Value of Quantitative and Qualitative Analyses of Circulating Cell-Free DNA as Diagnostic Tools for Hepatocellular Carcinoma: A Meta-Analysis

Qualitative and quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of hepatocellular carcinoma (HCC). Many studies have evaluated these approaches, but the results have been variable. This meta-analysis is the first to synthesize these published results and evaluate the use of circulating cfDNA values for HCC diagnosis.All articles that met our inclusion criteria were assessed using QUADAS guidelines after the literature research. We also investigated 3 subgroups in this meta-analysis: qualitative analysis of abnormal concentrations of circulating cfDNA; qualitative analysis of single-gene methylation alterations; and multiple analyses combined with alpha-fetoprotein (AFP). Statistical analyses were performed using the software Stata 12.0. We synthesized these published results and calculated accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratios [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence intervals [95% CIs]). Data were pooled using bivariate generalized linear mixed model. Furthermore, summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize overall test performance. Heterogeneity and publication bias were also examined.A total of 2424 subjects included 1280 HCC patients in 22 studies were recruited in this meta-analysis. Pooled sensitivity and specificity, PLR, NLR, DOR, AUC, and CIs of quantitative analysis were 0.741 (95% CI: 0.610–0.840), 0.851 (95% CI: 0.718–0.927), 4.970 (95% CI: 2.694–9.169), 0.304 (95% CI: 0.205–0.451), 16.347 (95% CI: 8.250–32.388), and 0.86 (95% CI: 0.83–0.89), respectively. For qualitative analysis, the values were 0.538 (95% CI: 0.401–0.669), 0.944 (95% CI: 0.889–0.972), 9.545 (95% CI: 5.298–17.196), 0.490 (95% CI: 0.372–0.646), 19.491 (95% CI: 10.458–36.329), and 0.87 (95% CI: 0.84–0.90), respectively. After combining with AFP assay, the values were 0.818 (95% CI: 0.676–0.906), 0.960 (95% CI: 0.873–0.988), 20.195 (95% CI: 5.973–68.282), 0.190 (95% CI: 0.100–0.359), 106.270 (95% CI: 22.317–506.055), and 0.96 (95% CI: 0.94–0.97), respectively.The results in this meta-analysis suggest that circulating cfDNA have potential value for HCC diagnosis. However, it would not be recommended for using independently, which is based on the nonrobust results. After combining with AFP, the diagnostic performance will be improved. Further investigation with more data is needed.     

Identification of Circulating MicroRNAs as Novel Potential Biomarkers for Gastric Cancer Detection: A Systematic Review and Meta-Analysis

Background

Recent studies show that microRNAs (miRNAs) in serum or plasma can be stably detected and used as potential biomarkers in cancer diagnosis.

Objectives

To systematically evaluate circulating miRNAs from numerous gastric cancer (GC) expression profiling studies and to determine miRNA biomarkers for GC detection.

Methods

A systematic review and meta-analysis of published studies comparing the circulating miRNA expressions between GC patients and healthy controls were carried out. An miRNA ranking system that considered the number of comparisons in agreement, total number of samples, and average fold change was used. Then the receiver-operating characteristic curve (ROC) results of the top miRNAs were combined to further evaluate their diagnostic value by using Meta-disc 1.4.

Results

A total of 35 miRNAs were reported in the 22 included studies, with 7 miRNAs reported in at least 2 studies. MiR-21 is the most consistently reported miRNA with upregulation. In further analysis, the sensitivity, specificity, and area under the curve of summary ROC for miR-21 in GC diagnosis are 0.78 (95 % CI 0.71–0.85), 0.89 (95 % CI 0.82–0.94), and 0.91, respectively.

Conclusion

Circulating miR-21 can serve as a potential biomarker for detection of GC.     

