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Background: Chronic pain after breast cancer surgery affects up to 60% of patients. Evidence supports the fact that pain outwith the surgical site is a significant issue. This systematic review and meta-analysis sought to evaluate the prevalence of non-surgical site pain (NSSP) in women after breast cancer surgery at 6 months post-operatively. Methods: Adult women with a confirmed breast cancer diagnosis who had undergone breast cancer surgery were identified. The outcome pursued was pain outwith the surgical site measured on either NRS/VRS or VAS rating scale. CENTRAL, Embase, PubMed, MEDLINE, CINAHL, PsycInfo, Web of Science, and Scopus were searched to identify studies that examined NSSP after breast cancer surgery at 6 months. Data were gathered via pre-piloted Excel forms and analysed both quantitively and qualitatively. Meta-analysis was carried out using a random-effects model to assess risk difference with 95% confidence interval (CI). Results: A total of sixteen studies were identified for inclusion. Eleven studies failed to provide sufficient data and consequently were analysed qualitatively. Five studies were adequate for quantitative analysis, including a total of 995 patients. Meta-analysis identified a risk difference of 18% (95% CI: 5–31%) between patients who had breast cancer surgery and a reference, however, this is low-quality evidence. Conclusion: This review has highlighted that breast cancer surgery increases the risk of pain outwith the surgical site postoperatively. It was additionally identified that NSSP data are often gathered in research yet rarely presented in results or highlighted as a primary outcome. As the quality of evidence was low, research specifying NSSP as a primary outcome is required to provide more certainty. [ABSTRACT FROM AUTHOR]

Background/Aims: Von Hippel-Lindau gene (VHL) has been reported as a tumor-suppressor gene in some cancers. However, the association between VHL promoter hypermethylation and renal cell carcinoma (RCC) remains to be clarified. We are the first to systematically integrate published papers to assess the role of hypermethylated VHL in RCC. Methods: The potential relevant papers were searched via PubMed, Embase, EBSCO, CNKI, and Wanfang databases. The overall odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to evaluate the relationship between VHL promoter hypermethylation and RCC. Results: Finally, a total of 1,998 RCC patients and 294 controls from 13 eligible articles were included in this meta-analysis. Under the fixed-effects model, the pooled OR from seven studies including 596 RCC and 294 nonmalignant samples showed that VHL promoter hypermethylation was significantly higher in cancer than in controls (OR = 7.93, 95% CI = 2.84-22.15, P < 0.001). Subgroup analysis based on ethnic population and testing method revealed that hypermethylated VHL had a significantly similar OR value in different races and detection methodologies. No significant association was found between hypermethylated VHL and tumor grade, tumor stage, tumor size, histological types, and lymph node status in cancer (all P > 0.05). In the current study, there was no evidence of publication bias as determined by Egger's test (all P > 0.05). Conclusions: In the investigated patients, VHL promoter hypermethylation, which may play an important role in carcinogenesis of RCC, is significantly associated with an increased risk of RCC. However, VHL promoter hypermethylation is not correlated with specific clinicopathological characteristics. Additional future studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Background/Aims: Von Hippel-Lindau gene (VHL) has been reported as a tumor-suppressor gene in some cancers. However, the association between VHL promoter hypermethylation and renal cell carcinoma (RCC) remains to be clarified. We are the first to systematically integrate published papers to assess the role of hypermethylated VHL in RCC. Methods: The potential relevant papers were searched via PubMed, Embase, EBSCO, CNKI, and Wanfang databases. The overall odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to evaluate the relationship between VHL promoter hypermethylation and RCC. Results: Finally, a total of 1,998 RCC patients and 294 controls from 13 eligible articles were included in this meta-analysis. Under the fixed-effects model, the pooled OR from seven studies including 596 RCC and 294 nonmalignant samples showed that VHL promoter hypermethylation was significantly higher in cancer than in controls (OR = 7.93, 95% CI = 2.84- 22.15, P < 0.001). Subgroup analysis based on ethnic population and testing method revealed that hypermethylated VHL had a significantly similar OR value in different races and detection methodologies. No significant association was found between hypermethylated VHL and tumor grade, tumor stage, tumor size, histological types, and lymph node status in cancer (all P > 0.05). In the current study, there was no evidence of publication bias as determined by Egger's test (all P > 0.05). Conclusions: In the investigated patients, VHL promoter hypermethylation, which may play an important role in carcinogenesis of RCC, is significantly associated with an increased risk of RCC. However, VHL promoter hypermethylation is not correlated with specific clinicopathological characteristics. Additional future studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Renal size is often used as a marker for nephron numbers as estimation of glomerular numbers is not yet possible in vivo. However, the validity of an association between the two is questionable. As a proper marker for nephron number in an individual is needed in clinical practice, this study was designed to assess the association between renal size and nephron numbers. Methods: An individual patient data meta-analysis was performed on data retrieved with a PubMed and Embase search. Only studies were included that described individual human data on kidney size and nephron numbers determined by stereology, the gold standard methodology to estimate nephron numbers. As renal size increases until the end of puberty, and nephron numbers decline after the age of 60 years, only data from individuals aged 18-60 years without renal disease were included. Results: Six papers were identified that provided data on renal weight and nephron numbers from 114 individuals. Backward linear regression identified kidney weight and race as the only 2 significant factors explaining nephron numbers (R square 0.085, p=0.007). Controlling for race, there was a significant correlation between nephron number and kidney weight (r=0.231, r square=0.053, p=0.01). Conclusion: These data indicate that only ∼5% of the variation in nephron numbers is explained by differences in renal size. Renal size in adulthood should not be used as a marker for nephron numbers in an individual. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: The goal of this meta-analysis was to assess the use of FDG-PET in the diagnosis of primary bone and soft tissue sarcomas.Subjects and Methods: Several databases, including PubMed, Embase, Cochrane Library, and Web of Science, were searched. In addition to sensitivity and specificity, the diagnostic accuracy region for detecting and grading sarcomas were pooled using bivariate and hierarchical summary receiver-operating characteristic (HSROC) models. Subgroup analysis included pooling soft tissue and bone sarcomas separately, and sensitivity analysis included high-quality studies. The quality of eligible studies was assessed using QUADAS-2.Results: Of the 1,258 papers screened, 21 studies satisfied the inclusion criteria. The pooled sensitivity and specificity of FDG-PET combined with CT for the detection of sarcomas were 89.2 and 76.3%, respectively. These diagnostic accuracy measures were higher when combined with CT than those of PDG-PET alone. Diagnostic accuracy for bone and soft tissue lesions were comparable but slightly better for soft tissue tumors. Pooling only the high-quality studies with low risk of bias yielded a sensitivity of 88.5% and specificity reduced to 65.6%. There was no evidence for publication bias, but significant heterogeneity among the studies was apparent. This study also showed that FDG-PET can efficiently differentiate between benign and malignant tumors, with a mean standard uptake value of maximally 2.52 units in benign and 6.81 units in malignant tumors (89.2% sensitivity and 75.1% specificity).Conclusion: Our findings indicate FDG-PET can efficiently differentiate between benign and malignant bone and soft tissue tumors. We also found that FDG-PET improves accuracy in diagnosing soft tissue sarcomas when combined with CT. [ABSTRACT FROM AUTHOR]

Introduction: While SARS-CoV-2's main transmission route is through respiratory droplets, research has found that viral RNA could be detected in blood samples, causing concerns over the safety of blood donations and blood products. This paper therefore aims to systematically search for studies that have addressed their country's lack of donations and analyse the risk of blood transfusion-transmission. As such, it will answer the question "should blood services focus more on donation vigilance or worry more about the risks of transmission through blood products?" Methods: 38 articles were identified through a systematic review adopting the PRISMA and STROBE guidelines. Meta-analysis was conducted using OpenMeta software. Results: The average decrease in blood donations was found to be 38%, with some regions showing up to 67% decrease. To assess the risk of actual blood transfusion-transmission, three datasets were analysed. Firstly, the viral load in COVID-19 patients was studied and found to have less than 1% detection rate (ARD = −0.831, 95% −0.963, −0.699). Secondly, the prevalence of finding viral RNA in a pool of donations was nearly −1.503 (ARD = −1.538, −1.468). Lastly, recipients who were given blood products of positive donors were found to be −0.911 (ARD 95% = –1.247, −0.575). Discussion/Conclusion: Blood centres should focus more on launching initiatives and policies that would increase their countries' blood supply as the virus has no direct threat to blood safety. [ABSTRACT FROM AUTHOR]

Background/Aims: Accumulating studies have reported that IGF-1R (Insulin-like growth factor-1 receptor) is aberrantly expressed in NSCLC (non-small cell lung cancer), but the role of IGF-1R in NSCLC remains controversial. The present paper assessed the precise role of IGF-1R in NSCLC. Methods: We comprehensively searched PubMed, EMBASE, and Web of Science in March 2017. Combined HRs and ORs were used to evaluate the prognostic and clinicopathological significance of IGF-1R in NSCLC respectively. Results: A total of 10 eligible studies including 8 on overall survival, and 10 on clinicopathological features were identified from the databases. The results showed that high expression of IGF-1R was associated with shorter OS (overall survival) of NSCLC patients (pooled HR 1.17,95 % CI 1.00-1.36). In addition, we found that IGF-1R was related to smoking status (OR=1.82, 95 % CI=1.35-2.44) and IGF-1R tended to be highly expressed in SCC (squamous cell carcinoma) (OR=3.40 95 % CI: 1.95-5.95). Conclusions: In summary, this meta-analysis revealed that high expression of IGF-1R was associated with poor prognosis in NSCLC. [ABSTRACT FROM AUTHOR]

