Association between Cryptosporidium infection and cancer: A systematic review and meta-analysis

The link between cryptosporidiosis and cancer has been suggested by some epidemiological studies. This systematic review and meta-analysis was conducted to further understand this relationship. In the current study, six electronic databases were reviewed for Cryptosporidium infection in cancer patients. We used random effects model and 95% confidence intervals (CI) to determine the overall odds ratio (OR). Heterogeneity was calculated with Cochran's Q test and I²statistic. In total, 19 studies involving 3562 individuals with case-control (nine) and cross-sectional (ten) designs were included in our project. The pooled overall random effect favored a statistically significant increased risk of Cryptosporidium infection in cancer patients compared with non-cancer individuals [OR = 3.3; 95% CI: 2.18–4.98]. The overall heterogeneity was medium (χ² = 25.77; I² = 30.2%, P = .11). The pooled ORs in case-control and cross-sectional studies were [OR = 5.60; 95% CI: 3.43–9.13; χ² = 5.51; I² = 0.00%, P = .70] and [OR = 2.08; 95% CI: 1.18–3.67; χ² = 13.69; I² = 34.3, P = .13], respectively. T-value and P-value were 0.54 and 0.57 based on the results of Harbord's modified's regression test. In summary, this meta-analysis demonstrates that Cryptosporidium infection is associated with cancer. Also, it found that study design and year of publication are the specific sources of heterogeneity. Further studies should be carried out to investigate the impact of Cryptosporidium infection in the onset or development of cancer in the future.     

An Updated Study to Determine Association between Gadolinium-Based Contrast Agents and Nephrogenic Systemic Fibrosis

Background

Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder disease affecting patients with advanced renal disease. Although multiple studies have indicated an association between gadolinium-based contrast agents (GBCAs) and NSF, some studies published after 2007 found no association. We therefore performed a meta-analysis to evaluate the association and analyze related (co)factors.

Methods

Studies for analysis were identified by searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials through December 2014. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the fixed-effects model. Statistical heterogeneity was assessed by Q statistics and the I² test. Publication bias was evaluated using Begg’s test, Egger’s test, funnel plot, and classic fail-safe N. Study quality was assessed using the Newcastle-Ottawa Scale. We also conducted sensitivity analyses, subgroup analyses and a cumulative meta-analysis. All statistical analyses were performed using Comprehensive Meta-Analysis 2.0.

Results

A total of 14 studies (6,398 patients) met the inclusion criteria, but 3 were excluded since they reported no NSF events. Meta-analysis of controlled trials indicated a significant association between GBCAs and NSF development (OR = 16.504; 95% CI: 7.455–36.533; P < 0.001) and between gadodiamide and NSF (OR = 20.037; 95% CI: 3.725–107.784; P < 0.001). No statistical heterogeneity was observed across studies (P = 0.819, I² = 0%; P = 0.874, I² = 0%, respectively). Cumulative analysis demonstrated that the pooled ORs for association between GBCAs and NSF decreased post-2007 compared to pre-2007 (OR = 26.708; 95% CI: 10.273–69.436; P<0.001).

Conclusions

Although this updated meta-analysis found a significant association between GBCAs and the incidence of NSF in patients with advanced renal disease, the association decreased after 2007. More studies, especially randomized controlled trials, are warranted to examine the potential association between GBCAs other than gadodiamide and NSF.     

Association of PDE4B Polymorphisms with Susceptibility to Schizophrenia: A Meta-Analysis of Case-Control Studies

Background

The PDE4B single nucleotide polymorphisms (SNPs) have been reported to be associated with schizophrenia risk. However, current findings are ambiguous or even conflicting. To better facilitate the understanding the genetic role played by PDE4B in susceptibility to schizophrenia, we collected currently available data and conducted this meta-analysis.

Methods

A comprehensive electronic literature searching of PubMed, Embase, Web of Science and Cochrane Library was performed. The association between PDE4B SNPs and schizophrenia was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs) under allelic, dominant and recessive genetic models. The random effects model was utilized when high between-study heterogeneity (I² > 50%) existed, otherwise the fixed effects model was used.

Results

Five studies comprising 2376 schizophrenia patients and 3093 controls were finally included for meta-analysis. The rs1040716 was statistically significantly associated with schizophrenia risk in Asian and Caucasian populations under dominant model (OR = 0.87, 95% CI: 0.76–0.99, P = 0.04). The rs2180335 was significantly related with schizophrenia risk in Asian populations under allelic (OR = 0.82, 95% CI: 0.72–0.93, P = 0.003) and dominant (OR = 0.75, 95% CI: 0.64–0.88, P < 0.001) models. A significant association was also observed between rs4320761 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.75–1.00, P = 0.048). In addition, a strong association tendency was found between rs6588190 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.76–1.00, P = 0.055).

