The Association of HMGB1 Expression with Clinicopathological Significance and Prognosis in Hepatocellular Carcinoma: A Meta-Analysis and Literature Review

Background

Hepatocellular carcinoma (HCC) is the fifth most common cancer, and it is the second most common cancer-related mortality globally. The prognostic value of high mobility group box 1 (HMGB1) remains controversial. The purpose of this study is to conduct a meta-analysis and literature review to evaluate the association of HMGB1 expression with the prognosis of patients with HCC.

Methods

A detailed literature search was made in Medline, Google Scholar and others for related research publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, Hazard Ratio (HR) and mean difference with corresponding confidence intervals (CIs) were calculated and summarized respectively.

Results

10 relevant articles were included for this meta-analysis study. HMGB1 mRNA levels in HCC were significantly higher than those in normal (p<0.00001) and para-tumor tissues (p = 0.002) respectively. The protein levels of HMGB1 in HCC were significantly higher than those in para-tumor tissues (p = 0.005). Two studies reported the serum HMGB1 levels in patients with HCC of TNM stages, and indicating significantly different between stage I and II, stage II and III, as well as stage III and IV (two studies showed p<0.01 and p<0.001 respectively). The overall survival (OS) was significantly shorter in HCC patients with high HMGB1 expression compared those with low HMGB1 expression and the pooled HR was 1.31 with 95% CI 1.20–1.44, Z = 5.82, p<0.0001. Two additional studies showed that there were higher serum HMGB1 levels in patients with chronic hepatitis than those in healthy people (p<0.05).

Conclusions

The results of this meta-analysis suggest that HMGB1 mRNA and protein tissue levels in the patients with HCC are significantly higher than those in para-tumor and normal liver tissues respectively. Tissue HMGB1 overexpression is a potential biomarker for HCC diagnosis, and it is significantly associated with the prognosis of patients with HCC.     

Prognosis of Differentiated Thyroid Carcinoma in Patients with Graves Disease: A Systematic Review and Meta-Analysis

Objective: It is still controversial whether differentiated thyroid carcinoma (DTC) in patients with Graves disease (GD) can be more aggressive than non-Graves DTC. We conducted a systematic review and meta-analysis to examine the association between GD and prognosis in patients with DTC.Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2019. We included published studies that compared the risk of mortality and prognosis between DTC patients with GD and those with non-GD. Data from each study were combined using the random-effects model.Results: Twenty-five studies from February 1988 to May 2018 were included (987 DTC patients with GD and 2,064 non-Graves DTC patients). The DTC patients with GD had a significantly higher risk of associated multifocality/multicentricity (odds ratio, 1.45; 95% confidence interval, 1.04 to 2.02; I², 6.5%; P =.381) and distant metastasis at the time of cancer diagnosis (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; I², 0.0%; P =.497), but this was not associated with DTC-related mortality and recurrence/persistence during follow-up.Conclusion: Our meta-analysis demonstrates a statistically significant increased risk of multifocality/multicentricity and distant metastasis at the time of cancer diagnosis in DTC patients with GD than those without GD.Abbreviations: CI = confidence interval; DTC = differentiated thyroid carcinoma; GD = Graves disease; LN = lymph node; OR = odds ratio; PTC = papillary thyroid carcinoma; TC = thyroid carcinoma; TSAb = thyroid-stimulating antibody; TSH = thyroid-stimulating hormone     

Laparoscopic Versus Open Radical Nephrectomy for Renal Cell Carcinoma: a Systematic Review and Meta-Analysis