Background/Aims: The prognostic power of the levels of total CD44 and its isoform CD44v6 for patients with gastric cancer (GC) remains controversial. Therefore, our study aims to generalize the clinicopathological and prognostic significance of these two proteins in GC. Methods: A literature search of the PubMed, Web of Science and Embase databases was conducted to identify eligible studies. The odds ratio (OR) with a 95% confidence interval (CI) was used to assess the effects. Results: In all, 42 studies including 6,229 patients were included in this analysis. Total CD44 was mentioned in 21 papers, and the results showed that CD44 was positively correlated with the T category, the N category, distant metastasis, lymphatic invasion and TNM stage. Moreover, patients with CD44 overexpression had a lower 5-year overall survival (OS) rate (OR = 3.35, 95%CI = 1.83-6.13). CD44v6 was mentioned in 24 studies, with results that were similar to those for total CD44. However, total CD44 or CD44v6 expression was not correlated with tumor size and histological grade. Conclusion: High CD44 or CD44v6 expression levels were correlated with cancer progression and poor prognosis in patients with GC. Both CD44 and CD44v6 may be useful diagnostic or prognostic biomarkers for GC. [ABSTRACT FROM AUTHOR]

Background/Aims: Whether patients with RAS mutation metastatic colorectal cancer (mCRC) obtain benefits from bevacizumab added to first-line chemotherapy remains unclear. Methods: PubMed, Cochrane Systematic Reviews, the Cochrane Collaboration Central Register of Controlled Clinical Trials, ClinicalTrials.gov, and the American Society of Clinical Oncology and European Society for Medical Oncology databases were searched to identify abstracts for randomized controlled trials (RCTs) evaluating the efficacy of bevacizumab for the first-line treatment of patients with RAS mutations mCRC from inception to the end of April 2016. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were estimated. Results: Ten eligible papers reporting six RCTs were included. In the network meta-analysis of patients with RAS mutations, bevacizumab + chemotherapy prolonged PFS compared with chemotherapy alone (HR 0.75, 95% CI 0.51-1.10), but the difference was not statistically significant. Bevacizumab + chemotherapy did not prolong OS compared with chemotherapy alone (HR 1.10, 95% CI 0.73-1.66). Conclusion: There was insufficient evidence to definitively state that patients with RAS mutations mCRC could benefit from bevacizumab combined with chemotherapy as first-line treatment. [ABSTRACT FROM AUTHOR]

Background/Aims: Coronary heart disease is characterized by vascular stenosis or occlusion resulting in myocardial ischemia, hypoxia and necrosis. In China, the combination of aspirin and Fufang Danshen Diwan (FDD), a traditional Chinese medicine formula, has been suggested in the treatment of coronary heart disease. There have been several studies comparing the effectiveness of aspirin alone and in combination with FDD to treat coronary artery disease; however, it remains unclear whether combined aspirin therapy is superior. This study was thus designed to clarify this issue through a systematic review and meta-analysis. Methods: Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and analyzed using Cochrane software Revman 5.1. Results: Fourteen randomized controlled trials enrolling 1367 subjects were included. Metaanalyses revealed that aspirin in combination with FDD was significantly more effective at alleviating angina pectoris and improving electrocardiogram (ECG) results relative to aspirin therapy alone, reflected by the summary effects for the clinical markedly effective (OR = 2.45; 95% CI 1.95-3.08) and the total effective (OR = 3.92; 95% CI 2.87-5.36) rates. In addition, combined aspirin and FDD was significantly more efficacious than aspirin monotherapy at improving blood lipid levels, as indicated by the following outcomes: 1) reduction of TC level (SMD -1.12; 95% CI -1.49 to -0.76 ); 2) reduction of TG level (SMD -0.94; 95% CI -1.15 to -0.74 ); 3) reduction of LDL level (SMD -0.68; 95% CI -0.88 to -0.48); and 4) improvement of HDL level (SMD 0.52; 95% CI 0.04 to 0.99 ). No serious adverse events were reported in any of the included trials. Conclusion: The present meta-analysis demonstrated that aspirin in combination with FDD was more effective than aspirin alone for treating coronary heart disease. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefits and long-term effectiveness of FDD for the treatment of coronary heart disease. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the effects of gonadotropin-releasing hormone agonists (GnRHas) on pregnancy outcomes, premature ovarian failure (POF), menstrual recovery, disease-free survival (DFS), and adverse events in premenopausal breast cancer patients during gonadal chemotherapy. Methods: We systematically searched PubMed, Cochrane Library, and Embase databases. The trials were eligible if they included premenopausal breast cancer patients treated with chemotherapy alone or with concurrent GnRHa and reported ovarian function recovery data. Heterogeneity for the eligible data was assessed, and a pooled risk ratio (RR) with 95% confidence interval (CI) was calculated. A meta-analysis was conducted using a fixed-effect model. Results: Fifteen randomized controlled trials were included in this analysis. The results indicated that GnRHa combined with chemotherapy significantly increased pregnancy rates compared with chemotherapy alone (RR = 1.76; 95% CI: 1.16–2.67) and decreased rates of POF (RR = 0.42; 95% CI: 0.35–0.51). For secondary endpoints, the GnRHa group improved menstrual recovery rates (RR = 1.20; 95% CI: 1.11–1.30) and decreased the rate of amenorrhea 1–2 years after chemotherapy (RR = 0.50; 95% CI: 0.40–0.63). Furthermore, the 5-year DFS and overall survival (OS) rates were significantly improved in the GnRHa group. Conclusion: For premenopausal breast cancer patients receiving gonadal toxic chemotherapy, adjuvant chemotherapy with GnRHa can better protect the ovarian function of patients, reduce the rate of POF and amenorrhea, and improve the pregnancy rate, menstrual recovery rate, DFS rate, and OS rate of patients. [ABSTRACT FROM AUTHOR]

Objective: Mutations of the tumor protein p53 (TP53) gene were considered to be associated with an unfavorable prognosis in acute myeloid leukemia (AML). This meta-analysis aimed to systematically elucidate the prognostic value of TP53 mutation in adult patients with AML. Method: A comprehensive literature search was conducted for eligible studies published before August 2021. The primary endpoint was overall survival (OS). Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated for prognostic parameters. Subgroup analyses based on intensive treatment were performed. Results: Thirty-two studies with 7,062 patients were included. As compared to wild-type carriers, AML patients with TP53 mutations had significantly shorter OS (HR: 2.40, 95% CI: 2.16–2.67, I2: 46.6%). Similar results were found in DFS (HR: 2.87, 95% CI: 1.88–4.38), EFS (HR: 2.56, 95% CI: 1.97–3.31), and RFS (HR: 2.40, 95% CI: 1.79–3.22). Mutant TP53 predicted inferior OS (HR: 2.77, 95% CI: 2.41–3.18) in the intensively treated AML subgroup, compared with the non-intensively treated group (HR: 1.89, 95% CI: 1.58–2.26). Among intensively-treated AML patients, the age of 65 did not affect the prognostic value of TP53 mutations. Besides, TP53 mutation was also strongly associated with an elevated risk of adverse cytogenetics, which conferred a dismal OS in AML patients (HR: 2.03, 95% CI: 1.74–2.37). Conclusion: TP53 mutation exhibits a promising potential for discriminating AML patients with a worse prognosis, thus being capable of serving as a novel tool for prognostication and therapeutic decision-making in the management of AML. [ABSTRACT FROM AUTHOR]

Background: Body dissatisfaction has been identified as a psychological correlate of obesity that is related to disordered eating, poor self-esteem, and depression. However, not all individuals with obesity are equally vulnerable to these correlates, and 'normative discontent' is present in individuals with normal weight, too. In this light, the complex relationship of body image and individual weight status seems like a worthwhile direction of research inquiry. As such, this review aims to systematically explore the degree of body dissatisfaction in individuals with obesity compared to normal-weight individuals. Methods: A systematic literature search was conducted. All quantitative studies of adult samples reporting results regarding differences in body dissatisfaction between individuals with normal weight and obesity were included. Results: 17 articles were found. Across studies, individuals with obesity reported higher body dissatisfaction than normal-weight individuals (questionnaires: d = 0.89, 95% CI = 0.63-1.16, p < 0.001; silhouette scales: d = 1.41, 95% CI = 0.57-2.25, p < 0.001). Meta-regression revealed a significant association of female gender and higher body dissatisfaction (b = 0.60, p = 0.007). Conclusion: The findings underline the severity of body dissatisfaction among individuals with obesity and especially among women. Future research recommendations are discussed. [ABSTRACT FROM AUTHOR]