Conclusion

This meta-analysis suggests that PDE4B SNPs are genetically associated with susceptibility to schizophrenia. However, due to limited sample size, more large-scale, multi-racial association studies are needed to further clarify the genetic association between various PDE4B variants and schizophrenia.     

Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis

BackgroundThe tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.ObjectiveOur aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate.MethodsSystematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GI side-effects that included ferrous sulfate and a comparator that was either placebo or intravenous (IV) iron. Random effects meta-analysis modelling was undertaken and study heterogeneity was summarised using I² statistics.ResultsForty three trials comprising 6831 adult participants were included. Twenty trials (n = 3168) had a placebo arm and twenty three trials (n = 3663) had an active comparator arm of IV iron. Ferrous sulfate supplementation significantly increased risk of GI side-effects versus placebo with an odds ratio (OR) of 2.32 [95% CI 1.74–3.08, p<0.0001, I² = 53.6%] and versus IV iron with an OR of 3.05 [95% CI 2.07-4.48, p<0.0001, I² = 41.6%]. Subgroup analysis in IBD patients showed a similar effect versus IV iron (OR = 3.14, 95% CI 1.34-7.36, p = 0.008, I² = 0%). Likewise, subgroup analysis of pooled data from 7 RCTs in pregnant women (n = 1028) showed a statistically significant increased risk of GI side-effects for ferrous sulfate although there was marked heterogeneity in the data (OR = 3.33, 95% CI 1.19-9.28, p = 0.02, I² = 66.1%). Meta-regression did not provide significant evidence of an association between the study OR and the iron dose.ConclusionsOur meta-analysis confirms that ferrous sulfate is associated with a significant increase in gastrointestinal-specific side-effects but does not find a relationship with dose.     

Dietary Fat Intake and Risk of Gastric Cancer: A Meta-Analysis of Observational Studies

Background and Objectives

Consumption of dietary fat has been reported to be associated with gastric cancer risk, but the results of epidemiologic studies remain inconsistent. We conducted a meta-analysis to summarize the evidence regarding the association between dietary fat intake and gastric cancer risk.

Methods

A comprehensive search of PubMed and EMBASE was performed to identify observational studies providing quantitative estimates between dietary fat and gastric cancer risk. Random effects model was used to calculate the summary relative risk(SRR) in the highest versus lowest analysis. Categorical dose-response analysis was conducted to quantify the association between dietary fat intake and gastric cancer risk. Heterogeneity among studies was evaluated using I² and tau2(between study variance)statistics. Subgroup analysis and publication bias analysis were also performed.

Results

Twenty-two articles were included in the meta-analysis. The SRR for gastric cancer was 1.18 for individuals with highest intake versus lowest intake of total fat (95% confidence interval [CI]: 0.999–1.39; n = 28; P< 0.001; tau² = 0.12; I² = 69.5%, 95% CI: 55%-79%) and 1.08 with a daily increase in total fat intake (20 g/d) (95%CI: 1.02–1.14; n = 6; P = 0.09; tau² = 0.002; I² = 46.8%, 95% CI: 0%-79%). Positive association between saturated fat intake (SRR = 1.31; 95%CI: 1.09–1.58;n = 18;P<0.001; tau² = 0.08; I² = 60.6%, 95% CI: 34%-76%), inverse association between polyunsaturated fat intake (SRR = 0.77; 95%CI: 0.65–0.92; n = 16; P = 0.003; tau² = 0.06; I² = 56.2%, 95% CI: 23%-75%) and vegetable fat intake (SRR = 0.55; 95%CI: 0.41–0.74; n = 4;P = 0.12; tau² = 0.04; I² = 48.6%, 95% CI: 0%-83%), and no association between monounsaturated fat intake (SRR = 1.00; 95%CI: 0.79–1.25; n = 14; P< 0.001; tau² = 0.10; I² = 63.0%, 95% CI: 34%-79%) and animal fat intake (SRR = 1.10; 95%CI: 0.90–1.33; n = 6; P = 0.13;tau² = 0.02; I² = 42.0%, 95% CI: 0%-70%) and gastric cancer risk were observed.