Development of the AL-O-A Score for Delirium Screening in Acute Internal Medicine: a Monocentric Prospective Study

BackgroundDelirium occurs frequently in acute internal medicine wards and may worsen the patient’s prognosis; it deserves a fast, systematic screening tool.ObjectiveDevelop a delirium screening score for inpatients admitted to acute internal medicine wards.DesignA monocentric prospective study between November 2019 and January 2020.ParticipantsTwo hundred and seventeen adult inpatients.Main MeasuresWithin 48 h of hospital admission, physicians administered an index test to participants which explored potential predictors associated with the fluctuation of mental state, inattention, disorganised thinking and altered level of consciousness. On the same day, patients underwent a neuropsychological evaluation (reference standard) to assess for delirium. The score was constructed using a backward stepwise logistic regression strategy. Areas under the receiver operating curves (AUC) and calibration curves were drawn to calculate the score’s performance. The score was tested on subgroups determined by age, sex and cognitive status.ResultsThe AL-O-A score (“abnormal or fluctuating ALertness, temporospatial Orientation and off-target Answers”) showed excellent apparent (AUC 0.95 (95% CI 0.91–0.99)) and optimism-corrected discrimination (AUC 0.92 (95% CI 0.89–0.96)). It performed equally well in subgroups with and without cognitive impairment (AUC 0.93 (95% CI 0.88–0.99) vs 0.92 (95% CI 0.80–0.99)); in men and women (AUC 0.96 (95% CI 0.94–0.99) vs 0.95 (95% CI 0.89–0.99)); and in patients younger and older than 75 years old (AUC 0.98 (95% CI 0.95–0.99) vs 0.93 (95% CI 0.87–0.99)).ConclusionsA simple, 1-min screening test (AL-O-A score), even administered by an untrained professional, can identify delirium in internal medicine patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06502-w.KEY WORDS: delirium, internal medicine, inpatients, adult, prospective study, score     

Predictive Value of Serum miR-10b,miR-29c,and miR-205 as Promising Biomarkers in Esophageal Squamous Cell Carcinoma Screening

Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide. The high mortality of ESCC is mainly due to late diagnosis. Current detection methods have their own weakness, including high costs and invasive procedures. MicroRNA assays are shown to have great potential to be accurate and noninvasive methods for ESCC screening. In this study, we selected 3 microRNAs, miR-10b, miR-29c, and miR-205, to assess their diagnostic value in ESCC screening. Fifty ESCC patients and 50 healthy controls are recruited in our study. Blood samples are collected from the total 100 participants. MicroRNAs were extracted from serum and quantified by qRT-PCR, which their relative expressions were normalized by internal control, U6 snRNA. Statistical analyses were conducted to compare microRNAs level as well as other clinical characteristics between 2 groups. The levels of serum miR-29c and miR-205 were significantly downregulated in ESCC patients compared with healthy volunteers. In contrast, ESCC patients appeared to have a higher level of miR-10b than healthy controls. ROC curve analyses revealed that the AUC value for miR-10b, miR-29c, and miR-205 were 0.85 (95% CI: 0.79–0.93; sensitivity = 76%; specificity = 84%), 0.72 (95% CI: 0.62–0.82; sensitivity = 68%; specificity = 68%), and 0.72 (95% CI: 0.62–0.83; sensitivity = 70%; specificity = 64%), respectively, suggesting that miR-10b, miR-29c, and miR-205 have great potential to be noninvasive screening tools for ESCC detection.     

Value of clinical tests in diagnosing anterior cruciate ligament injuries: A systematic review and meta-analysis