Background: Risk factors like female sex, fistula location, hypertension, albumin, diabetes, arteriovenous graft (AVG), age, and other factors are related to arteriovenous fistula thrombus (AVFT), but the consistency and magnitude of their associations have not been confirmed by meta-analysis. Objectives: The purpose of this study was to provide a comprehensive and up-to-date synthesis of evidence on the association between potential risk factors and AVFT. Methods: In this systematic review and meta-analysis, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for articles published up to April 20th, 2022, and cohort, cross-sectional, and case-control studies examining the association (odds ratio [OR]) between potential risk factors and AVFT were identified. The other inclusion criteria were sufficient data for analysis and nonoverlapping datasets, excluding reviews, meta-analyses, and articles with overlapping datasets. Extracted variables included first author, publication year, study type, sample size, percentage of women, vascular access type, risk or protective factors, and measure of association (adjusted estimates of effect of all risk factors). The study protocol is registered at PROSPERO (CRD42020201884) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Among the 27 identified studies, data from 24 cohort, 2 case-control, and 1 cross-sectional study were included in this review. When compared to non-AVFT, our data showed that the significant risk factors were AVG (pooled OR = 6.28, 95% CI = 1.79–22.02, p = 0.004, I2 = 87%), age (pooled OR = 1.06, 95% CI = 1.00–1.13, p = 0.05, I2 = 98%), female sex (pooled OR = 2.62, 95% CI = 2.56–2.69, p < 0.00001, I2 = 0%), C-reactive protein (pooled OR = 1.18, 95% CI = 1.08–1.30, p = 0.0005, I2 = 90%), fistula site (distal) (pooled OR = 3.64, 95% CI = 1.74–7.62, p = 0.0006, I2 = 47%), hypertension (pooled OR = 1.21, 95% CI = 1.00–1.47, p = 0.05, I2 = 46%), CD34+KDR+ cell (pooled OR = 1.85, 95% CI = 1.33–2.57, p = 0.0002, I2 = 0%), and eprex use (pooled OR = 5.36, 95% CI = 1.82–15.77, p = 0.002, I2 = 0%). Conclusions: The meta-analysis suggests that AVG, age, female sex, CRP level, fistula site (distal), hypertension, CD34+KDR+ cell, and the use of eprex are independent risk factors for AVFT. Therefore, clinical medical staff should treat these risk factors carefully, identify them early, and prevent them early to reduce the occurrence of AVFT. [ABSTRACT FROM AUTHOR]

Background: The outbreak of COVID-19 has resulted in more than 200 million infections and 4 million deaths. The blood derivative therapy represented by intravenous immunoglobulin (IVIG) and convalescent plasma (CP) therapy may be the promising therapeutics for COVID-19. Methods: A systematic article search was performed for eligible studies published up to August 3, 2021, through the PubMed, Embase, Cochrane Library. The included articles were screened by using rigorous inclusion and exclusion criteria. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated. Results: A total of 5 IVIG therapy and 13 CP therapy randomized controlled trials were included with a sample size of 13,696 subjects diagnosed with COVID-19. IVIG could reduce the mortality compared with the control group (RR 0.65, 95% CI: 0.46–0.93, p = 0.02). The use of CP did not effectively reduce the mortality (RR 0.97, 95% CI: 0.91–1.03, p = 0.38), the length of hospital stay (MD −0.47, 95% CI: −4.13 to 3.20, p = 0.80), and the mechanical ventilation use (RR = 0.98, 95% CI: 0.89–1.07, p = 0.62) of the patients with COVID-19. Treatment with IVIG or CP was not significantly associated with an increase in reported adverse events (RR 1.07, 95% CI: 0.94–1.22, p = 0.28). Conclusions: Treatment with IVIG could be effective and safe to improve survival for patients with COVID-19. But the benefit of CP in the treatment of COVID-19 is limited. The certainty of the evidence was moderate for all outcomes. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis was designed to evaluate the antihypertensive efficacy of intravascular renal denervation (RDN) in patients with essential hypertension, especially to determine the magnitude of blood pressure (BP) reduction with RDN therapy using second-generation catheters. Methods: PubMed was searched to identify randomized sham-controlled trials from inception through August 2021. The endpoints were changes in 24-h ambulatory BP or office BP. This meta-analysis was performed by calculating the weighted mean difference (WMD) with 95% confidence interval (CI) using the random-effects model when the I2 index was <50%. A fixed-effects model was used when the I2 index was ≥50%. Results: A total of 1,297 patients were included in 8 randomized, sham-controlled trials in this meta-analysis. Intravascular RDN reduced 24-h ambulatory systolic BP (SBP) −3.02 (WMD, 95% CI: −4.95, −1.10, p < 0.01) and diastolic BP (DBP) −1.66 (WMD, 95% CI: −2.44, −0.88, p < 0.001) mm Hg, respectively. In the studies using first-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were −2.67 (95% CI: −5.08, −0.27; p < 0.05; I2 = 0%, p = 0.53) and −0.82 (95% CI: −2.19, 0.56; p > 0.05; I2 = 0%, p = 0.64) mm Hg. In the studies using second-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were −3.14 (95% CI: −5.94, −0.33, p < 0.05; I2 = 71%, p = 0.008) and −2.06 (95% CI: −3.02, −1.11, p < 0.001; I2 = 50%, p = 0.09) mm Hg. Intravascular RDN using second-generation catheters reduced office SBP −6.30 (WMD, 95% CI: −7.67, −4.93, p < 0.001; I2 = 43%, p = 0.14) and DBP −3.88 (WMD, 95% CI: −4.44, −3.33, p < 0.001; I2 = 42%, p = 0.14) mm Hg, respectively. Conclusions: Intravascular RDN using second-generation catheters reduces ambulatory and office BP in patients with essential hypertension. The selection of appropriate hypertensive patients may be the major challenge for the performance of intravascular RDN in routine clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: The tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene produces ubiquitin-editing protein A20, which inhibits nuclear factor-κB (NF-κB) activation in a variety of signaling pathways. We examined the association between TNFAIP3 polymorphisms and rheumatoid arthritis (RA) susceptibility. Methods: MEDLINE, Embase, Scopus, and Web of Science were searched for available articles on TNFAIP3 polymorphisms in RA patients from inception until July 11, 2022. We included case-control studies on the association between rs2230926 and rs5029937 polymorphisms of TNFAIP3 and RA, and we excluded studies that contained overlapping data. We scored the quality of each study included based on the Newcastle-Ottawa Scale. Meta-analyses evaluated the association between TNFAIP3 polymorphisms and RA susceptibility in diverse ethnic populations and was verified through trial sequential analysis (TSA). This meta-analysis was registered in the PROSPERO register (number: CRD42022345160). There was no funding source. Results: Seventeen studies were chosen for meta-analysis. Ten studies for rs2230926, and seven for rs5029937. An association was noted between TNFAIP3 rs2230926 G allele and RA in all subjects (odds ratio [OR] = 1.389; 95% confidence interval [CI] = 1.161−1.662; p < 0.001). Ethnicity-specific analysis showed significant association of rs2230926 G allele with RA in Europeans and Asians (OR = 1.642; 95% CI = 1.099–2.452; p = 0.015; OR = 1.404; 95% CI = 1.262−1.562; p < 0.001). An association was also noted between TNFAIP3 rs5029937 T allele and RA in all subjects (OR = 1.389; 95% CI = 1.207−1.785; p < 0.001). An ethnicity-specific meta-analysis revealed a significant association of the rs5029937 T allele with RA in Europeans and Asians. Dominant model analysis showed the same pattern for TNFAIP3 rs2230926 G and rs5029937 T alleles in Europeans and Asians, suggesting an association between rs2230926 G and rs5029937. TSA indicated a robust association between the TNFAIP3 polymorphisms and the risk of RA. Conclusion:TNFAIP3 rs2230926 and rs5029937 polymorphisms are associated with RA susceptibility in European and Asian populations. However, the data were not stratified by parameters such as rheumatoid factor status, disease activity, or environmental variables. [ABSTRACT FROM AUTHOR]

Objective: Left ventricular thrombosis (LVT) is a common complication of acute ST-segment elevation myocardial infarction (STEMI). This study attempted to synthesize the available evidence to understand the incidence and risk factors of LVT in acute STEMI patients undergoing primary percutaneous coronary intervention (PCI).Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science for studies published from January 2001 to January 2022. The random-effects and fixed-effects model meta-analysis estimated pooled incidence, mean difference (MD), odds ratio (OR), and 95% confidence interval (CI). The Review Manager 5.4 software was used for meta-analysis performance.Results: The results of meta-analysis showed that the incidence of LVT in acute STEMI treated by primary PCI was 4% (95% CI [0.03, 0.05]), and the overall pooled incidence in patients with anterior STEMI was 10.0% (95% CI [0.07, 0.12]). Anterior STEMI (OR = 11.93, 95% CI [6.25, 22.78], p = 0.0003), left anterior descending-related infarct (OR = 6.85, 95% CI [3.70, 12.66], p < 0.00001), left ventricular wall motion abnormalities (OR = 7.53, 95% CI [3.18, 17.82], p < 0.00001), and lower post-PCI LVEF (MD = 13.78, 95% CI [12.15, 15.41], p < 0.00001) were risk factors for post-PCI LVT.Conclusion: The incidence of LVT after acute STEMI in the PCI era remains high. This study provides a preliminary overview of STEMI patients at risk for post-PCI LVT and will help the design of prospective randomized controlled trials for the management and prevention of LVT. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia is an independent risk factor for diabetic kidney disease (DKD) progression. Previous animal and cohort studies have reported that allopurinol administration could be of therapeutic benefit in diabetic subjects. However, there has been controversy regarding the effects of allopurinol on DKD. Objectives: The aim of our study was to investigate the efficacy of allopurinol on renal function in patients with DKD by meta-analysis of randomized controlled trials. Method: PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2020. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was the change in albuminuria and serum uric acid (UA). Two reviewers independently assessed for risk of bias and extracted data. Standardized mean difference (SMD) or weighted mean difference (WMD) was calculated with random effects models and was reported with corresponding 95% confidence intervals (CIs). Grading of Recommendations Assessment, Development, and Evaluation (GRADE) of the evidence was performed after meta-analysis. International prospective register of systematic reviews registration CRD42020219132. Results: From 642 potentially relevant citations, 3 studies were ultimately included. Our results showed evident reduction in serum UA after allopurinol intervention (WMD = −103.80, 95% CI −159.05, −48.55, I2 = 76%; p = 0.04), with a high GRADE of evidence. However, allopurinol did not significantly improve GFR (WMD = 1.07, 95% CI −1.68, 3.82, I2 = 33%; p = 0.45), with a moderate GRADE of evidence. There was no significant difference on improvement of albuminuria in patients of allopurinol and those in placebo groups (SMD = −0.26, 95% CI −1.03, 0.52, I2 = 94%; p = 0.52), with a moderate GRADE of evidence. Conclusions: The present research showed that allopurinol did not significantly improve renal function and albuminuria in patients with DKD. [ABSTRACT FROM AUTHOR]