Conclusions

Our results suggest that intake of total fat is potentially positively associated with gastric cancer risk, and specific subtypes of fats account for different effects. However, these findings should be confirmed by further well-designed cohort studieswith detailed dietary assessments and strict control of confounders.     

Critical Appraisal of Bivalirudin versus Heparin for Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials

Percutaneous coronary intervention with bivalirudin plus bail-out glycoprotein IIb/IIIa inhibitors has been shown to be as effective as unfractionated heparin plus routine glycoprotein IIb/IIIa inhibitors in preventing cardiac ischemic events, but with a lower bleeding risk. It is unknown whether bivalirudin would have the same beneficial effects if compared with heparin when the use of glycoprotein IIb/IIIa inhibitors was similar between treatment arms. We searched the MEDLINE, Web of Science, and Cochrane databases from inception until March 2015 for randomized trials that compared bivalirudin to heparin in patients undergoing percutaneous coronary intervention. We required that the intended use of glycoprotein IIb/IIIa inhibitors was similar between the study groups. Summary estimates were principally constructed by the Peto method. Fifteen trials met our inclusion criteria, which yielded 25,824 patients. Bivalirudin versus heparin was associated with an increased hazard of stent thrombosis (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.15-1.92, P = .002, I² = 16.9%), with a similar hazard of myocardial infarction (OR 1.09, 95% CI 0.98-1.22, P = .11, I² = 35.8%), all-cause mortality (OR 0.88, 95% CI 0.72-1.08, P = .21, I² = 31.5%) and major adverse cardiac events (OR 1.04, 95% CI 0.94-1.14, P = .46, I² = 53.9%). Bivalirudin was associated with a reduced hazard of major bleeding (OR 0.80, 95% CI 0.70-0.92, P = .001, I² = 63.5%). The dose of heparin in the control arm modified this association; when the dose of unfractionated heparin in the control arm was ≥ 100 units/kg, bivalirudin was associated with a reduction in major bleeding (OR 0.55, 95% CI 0.45-0.68, P < .0001), but when the dose of unfractionated heparin was ≤ 75 units/kg, bivalirudin was not associated with reduction in bleeding (OR 1.09, 95% CI 0.91-1.31, P = .36). Among patients undergoing PCI, bivalirudin was associated with an increased hazard of stent thrombosis. Bivalirudin may be associated with a reduced hazard of major bleeding; however, this benefit was no longer apparent when compared with a dose of unfractionated heparin ≤ 75 units/kg.     

Socioeconomic differences in prostate cancer treatment: A systematic review and meta-analysis

BackgroundSince the 1990s, most nations have had a reduction or stabilisation in prostate cancer mortality. However, socioeconomic differences in disease specific mortality and survival have persisted. This has been partially attributed to differences in treatment choices. The aim of this systematic review and meta-analysis was to describe and quantify socioeconomic differences in use of prostate cancer treatment in the literature.MethodsMEDLINE, CINAHL and Embase were searched from 01 January 2000–01 April 2021 to identify articles that reported use of prostate cancer treatment by socioeconomic status. Random effects meta-analysis was used to analyse socioeconomic differences in treatment where there was more than one study for treatment type. A modified version of the Newcastle-Ottawa Scale was used to assess risk of bias.ResultsOut of 7267 articles identified, eight met the inclusion criteria and six were analysed using meta-analysis. Meta-analysis could only be completed for non-active treatment (watchful waiting/active surveillance). Lower education was associated with non-active treatment (OR=0.90, [95% CI 0.83–0.98], p=0.02, I²=67%), however, level of income was not (OR=0.87, [CI 0.75–1.02], p=0.08, I²=94%). Sensitivity analysis of studies where active surveillance was the outcome (n=3), indicated no associations with level of income (OR=0.91, [95% CI 0.82–1.01], p=0.08, I²=52%) or education (OR=0.88, [95% CI 0.70–1.10], p=0.25, I²=79%). All studies were assessed as high-risk of bias.DiscussionThe relationship between socioeconomic status and prostate cancer treatment depended on the socioeconomic variable being used, the treatment type and how it was defined in research. Considerable methodological limitations were identified. Further research should improve on previous findings and address current gaps.     

Is Plasmodium vivax Malaria a Severe Malaria?: A Systematic Review and Meta-Analysis

Background

Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection.