Objectives:This study compared 4 clinical tests with reference to magnetic resonance imaging and arthroscopic visualization to comprehensively evaluate their diagnostic value for anterior cruciate ligament injuries.Methods:We systematically searched 10 electronic databases from January 1, 2010, to May 1, 2021. Two reviewers collected data in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analyses 2020 guidelines. The quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. A meta-analysis was performed using Meta-Disc version 1.4 and Stata SE version 15.0.Results:Eighteen articles involving 2031 participants were included. The results of the meta-analysis showed that for the Lachman test, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnosis odds ratio, area under the curve (AUC) of summary receiver operating characteristic (SROC), and Q* were 0.76 (95% CI, 0.73–0.78), 0.89 (95% CI, 0.87–0.91), 5.65 (95% CI, 4.05–7.86), 0.28 (95% CI, 0.23–0.36), 22.95 (95% CI, 14.34–36.72), 0.88, and 0.81, respectively. For the anterior drawer test, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnosis odds ratio, AUC of SROC, and Q* were 0.64 (95% CI, 0.61–0.68), 0.87 (95% CI, 0.84–0.90), 3.57 (95% CI, 2.13–5.96), 0.44 (95% CI, 0.32–0.59), 8.77 (95% CI, 4.11–18.74), 0.85, and 0.78, respectively. For the pivot shift test, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnosis odds ratio, AUC of SROC, and Q* were 0.59 (95% CI, 0.56–0.62), 0.97 (95% CI, 0.95–0.98), 13.99 (95% CI, 9.96–19.64), 0.44 (95% CI, 0.35–0.55), 29.46 (95% CI, 15.60–55.67), 0.98, and 0.94, respectively. For the lever sign test, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnosis odds ratio, AUC of SROC, and Q* were 0.79 (95% CI, 0.75–0.83), 0.92 (95% CI, 0.87–0.95), 9.56 (95% CI, 2.76–33.17), 0.23 (95% CI, 0.12–0.46), 47.38 (95% CI, 8.68–258.70), 0.94, and 0.87, respectively.Conclusions:Existing evidence shows that these clinical tests have high diagnostic efficacy for anterior cruciate ligament injuries, and that every test has its own advantages and disadvantages. However, the above results should be validated through additional studies, considering the limited quality and quantity of our sample.     

The Association of Common Functional Polymorphisms in Mir-146a and Mir-196a2 and Hepatocellular Carcinoma Risk: Evidence from a Meta-Analysis

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) located in the miRNAs influence the function of mature miRNAs and may contribute to cancer development. Studies investigating the association between miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. We performed a meta-analysis of all available studies to summarize this situation.Eligible studies were identified by search of electronic databases including PubMed, Embase, and Cochrane library for the period up to August 2014. The association of miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).Finally, a total of 12 studies with 4171 cases and 4901 controls were included for miR-146a rs2910164 polymorphism and 10 studies with 4687 cases and 4990 controls were available for miR-196a2 rs11614913 polymorphism. With respect to miR-146a rs2910164 polymorphism, statistical significant increased HCC risk was found when all studies were pooled into the meta-analysis (GG+CG vs CC: OR = 1.097, 95% CI 1.005–1.197, P = 0.037). In subgroup analyses by ethnicity, source of control, and HWE in controls, significant increase of HCC risk was found in Asians, population-based studies, and studies consistent with HWE, but not in Caucasians, hospital-based studies, and studies inconsistent with HWE. With respect to miR-196a2 rs11614913 polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses.The results suggest that the miR-146a rs2910164 polymorphism contributes to increased HCC susceptibility, especially in Asian populations. Further large and well-designed studies are required to validate this association.     

Diagnostic accuracy of different computer-aided diagnostic systems for prostate cancer based on magnetic resonance imaging: A systematic review with diagnostic meta-analysis

Background:Computer-aided detection (CAD) system for accurate and automated prostate cancer (PCa) diagnosis have been developed, however, the diagnostic test accuracy of different CAD systems is still controversial. This systematic review aimed to assess the diagnostic accuracy of CAD systems based on magnetic resonance imaging for PCa.Methods:Cochrane library, PubMed, EMBASE and China Biology Medicine disc were systematically searched until March 2019 for original diagnostic studies. Two independent reviewers selected studies on CAD based on magnetic resonance imaging diagnosis of PCa and extracted the requisite data. Pooled sensitivity, specificity, and the area under the summary receiver operating characteristic curve were calculated to estimate the diagnostic accuracy of CAD system.Results:Fifteen studies involving 1945 patients were included in our analysis. The diagnostic meta-analysis showed that overall sensitivity of CAD system ranged from 0.47 to 1.00 and, specificity from 0.47 to 0.89. The pooled sensitivity of CAD system was 0.87 (95% CI: 0.76–0.94), pooled specificity 0.76 (95% CI: 0.62–0.85), and the area under curve (AUC) 0.89 (95% CI: 0.86–0.91). Subgroup analysis showed that the support vector machines produced the best AUC among the CAD classifiers, with sensitivity ranging from 0.87 to 0.92, and specificity from 0.47 to 0.95. Among different zones of prostate, CAD system produced the best AUC in the transitional zone than the peripheral zone and central gland; sensitivity ranged from 0.89 to 1.00, and specificity from 0.38 to 0.85.Conclusions:CAD system can help improve the diagnostic accuracy of PCa especially using the support vector machines classifier. Whether the performance of the CAD system depends on the specific locations of the prostate needs further investigation.     