Background: Pathophysiological overlaps exist between diabetes and primary open-angle glaucoma (POAG) and presence of diabetes increases the risk of POAG. Considering that diabetic retinopathy (DR) is an ocular complication of diabetes, one could speculate that DR as a severity measure may associate with or even predict POAG. Given that POAG is asymptomatic in early stages, an association to DR may prove clinically important and facilitate an earlier diagnosis of POAG. Objectives: The aim of the study was to investigate if DR is associated with and predictive of POAG. Method: We systematically searched 11 literature databases on May 12, 2021. We screened a total of 1,535 records and found six studies eligible for qualitative and quantitative analysis. Two independent authors reviewed the studies, extracted data, and evaluated risk of bias within individual studies. Studies were reviewed qualitatively, and meta-analyses were made based on the odds ratios (ORs) with 95% confidence intervals (CI) of the association between DR and POAG using the random-effects model. Subgroup analyses were made on the association between subtypes of DR and POAG. Results: Six studies (two longitudinal and four cross-sectional) were eligible for review with a total of 255,614 patients with diabetes, of which 20,483 patients had any degree of DR and 5,258 had POAG. All studies were based on patients with type 2 diabetes except one with both type 1 and type 2 patients. Any DR was not associated with POAG (OR 1.17; 95% CI: 0.58–2.35; p = 0.65). Further stratification revealed that neither cross-sectional (OR 1.00; 95% CI: 0.56–1.81, p = 0.99) nor longitudinal studies (OR 1.47; 95% CI: 0.57–3.78, p = 0.43) demonstrated an association between DR and POAG. Conclusions: We did not find convincing evidence of an associations between DR and prevalent or incident POAG. [ABSTRACT FROM AUTHOR]

Background: Previous studies identified myopia as a risk factor for primary open-angle glaucoma (POAG). However, recent studies have shown different results, and the definitive relationship between myopia and POAG remains controversial. Objectives: The aim of this study was to investigate the relationship between myopia and POAG. Methods: Published articles were searched from PubMed, Embase, and Scopus databases between 1970 and 2020. A pooled analysis of the odds ratios (ORs) was performed using a random-effects model. Results: Data on the association between myopia and POAG were obtained from 16 cross-sectional studies, and the pooled OR was 2.26 (95% confidence interval [CI], 1.77–2.89, p < 0.001) in random-effects model (I2 = 86%; p < 0.01). For the relationship of myopia and POAG progression, data from 7 longitudinal cohort studies were included, and the pooled OR was 0.85 (95% CI, 0.73–0.99, p = 0.042) in the random-effects model (I2 = 88%; p < 0.01). Conclusion: Our findings demonstrated that myopia may be a risk factor associated with POAG and a possible protective factor for POAG progression. It may be due to myopia with the presence of a lamina cribrosa defect, slowing down the visual field loss and also POAG progression. Further research for underlying mechanisms is still needed. [ABSTRACT FROM AUTHOR]

Introduction: Periductal mastitis (PDM) is a complex benign breast disease with a prolonged course and a high risk of recurrence after treatment. There are many available treatments for PDM, but none is widely accepted. This study aims to evaluate the various treatment failure rates (TFR) of different invasive treatment measures by looking at recurrence and persistence after treatment. In this way, it sets out to inform better clinical decisions in the treatment of PDM. Methods: We searched PubMed, Embase, and Cochrane Library databases for eligible studies about different treatment regimens provided to PDM patients that had been published before October 1, 2019. We included original studies written in English that reported the recurrence and/or persistence rates of each therapy. Outcomes were presented as pooled TFR and 95% CI for the TFR. Results: We included 27 eligible studies involving 1,066 patients in this study. We summarized 4 groups and 10 subgroups of PDM treatments, according to the published studies. Patients treated minimally invasively (group 1) were subdivided into 3 subgroups and pooled TFR were calculated as follows: incision and drainage (n = 73; TFR = 75.6%; 95% CI 27.3–100%), incision alone (n = 74; TFR = 20.1%; 95% CI 0–59.9%), and breast duct irrigation (n = 123; TFR = 19.4%; 95% CI 0–65.0%). Patients treated with a minor excision (excision of the infected tissue and related duct; group 2) were divided into 4 subgroups and pooled TFR were calculated as follows: wound packing alone (n = 127; TFR = 2.1%; 95% CI 0–5.2%), primary closure alone (n = 66; TFR = 37.1%; 95% CI 9.5–64.8%), primary closure under antibiotic treatment cover (n = 55; TFR = 4.8%; 95% CI 0–11.4%) , and additional nipple part removal (n = 232; TFR = 9.6%; 95% CI 5.8–13.4%). Patients treated with a major excision (excision of the infected tissue and the major duct; group 3) included the following 2 subgroups: patients treated with a circumareolar incision (n = 142; TFR = 7.5%; 95% CI 0.4–14.7%) and patients treated with a radial incision of the breast (n = 78; TFR = 0.6%; 95% CI 0–3.6%). Group 4 contained patients receiving different major plastic surgeries. The pooled TFR of this group (n = 86) was 3.4% (95% CI 0–7.5%). Conclusion: Breast duct irrigation, which is the most minimally invasive of all of the treatment options, seemed to yield good outcomes and may be the first-line treatment for PDM patients. Minor excision methods, except for primary closure alone, might be enough for most PDM patients. Major excision, especially with radial incision, was a highly effective salvage therapy. The major plastic surgery technique was also acceptable as an alternative treatment for patients with large lesions and concerns about breast appearance. Incision and drainage and minor excision with primary closure alone should be avoided for PDM patients. Further research is still needed to better understand the etiology and pathogenesis of PDM and explore more effective treatments for this disease. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging can be used to diagnose breast cancer (BC).Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. Objectives: This analysis aimed to compare ADC values between molecular subtypes of BC based on a large sample of patients. Method: The MEDLINE library and Scopus database were screened for the associations between ADC and molecular subtypes of BC up to April 2020. The primary end point of the systematic review was the ADC value in different BC subtypes. Overall, 28 studies were included. Results: The included studies comprised a total of 2,990 tumors. Luminal A type was diagnosed in 865 cases (28.9%), luminal B in 899 (30.1%), human epidermal growth factor receptor (Her2)-enriched in 597 (20.0%), and triple-negative in 629 (21.0%). The mean ADC values of the subtypes were as follows: luminal A: 0.99 × 10–3 mm2/s (95% CI 0.94–1.04), luminal B: 0.97 × 10–3 mm2/s (95% CI 0.89–1.05), Her2-enriched: 1.02 × 10–3 mm2/s (95% CI 0.95–1.08), and triple-negative: 0.99 × 10–3 mm2/s (95% CI 0.91–1.07). Conclusions: ADC values cannot be used to discriminate between molecular subtypes of BC. [ABSTRACT FROM AUTHOR]