Methods/Principal Findings

We searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04–5.68, I ²:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83–5.1, I ²:83%), the 5–15 year-age group (OR: 0.6, 95% CI: 0.31–1.16, I ²:81%) and adults (OR: 0.83, 95% CI: 0.67–1.03, I ²:25%). Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64–18.94, I ²: 92%), the 5–15 year-age group (OR:0.71, 95% CI: 0.06–8.57, I ²:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62–0.92, I ²:0%). Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5–0.76, I ²:0%), while this was comparable in the 5–15 year- age group (OR: 0.43, 95% CI:0.06–2.91, I ²:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59–1.01, I ²:0%).

Conclusion

Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt early detection. Subsequent treatment and monitoring of complications can be life-saving.     

Association between Glu504Lys Polymorphism of ALDH2 Gene and Cancer Risk: A Meta-Analysis

BackgroundThe association of the aldehyde dehydrogenases-2 (ALDH2) Glu504Lys polymorphism (also named Glu487Lys, or rs671) and cancers has been investigated. This meta-analysis aims to comprehensively assess the influence of this polymorphism on the overall cancer risk.MethodsEligible publications were retrieved according to inclusion/exclusion criteria and the data were analyzed using the Review Manager software (V5.2).ResultsA meta-analysis based on 51 case-control studies consisting of 16774 cases and 32060 controls was performed to evaluate the association between the ALDH2 Glu504Lys polymorphism and cancer risk. The comparison of genotypes Lys+ (Lys/Lys and Lys/Glu) with Glu/Glu yielded a significant 20% increased cancer risk (OR = 1.20, 95%CI: 1.03–1.39, P = 0.02, I² = 92%). Subgroup analysis by cancer type indicated a significantly increased UADT cancer risk (OR = 1.39, 95%CI: 1.11–1.73, P = 0.004, I² = 94%) in individuals with the Lys+ genotypes. Subgroup analysis by country indicated that individuals from Japan with the Lys+ genotypes had a significant 38% increased cancer risk (OR = 1.38, 95%CI: 1.12–1.71, P = 0.003, I² = 93%).ConclusionsOur results indicated that the ALDH2 Glu504Lys polymorphism is a susceptible loci associated with overall cancers, especially esophageal cancer and among Japanese population.     

The Association of Platelet Count with Clinicopathological Significance and Prognosis in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

ObjectiveElevated platelet count (PC), a measure of systemic inflammatory response, is inconsistently reported to be associated with poor prognosis in patients with renal cell carcinoma (RCC). We conducted a systematic review and meta-analysis to clarify the significance of PC in RCC prognosis.MethodsPubMed, Embase, and Web of Science databases were searched to identify eligible studies to evaluate the associations of PC with patient survival and clinicopathological features of RCC.ResultsWe analyzed 25 studies including 11,458 patients in the meta-analysis and categorized the included articles into three groups based on RCC stage. An elevated PC level was associated with poor overall survival (OS, hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.87-2.67, P<0.001) and cancer-specific survival (CSS, HR 2.59, 95% CI 1.92-3.48, P<0.001) when all stages were examined together; with poor CSS (HR 5.09, 95% CI 2.41-10.73, P<0.001) and recurrence-free survival (HR 6.68, 95% CI 3.35-13.34, P<0.001) for localized RCC; with poor OS (HR 2.00, 95% CI 1.75-2.28, P<0.001) for metastatic RCC; and with poor OS (HR 2.05, 95% CI 1.04-4.03, P = 0.038), CSS (HR 3.38, 95% CI 1.86-6.15, P<0.001), and PFS (HR 2.97, 95% CI 1.47-6.00, P = 0.002) for clear cell RCC. Furthermore, an elevated PC level was significantly associated with TNM stage (OR 3.11, 95% CI 1.59-6.06, P = 0.001), pathological T stage (OR 3.13, 95% CI 2.60-3.77, P<0.001), lymph node metastasis (OR 4.01, 95% CI 2.99-5.37, P<0.001), distant metastasis (OR 3.85, 95% CI 2.46-6.04, P<0.001), Fuhrman grade (OR 3.70, 95% CI 3.00-4.56, P<0.001), tumor size (OR 4.69, 95% CI 2.78-7.91, P<0.001) and Eastern Cooperative Oncology Group score (OR 5.50, 95% CI 3.26-9.28, P<0.001).ConclusionAn elevated PC level implied poor prognosis in patients with RCC and could serve as a readily available biomarker for managing this disease.     

CYP2D6*4 Allele Polymorphism Increases the Risk of Parkinson’s Disease: Evidence from Meta-Analysis

Background

Many epidemiological studies have been conducted to explore the association between a single CYP2D6 gene polymorphism and Parkinson’s disease (PD) susceptibility. However, the results remain controversial.