BACKGROUND: The aim of this study is to summarize and quantify the current evidence on the therapeutic efficacy of laparoscopic radical nephrectomy (LRN) compared with open radical nephrectomy (ORN) in patients with renal cell carcinoma (RCC) in a meta-analysis. METHODS: Data were collected by searching Pubmed, Embase, Web of Science, and ScienceDirect for reports published up to September 26, 2016. Studies that reported data on comparisons of therapeutic efficacy of LRN and ORN were included. The fixed-effects model was used in this meta-analysis if there was no evidence of heterogeneity; otherwise, the random-effects model was used. RESULTS: Thirty-seven articles were included in the meta-analysis. The meta-analysis showed that the overall mortality was significantly lower in the LRN group than that in the ORN group (odds ratio [OR] =0.77, 95% confidence interval [CI]: 0.62-0.95). However, there was no statistically significant difference in cancer-specific mortality (OR = 0.77, 95% CI: 0.55-1.07), local tumor recurrence (OR = 0.86, 95% CI: 0.65-1.14), and intraoperative complications (OR = 1.27, 95% CI: 0.83-1.94). The risk of postoperative complications was significantly lower in the LRN group (OR = 0.71, 95% CI: 0.65-0.78). In addition, LRN has been shown to offer superior perioperative results to ORN, including shorter hospital stay days, time to start oral intake, and convalescence time, and less estimated blood loss, blood transfusion rate, and anesthetic consumption. CONCLUSION: LRN was associated with better surgical outcomes as assessed by overall mortality and postoperative complications compared with ORN. LRN has also been shown to offer superior perioperative results to ORN.     

Clinicopathological and Prognostic Significance of Survivin Over-Expression in Patients with Esophageal Squamous Cell Carcinoma: A Meta-Analysis

Background

The prognostic significance of survivin for survival of patients with esophageal squamous cell carcinoma (ESCC) remains controversial. Thus, meta-analysis of the literatures was performed in order to demonstrate its expression impact on ESCC clinicopathological features and prognosis.

Methodology

Relevant literatures were searched using PubMed, EMBASE and Medline Databases. Revman5.0 software was used to pool eligible studies and summary hazard ratio (HR). Correlation between survivin expression and clinicopathological features of ESCC was analyzed.

Principal Findings

Final analysis of 523 patients from 7 eligible studies was performed. Combined HR of survivin location in nuclei suggested that survivin expression has an unfavorable impact on ESCC patients'' survival (n = 277 in 3 studies; HR = 1.89, 95% CI: 1.45–2.96; Z = 4.69; P<0.0001). Nevertheless, combined HR of survivin location in cytoplasm displayed that survivin expression has no significance for prognosis of ESCC patients (n = 113 in 2 studies; HR = 0.96, 95% CI: 0.96–5.69; Z = 0.04; P = 0.97); Combined odds ratio (OR) of survivin location in cytoplasm indicated that survivin expression is associated with ESCC advanced stage (n = 113 in 2 studies; OR = 0.36, 95% CI: 0.14–0.93; Z = 2.10; P = 0.04). Whereas, combined OR of survivin location in nuclei exhibited that survivin over-expression has no correlation with cell differentiation grade, lymph node status, depth of invasion, stage, and metastasis of ESCC.

Conclusions

This study showed that survivin expression detected by immunohistochemistry seems to be associated with a worse prognosis of ESCC patients. Survivin subcellular location may be an important factor impacting on ESCC development. Larger prospective studies should be performed to evaluate the status of survivin in predicting prognosis of patients with ESCC.     

The Difference in Prognosis between Renal Sinus Fat and Perinephric Fat Invasion for pT3a Renal Cell Carcinoma: A Meta-Analysis

Background

In the current Tumour-Node-Metastasis (TNM) classification system for renal cell carcinoma (RCC), both renal sinus fat invasion (SFI) and perinephric fat invasion (PFI) are defined as T3a, suggesting that the prognosis should be similar for the two pathologic findings. Several studies, however, have reported a worse prognosis for SFI in patients with a T3a tumor. In order to compare the prognosis of these two pathologic findings (SFI versus. PFI) in a more comprehensive way, this meta-analysis was performed.

Methods

To identify relevant studies, Medline, Embase, Cochrane Library, and Scopus database were searched from the inception until October 2014. A meta-analysis was performed using Review Manager 5.2 and STATA 11. Pooled Odds ratio (OR) and/or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association.

Results

A total of 6 studies including 1031 patients qualified for analysis. T3a RCC patients with SFI were significantly associated with poor cancer specific survival(CSS) (HR: 1.47, 95% CI: 1.19–1.83; P<0.001) compared to those with PFI. In T3aNx/N0M0 subgroup, SFI patients also showed a worse prognosis than those with PFI (CSS, HR: 1.94, 95% CI: 1.21–3.12; P = 0.006). T3a RCC patients with SFI had higher Furhman grade, greater possibility of lymph node metastasis, sarcomatoid differentiation and tumour necrosis. Main limitation is the relatively small number of included studies.