Purpose: Randomized clinical trials (RCT) are inconclusive regarding the role of dietary interventions in anthropometric measurements and survival in breast cancer patients. Our aim was to conduct a systematic review and meta-analysis to assess the effects of diet on these outcomes in women treated for early-stage breast cancer. Methods: Embase, MEDLINE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched for RCT comparing dietary interventions (individualized dietary counseling, prescription of a specific diet, or others) with usual care in women that were treated for early breast cancer. Primary outcomes were overall survival (OS) and disease-free survival (DFS); secondary outcome was a change in body mass index (BMI). Results: We found 12 RCT eligible for analysis, 7 of which were included in the quantitative analysis. Two studies reported OS and DFS and 6 reported BMI data. The hazard ratio (HR) for OS and DFS was 0.91 (95% confidence interval [CI] 0.77–1.07, p = 0.25) and 0.92 (95% CI 0.79–1.08, p = 0.31) for the intervention and control groups, respectively. Intervention was associated with BMI reduction in subjects who received a specific diet instead of counseling or other types of intervention (–0.67; 95% CI –1.14 to –0.21). Conclusions: Despite increasing survival among breast cancer patients due to better oncological treatments, there is still a lack of prospective data regarding the effects of dietary interventions in this population. We found positive association between prescription of specific diets in terms of anthropometric measures; there were no differences in OS or DFS. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have shown that the relationship between hypertension (HT) and contrast-associated acute kidney injury (CA-AKI) is not clear. We apply a systematic review and meta-analysis to assess the association between HT and CA-AKI. Methods: We searched for articles on the study of risk factors for CA-AKI in the Embase, Medline, and Cochrane Database of Systematic Reviews (by March 25, 2021). Two authors independently performed quality assessment and extracted data such as the studies' clinical setting, the definition of CA-AKI, and the number of patients. The CA-AKI was defined as a serum creatinine (SCr) increase ≥25% or ≥0.5 mg/dL from baseline within 72 h. We used fixed or random models to pool adjusted OR (aOR) by STATA. Results: A total of 45 studies (2,830,338 patients) were identified, and the average incidence of CA-AKI was 6.48%. There was an increased risk of CA-AKI associated with HT (aOR: 1.378, 95% CI: 1.211–1.567, I2 = 67.9%). In CA-AKI with a SCr increase ≥50% or ≥0.3 mg/dL from baseline within 72 h, an increased risk of CA-AKI was associated with HT (aOR: 1.414, 95% CI: 1.152–1.736, I2 = 0%). In CA-AKI with a Scr increase ≥50% or ≥0.3 mg/dL from baseline within 7 days, HT increases the risk of CA-AKI (aOR: 1.317, 95% CI: 1.049–1.654, I2 = 51.5%). Conclusion: Our meta-analysis confirmed that HT is an independent risk factor for CA-AKI and can be used to identify risk stratification. Physicians should pay more attention toward prevention and treatment of patients with HT in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Discoidin domain receptors (DDRs) belong to the receptor tyrosine kinases family and are activated by different types of collagens, which play roles in various physiological processes. An abnormal expression of DDRs is reported in different types of cancers. Despite many reports about the association and roles of high DDR expression levels in cancers, the prognostic values of DDRs are still unclear. This meta-analysis was performed to evaluate the prognostic effect of DDRs in different tissue cancers. Method: A literature search was performed in several related databases to find eligible English articles. Based on our research, 20 appropriate studies with 2,602 patients were selected till October 5, 2020. The pooled hazard ratio (HR) with a corresponding 95% confidence interval (CI) was computed to evaluate the strength of correlation between DDRs and survival of cancer patients. Result: Pooling results showed that a high DDR expression was significantly associated with poorer overall survival (OS) (HR = 1.304, 95% CI 1.007–1.69, p = 0.04). Subgroup analysis based on cancer type revealed a significant link between a high DDR expression level and poor OS both in gastrointestinal (pooled HR = 1.78, 95% CI 1.214–2.624, p = 0.003) and urological cancers (pooled HR = 1.42, 95% CI 1.062–1.82, p = 0.018). Conclusion: Our meta-analysis results suggest that high DDRs expression has the potential to be used as a biomarker of poor prognosis in cancers. [ABSTRACT FROM AUTHOR]

Objective: Transcription factor SOX2 (sex-determining region Y-box 2) has a crucial role in the maintenance of the stem cell state. However, current evidence regarding the role of SOX2 in breast cancer is conflicting. We conducted this meta-analysis to clarify the association of SOX2 expression with clinical and molecular features and its prognostic effect on breast cancer. Methods: All relevant articles were searched using electronic databases. The pooled odds ratios (ORs) or hazard ratios (HRs: multivariate Cox survival analysis) with their 95% confidence intervals (CIs) were calculated. Results: A final total of 18 studies containing 3,080 patients with breast cancer were included. SOX2 protein expression was not related to age, menopausal status, lymph node metastasis, lymphovascular invasion, molecular estrogen receptor status, progesterone receptor status, triple-negative status, and the overall survival in breast cancer, but was closely associated with advanced tumor grade (grade 3 vs. grade 1–2: OR = 2.74, 95% CI = 1.85–4.06, p < 0.001), clinical stage (stage 3–4 vs. stage 0–2: OR = 2.46, 95% CI = 1.37–4.40, p = 0.002), pT stage (T stage 2–4 vs. T stage 1: OR = 1.52, 95% CI = 1.07–2.17, p = 0.019), molecular human epidermal growth factor receptor 2 (HER2) status (positive vs. negative: OR = 1.61, 95% CI = 1.21–2.14, p = 0.001), epidermal growth factor receptor (EGFR) status (positive vs. negative: OR = 2.21, 95% CI = 1.13–4.33, p = 0.021), and worse disease-free survival (DFS) (HR = 2.66, 95% CI = 1.20–5.91, p = 0.016) of breast cancer. Conclusions: SOX2 expression is correlated with breast cancer progression, HER2 status, and EGFR status, and may be an independent prognostic marker for predicting poor DFS. [ABSTRACT FROM AUTHOR]

Background: A meta-analysis was performed to evaluate the association of chronic kidney disease (CKD) and acute kidney injury (AKI) with the clinical prognosis of patients with coronavirus disease 2019 (COVID-19). Methods: The PubMed, EMBASE, Cochrane Library, medRxiv, Social Science Research Network, and Research Square databases (from December 1, 2019 to May 15, 2020) were searched to identify studies that reported the associations of CKD/AKI and disease severity/mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and meta-regression was performed. Results: In total, 42 studies enrolling 8,932 participants were included in this meta-analysis. The quality of most included studies was moderate to high. Compared with patients without previously diagnosed CKD, those with CKD had a significantly increased risk of progressing to a severe condition (OR 2.31, 95% CI 1.64–3.24) or death (OR 5.11, 95% CI 3.36–7.77). Similarly, compared with patients without AKI, those with AKI had a significantly increased risk of progressing to a severe condition (OR 11.88, 95% CI 9.29–15.19) or death (OR 30.46, 95% CI 18.33–50.59). Compared with patients with previously diagnosed CKD, those with AKI were more likely to progress to a severe condition (pgroup < 0.001, I2 = 98.3%) and even to death (pgroup < 0.001, I2 = 96.5%). Age had a significant impact on the association between CKD and disease severity (p = 0.001) but had no impact on the associations between AKI and disease severity (p = 0.80), between CKD and mortality (p = 0.51), or between AKI and mortality (p = 0.86). Four important complications (cardiac injury, shock, acute respiratory distress syndrome, and liver injury) did not significantly affect the associations between CKD/AKI and disease severity/mortality, indicating that CKD/AKI may be independent clinical prognostic indicators for patients with COVID-19. Conclusions: In COVID-19 patients, CKD/AKI was associated with worse outcomes compared with those without CKD/AKI. AKI was associated with higher risks of severity and mortality than CKD. [ABSTRACT FROM AUTHOR]

Background: The metabolic syndrome (MetS) represents a clustering of risk factors for cardiovascular diseases that includes abdominal obesity, hypertension, dyslipidemia, and insulin resistance. Objectives: The objective of this study was to reassess the parent-offspring association of MetS since the available findings are still controversial. Methods: The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All studies comparing MetS status between the offspring of parents with MetS and offspring of parents without MetS were included in the analysis. Results: A total of 9 studies met the inclusion criteria and they were analyzed. Offspring of at least 1 parent with MetS had a higher risk of MetS (OR 3.88, 95% CI 2.58–5.83, p < 0.001). Sons and daughters of fathers with MetS both had a higher risk of MetS (OR 2.31, 95% CI 1.70–3.12, p < 0.001, and OR 1.73, 95% CI 1.37–2.18, p < 0.001, respectively). Sons and daughters of mothers with MetS both had a higher risk of MetS (OR 1.95, 95% CI 1.37–2.76, p = 0.0002, and OR 1.91, 95% CI 1.54–2.35, p < 0.001, respectively). Conclusion: This meta-analysis showed that there is a higher risk of MetS in the offspring of parents with MetS. However, there was no differential association of MetS according to gender and/or age of the offspring. [ABSTRACT FROM AUTHOR]

Introduction: BK virus (BKV) infection in renal transplant (RT) recipients can cause hemorrhagic cystitis, transient renal dysfunction, and BKV nephropathy (BKVN). The prevalence and significance of BKV in RT recipients remain to be clarified in the Iranian population. The purpose of this review is to summarize the overall prevalence of BKV infection in RT recipients from previously published studies in Iran. Methods: We systematically reviewed articles through a comprehensive search of the main electronic and Persian national databases up to November 2019. Results: The overall pooled prevalence of BKV infection among the Iranian population was 23% (95% CI; 15–33%). Comparing these studies revealed that the prevalence of BKV in plasma samples ranges from 3 to 40%, in renal biopsies 1–13%, and in urine samples 10–49%. Due to substantial heterogeneity among reported studies (I2 = 93%, p < 0.01), random-effect meta-analysis was performed. BKV infection rate was slightly higher in women than men (16%, p = 0.04 vs. 14%, p < 0.01, respectively). The majority of the studies employed real-time PCR (24%, I2 = 93, p < 0.01) and analyzed plasma samples alone or in combination with other types of specimens. BKV prevalence from 5 cities among the Iranian population showed a higher prevalence rate in Guilan. Conclusion: Our analysis provides a preliminary estimate of the epidemiology of BKV infection in RT recipients in Iran. These results arouse a need for more epidemiological studies of BKV infection in different unanalyzed regions in Iran. Early detection of BKV in RT recipients helps timely nephropathy diagnosis and prevents graft loss. [ABSTRACT FROM AUTHOR]

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign breast disease without any definitive therapeutic strategy. It is controversial whether to use conservative or surgical treatment of IGM and high-level evidence-based medicine data are lacking. The purpose of this study was to systemically evaluate the clinical effectiveness of the conservative versus surgical treatment for IGM. Methods: In this meta-analysis, we searched PubMed, EMbase, ScienceDirect, and Web of Science for comparative studies about the conservative versus surgical treatment of IGM. Two researchers independently identified reports and extracted data. We used Stata 11 for data analysis. A meta-analysis was performed to investigate the differences in the recurrence rate of conservative and surgical treatment using a random effects model. Results: A total of 10 studies involving 1,101 patients were included. The results demonstrated that there was no significant difference in the recurrence rate among patients who were treated by nonsurgical therapy and surgical treatment. No publication bias was detected. Conclusion: This meta-analysis demonstrates that both the conservative and surgical treatment approaches have appropriate efficacy in IGM treatment and relapse. Further randomized controlled trials with longer follow-up periods are required to confirm the advantages of each approach. [ABSTRACT FROM AUTHOR]