Objectives

To clarify the effects of a single CYP2D6 gene polymorphism on the risk of PD, a meta-analysis of all available studies relating to CYP2D6*4 polymorphism and the risk of PD was conducted.

Methods

A comprehensive literature search of PubMed, EMBASE, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2013 was conducted. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated. Meta-regression, Galbraith plots, subgroup analysis, sensitivity analysis, and publication bias analysis were also performed.

Results

Twenty-two separate comparisons consisting of 2,629 patients and 3,601 controls were included in our meta-analysis. The pooled analyses showed a significant association between CYP2D6*4G/A polymorphism and PD risk in all of the comparisons (A vs. G allele: OR = 1.28, 95% CI = 1.14–1.43, P = 0.001; AA vs. GG: OR = 1.43, 95% CI = 1.06–1.93, P = 0.018; AG vs. GG: OR = 1.22, 95% CI = 1.06–1.40, P = 0.006; AG+AA vs. GG: OR = 1.26, 95% CI = 1.10–1.44, P = 0.001; AA vs. AG+GG: OR = 1.37, 95% CI = 1.02–1.83, P = 0.036). In subgroup analysis stratified by ethnicity, significant associations were also demonstrated in Caucasians but not in Asians. No significant association was found in subgroup analysis stratified by age of onset or disease form.

Conclusions

We concluded that the CYP2D6*4G/A polymorphism denotes an increased genetic susceptibility to PD in the overall population, especially in Caucasians. Further large and well-designed studies are needed to confirm this association.     

Maternal body mass index and risk of testicular cancer in male offspring: A systematic review and meta-analysis

Objectives: To date a number of studies have examined the association between maternal weight and testicular cancer risk although results have been largely inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods: Search strategies were conducted in Ovid Medline (1950–2009), Embase (1980–2009), Web of Science (1970–2009), and CINAHL (1937–2009) using keywords for maternal weight (BMI) and testicular cancer. Results: The literature search produced 1689 hits from which 63 papers were extracted. Only 7 studies met the pre-defined criteria. Random effects meta-analyses were conducted. The combined unadjusted OR (95% CI) of testicular cancer in the highest reported category of maternal BMI compared with the moderate maternal BMI was 0.82 (0.65–1.02). The Cochran's Q P value was 0.82 and the corresponding I² was 0%, both indicating very little variability among studies. The combined unadjusted OR (95% CI) for testicular cancer risk in the lowest reported category of maternal BMI compared to a moderate maternal BMI category was 0.88 (0.65–1.20). The Cochran's Q P value was 0.05 and the corresponding I² was 54%, indicating evidence of statistical heterogeneity. The combined unadjusted OR (95% CI) of testicular cancer risk per unit increase in maternal BMI was 1.01 (0.97–1.06). The Cochran's Q test had a P value of 0.05 and the corresponding I² was 55% indicating evidence of statistical heterogeneity. Conclusion: This meta-analysis, which included a small number of studies, showed that a higher maternal weight does not increase the risk of testicular cancer in male offspring. Though an inverse association between high maternal BMI and testicular cancer risk was detected, it was not statistically significant. Further primary studies with adjustment for appropriate confounders are required.     

Effects of Nucleotides Supplementation of Infant Formulas on Plasma and Erythrocyte Fatty Acid Composition: A Meta-Analysis

Objective

Nucleotides (NTs) have been added to infant formulas for several years due to their health benefits. However, studies have reported inconsistent findings regarding the association between NTs and fatty acid (FA) composition. A meta-analysis was performed to assess the effects of NTs supplementation of infant formula on erythrocyte and plasma FA composition.

Methods

Randomized controlled trials that evaluated the association between NTs supplementation and FA composition and were published before October 2014 were included. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using Q and I ² tests.

Results

Eight studies (364 infants) were included in the meta-analysis. NTs supplementation did not affect the concentrations of total saturated FAs (SMD= 0.05; 95% CI= -0.23–0.32; P = 0.75) or total monounsaturated FAs (SMD= -0.01; 95% CI= -0.28–0.27; P = 0.95) in erythrocyte membranes. Erythrocyte total n-3 (SMD= 0.15; 95% CI= -0.11–0.41; P = 0.27) and n-6 PUFA (SMD= -0.16; 95% CI= -0.42–0.10, P = 0.22) concentrations did not increase with NTs supplementation. The concentrations of erythrocyte n-3 PUFA (18:3, 20:5, 22:5, and 22:6) and n-6 PUFA (18:2, 20:3, 20:4, and 22:4) were not affected by NTs supplementation. NTs significantly increased plasma concentrations of 18:2 n-6 (SMD= 0.90; 95% CI= 0.47–1.33; P < 0.0001), 20:3 n-6 (SMD= 0.56; 95% CI= 0.14–0.97; P = 0.009), and 20:4 n-6 PUFA (SMD= 0.92; 95% CI= 0.50–1.35; P < 0.0001), and significantly decreased the concentration of plasma 18:3 n-3 PUFA (SMD= -0.60; 95% CI -1.12 to -0.09; P = 0.02). No effect was obtained on plasma 20:2 n-6 PUFA concentrations (SMD= 0.06; 95 % CI, -1.03 to -0.2; P = 0.93).