AFP-L3 for the diagnosis of early hepatocellular carcinoma: A meta-analysis

Background:The present study aimed to systematically evaluate the diagnostic value of an isoform of alpha-fetoprotein (AFP), AFP-L3, for early hepatocellular carcinoma (HCC) by a meta-analysis.Methods:Diagnostic reports of AFP-L3% in early HCC were searched in the PubMed, Web of Science, Cochrane Library, and Embase databases up to December 2019. The retrieved literature was reviewed, and eligible articles were selected. Data were extracted from the eligible articles, and the risk of bias was evaluated according to the Quality Assessment of Diagnostic Accuracy Studies scale. Statistical analyses were conducted by MetaDiSc1.4 and RevMan5.3 software. The sensitivities, specificities, and diagnostic odds ratios were pooled. The summary receiver operating characteristic curve was drawn, and the area under the curve was calculated.Results:Six studies with acceptable quality were included in the meta-analysis involving 2447 patients. No threshold effect was observed among the 6 studies, but there was obvious heterogeneity. The pooled sensitivity, specificity, and positive and negative likelihood ratios of AFP-L3% for the diagnosis of early HCC were 0.34 (95% CI 0.30–0.39, P < .0001), 0.92 (95% CI 0.91–0.93, P < .0001), 4.46 (95% CI 2.94–6.77, P = .0033), and 0.71 (95% CI 0.61–0.82, P = .0004), respectively. The diagnostic odds ratio was 6.78 (95% CI 4.02–11.44, P = .0074). The the area under the curve of the summary receiver operating characteristic was 0.755 (95% CI 0.57–0.94).Conclusion:AFP-L3% has high specificity but low sensitivity for diagnose early HCC, suggesting that AFP-L3% is more valuable for excluding HCC in conditions with elevated AFP than for diagnosing early HCC. In addition, a hypersensitive detection method can improve the diagnostic accuracy of AFP-L3% for early HCC.     

MRI versus CT for the detection of pulmonary nodules: A meta-analysis

Background:Computed tomography (CT) is the current gold standard for the detection of pulmonary nodules but has high radiation burden. In contrast, many radiologists tried to use magnetic resonance imaging (MRI) to replace CT because MRI has no radiation burden associated. Due to the lack of high-level evidence of comparison of the diagnostic accuracy of MRI versus CT for detecting pulmonary nodules, it is unknown whether CT can be replaced successfully by MRI. Therefore, the aim of this study was to compare the diagnostic accuracy of MRI versus CT for detecting pulmonary nodules.Methods:Electronic databases PubMed, EmBase, and Cochrane Library were systematically searched from their inception to September 2017 to identify studies in which CT/MRI was used to diagnose pulmonary nodules. According to true positive, true negative, false negative, and false positive extracted from the included studies, we calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) using Stata version 14.0 software (STATA Corp, TX).Results:A total of 8 studies involving a total of 653 individuals were included. The pooled sensitivity, specificity, PLR, NLR, and AUC were 0.91 (95% confidence interval [CI]: 0.80–0.96), 0.76 (95%CI: 0.58–0.87), 3.72 (95%CI: 2.05–6.76), 0.12 (95%CI: 0.06–0.27), and 0.91 (95%CI: 0.88–0.93) for MRI respectively, while the pooled sensitivity, specificity, PLR, NLR, and AUC for CT were 1.00 (95%CI: 0.95–1.00), 0.99 (95%CI: 0.78–1.00), 79.35 (95%CI: 3.68–1711.06), 0.00 (95%CI: 0.00–0.06), and 1.00 (95%CI: 0.99–1.00), respectively. Further, we compared the diagnostic accuracy of CT versus MRI and found that compared with MRI, CT shows statistically higher sensitivity (odds ratio [OR] for MRI vs CT: 0.91; 95%CI: 0.85–0.98; P value .010), specificity (OR: 0.82; 95%CI: 0.69–0.97; P value .019), PLR (OR: 0.29; 95%CI: 0.10–0.83; P value 0.02), AUC (OR: 0.91; 95%CI: 0.89–0.94; P value < .001), and lower NLR (OR: 8.72; 95%CI: 1.57–48.56; P value .013).Conclusion:Our study suggested both CT and MRI have a high diagnostic accuracy in diagnosing pulmonary nodules, while CT was superior to MRI in sensitivity, specificity, PLR, NLR, and AUC, indicating that in terms of the currently available evidence, MRI could not replace CT in diagnosing pulmonary nodules.     