Background/Aims: This meta-analysis evaluated the effects of remote ischemic preconditioning (RIPC) on the risk of contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention/coronary angiography (PCI/CA). Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) that assessed the effect of RIPC on CIN in patients undergoing PCI/CA. The main outcomes of interest were the incidence of CIN 48–72 h after CA, the levels of serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and estimated glomerular filtration rate (eGFR), mortality, and requirement of hemodialysis and rehospitalization. The analysis was conducted using the random-effect model due to the expected heterogeneity among different studies. Results: In total, 16 trials covering 2,048 patients were identified. By assessing the methodological quality of the included studies through the Coch-rane risk of bias, we found that of the 16 RCTs, 3 had a low risk of bias, 6 a high, and 7 an unclear risk. The application of RIPC decreased the incidence of CIN (relative risk, RR, 0.50, 95% confidence interval, CI, 0.39–0.65; p < 0.001). Subgroup analyses showed that RIPC decreased the incidence of CIN in patients with eGFR <60 mL/min/1.73 m2 (RR 0.53, 95% CI 0.38–0.75; p < 0.001) but not in patients with eGRF ≥60 mL/min/1.73 m2 (RR 0.82, 95% CI 0.35–1.94; p = 0.66) at baseline. Furthermore, the increase in serum creatinine was significantly lower in patients with RIPC compared to control patients (standardized mean difference –1.41, 95% CI –2.46 to –0.35; p = 0.009). Conclusions: Based on 16 RCTs, this meta-analysis shows that RIPC can reduce the risk of CIN in patients with moderate renal impairment undergoing PCI/CA. However, this needs to be confirmed by further high-quality evidence. [ABSTRACT FROM AUTHOR]

Background: The metabolic syndrome (MetS) has been associated with the pathogenesis and prognosis of various malignant tumors. In this systematic review and meta-analysis, we explored the relationship between MetS and breast cancer (BC). Methods: Relevant studies were systematically searched on Ovid MEDLINE, Embase, Cochrane database, and PubMed up to September 16, 2019, using "breast cancer" and "metabolic syndrome" as keywords. Eligible studies with clear definition of MetS, available data, and relationships between MetS and BC were evaluated using a risk ratio (RR) and its 95% confidence interval (CI). Results: Twenty-five studies, including 13 cohort studies and 12 case-control studies, met the inclusion criteria, which assessed a total of 392,583 female participants and 19,628 BC patients. The results revealed a statistically significant increase by 52% of the risk of BC in adult females with MetS (RR = 1.49, 95% CI = 1.31–1.70, p < 0.0001). Postmenopausal MetS patients may have a twofold risk to suffer BC (RR = 2.01, 95% CI = 1.55–2.60, p < 0.001). The risk of BC increased markedly with the number of MetS components: RR = 1.00 for 1 component (p = 0.976), RR = 1.40 for 2 components (p = 0.121), and RR = 1.98 for >3 components (p < 0.001). The risk factors associated with BC were obesity, hypertension, and diabetes (RR = 1.33, 1.19, and 1.30 respectively, all p < 0.001). Conclusions: Our study demonstrated that MetS is highly related with BC. In postmenopausal patients with ≥2 MetS components or a combination of obesity, hypertension, and diabetes, routine BC screening could help to detect BC at an early stage. [ABSTRACT FROM AUTHOR]

Cancer treatments may affect the sleep quality and even future quality of life of women with breast cancer. A meta-analysis was performed to understand the changes in the sleep quality of women with breast cancer during their treatment period. In a systematic literature review in compliance with the PRISMA guidelines, we searched for articles published between 2000 and 2018 in databases. A total of 12 study articles were included. The standardized mean differences of the pooling effect size of sleep quality between the period before treatment and 1–8 weeks, 9–16 weeks, 17–24 weeks, and 25–56 weeks after the commencement of treatment were –0.020, –0.162, 0.075, and 0.216, respectively. Although the differences were not statistically significant, in view of the heterogeneity among the studies, we conducted further analysis using a linear mixed effect model. The overall results indicated poorer sleep quality as time passed from the start of the first treatment (p = 0.014). The results of this study revealed that patients experienced better sleep quality in the initial months after the beginning of treatment; however, their sleep quality became poorer between 4 months to approximately 1 year after the beginning of treatment, compared with the sleep quality before treatment, and continued to decline rather than improve during the follow-up period. [ABSTRACT FROM AUTHOR]

Objective: An association of Epstein-Barr virus (EBV) infection with breast carcinoma (BC) risk has so far been disputed in the literature. Therefore, we performed a meta-analysis to clarify this relationship.Materials and Methods: An electronic database search for eligible case-control studies was performed using PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang Data until May 17, 2018. The pooled OR and 95% CI were used to estimate the relationship between EBV infection and BC risk using a fixed or random-effects model depending on heterogeneity. Subgroup analysis and meta-regression were used to explore the heterogeneity. Publication bias was assessed using Egger's and Harbord's tests.Results: A total of 16 studies with 1,279 patients and 814 controls were reviewed based on our inclusion and exclusion criteria. Compared with the control group, EBV infection had a significant association with BC risk (OR 4.75, 95% CI 2.53-8.92, p < 0.01) with significant heterogeneity observed (I2 = 65.3%). The subgroup analysis revealed that region and tissue type might explain potential sources of heterogeneity. The sensitivity analyses yielded stable results. No significant publication bias was observed.Conclusion: The current results suggest that EBV infection is significantly associated with increased risk of BC. [ABSTRACT FROM AUTHOR]

Objective: Granulomatous lobular mastitis (GLM) is infrequently diagnosed. This study aimed to evaluate the efficacy and safety of managements for GLM in the nonlactation period. Methods: Publications were retrieved from PubMed, EMBASE, and the Cochrane library on September 10, 2018. We pooled and compared the outcome parameters and complete remission (CR) rates between different treatments using a meta-analysis. Results: Twenty-one publications including 970 patients treated with surgical excision, steroids, abscess drainage, antibiotics, and observation were included. Surgery significantly improved CR rate compared with steroids (p = 0.0003). There was no difference in the CR rate in patients treated with surgery alone or combined with steroids (p = 0.28). Surgery showed borderline significant efficacy in the CR rate compared with antibiotics (p = 0.06) and abscess drainage (p = 0.06). No difference was observed in effectiveness between observation and surgical management in patients diagnosed with early GLM and mild symptoms. Conclusions: Although surgery was the ideal management for GLM, steroids and antibiotics might be ideal managements for GLM patients who are worried about surgical scars. Observation was an impressive alternative for patients with early GLM. [ABSTRACT FROM AUTHOR]

Objective: To assess the long-term effects including all-cause mortality, cardiovascular mortality, and fracture incidence, of cinacalcet on secondary hyperparathyroidism (SHPT) in patients on dialysis. Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception to October 2018. Randomized controlled trials (RCTs) and cohort design prospective observational studies assessing cinacalcet for the treatment of SHPT in dialysis patients were included. Data extraction was independently completed by 2 authors who determined the methodological quality of the studies and extracted data in duplicate. Study-specific risk estimates were tested by using a fixed effects model. Results: A total of 14 articles with 38,219 participants were included, of which 10 RCTs with 7,471 participants and 4 prospective observational studies with 30,748 participants fulfilled the eligibility criteria. Compared with no cinacalcet, cinacalcet administration reduced all-cause mortality (relative risk [RR] 0.91, 95% CI 0.89–0.94, p < 0.001) and cardiovascular mortality (RR 0.92, 95% CI 0.89–0.95, p < 0.001), but it did not significantly reduce the incidence of fractures (RR 0.93, 95% CI 0.87–1.00, p = 0.05). Conclusions: The results of this meta-analysis indicated that the treatment of SHPT with cinacalcet may in fact reduce all-cause mortality and cardiovascular mortality among patients receiving maintenance dialysis. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this research was to conduct a meta-analysis of the role that physical activity (PA) plays in influencing the critical proinflammatory cytokine levels associated with overweight/obese children and adolescents to explore the effectiveness of exercise intervention within this population. Methods: With searches of the PubMed, EMBASE, and CENTRAL databases, we updated our meta-analysis up to November 2018. The randomized controlled trials (RCT) evaluated the ability of exercise training to increase the following factors in children and/or adolescents classified as obese or overweight: tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C-reactive protein (CRP). Results: Eleven RCT comprising 623 children and/or adolescents who were obese or overweight (i.e., 393 with PA and 230 controls) were suitable for use in this study. The meta-analysis showed that PA in general was associated with a significant reduction of CRP levels (mean difference = –0.45 mg/L, p = 0.02) in overweight/obese children and adolescents. Based on 115 overweight and obese youths, this study suggests that PA does not significantly mitigate IL-6 levels (mean difference = –0.39 pg/mL, p = 0.08), although there was a trend towards a reduction. Additionally, no close connection was observed between PA and TNF-α levels at 0.04 pg/mL (p = 0.78). Moreover, meta-regression analysis revealed a statistical association between CPR levels and changes in BMI or changes in adiponectin; likewise, IL-6 levels dramatically impacted the effect of exercise on changes in adiponectin. Conclusions: PA was associated with significantly reduced CRP levels, whereas there was no significant association with IL-6 or TNF-α in overweight/obese children or adolescents; however, there was a trend towards a reduction of IL-6. [ABSTRACT FROM AUTHOR]