Conclusions

Our meta-analysis revealed that NTs supplementation significantly increased plasma 18:2 n-6, 20:3 n-6, and 20:4 n-6 PUFA concentrations in infants, but did not affect erythrocyte FA composition.     

Associations between Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms and Non-Alcoholic Fatty Liver Disease (NAFLD) Risk: A Meta-Analysis

BackgroundC677T and A1298C are the most common allelic variants of Methylenetetrahydrofolate Reductase (MTHFR) gene. The association between MTHFR polymorphisms and the occurrence of non-alcoholic fatty liver disease (NAFLD) remains controversial. This study was thus performed to examine whether MTHFR mutations are associated with the susceptibility to NAFLD.MethodsA first meta-analysis on the association between the MTHFR polymorphisms and NAFLD risks was carried out via Review Manager 5.0 and Stata/SE 12.0 software. The on-line databases, such as PubMed, EMBASE, CENTRAL, WOS, Scopus and EBSCOhost (updated to April 1^st, 2016), were searched for eligible case-control studies. The odd radio (OR), 95% confidence interval (CI) and P value were calculated through Mantel-Haenszel statistics under random- or fixed-effect model.ResultsEight articles (785 cases and 1188 controls) contributed data to the current meta-analysis. For C677T, increased NAFLD risks were observed in case group under homozygote model (T/T vs C/C, OR = 1.49, 95% CI = 1.03~2.15, P = 0.04) and recessive model (T/T vs C/C+C/T, OR = 1.42, 95% CI = 1.07~1.88, P = 0.02), but not the other genetics models, compared with control group. For A1298C, significantly increased NAFLD risks were detected in allele model (C vs A, OR = 1.53, 95% CI = 1.13~2.07, P = 0.006), homozygote model (C/C vs A/A, OR = 2.81, 95% CI = 1.63~4.85, P = 0.0002), dominant model (A/C+C/C vs A/A, OR = 1.60, 95% CI = 1.06~2.41, P = 0.03) and recessive model (C/C vs A/A+A/C, OR = 2.08, 95% CI = 1.45~3.00, P<0.0001), but not heterozygote model.ConclusionT/T genotype of MTHFR C677T polymorphism and C/C genotype of MTHFR A1298C are more likely to be associated with the susceptibility to NAFLD.     

The Effectiveness of Thyroid Hormone Replacement Therapy on Heart Failure and Low-Triiodothyronine Syndrome: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveThe purpose of this study was to conduct a systematic review and meta-analysis evaluating the role of thyroid hormone therapy in patients with heart failure and low-triiodothyronine syndrome.MethodsThe electronic databases PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biology Medicine disc were systematically searched to identify eligible studies published before November 27, 2021. The mean difference was pooled for randomized controlled trials using a random-effects model.ResultsThe meta-analysis showed that thyroid hormone treatment improved the left ventricular ejection fraction (weighted mean difference [WMD] 5.61, 95% confidence interval [CI]: 4.38 to 6.85, I² = 63.12%, P < 0.01). The cardiac output improved with thyroid hormone therapy (WMD 0.65, 95% CI: 0.42 to 0.89, I² = 84.28%, P < 0.01). The early-to-late diastolic transmitral flow velocity in the thyroid hormone group was also improved compared to the control group (WMD 0.29, 95% CI: 0.15 to 0.42, I² = 95.08%, P < 0.01). The left ventricular diastolic dysfunction was decreased with thyroid hormone treatment (WMD ?5.17, 95% CI: ?7.47 to ?2.88, I² = 90.18%, P < 0.01). The brain natriuretic peptide decreased with thyroid hormone treatment (standardized mean difference ?1.49, 95% CI: ?2.15 to ?0.84, I² = 90.18%, P < 0.01). Noradrenaline decreased with thyroid hormone therapy (WMD ?349.86, 95% CI: ?401.05 to ?298.67, I² = 0%, P < 0.01). Free triiodothyronine increased with thyroid hormone treatment (standardized mean difference 2.18, 95% CI: 0.75 to 2.60, I² = 98.20%, P < 0.01).ConclusionThis meta-analysis showed that thyroid hormone replacement therapy was effective in patients with heart failure and low-triiodothyronine syndrome.     