Adenosine deaminase from the cerebrospinal fluid for the diagnosis of tuberculous meningitis: A meta-analysis

Objective

To comprehensively evaluate the diagnostic efficacy of adenosine deaminase in cerebrospinal fluid (CSF) for tuberculous meningitis (TBM), and the potential influence of patients' age groups and cutoffs of measured adenosine deaminase.

Methods

Systematic review and meta-analysis of relevant studies retrieved from PubMed, Embase, and Web of Science databases. Pooled sensitivity and specificity were calculated with a random-effect model.

Results

Overall, 43 studies with 1653 patients with TBM and 3417 controls without were included. Pooled results showed that adenosine deaminase in CSF is associated with satisfactory diagnostic efficacy for TBM, with a pooled sensitivity of 0.86 (95% confidence interval [CI]: 0.82–0.90), specificity of 0.89 (95% CI: 0.86–0.91), positive likelihood ratio of 7.70 (95% CI: 6.16–9.63), and negative likelihood ratio of 0.15 (95% CI: 0.12–0.20). The pooled receiver operating characteristic (AUC) was 0.94 (95% CI: 0.91–0.96), suggesting good performance. Subgroup analyses showed good diagnostic efficacies of adenosine deaminase in CSF for both adults (AUC 0.95) and children (AUC 0.96) with TBM. AUCs indicating the diagnostic accuracies of adenosine deaminase in CSF for TBM were 0.93 for studies with cutoffs <10 U/L and and 0.94 for a cutoff =10 U/L, but only 0.90 for studies with cutoffs >10 U/L.

Conclusions

Measuring adenosine deaminase of CSF shows satisfactory diagnostic efficacy for TBM in children and adults, particularly if using a cutoff ≤10 U/L.     

Clinical role of miR-421 as a novel biomarker in diagnosis of gastric cancer patients: A meta-analysis

Background:Gastric cancer (GC) has been identified as one of the most common malignancies. It was found that microRNAs can be used as potential biomarkers for GC diagnosis. The aim of this study was to estimate the diagnostic value of 4 potential microRNAs in GC.Methods:PubMed, Embase, Cochrane Library, and Web of Science were used to search published studies. The quality of the studies was scored with the Quality Assessment of Diagnostic Accuracy Studies. The pooled sensitivity and specificity, diagnostic odds ratio (DOR) and area under the curve (AUC) were calculated. The heterogeneity was evaluated using Cochrane Q statistics and the inconsistency index.Results:A total of 22 studies reporting the diagnostic value of miR-21 (n = 9), miR-106 (n = 10), miR-421 (n = 5) and miR-223 (n = 3) were included. Quality Assessment of Diagnostic Accuracy Studies scores showed the high quality of the selected 22 articles. The random effects model was adopted by evaluating the heterogeneity between articles. The DOR, AUC, and Q value of miRNA-21 were 12.37 (95% confidence interval [CI]: 5.36–28.54), 0.86 and 0.79, respectively. The DOR, AUC and Q value of miRNA-106 were 12.98 [95% CI: 7.14–23.61], 0.85 and 0.78, respectively. The DOR, AUC and Q value of miRNA-421 were 27.86 [95% CI: 6.04–128.48], 0.92 and 0.86, respectively. The DOR, AUC and Q value of miRNA-223 were 18.50 [95% CI: 7.80–43.86], 0.87 and 0.80, respectively. These results indicate that miRNA-421 has the highest diagnostic accuracy, followed by miR-223, miRNA-21, and miRNA-106 among the 4 microRNAs in GC.Conclusions:miR-21, miR-106, miR-421, and miR-223 have good diagnostic efficacy, especially miR-421, could be used as auxiliary diagnostic indicator for GC.     