Conclusion

The present meta-analysis suggested that SFI is associated with worse CSS in patients with pT3a RCC. However, due to the small number of included studies, future studies with a large sample size are required to further verify our findings.     

The Correlation of MGMT Promoter Methylation and Clinicopathological Features in Gastric Cancer: A Systematic Review and Meta-Analysis

The silencing of the tumor suppressor gene O-6-methylguanine-DNA methyltransferase (MGMT) by promoter methylation commonly occurs in human cancers. The relationship between MGMT promoter methylation and gastric cancer (GC) remains inconsistent. This study aimed to evaluate the potential value of MGMT promoter methylation in GC patients. Electronic databases were searched to identify eligible studies. The pooled odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were used to evaluate the effects of MGMT methylation on GC risk and clinicopathological characteristics. In total, 31 eligible studies including 2988 GC patients and 2189 nonmalignant controls were involved in meta-analysis. In the pooled analysis, MGMT promoter methylation was significantly associated with GC risk (OR = 3.34, P < 0.001) and substantial heterogeneity (P < 0.001). Meta-regression and subgroup analyses based on the testing method, sample material and ethnicity failed to explain the sources of heterogeneity. Interestingly, MGMT methylation showed a trend associated with gender, and methylation is lower in males compared with females (OR = 0.76, 95% CI = 0.56–1.03). We did not find a significant association in relation to tumor types, clinical stage, age status or H. pylori status in cancer (all P > 0.1). MGMT promoter methylation may be correlated with the prognosis of GCs in disease free survival (DFS) or overall survival (OS) for univariate analysis. MGMT promoter methylation may play a crucial role in the carcinogenesis and prognosis of GC. MGMT methylation was not correlated with tumor types, clinical stage, age status, H. pylori status. However, the result of the association of MGMT methylation and gender should be considered with caution.     

Prognostic Significance of MET Amplification and Expression in Gastric Cancer: A Systematic Review with Meta-Analysis

Background and Aims

MET, the hepatocyte growth factor receptor, is a receptor tyrosine kinase overexpressed and activated in a subset of gastric cancer. Several studies investigated the relationship between MET amplification and expression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. We performed a systematic review and meta-analysis to determine the influence of MET amplification and expression on prognosis in gastric cancer.

Methods

MEDLINE and EMBASE were searched for studies that explored the association between MET amplification and expression with survival in patients with gastric cancer up to 1 April, 2013. Data of individual hazard ratios (HRs) and 95% confidence intervals (CIs) for meta-analyses were extracted from the publications and combined in pooled HRs.

Results

Fourteen studies involving 2,258 patients with gastric cancer were included. It was suggested that MET overexpression had an unfavorable impact on survival of patients with gastric cancer, with HRs (95% CIs) of 2.57 (95% CI: 1.97–3.35) overall, 2.82 (95% CI: 1.86–4.27) among studies using amplification for measure scale of MET and 2.42 (95% CI: 1.66–3.54) for expression. The magnitude of association was reduced whereas remained statistically significant in high quality studies or in larger sample size studies and corresponding HRs were 2.18(1.76, 2.70) and 2.35(1.93, 2.87), respectively, without significant heterogeneity.

Conclusion

The findings from present study indicated that higher MET gene amplification and expression in gastric cancer was an indicator of poor prognosis.     

CD133 Expression and the Prognosis of Colorectal Cancer: A Systematic Review and Meta-Analysis

Objective

CD133 has recently been reported as a marker of cancer stem-like cells in colorectal cancer (CRC). However, its predictive value in CRC still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and clinicopathological features and the outcome of CRC patients by performing a meta-analysis.

Methods

A comprehensive literature search for relevant studies published up to December 2012 was performed using PubMed, MEDLINE and ISI Web of Science. Only articles in which CD133 antigen was detected in situ localisation by immunohistochemical staining were included. This meta-analysis was done using RevMan 4.2 software.