Association of polymorphic markers of chemokine genes,their receptors,and <Emphasis Type="Italic">CD14</Emphasis> gene with coronary atherosclerosis

Atherosclerosis represents an inflammatory response to the disturbance of the endothelial layer in the arterial bloodstream. In the present study, an analysis of associations of polymorphic markers for the genes controlling synthesis of proteins involved in atherosclerosis pathogenesis in coronary atherosclerosis (CA) patients (217 subjects) and in a control group (250 subjects) was conducted. The following genes were examined: rs991804 (CCL2 gene), rs1126579 (CXCR2 gene), rs4074 (CXCL1 gene), rs4073 (CXCL8 gene), rs333 (CCR5 gene), rs2471859 (CXCR4 gene), rs1801157 (CXCL12 gene), and rs2569190 (CD14 gene). Using the Monte Carlo and Markov chain (APSampler) method, allele/genotype combinations associated with both low and high CA risk were revealed. The most important findings included the following: CXCR4*T/T + CCL2*C + CCR5*I/I (P_perm = 1 × 10^–6, OR = 0.44, 95% CI 0.3–0.63), CXCR2*C + CD14*C + CXCL12*G + CCL2*C + CCR5*D (P_perm = 4 × 10^–6, OR = 5.78, 95% CI 2.34–14.28), CD14*C + CCL2*C/C + CCR5*D (P_perm = 6.3 × 10^–6, OR = 5.81, 95% CI 2.17–15.56), CXCL8*A + CXCR2*C + CD14*T + CXCR4*C (P_perm = 0.01, OR = 3.21, 95% CI 1.63–6.31).     

Human leukocyte antigen genotype and risk of HIV disease progression before and after initiation of antiretroviral therapy

While the human leukocyte antigen (HLA) genotype has been associated with the rate of HIV disease progression in untreated patients, little is known regarding these relationships in patients using highly active antiretroviral therapy (HAART). The limited data reported to date identified few HLA-HIV disease associations in patients using HAART and even occasional associations that were opposite of those found in untreated patients. We conducted high-resolution HLA class I and II genotyping in a random sample (n = 860) of HIV-seropositive women enrolled in a long-term cohort initiated in 1994. HLA-HIV disease associations before and after initiation of HAART were examined using multivariate analyses. In untreated HIV-seropositive patients, we observed many of the predicted associations, consistent with prior studies. For example, HLA-B*57 (β = −0.7; 95% confidence interval [CI] = −0.9 to −0.5; P = 5 × 10⁻¹¹) and Bw4 (β = −0.2; 95% CI = −0.4 to −0.1; P = 0.009) were inversely associated with baseline HIV viral load, and B*57 was associated with a low risk of rapid CD4⁺ decline (odds ratio [OR] = 0.2; 95% CI = 0.1 to 0.6; P = 0.002). Conversely, in treated patients, the odds of a virological response to HAART were lower for B*57:01 (OR = 0.2; 95% CI = 0.0 to 0.9; P = 0.03), and Bw4 (OR = 0.4; 95% CI = 0.1 to 1.0; P = 0.04) was associated with low odds of an immunological response. The associations of HLA genotype with HIV disease are different and sometimes even opposite in treated and untreated patients.     

Prognostic and clinical significance of focal adhesion kinase expression in breast cancer: A systematic review and meta-analysis

