Prognostic impact of myosteatosis in patients with colorectal cancer: a systematic review and meta-analysis

Background: Myosteatosis has been reported to be a novel biomarker that could predict survival outcomes in patients with colorectal cancer. However, results have been conflicting. This systematic review and meta-analysis aimed to evaluate the long-term impact of myosteatosis on the survival of these patients. Methods: A systematic search of PubMed, Embase, and Cochrane up to 27 November 2019 generated 7022 records. Studies that reported hazard ratio (HR) for overall survival, cancer-specific survival, or disease-free survival based on myosteatosis or radiodensity were included. A total of 110 full-text articles were considered for inclusion, and 14 were selected for qualitative analysis. Inverse variance method was used with random effects model for data analysis. Results: The total number of enrolled patients included in the meta-analysis was 6518 for univariate and 8572 for multivariate HR analysis, from 12 and 10 studies, respectively. Patients with myosteatosis had a significant increase in overall mortality compared with non-myosteatosis patients by both univariate analysis [HR 1.38, 95% confidence interval (CI) 1.21 to 1.58, P < 0.00001] and multivariate analysis (HR 1.55, 95% CI 1.23 to 1.96, P < 0.00001). In subgroup analysis based on studies that reported HRs of both sarcopenia and myosteatosis, the negative effect of myosteatosis on overall survival was independent of sarcopenia using univariate values (sarcopenia HR 1.48, 95% CI 1.14 to 1.91, P = 0.003 vs. myosteatosis HR 1.51, 95% CI 1.17 to 1.96, P = 0.002) and multivariate values (sarcopenia HR 1.28, 95% CI 1.09 to 1.49, P = 0.002 vs. myosteatosis HR 1.38, 95% CI 1.07 to 1.80, P = 0.001). Conclusions: This meta-analysis demonstrates that myosteatosis is associated with worse overall survival in patients with colorectal cancer. More investigation is needed to standardize the measurement protocol for myosteatosis and to further optimize its prognostic power for colorectal cancer patients.ope

Genome-Wide Association Studies Of Depression And Alzheimer’s: Identifying Pleiotropic Snps

Background: Alzheimer’s disease (AD) has been rising globally, making it important to understand risk factors. Depression has been identified as a risk factor in epidemiological studies and meta-analysis. The possible mechanism could be pleiotropic. This study sought to identify the pleiotropic SNPs associated with depression and AD so that can understand the relationship between the two diseases more evident.Methods: The sample was from the UK biobank population, using the White European subpopulation. Depression was defined using self-reported depression status and electronic medical records. Proxy AD was defined by biological mother and father’s AD status. Two univariate association analysis was conducted using a linear mixed model in REGENIE. A p-value comparison was conducted for both analyses. Linkage disequilibrium (LD) clumping was conducted using a four MB region surrounding the index variant and an r2 threshold of 0.2. Results: The study had 406,7394 individuals in the depression sample and 409,704 individuals in the AD sample. The univariate analysis for depression identified five genome-wide significant SNPs, and the univariate analysis for AD identified 1,319 genome-wide significant SNPs. The p-value comparison found that 36 genome-wide significant SNPs for AD were genome-wide nominal for depression, with SNPs chromosome 8 having p-values for depression less than 0.001. The LD clumping identified a region in chromosome 19 associated with genes APOE and TOMM40. The leading SNP was rs2075650 and associated with the two phenotypes. Conclusion: The study found SNPs associated with depression and AD. Furthermore, SNP rs2075650 on chromosome 19 seems promising in understanding the relationship between depression and AD. Further studies must be conducted to understand the association that can lead to prevention methods

A mixed effect model for bivariate meta-analysis of diagnostic test accuracy studies using a copula representation of the random effects distribution

