the data of 14 meta-analyses of observational studies and randomized controlled trials on associations between statin use and different CKD groups - CKD, CKD stage 5D, and kidney transplant recipients. We also assessed the strength of evidence of the re-analyzed outcomes, which were determined from the criteria, including the statistical significance of the p-value of random-effects, as well as fixed-effects meta-analyses, small-study effects, between-study heterogeneity, and a 95% prediction interval. RESULTS: For CKD patients, statin use showed suggestive evidence for an association with reduced all-cause mortality [relative risk (RR) 0.77, 95% confidence interval (0.69-0.87)]. For kidney transplant recipients, statin use showed suggestive evidence for an association with reduced cardiovascular mortality [RR 0.67, 95% CI (0.50-0.90)]. However, for patients on dialysis, statins showed neither cardiovascular [RR 0.93, 95% CI (0.86-1.01)] nor all-cause mortality [RR 0.98, 95% CI (0.89-1.08)] benefits. CONCLUSIONS: Our finding indicates that statin could improve all-cause and cardiovascular mortality in patients with non-dialysis CKD.

Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimer's disease: an umbrella review and re-analysis of data from meta-analyses.

OBJECTIVE: Alzheimer's disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger's test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.

Body mass index and mortality in patients with cardiovascular disease: an umbrella review of meta-analyses.

OBJECTIVE: Although many previous meta-analyses of epidemiological studies have demonstrated a relationship between body mass index (BMI) and mortality, inconsistent findings among cardiovascular disease patients have been observed. Thus, we performed an umbrella review to understand the strength of evidence and validity of claimed associations between BMI and mortality in patients with cardiovascular diseases. MATERIALS AND METHODS: We comprehensively re-analyzed the data of meta-analyses of observational studies and randomized controlled trials on associations between BMI and mortality among patients with cardiovascular diseases. We also assessed the strength of evidence of the re-analyzed outcomes, which were determined from the criteria including statistical significance of the p-value of random-effects, as well as fixed-effects meta-analyses, small-study effects, between-study heterogeneity, and a 95% prediction interval. RESULTS: We ran comprehensive re-analysis of the data from the 21 selected studies, which contained a total of 108 meta-analyses; 23 were graded as convincing evidence and 12 were suggestive, 42 were weak, and 23 were non-significant. CONCLUSIONS: Underweight increased mortality in acute coronary syndrome (ACS), heart failure, and after therapeutic intervention for patients with cardiovascular diseases. Overweight, on the other hand decreased mortality in patient's ACS, atrial fibrillation, and heart failure with convincing evidence.

Cesium-filled single wall carbon nanotubes as conducting nanowires: scanning tunneling spectroscopy study.

Metal-filled single wall carbon nanotubes (SWCNTs) are examined for possible application to conducting wires in nanoelectronics architecture. The local electronic structure of SWCNTs partially filled with cesium atoms is studied with scanning tunneling spectroscopy. The conduction and valence bands are shifted downward with two localized states in the gap at the location where the Cs atoms are filled. From a first-principles calculation, we confirm that these two gap states are bound states originating from the two lowest conduction bands.

Distribution characteristics of PCBs in the sediments of the lower Nakdong River, Korea.

The objective of this study is to investigate the distribution characteristics of polychlorinated biphenyl (PCB) congeners in sediments of the lower Nakdong River of Korea. The sediments were collected using a grab sampler in May 1999. PCBs were extracted in the Soxhlet extractor and cleaned by using adsorption chromatographic techniques and concentrated sulfuric acid. A HP6890 gas chromatograph equipped with an electron capture detector was used for quantification. The results of congener specific analysis showed that the total concentration is ranged over 1.1-141 ng/g dry weight. The levels of PCB congeners are significantly correlated with the total organic carbons (TOC) in the sediments. The major fractions of PCBs in these sediments are congeners containing 4, 5 or 6 chlorine atoms per biphenyl molecule.

Serodiagnosis of cysticercosis by ELISA-inhibition test using monoclonal antibodies.

Monoclonal antibodies (Mabs) were produced against crude scolex extract of T. solium metacestodes, and applied to ELISA-inhibition test for improving the specificity of serodiagnosis of human cysticercosis. Four hybridomas secreting species-specific anticysticercal Mabs (Cya-1, Cya-7, Cya-28 and Cya-31) were selected. Each Mab reacted on antigenic components of 25.5 kDa (Cya-1), 28 kDa (Cya-7), 87.5 kDa (Cya-28), and 12.5 kDa (Cya-31). IFA showed that Cya-1 was located at the calcium corpuscles, and Cya-7 at the loose connective tissue of T. solium metacestode scolex. Cya-28 and Cya-31 reacted on the tegument of the scolex. By conventional ELISA, 23 out of 28 (82.1%) cysticercosis patients were found serologically positive, but 1 out of 9 (11.1%) sparganosis cases and 6 out of 31 (19.4%) paragonimiasis cases showed false positives. By ELISA-inhibition test using species-specific anti-cysticercal Mab Cya-7, 19 out of 28 (67.9%) cysticercosis cases were found serologically positive, but there were no false positives in other parasitic infections.