A new prognostic index for overall survival in malignant pleural mesothelioma: the rPHS (regimen, PS, histology or stage) index.

First published online: April 2, 2015[Objective] Existing prognostic indices for malignant pleural mesothelioma do not incorporate the recent advances in oncology care. The purpose of this study was to provide a prognostic index for overall survival in malignant pleural mesothelioma patients treated with chemotherapy with pemetrexed or best supportive care in the recent clinical setting. [Methods] A retrospective cohort study was performed in two hospitals in Japan (2007–13). The primary outcome was overall survival. The Cox proportional hazards model was used for multivariable analyses to identify prognostic factors. A final model was chosen based on both clinical and statistical significance. [Results] A total of 283 patients (chemotherapy: n = 228, best supportive care: n = 55) were enrolled in the study. On multivariate analysis, regimen including platinum plus pemetrexed, a performance status >0, non-epithelial histological type and Stage IV disease predicted poor overall survival in chemotherapy patients. As hazard ratios of individual risk factors were approximately similar, a prognostic index for overall survival was constructed by counting the risk factors. Median overall survival in chemotherapy patients decreased by each one-point increase in this count: 1030 days for zero; 658 days for one; 373 days for two; 327 days for three; 125 days for four. Internal validation using the bootstrapping technique showed robustness of the model (c-index, 0.677; 95% confidence interval, 0.624–0.729). Further, the discrimination was consistent in best supportive care patients (c-index, 0.799; 95% confidence interval, 0.725–0.874). [Conclusions] This novel index can provide clinicians and malignant pleural mesothelioma patients with a better framework for discussing prognosis at the time of diagnosis

Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout

Objective The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. Methods We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). Results This new approach enabled us to identify two novel gout loci (rs7927466 of CNTN5 and rs9952962 of MIR302F) and one suggestive locus (rs12980365 of ZNF724) at the genome-wide significance level (p<5.0×10– 8). The present study also identified the loci of ABCG2, ALDH2 and SLC2A9. One of them, rs671 of ALDH2, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three ‘gout vs AHUA GWAS’-specific loci (CNTN5, MIR302F and ZNF724) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. Conclusions This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals

Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals

Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci (P<5 × 10–8) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci—TMEM18, TM4SF4, MXD3-LMAN2, PSORS1C1-PSORS1C2, and HNF4A—are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578, is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout

Effect of chest tube position on the success rate of pleurodesis: A retrospective cohort study

Background: Malignant pleural effusion reduces cancer patients’ quality of life. Some experts have suggested that chest tubes should be directed posteriorly during pleurodesis. We conducted this study to clarify whether a posteriorly positioned chest tube has a better success rate than does an interlobular or anterior one. Methods: We performed a retrospective chart review of patients undergoing pleurodesis between April 2011 and September 2016, and 86 patients were enrolled and divided into two groups based on the chest tube position: posterior (group 1) and others [interlobular and anterior (group 2)]. The primary endpoint was the success rate of pleurodesis, and the secondary endpoint was the complication rate (pain and fever). P < 0.05 was considered to be significant. Results: In total, 66, 20 patients were included in groups 1 and 2, respectively. Complete and partial success was achieved in 57 (86%) and 15 (75%) patients in groups 1 and 2, respectively. The success rates were similar in all groups (p = 0.39). Complications were observed in 51 (77%) and 16 (80%) patients in groups 1 and 2, respectively (p = 0.99). Between the two groups, there was no statistically significant difference in terms of age and sex. Conclusions: In malignant pleural effusion, the success rates of pleurodesis may be similar regardless of the position of the tube. However, this is a retrospective study with insufficient participants. Hence, further investigation is required

Meta-analysis confirms an association between gout and a common variant of <i>LRRC16A</i> locus

Meta-analysis confirms an association between gout and a common variant of <i>LRRC16A</i> locu