Results

We found that a total of 15 studies involving 810 CD133-high and 1487 CD133-low patients met the inclusion criteria for the analysis of 5-year overall survival (OS) rate. In a random-effects model, the results showed that CD133-high expression in colorectal cancer was an independent prognostic marker correlating with both OS rate (RR = 0.67, 95%CI 0.54–0.82, P<0.01) and disease free survival (DFS) rate (RR = 0.71, 95%CI 0.52–0.96, P = 0.03). CD133-high expression was also associated with more T3,4 tumor invasion, N positive and vascular invasion cases, corresponding to a risk difference of 1.12 (95%CI 1.01–1.23, P = 0.03), 1.31 (95%CI 1.06–1.63, P = 0.01) and 1.24 (95%CI 1.08–1.41, P<0.01), respectively. However, when types of histology, lymphatic invasion and distant metastasis were considered, CD133 overexpression was not significantly related with these clinicopathological parameters.

Conclusion

Our meta-analysis results suggest that CD133 is an efficient prognostic factor in CRC. Higher CD133 expression is significantly associated with poorer clinical outcome and some clinicopathological factors such as T category, N category and vascular invasion in CRC patients.     

Association between Dental Caries and Down Syndrome: A Systematic Review and Meta-Analysis

Scientific evidence of susceptibility to dental caries in the population with Down Syndrome (DS) is limited and conflicting, making it difficult to establish firm conclusions. The aim of this systematic review and meta-analysis was to obtain scientific evidence of the possible association between dental caries and individuals with DS, compared to individuals without DS (control). An electronic search of five databases was performed, with no language or publication date restrictions. The studies were selected by two independent reviewers (Kappa = 0.83). The systematic review included 13 studies, while eight studies were included in the meta-analysis. The studies are presumably all at risk of bias given their observational character. Two of these evaluated the presence or absence of caries in permanent and deciduous teeth, and six evaluated the mean DMFT index in permanent teeth. Combined odds ratios (OR), standard difference, standard error and a 95% confidence interval (CI) were obtained. The vast majority of the studies found that individuals from control groups had more carious lesions or caries experience than those with DS. The results were statistically significant in seven studies (p<0.05). Meta-analysis of two studies revealed that individuals with DS had a lower dental caries than those in the control group (OR = 0.36; 95% CI = 0.22–0.57). In six studies, individuals with DS had a significantly lower mean DMFT index than individuals from the control group (Sd = -0.18; SE = 0.09; 95% CI = -0.35–-0.02). The quality of the studies varied and in general had a high risk of bias. Scientific evidence suggests that individuals with DS have fewer dental caries than individuals without DS.     

TGF-beta1 Gene Polymorphism in Association with Diabetic Retinopathy Susceptibility: A Systematic Review and Meta-Analysis

Background

Transforming growth factor-beta (TGF-β1) gene has been regarded as an important mechanism in angiogenesis, endothelial cell proliferation, adhesion,and the deposition of extracellular matrix. The TGF-β1 gene may be involved in the development of diabetic retinopathy (DR) through disrupting angiogenesis. However, studies investigating the relationship between −509C/T and +869T/C(L10P) polymorphisms and DR yielded contradictory and inconclusive outcomes. In order to realize these ambiguous findings, a meta-analysis was performed to assess the association between the TGF-β1 gene polymorphisms and susceptibility to DR.

Methodology/Principal Findings

We conducted a search of all English reports on studies for the association between the TGF-β1 gene polymorphisms and susceptibility to DR using Medline, the Cochrane Library, EMbase, Web of Science, Google (scholar), and all Chinese reports were identified manually and on-line using CBMDisc, Chongqing VIP database, and CNKI database. The strict selection criteria and exclusion criteria were determined, and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. The fixed or random effect model was selected based on the heterogeneity test among studies. Publication bias was estimated using Begg''s funnel plots and Egger''s regression test.

Results

A total of three studies were included in the meta-analysis and all included studies analyzed patients with type 2 diabetes. For +869T/C(L10P) polymorphism, significant association was observed in an allele model (L versus P: OR = 1.34, 95%CI = 1.03–1.73) and the recessive model (LL versus LP+PP: OR = 1.70, 95%CI = 1.13–2.56). As regards −509C/T polymorphism, no obvious associations were found for all genetic models.