Objective: Breast conservation therapy (BCT) for female patients with multifocal or multicentric (MF/MC) breast cancer remains controversial. The purpose of the present meta-analysis was to explore whether BCT was feasible for female patients with MF/MC breast cancer and to compare the results of treatment with those of female patients with unifocal breast cancer who underwent BCT and female patients with MF/MC breast cancer who underwent mastectomy. Methods: Online databases, including PubMed and Embase, were independently searched from inception to January 2018 and reviewed by two authors. The present meta-analysis compared local relapse (LR) of BCT versus mastectomy for patients with MF/MC breast cancer and LR of patients with unifocal breast cancer versus patients with MF/MC breast cancer who underwent BCT. Ten studies comprising 19,272 patients were included. Results: The cumulative incidence of LR was 5.6% (65/1,163) for MF/MC disease treated with BCT, 4.2% (750/17,656) for unifocal disease treated with BCT, and 2.0% (9/453) for MF/MC disease treated with mastectomy. Thus, the cumulative incidence of LR for MF/MC patients treated with BCT was significantly higher than for mastectomy (p < 0.001). However, the forest plot analysis showed no significant differences in LR between BCT and mastectomy procedures (OR = 1.22, 95% CI = 0.49–3.00, p = 0.67, I2 = 0%). Compared with the unifocal group treated with BCT, BCT for MF/MC breast cancer showed a significant difference in LR (OR = 2.25, 95% CI = 1.48–3.42, p = 0.0001, I2 = 0%). Conclusion: The LR of BCT for patients with MF/MC breast cancer was higher than that of BCT for patients with unifocal breast cancer. However, no significant difference was found in the incidence of LR between the BCT group and the mastectomy group in patients with MF/MC breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To conduct a meta-analysis of evidence from randomized controlled trails (RCTs) of different doses of intravenous immunoglobulin (IVIG) in children with severe hand, foot and mouth disease (HFMD) to provide the scientific basis for clinical practice.Methods: A search of PubMed-Medline, CNKI, Wanfang, and VIP database (until June 30, 2017) was performed and Software RevMan5.3 was used to evaluate the effect of different doses of IVIG on HFMD in RCTs. We used random-effects models (or fixed-effects models) and generic inverse variance methods to process quantitative data, followed by a leave-one-out method for sensitivity analysis.Results: From a total of 420 entries identified via searches, 8 RCTs involving 1,450 patients were included in the final analysis. The results of the meta-analysis showed that compared with conventional therapy alone, conventional therapy combined with IVIG had shorter fever clearance time, shorter rash regression time, and shorter clinical cure time. Subgroup analyses showed that the high-dose group (1 g/kg/day) had shorter fever clearance time (p < 0.05), shorter rash regression (p< 0.05), shorter remission time of neurological symptoms (p < 0.05), but longer clinical cure time (p > 0.05).Conclusion: The high-dose group has a better prognosis; however, the advantages and disadvantages should be carefully considered when deciding the doses in the treatment of severe HFMD. [ABSTRACT FROM AUTHOR]

Background/Aims: Vitamin D (VD) is widely recognized as renal protective. However, whether VD supplementation provides benefit to patients with diabetic nephropathy (DN) remains controversial. Here, we performed a meta-analysis to systematically evaluate the impact of VD supplementation on indexes of renal function, inflammation and glycemic control in DN patients, and to explore the potential renal protective mechanism of VD. Methods: We searched Pubmed, Embase, Cochrane Library, and three major Chinese biomedical databases (CNKI, WANGFANG and VIP) for randomized controlled trials (RCTs) examining the effects of VD or its analogs in DN patients, published between September 2007 and July 2018. Quality assessment and data extraction were performed independently by two authors, according to the Cochrane systematic review methods. Meta-analysis based on the extracted results were performed via Revman 5.2 software. Results: We included 20 RCTs representing 1,464 patients with DN in this meta-analysis. VD supplementation significantly reduced 24-hour urine protein [MD = -0.26; 95% CI (-0.34, -0.17); P < 0.00001; I2 = 95%], UAER [MD = -67.36; 95% CI (-91.96, -42.76); P < 0.00001; I2 = 97%], hs-CRP [MD = -0.69; 95% CI (-0.86,-0.53); P < 0.00001; I2 = 0%], TNF-α [MD = -56.79; 95% CI (-77.05, -36.52); P < 0.00001; I2 = 89%] and IL-6 [MD = -0.73; 95% CI(-1.03, -0.44); P < 0.00001; I2 = 0%]. However, VD supplementation failed to decrease SCr [MD = -0.83; 95% CI (-3.67,2.02); P = 0.57; I2 = 0%] or increase eGFR [MD = 2.13; 95% CI (-2.06, 6.32); P = 0.32; I2 = 0%]. In addition, VD supplementation showed no impact on indexes of glycemic control, such as HbA1c [MD = 0.01; 95% CI (-0.09, 0.11); P = 0.84; I2 = 0%] and FBG [MD = -0.05; 95% CI (-0.29, 0.20); P = 0.70; I2 = 0%]. Analysis of 24-hour urine protein, SCr, eGFR, hs-CRP or HbA1c revealed no difference between subgroups based on the type of VD supplementation, including calcitriol, alfacalcidol and vitamin D3, and the dose or duration of calcitriol usage. Conclusion: In patients with DN, VD supplementation provides beneficial effects on 24-hour urine protein and inflammation indexes, but not on SCr, eGFR or glycemic control indexes. More RCTs that comprehensively evaluate the impact of VD supplementation on indexes of renal function, inflammation and glycemic control in DN atients are required in order to reach conclusive results. [ABSTRACT FROM AUTHOR]

Background/Aims: Serum apolipoprotein A1 (apoA1) has been reported to be abnormally expressed in several malignancies. However, the prognostic role of apoA1 in solid tumors is still controversial. We conducted this meta-analysis to obtain a more accurate evaluation of prognostic significance of apoA1 in Chinese patients with solid tumors. Methods: A comprehensive literature search of electronic databases was carried out up to August 2018. We included studies investigating the association between pretreatment serum apoA1 level and clinicopathological features, including survival outcomes, in solid tumors. Hazard ratios (HRs) and odds ratio (ORs) with 95% confidence intervals (CIs) were applied as effect size estimates. Results: A total of 13 studies and 8052 patients were included in our meta-analysis. Elevated level of pretreatment serum apoA1 was markedly associated with an improved OS (pooled HR = 0.608, 95% CI = 0.557 - 0.665, P < 0.001). The statistical significances were observed in all cancer types, including digestive system malignancies (pooled HR = 0.633; 95% CI = 0.550-0.727; P < 0.001), urinary system cancers (pooled HR = 0.471; 95% CI = 0.352-0.630; P < 0.001), nasopharyngeal cancer (pooled HR = 0.642; 95% CI = 0.538-0.766; P < 0.001) and nonsmall cell lung cancer (pooled HR = 0.526; 95% CI = 0.329-0.841; P = 0.007), but not in breast cancer (pooled HR = 0.573; 95% CI = 0.266-1.246; P = 0.155). Meanwhile, cancer patients with a low level of serum apoA1 suffered an unfavorable DFS (pooled HR = 0.714, 95% CI = 0.603 - 0.845, P < 0.001). Moreover, abnormal serum apoA1 was significantly correlated to tumor size (pooled OR = 0.640, 95% CI = 0.475 - 0.863, P = 0.003), tumor differentiation (pooled HR = 0.724, 95% CI = 0.565 - 0.929, P = 0.011), and tumor stage (pooled HR = 0.493, 95% CI = 0.384 - 0.633, P < 0.001). Conclusion: Elevated level of pretreatment serum apoA1 was significantly associated with longer survival in patients with solid tumors. Pretreatment serum apoA1 could serve as a novel positive factor for malignant patient prognosis in Chinese population. [ABSTRACT FROM AUTHOR]

Background/Aims: Serum apolipoprotein A1 (apoA1) has been reported to be abnormally expressed in several malignancies. However, the prognostic role of apoA1 in solid tumors is still controversial. We conducted this meta-analysis to obtain a more accurate evaluation of prognostic significance of apoA1 in Chinese patients with solid tumors.Methods: A comprehensive literature search of electronic databases was carried out up to August 2018. We included studies investigating the association between pretreatment serum apoA1 level and clinicopathological features, including survival outcomes, in solid tumors. Hazard ratios (HRs) and odds ratio (ORs) with 95% confidence intervals (CIs) were applied as effect size estimates. Results: A total of 13 studies and 8052 patients were included in our meta-analysis. Elevated level of pretreatment serum apoA1 was markedly associated with an improved OS (pooled HR = 0.608, 95% CI = 0.557 – 0.665, P < 0.001). The statistical significances were observed in all cancer types, including digestive system malignancies (pooled HR = 0.633; 95% CI = 0.550–0.727; P < 0.001), urinary system cancers (pooled HR = 0.471; 95% CI = 0.352–0.630; P < 0.001), nasopharyngeal cancer (pooled HR = 0.642; 95% CI = 0.538–0.766; P < 0.001) and non-small cell lung cancer (pooled HR = 0.526; 95% CI = 0.329–0.841; P = 0.007), but not in breast cancer (pooled HR = 0.573; 95% CI = 0.266–1.246; P = 0.155). Meanwhile, cancer patients with a low level of serum apoA1 suffered an unfavorable DFS (pooled HR = 0.714, 95% CI = 0.603 – 0.845, P < 0.001). Moreover, abnormal serum apoA1 was significantly correlated to tumor size (pooled OR = 0.640, 95% CI = 0.475 – 0.863, P = 0.003), tumor differentiation (pooled HR = 0.724, 95% CI = 0.565 – 0.929, P = 0.011), and tumor stage (pooled HR = 0.493, 95% CI = 0.384 – 0.633, P < 0.001). Conclusion: Elevated level of pretreatment serum apoA1 was significantly associated with longer survival in patients with solid tumors. Pretreatment serum apoA1 could serve as a novel positive factor for malignant patient prognosis in Chinese population. [ABSTRACT FROM AUTHOR]