Comprehensive Characterization of Serum MicroRNA Profile in Response to the Emerging Avian Influenza A (H7N9) Virus Infection in Humans

A novel avian-origin influenza A (H7N9) virus recently occurred in China and caused 137 human infection cases with a 32.8% mortality rate. Although various detection procedures have been developed, the pathogenesis of this emerging virus in humans remains largely unknown. In this study, we characterized serum microRNA (miRNA) profile in response to H7N9 virus infection using TaqMan Low Density Arrays. Upon infection, a total of 395 miRNAs were expressed in the serum pool of patients, far beyond the 221 in healthy controls. Among the 187 commonly expressed miRNAs, 146 were up-regulated and only 7 down-regulated in patients. Further analysis by quantitative RT-PCR revealed that the serum levels of miR-17, miR-20a, miR-106a and miR-376c were significantly elevated in patients compared with healthy individuals (p < 0.05). Receiver operating characteristic (ROC) curves were constructed to show that each miRNA could discriminate H7N9 patients from controls with area under the curve (AUC) values ranging from 0.622 to 0.898, whereas a combination of miR-17, miR-20a, miR-106a and miR-376c obtained a higher discriminating ability with an AUC value of 0.96. Our findings unravel the significant alterations in serum miRNA expression following virus infection and manifest great potential of circulating miRNAs for the diagnosis of viral diseases.     

The Association Between Body Mass Index and the Prognosis and Postoperative Complications of Hepatocellular Carcinoma: A Meta-Analysis

Previous studies have reported the association between excess body mass index (BMI) and increased risk of hepatocellular carcinoma (HCC). However, whether BMI is associated with the prognosis and postoperative complications of HCC is still not clear.We searched PubMed and Embase for relevant studies published until the date of August 30, 2014. Additional studies were manually identified by searching reference lists of retrieved articles. Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) for overall survival (OS), disease-free survival (DFS), and risk ratios (RRs) with 95% CIs for postoperative complications were calculated using random effects or fixed effects models according to heterogeneities between studies.A total of 14 studies were included in the present meta-analysis. The pooled results showed that excess BMI was not significantly associated with improved OS (HR = 0.94; 95% CI: 0.74–1.19, P = 0.588) or DFS (HR = 0.93; 95% CI: 0.79–1.10, P = 0.382). In addition, higher BMI was not associated with increased rate of a number of complications including ascites (RR = 1.25, 95% CI: 0.94–1.65, P = 0.119), bile leaks (RR = 1.22, 95% CI: 0.81–1.83, P = 0.345), and 30-day mortality (RR = 1.05, 95% CI: 0.57–1.96, P = 0.871). However, HCC patients with higher BMI had increased incidence of wound infections (RR = 2.17, 95% CI: 1.28–3.68, P = 0.004).BMI was not an independent prognostic factor for the evaluation of the prognosis in HCC patients, and it was not associated with postoperative complications except for wound infections that as significantly associated with higher BMI scores.     

Expression of miR-126 and miR-508-5p in endothelial progenitor cells is associated with the prognosis of chronic heart failure patients

Background

MicroRNA (miRNA) expression profiles in endothelial progenitor cells (EPCs) contribute to EPC dysfunction in patients suffering from coronary artery disease. However, it remains unclear whether miRNA expression in EPCs is associated with the prognosis of chronic heart failure (CHF) secondary to ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM).