BackgroundThe prognostic significance of focal adhesion kinase (FAK) in breast cancer remains controversial. Here, we conducted a meta-analysis to explore the prognostic value of FAK expression in breast cancer.Materials and methodsPossible prognostic significance of protein or mRNA expression of FAK in breast cancer was investigated with searches of electronic databases for relevant publications. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted from eligible studies.ResultsA total of eight eligible studies which included 2604 participants were analyzed in this meta-analysis. Increased expression of FAK protein was found to significantly correlate with shorter overall survival (OS) (HR = 1.43, 95% CI: 1.12–1.83; P = 0.004), and not with disease-free survival (HR = 1.31, 95% CI: 0.92–1.85; P = 0.14). Elevated FAK protein expression was also associated with negative estrogen receptor (ER) expression (OR, 1.34; 95% CI, 1.06–1.68; P = 0.01), negative progesterone receptor (PR) expression (OR, 1.54; 95% CI, 1.22–1.93; P < 0.001), positive human epidermal growth factor receptor 2 (HER2) expression (OR, 1.64; 95% CI, 1.28–2.09; P < 0.001), triple-negative breast cancer (TNBC) (OR, 1.57; 95% CI, 1.14–2.17; P = 0.006), high nuclear grade (OR, 1.70; 95% CI, 1.05–2.78; P = 0.03), high Ki-67 expression level (OR, 2.87; 95% CI, 1.94–4.24; P < 0.001), and positive p53 status (OR, 2.28; 95% CI, 1.58–3.29; P < 0.001).ConclusionOur meta-analysis identifies an association between increased FAK protein expression and worse OS among breast cancer patients. Moreover, enhanced FAK expression is associated with negative ER expression, negative PR expression, positive HER2 expression, TNBC, high nuclear grade, high Ki-67 expression level, and positive p53 status in breast carcinoma.     

Interferon Gamma +874T/A Polymorphism Increases the Risk of Hepatitis Virus-Related Diseases: Evidence from a Meta-Analysis

BackgroundInterferon gamma (IFN-γ) is a key regulatory cytokine, which plays an important role in antiviral defense of an infected host. However, the association between the IFN-γ +874T/A gene polymorphism and hepatitis virus-related diseases is heterogeneous.MethodsBased on the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, a comprehensive literature search of eligible studies in Embase, Pubmed, and the Cochrane Library was undertaken through November 2014. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were used to measure the strength of the models.ResultsSeventeen case-control articles, including 24 studies with 5503 individuals, met the inclusion criteria. The results indicated a statistically significant association between the IFN-γ +874T/A polymorphism and hepatitis virus—related diseases in a recessive gene model (AA vs. TT+TA: OR=1.350, 95% CI=1.101-1.657, P=0.004, I²%=54.3, and P_Q=0.001 for heterogeneity), especially in Asians (OR=1.407, 95% CI=1.035-1.911, P=0.029, I²%=61.9, and P_Q=0.005 for heterogeneity) and hepatitis B virus (HBV)–related disease (OR=1.486, 95% CI=1.195–1.849, P=0.000, I²%=40.4, and P_Q=0.053 for heterogeneity).ConclusionsThe evidence suggests that the IFN-γ +874T/A polymorphism increases the risk of hepatitis virus—related diseases, especially in Asians and HBV—related diseases. Further studies on this topic in different ethnicities, especially genome-wide association studies, should be conducted to strengthen our results.     

Incidental Thyroid Cancer in Toxic and Nontoxic Goiter: is TSH Associated with Malignany Rate? Results of A Meta-Analysis

ObjectiveIn the last 6 years, several studies reported a positive association between thyrotropin (TSH) and papillary cancer risk. The rationale is based on stimulatory action exerted by TSH on thyroid cell proliferation and/ or progression of a pre-existing papillary carcinoma. To validate this hypothesis, we performed a meta-analysis comparing the incidence of thyroid cancer in 2 groups of patients who underwent surgery for toxic or nontoxic nodular goiter.MethodsUsing data from 2,150 patients with toxic multinodular goiter (TMNG) and 873 patients with toxic adenoma (TA), the overall incidence of thyroid cancer (and 95% confidence interval [CIs]) was estimated to be 5.9% (3.9 to 8.3) for patients with TMNG and 4.8% (2.5 to 7.9) for patients with TA. Four studies were included in the meta-analysis with a total of 1,964 subjects undergoing thyroidectomy for allegedly benign thyroid disease (520 patients with TMNG or TA and 1,444 for multinodular goiter [MNG] or uninodular goiter [UNG]).ResultsWe did not find any significant differences in the risk of incidental thyroid cancer (ITC) in patients with TMNG versus MNG (odds ratio [OR]: 0.91, 95% CI: 0.47 to 1.77, I⁴: 62.6%), TA versus uninodular goiter (UNG) (OR: 0.46, 95% CI: 0.12 to 1.79, I⁵: 12%), and TMNG or TA versus MNG or UNG (pooled analysis) (OR: 0.86, 95% CI: 0.46 to 1.60, I⁶: 51.5%).ConclusionsThe results of this meta-analysis did not confirm an association between low TSH values and lower thyroid cancer rate, at least in patients with nodular disease. (Endocr Pract. 2013;19:212-218)