Conclusions

This meta-analysis suggested that the +869T/C(L10P) polymorphism in TGFβ1 gene would be a potential protect factor for DR. However, the −509C/T polymorphism is not associated with DR.     

The Association of Sport Performance with ACE and ACTN3 Genetic Polymorphisms: A Systematic Review and Meta-Analysis

Background

Genetic polymorphism is suggested to be associated with human physical performance. The angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism and the α-actinin-3 gene (ACTN3) R577X polymorphism have been most widely studied for such association analysis. However, the findings are frequently heterogeneous. We aim to summarize the associations of ACE I/D and ACTN3 R577X with sport performance by means of meta-analysis.

Methods

We systematically reviewed and quantitatively summarized published studies, until October 31, 2012, on relationship between ACE/ACTN3 genetic polymorphisms and sports performance, respectively.

Results

A total of 366 articles on ACE and 88 articles on ACTN3 were achieved by literature search. A significant association was found for ACE II genotype compared to D allele carriage (DD+ID) with increased possibility of physical performance (OR, 1.23; 95% CI, 1.05–1.45). With respect to sport discipline, the II genotype was found to be associated with performance in endurance athletes (OR, 1.35; 95% CI, 1.17–1.55). On the other hand, no significant association was observed for ACTN3 RR genotype as compared to X allele carriage (XX+RX) (OR, 1.03; 95% CI, 0.92–1.15). However, when restricted the analyses to power events, a significant association was observed (OR, 1.21; 95% CI, 1.03–1.42).

Conclusion

Our results provide more solid evidence for the associations between ACE II genotype and endurance events and between ACTN3 R allele and power events. The findings suggest that the genetic profiles might influence human physical performance.     

Diagnostic Value of Liquid-Based Cytology in Urothelial Carcinoma Diagnosis: A Systematic Review and Meta-Analysis

Objective

To evaluate the value of liquid-based cytology (LBC) in the diagnosis of urothelial carcinoma.

Method

Diagnostic studies were searched for the diagnostic value of LBC in urothelial carcinoma in PubMed, Embase, Cochrane Library, Web of Science, CBM and CNKI. The latest retrieval date was September 2014. The data were extracted and the quality of the included studies was independently assessed by 2 reviewers. Stata 13 software was used to perform the statistical analysis. The research was conducted in compliance with the PRISMA statement.

Result

Nineteen studies, which included 8293 patients, were evaluated. The results of the meta-analysis showed that the pooled sensitivity and specificity of LBC were 0.58 (0.51–0.65) and 0.96 (0.93–0.98), respectively. The diagnostic odds ratio (DOR) was 31 (18–56) and the area under the curve (AUC) of summary receiver operating characteristic (SROC) was 0.83 (0.80–0.86). The post-test probability was 80% when a positive diagnosis was made. Compared with high grade urothelial carcinoma (HGUC), the sensitivity of detecting low-grade urothelial carcinoma (LGUC) was significantly lower, risk ratio of sensitivity was 0.54 (0.43–0.66), P<0.001. However, no significant sensitivity improvement was observed with LBC when compared with traditional cytospin cytology, risk ratio was 1.03 (0.94–1.14), P = 0.524.

Conclusion

Despite LBC having a pooled 58% positive rate for urothelial carcinoma diagnosis in our meta-analysis, no significant improvement in sensitivity was observed based on the studies evaluated. Further research is needed to validate these findings.     

Association Studies of ERCC1 Polymorphisms with Lung Cancer Susceptibility: A Systematic Review and Meta-Analysis

Background

Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial.

Objectives

An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (T>C), rs3212986 (C>A), rs3212961 (A>C), rs3212948 (G>C), rs2298881 (C>A).

Methods

Several major databases (MEDLINE, EMBASE and Scopus) and the Chinese Biomedical database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations.