Methods and results

One hundred six patients with CHF (55 ICM and 51 NICM) and 30 healthy controls were followed until the end of 24 months or when the end point was obtained (cardiovascular death). The miRNA expression profile was analyzed by TaqMan Human MicroRNA Array Set v2.0 in 30 randomly assigned samples (ICM = 10, NICM = 10, and healthy controls = 10). During the 24-month follow-up, 26 patients died from cardiovascular disease. Sixteen miRNAs (miR-126, miR-508-5p, miR-34a, miR-210, miR-490-3p, miR-513-5p, miR-517c, miR-518e, miR-589, miR-220c, miR-200a*, miR-186*, miR-7i*, miR-200b*, miR-595, and miR-662) were found to be differentially expressed between ICM and NICM patients. Survival analysis showed that miR-126 and miR-508-5p levels in EPCs were independent prognostic factors (P = 0.003; HR (hazard ratio): 0.19; 95% CI (confidence intervals): 0.06–0.58, P = 0.002; HR: 2.292; 95% CI: 1.37–3.84) for the outcome of ICM or NICM patients with CHF. Pathway enrichment analysis showed that the angiogenesis pathway was the most likely pathway regulated by miR-126 and miR-508-5p.

Conclusions

The miRNAs miR-126 and miR-508-5p are associated with the outcome of ICM and NICM patients with CHF. These two miRNAs could be useful in the diagnosis of CHF patients, and might provide novel targets for prevention and treatment of CHF.     

Effects of SGLT2 inhibitors on cardiovascular and renal outcomes in type 2 diabetes: A meta-analysis with trial sequential analysis

Background:It is unclear whether there are false positive or negative results in the effects of sodium-glucose transporter 2 (SGLT2) inhibitors on various cardiovascular and renal outcomes in patients with type 2 diabetes. We aimed to explore this issue by a meta-analysis with trial sequential analysis.Methods:We included randomized trials evaluating the effects of SGLT2 inhibitors on cardiorenal endpoints in type 2 diabetic patients. Eight endpoints evaluated in the study were fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, major adverse cardiovascular events (MACE), cardiovascular death or hospitalization for heart failure (CVD or HHF), all-cause death (ACD), cardiovascular death (CVD), hospitalization for heart failure (HHF), and kidney function progression (KFP). Meta-analysis and trial sequential analysis was conducted for each endpoint.Results:Seven randomized trials of SGLT2 inhibitors were included for pooled analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the risk of MACE (HR 0.89, 95% confidence interval [CI] 0.84–0.94), MI (HR 0.91, 95% CI 0.84–0.99), CVD (HR 0.86, 95% CI 0.79–0.93), CVD or HHF (HR 0.77, 95% CI 0.73–0.82), HHF (HR 0.67, 95% CI 0.62–0.74), KFP (HR 0.63, 95% CI 0.56–0.70), and ACD (HR 0.88, 95% CI 0.83–0.94), whereas SGLT2 inhibitors did not have significant effects on stroke (HR 0.98, 95% CI 0.88–1.09). Trial sequential analyses for MI and stroke showed that cumulative Z curve did not cross trial sequential monitoring boundary and required information size, whereas those for the other 6 endpoints showed that cumulative Z curve crossed trial sequential monitoring boundary and/or required information size.Conclusions:Compared with placebo, SGLT2 inhibitors conclusively reduce the risk of MACE, CVD or HHF, ACD, CVD, HHF, and KFP in patients with type 2 diabetes, whereas the effects of SGLT2 inhibitors on MI and stroke are not conclusive and need to be further assessed in future studies with the adequate sample size to reject or accept the effect size.     

CT-Base Pulmonary Artery Measurementin the Detection of Pulmonary Hypertension: A Meta-Analysis and Systematic Review

To summarize the performance of CT-based main pulmonary artery diameter or pulmonary artery to aorta ratio (PA:A ratio) measurement in detection of pulmonary hypertension by a systematic review and meta-analysis.A comprehensive literature search was performed to identify studies determining diagnostic accuracy of main pulmonary artery diameter or PA:A ratio measurement for pulmonary hypertension. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. A bivariate random-effects model was used to pool sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were used to summarize overall diagnostic performance.This meta-analysis included 20 publications involving 2134 subjects. Summary estimates for main pulmonary artery diameter measurement in the diagnosis of pulmonary hypertension were as follows: sensitivity, 0.79 (95% CI 0.72–0.84); specificity, 0.83 (95% CI 0.75–0.89); PLR, 4.68 (95% CI 3.13–6.99); NLR, 0.26 (95% CI 0.20–0.33); DOR, 18.13 (95% CI 10.87–30.24); and AUC 0.87. The corresponding summary performance estimates for using the PA:A ratio were as follows: sensitivity, 0.74 (95% CI 0.66–0.80); specificity, 0.81 (95% CI 0.74–0.86); PLR, 3.83 (95% CI, 2.70–5.43); NLR, 0.33 (95% CI 0.24–0.44); DOR, 11.77 (95% CI 6.60–21.00); and AUC 0.84.Both main pulmonary artery diameter and PA:A ratio are helpful for diagnosing pulmonary hypertension. Nevertheless, the results of pulmonary artery measurement should be interpreted in parallel with the results of traditional tests such as echocardiography.     