Diagnostic test accuracy studies typically report the number of true positives, false positives, true negatives and false negatives. There usually exists a negative association between the number of true positives and true negatives, because studies that adopt less stringent criterion for declaring a test positive invoke higher sensitivities and lower specificities. A generalized linear mixed model (GLMM) is currently recommended to synthesize diagnostic test accuracy studies. We propose a copula mixed model for bivariate meta-analysis of diagnostic test accuracy studies. Our general model includes the GLMM as a special case and can also operate on the original scale of sensitivity and specificity. Summary receiver operating characteristic curves are deduced for the proposed model through quantile regression techniques and different characterizations of the bivariate random effects distribution. Our general methodology is demonstrated with an extensive simulation study and illustrated by re-analysing the data of two published meta-analyses. Our study suggests that there can be an improvement on GLMM in fit to data and makes the argument for moving to copula random effects models. Our modelling framework is implemented in the package CopulaREMADA within the open source statistical environment R

Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: A Systematic Review and Individual Patient Data Meta-Analysis.

The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with N2O exposure in medical and recreational settings. We calculated the pooled estimates for the studied outcomes and assessed the potential bias related to population stratification using principal component analysis. Eighty-five publications met the inclusion criteria and reported on 100 patients with a median age of 27 years and 57% of recreational users. The most frequent outcomes were subacute combined degeneration (28%), myelopathy (26%), and generalized demyelinating polyneuropathy (23%). A T2 signal hyperintensity in the spinal cord was reported in 68% (57.2-78.8%) of patients. The most frequent clinical manifestations included paresthesia (80%; 72.0-88.0%), unsteady gait (58%; 48.2-67.8%), and weakness (43%; 33.1-52.9%). At least one hematological abnormality was retrieved in 71.7% (59.9-83.4%) of patients. Most patients had vitamin B12 deficiency: vitamin B12 &lt;150 pmol/L (70.7%; 60.7-80.8%), homocysteine &gt;15 µmol/L (90.3%; 79.3-100%), and methylmalonic acid &gt;0.4 µmol/L (93.8%; 80.4-100%). Consistently, 85% of patients exhibited a possibly or probably deficient vitamin B12 status according to the cB12 scoring system. N2O can produce severe outcomes, with neurological or hematological disorders in almost all published cases. More than half of them are reported in the setting of recreational use. The N2O-related burden is dominated by vitamin B12 deficiency. This highlights the need to evaluate whether correcting B12 deficiency would prevent N2O-related toxicity, particularly in countries with a high prevalence of B12 deficiency

A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

© 2014 Haider et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options

Correlation of Bcl-2 expression with prognosis and survival in patients with head and neck cancer: a systematic review and meta-analysis

Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The impossibility of properly entering into apoptosis directly influences uncontrolled growth and consequently tumor development and progression. Bcl-2 emerged as a key regulator in the balance between cell apoptosis and proliferation in apoptosis machinery. This systematic review and meta-analysis aimed to review all published studies investigating changes in Bcl-2 protein expression assessed by immunohistochemistry (IHC) and related to prognostic and survival values of patients with HNC. After applying the inclusion and exclusion factors, we reached the number of 20 articles included in the meta-analysis. The random-effect pooled HR (CI95%) value of OS related to Bcl-2 IHC expression in tissues from HNC patients was 1.80 (CI95% 1.21–2.67) (p 0.0001) and DFS was 1.90 (CI95% 1.26–2.86 (p 0.0001). The OS value for the specific oral cavity tumors was 1.89 (1.34–2.67), while in the larynx it was 1.77 (0.62–5.06), and the DFS in the pharynx was 2.02 (1.46–2.79). The univariate and multivariate analyses of OS were respectively 1.43 (1.11–1.86) and 1.88 (1.12–3.16), while in DFS it was 1.70 (0.95–3.03) and 2.08 (1.55–2.80). The OS considering a low cut-off for Bcl-2 positivity was 1.19 (0.60–2.37) and DFS was 1.48 (0.91–2.41), while studies with a high cut-off demonstrated OS of 2.28 (1.47–3.52) and DFS of 2.77 (1.74–4.40). Our meta-analysis demonstrates that Bcl-2 protein overexpression can result in worse LNM, OS, and DFS in patients with HNC, however, it is not a reliable conclusion, due to the wide divergences between the original studies and the fact that many studies have a very high range of confidence and also a high risk of bias