Results

Sixteen studies with 10,106 cases and 13,238 controls were included in this meta-analysis. Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of ERCC1 rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04–1.48, P = 0.02). However, such an association was disproportionately driven by a single study. Removal of that study led to null association. Moreover, initial analyses suggested that ERCC1 rs11615 exerts a more profound effect on the susceptibility of non-smokers to lung cancer than that of smokers. Moreover, no statistically significant association was found between remaining ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR = 0.78, 95% CI: 0.67–0.90, P = 0.001; dominant: CG/CC vs.GG, OR = 0.79, 95% CI: 0.69–0.91, P = 0.001).

Conclusion

Overall, this meta-analysis suggests that ERCC1 rs3212948 G>C, but not others, is a lung cancer risk-associated polymorphism. Carefully designed studies with large sample size involving different ethnicity, smoking status, and cancer types are needed to validate these findings.     

Serological Association of Chlamydia pneumoniae Infection with Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Background

We investigated the serological association of Chlamydia pneumoniae infection with age-related macular degeneration (AMD).

Methods

A systematic review and meta-analysis was performed. PubMed, Embase, Web of Science and the Association of Research in Vision and Ophthalmology abstracts were searched to identify studies investigating the serological association of Chlamydia pneumoniae infection with age-related macular degeneration. The quality of original studies was assessed using the Newcastle-Ottawa scale. Heterogeneity was explored with meta-regression. The odds ratios (ORs) and standardized mean differences (SMD) of Chlamydia pneumoniae infection between AMD patients and controls were pooled.

Results

In total, 9 studies met the inclusion criteria using the Newcastle-Ottawa scale scores ranging from 4 to 9. There was heterogeneity among studies due to a difference in the study designs and measurement of exposure to Chlamydia pneumoniae infection. The overall OR of Chlamydia pneumoniae infection with AMD was 1.11 (95% confidence interval: 0.78–1.57, P = 0.56). The overall SMD of antibody titer between AMD and control was 0.43 (95% confidence interval: −0.12 to 0.99, P = 0.13).

Conclusions

Evidence from the current published literature suggested no statistically significant association between Chlamydia pneumoniae infection and AMD.     

Association of VEGF Genetic Polymorphisms with Recurrent Spontaneous Abortion Risk: A Systematic Review and Meta-Analysis

Background

Studies of the associations between the genetic polymorphisms of the vascular endothelial growth factor (VEGF) gene and recurrent spontaneous abortion (RSA) have revealed conflicting results. The present meta-analysis was performed to provide a more precise estimation of these relationships and to explore potential sources of heterogeneity that may have influenced the reported disparities.

Methods

An extensive literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library through June 6, 2014. Crude odds ratio (OR) with 95% confidence intervals were calculated.

Results

10 case-control studies including 1,832 RSA patients and 2,271 healthy controls were identified. Meta-analysis indicated that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms in the VEGF gene correlated with elevated RSA risk. The rs1570360 variant was statistically significantly relevant to RSA risk among non-Asian populations. Interestingly, the rs3025039 variant was statistically significantly relevant to RSA risk among Asian populations.

Conclusions

The current meta-analysis indicates that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms increase RSA susceptibility. Moreover, rs1570360 and rs3025039 polymorphisms may play various roles in RSA susceptibility in various geographic groups.     

Association between Glaucoma and Obstructive Sleep Apnea Syndrome: A Meta-Analysis and Systematic Review

BackgroundObstructive sleep apnea syndrome (OSAS) is a common disease that increases the risk of diabetes, heart disease, and stroke. However, studies of an association between OSAS and glaucoma neuropathy have reported controversial findings.ObjectiveThe main purpose of this study was to evaluate whether a significant association exists between OSAS and glaucoma by performing a meta-analysis of previous studies.MethodsA comprehensive literature search using the PubMed and Embase databases was performed to identify cross-sectional, case-control, and cohort studies related to the topic. We estimated a pooled odds ratio (OR) for the association between OSAS and glaucoma, by a fixed- or random-effects model.ResultsIn total, 16 studies with 2,278,832 participants met the inclusion criteria: one retrospective cohort study reported an adjusted hazard ratio of glaucoma of 1.67 (95% CI = 1.30–2.17). Using a fixed-effects model, the pooled OR of six case-control studies was 1.96 (95% CI = 1.37 2.80). A significant association was also identified in a meta-analysis of nine cross-sectional studies using a random-effects model, which showed a pooled OR of 1.41 (95% CI = 1.11 1.79). However, the reported pooled estimates for case control studies and cross-sectional studies were based on unadjusted ORs.ConclusionsOur results suggest that OSAS is associated with the prevalence of glaucoma. However, this result was based only on unadjusted estimates. Prospective cohort studies designed to take into consideration potential confounders, or examination of data from interventional trials to determine whether a reduction in OSAS status is associated with a reduced incidence of glaucoma, are needed to clarify whether OSAS is an independent risk factor for glaucoma.     