High Expression of MicroRNA-196a Indicates Poor Prognosis in Resected Pancreatic Neuroendocrine Tumor

There is limited data on miRNA expression in pancreatic neuroendocrine tumors (PanNETs). In this study, we aimed to identify miRNAs that could be potential prognostic biomarkers of PanNETs in patients who underwent curative surgery.For miRNA target screening, 2 primary PanNETs and corresponding liver metastases were screened for miRNA expression by the NanoString nCounter analysis. Candidate miRNAs were selected by ≥2-fold difference of expression between metastatic versus primary tumor. For miRNA target validation, quantitative real-time PCR was performed for candidate miRNAs on 37 PanNETs and matched nonneoplastic pancreata, and the miRNA levels were correlated with the clinicopathological features and patient survival data.Eight miRNAs (miRNA-27b, -122, -142–5p, -196a, -223, -590–5p, -630, and -944) were selected as candidate miRNAs. Only miR-196a level was significantly associated with stage, and mitotic count. When PanNETs were stratified into high (n = 10) and low (n = 27) miRNA-196a expression groups, miRNA-196a-high PanNETs were significantly associated with advanced pathologic T stage (50.0% vs 7.4%), N stage (50.0% vs 3.7%), higher mitotic counts (60.0% vs 3.7%), and higher Ki-67-labeling indices (60.0% vs 22.2%). In addition, high miRNA-196a expression was significantly associated with decreased overall survival (P = 0.046) and disease-free survival (P < 0.001) during a median follow-up of 37.9 months with the hazard ratio for recurrence of 16.267 (95% confidence interval = 1.732–153.789; P = 0.015).MiRNA-196a level may be a promising prognostic marker of recurrence in resected PanNETs, although further experimental investigation would be required.     

Potential Role of Circulating MiR-21 in the Diagnosis and Prognosis of Digestive System Cancer: A Systematic Review and Meta-Analysis

Recent evidences indicate that circulating microRNAs (miRNAs) exhibit aberrant expression in the plasma of patients suffering from cancer compared to normal individuals, suggesting that it may be a useful noninvasion diagnostic method. MiR-21 plays crucial roles in carcinogenesis and can be served as a biomarker for the detection of various cancers. Therefore, the aim of this meta-analysis is to assess the potential role of miR-21 for digestive system cancer.By searching the PubMed, Embase, and Web of Science for publications concerning the diagnostic value of miR-21 for digestive system cancer, total of 23 publications were included in this meta-analysis. Receiver operating characteristic curves (ROC) were used to check the overall test performance. For prognostic meta-analysis, pooled hazard ratios (HRs) of circulating miR-21 for survival were calculated.Totally 23 eligible publications were included in this meta-analysis (15 articles for diagnosis and 8 articles for prognosis). For diagnostic meta-analysis, the summary estimates revealed that the pooled sensitivity and specificity were 0.76(95% CI = 0.70–0.82) and 0.84 (95% CI = 0.78–0.89). Besides, the area under the summary ROC curve (AUC) is 0.87. For prognostic meta-analysis, the pooled HR of higher miR-21 expression in circulation was 1.94 (95% CI = 0.99–3.82, P = 0.055), which indicated higher miR-21 expression could be likely to predict poorer survival in digestive system cancer. The subgroup analysis implied the higher expression of miR-21 was correlated with worse overall survival in the Asian population in digestive system cancer (HR = 2.41, 95% CI = 1.21–4.77, P = 0.012).The current evidence suggests circulating miR-21 may be suitable to be a diagnostic and prognostic biomarker for digestive system cancer in the Asians.