Association of Thyroid Function with Posttraumatic Stress Disorder: a Systematic Review and Meta-Analysis

Objective: To conduct a systematic review and meta-analysis describing the association of thyroid function with posttraumatic stress disorder (PTSD) in adults.Methods: The authors conducted a comprehensive search from databases’ inception to July 20, 2018. The meta-analysis included studies that reported mean values and standard deviation (SD) of thyroid hormone levels (thyroid-stimulating hormone &lsqb;TSH], free thyroxine &lsqb;FT4], free triiodothyronine &lsqb;FT3], total T4 &lsqb;TT4], and total T3 &lsqb;TT3]) in patients with PTSD compared with controls. Five reviewers worked independently, in duplicate, to determine study inclusion, extract data, and assess risk of bias. The mean value and SD of the thyroid function tests were used to calculate the mean difference for each variable. Random-effects models for meta-analyses were applied.Results: The meta-analysis included 10 observational studies at low-to-moderate risk of bias. Studies included 674 adults (373 PTSD, 301 controls). The meta-analytic estimates showed higher levels of FT3 (+0.28 pg/mL; P = .001) and TT3 (+18.90 ng/dL; P = .005) in patients with PTSD compared to controls. There were no differences in TSH, FT4, or TT4 levels between groups. In the subgroup analysis, patients with combat-related PTSD still had higher FT3 (+0.36 pg/mL; P = .0004) and higher TT3 (+31.62 ng/dL; P<.00001) compared with controls. Conversely, patients with non–combat-related PTSD did not have differences in FT3 or TT3 levels compared with controls.Conclusion: There is scarce evidence regarding the association of thyroid disorders with PTSD. These findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD.     

Anti-Tumor Effects of Metformin in Animal Models of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Background

Several studies have reported that metformin can reduce the risk of hepatocellular carcinoma (HCC) in diabetes patients. However, the direct anti-HCC effects of metformin have hardly been studied in patients, but have been extensively investigated in animal models of HCC. We therefore performed a systematic review and meta-analysis of animal studies evaluating the effects of metformin on HCC.

Methods

We collected the relevant studies by searching EMBASE, Medline (OvidSP), Web of Science, Scopus, PubMed Publisher, and Google Scholar. Studies were included according to the following inclusion criteria: HCC, animal study, and metformin intervention. Study quality was assessed using SYRCLE’s risk of bias tool. A meta-analysis was performed for the outcome measures: tumor growth (tumor volume, weight and size), tumor number and incidence.

Results

The search resulted in 573 references, of which 13 could be included in the review and 12 included in the meta-analysis. The study characteristics of the included studies varied considerably. Two studies used rats, while the others used mice. Only one study used female animals, nine used male, and three studies didn’t mention the gender of animals in their experiments. The quality of the included studies was low to moderate based on the assessment of their risk of bias. The meta-analysis showed that metformin significantly inhibited the growth of HCC tumour (SMD -2.20[-2.96,-1.43]; n=16), but no significant effect on the number of tumors (SMD-1.05[-2.13,0.03]; n=5) or the incidence of HCC was observed (RR 0.62[0.33,1.16]; n=6). To investigate the potential sources of significant heterogeneities found in outcome of tumor growth (I²=81%), subgroup analyses of scales of growth measures and of types of animal models used were performed.

Conclusion

Metformin appears to have a direct anti-HCC effect in animal models. Although the intrinsic limitations of animal studies, this systematic review could provide an important reference for future preclinical animal trials of good quality and clinical development.