Background/Aims: The purpose of this study was to probe the clinico-pathological significance and the underlying mechanism of miR-30d-5p expression in non-small cell lung cancer (NSCLC). Methods: We initially examined the level of miR-30d-5p expression in NSCLC and non-cancer tissues using RT-qPCR. Then, a series of validation analyses including a meta-analysis of data from microarray chips in Gene Expression Omnibus (GEO), data mining of the cancer genome atlas (TCGA) and an integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies were performed to examine the clinico-pathological value of miR-30d-5p expression in NSCLC. In vitro experiments were further conducted to investigate the impact of miR-30d-5p on NSCLC cell growth. The molecular mechanism by which miR-30d-5p regulates the pathogenesis of NSCLC was probed through a bioinformatics analysis of its target genes. Moreover, dual luciferase reporter assay was conducted to verify the targeting regulatory relationship between miR-30d-5p and CCNE2. Results: Based on results from RT-qPCR, GEO meta-analysis, TCGA data mining and the integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies, miR- 30d-5p expression was decreased in NSCLC tissues, and patients with NSCLC who presented with lower miR-30d-5p expression tended to display an advanced clinical progression. [ABSTRACT FROM AUTHOR]

Background/Aims: Several recent studies have demonstrated that Stathmin 1expression may be closely associated with prognosis in patients with various types of cancers. In the present study, we conducted a meta-analysis of all available studies in the English literature to assess the prognostic value of Stathmin 1expression in patients with solid cancers. Methods: The online databases PubMed, Embase, and Web of Science were searched for literature regarding Stathmin 1 and its association with patient outcomes associated with solid cancers. Results: A total of 23 articles including 26 studies that contained 5 335 patients were retrieved and analyzed. Our results indicated that high Stathmin 1 expression yielded a worse overall survival (OS) (hazard ratio [HR] = 2.17, 95% confidence interval [CI]: 1.81-2.60), disease-free survival (DFS) (HR = 2.46, 95% CI: 2.00-3.02), disease-specific survival (DSS) (HR = 1.98, 95% CI: 1.58- 2.47) and progression-free survival (PFS)/recurrence-free survival (RFS) (HR = 2.09, 95% CI: 1.51-2.89). Furthermore, the association of high Stathmin 1 expression with poor survival was significant even for sub-group analyses of different tumor types, ethnicities, methods used to calculate HRs, detected methods, and analysis types. Conclusion: In summary, this meta- analysis determined that high Stathmin 1 expression is associated with poor prognosis in patients with solid cancers and expression of this protein could be a clinically useful prognostic biomarker. [ABSTRACT FROM AUTHOR]

Background/Aims: Acute myeloid leukemia (AML) is a relapsed and refractory hematological malignancy with a lower morbidity but higher mortality. In addition to hematopoietic stem cell transplantation, chemotherapy is used as the front-line treatment. However, the diversity of available agents and the inconsistency of outcomes of relevant trials render treatment decision-making tough. Network meta-analysis (NMA) is an efficient statistical framework that makes a comprehensive comparison and provides a valuable clinical reference. Methods: All the potential trials were retrieved from the medical database and screened according to the inclusion and exclusion criteria. The main characteristics of each trial as well as the primary outcomes, including complete remission (CR), overall response rate (ORR), overall survival (OS), and event-free survival (EFS), were extracted. In addition, the network graph was plotted to illustrate the connections among the trials involved. Comparison results in the network were exhibited in a forest plot. Furthermore, the surface under the cumulative ranking curve (SUCRA) was introduced to rank the treatments for each endpoint. Results: A total of 11 trials were selected from 1,625 identifications. No significant difference in the common treatment was observed for the endpoints CR and ORR. In terms of OS, CPX-351 (HR: 0.77, 95% CrI: 0.63, 0.94) and HiDAC plus MK-8776 (HR: 0.80, 95% CrI: 0.68, 0.93) showed a superiority over the common salvage regimen in the short term, while HiDAC plus MK-8776 (HR: 0.80, 95% CrI: 0.70, 0.93) and Ara-C plus vosaroxin (HR: 0.86, 95% CrI: 0.74, 0.99) outperformed the common salvage regimen for the 3-year OS. In addition, clofarabine plus Ara-C (HR: 0.61, 95% CrI: 0.53, 0.69) and CPX-351 (HR: 0.71, 95% CrI: 0.60, 0.83) were confirmed to be efficacious in enhancing the rate of EFS. Conclusion: Referring to the network outcome and SUCRA value, clofarabine plus Ara-C (CR: 79.05%, ORR: 80.02%) and Ara-C plus vosaroxin (CR: 75.42%, ORR: 73.43%) were potentially the top two choices for both CR and ORR. CPX-351 (1-year OS: 91.36%), HiDAC plus MK-8776 (3-year OS: 94.23%) and clofarabine plus Ara-C (1-year EFS: 97.34%) yielded the highest probabilities to be the optimal choices for 1-year OS, 3-year OS and 1-year EFS, respectively. [ABSTRACT FROM AUTHOR]

Background/Aims: Previous studies on the effect of metformin therapy on survival of pancreatic cancer patients obtained inconsistent findings. To reevaluate the prognostic value of metformin adjuvant treatment, a meta-analysis was carried out. Methods: Relevant articles addressing the association between metformin use and pancreatic cancer survival were electronically searched to identify eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Results: Totally, seventeen studies involving 36791 participants were included. Overall, metformin use was found to be significantly associated with a favorable OS (HR=0.88, 95% CI=0.80-0.97). Subgroup analyses by ethnicity showed a significantly reduced risk of death for metformin users compared with non-users in Asians (HR=0.74, 95% CI=0.58-0.94) but nonsignificant in Caucasians. When stratified by clinical stage, a remarkable reduction of mortality risk in patients at stage I-II treated with metformin (HR=0.76, 95% CI=0.68-0.86) was found as well as the group at stage I-IV (HR=0.88, 95% CI=0.79-0.99), but not in patients at stage III-IV. In the stratification analyses based on treatment strategy, metformin therapy was found to be associated with a better clinical outcome in patients receiving surgery or comprehensive therapy (HR=0.73, 95% CI=0.62-0.87; HR=0.88, 95% CI=0.79-0.97) but not chemotherapy. However, the overall analysis failed to show a significant association between metformin use and DFS (HR=1.54, 95% CI=0.94 -2.50) with only 2 studies enrolled. Conclusion: The current study has evidenced a significant association of metformin adjuvant treatment with the survival benefit for pancreatic cancer patients, suggesting a potentially available option for the treatment. Further investigation is needed. [ABSTRACT FROM AUTHOR]

Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Recent studies have reported the importance of tubulin alpha 4b (TUBA4B), a long non-coding RNA, in the development of several cancers; however, studies on its clinical significance are rare. In the present meta-analysis, we investigated whether TUBA4B can be used as a prognostic biomarker in human cancers. Methods: A comprehensive search was performed in PubMed, Embase, Web of Science, and the Gene Expression Omnibus databases. Hazard ratios from individual studies were calculated and pooled using a random-effects or fix-effects model. The pooled hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the value of TUBA4B. The expression of TUBA4B was evaluated in lung cancer tissue arrays by fluorescence in situ hybridization assay. Additionally, a sensitivity analysis and Begg’s test were conducted. Results: We found that TUBA4B was significantly correlated with overall survival (OS) (HR = 1.33, 95% CI: 1.16–1.52, P=0.000), disease-free survival (DFS; HR = 1.25, 95% CI: 1.06–1.48, P=0.007), and recurrence-free survival (RFS; HR = 1.42, 95% CI: 1.26–1.60, P=0.000). In addition, TUBA4B was a risk factor for lung cancer (HR = 1.24, 95% CI: 1.03–1.49, P=0.021), colon cancer (HR = 1.67, 95% CI: 1.02–2.74, P=0.042), breast cancer (HR = 1.52, 95% CI: 1.10–2.12, P=0.012), and ovarian cancer (HR = 1.67, 95% CI: 1.18–2.36, P=0.004). Moreover, LncRNA-TUBA4B was significantly lower expression in tumor tissues than normal lung tissues (P< 0.001). The expression of lncRNA-TUBA4B was decreased with the progression of lung cancer stage. A subgroup meta-analysis based on data resource, sample size, region, patient numbers, and tumor type was further performed. Our studies revealed that tumor tissues with low levels of TUBA4B was significantly associated with short OS, DFS, and RFS in cancer patients. Conclusion: The present findings suggest that TUBA4B can be a novel biomarker for the prognosis of various cancers. [ABSTRACT FROM AUTHOR]

Background/Aims: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme catalyzing the initial and rate-limiting steps in the kynurenine pathway, which converts tryptophan into kynurenine. Upregulation of IDO1 decreases tryptophan levels and increases the accumulation of kynurenine and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence has shown that IDO1 is highly expressed in various cancer types and associated with poor prognosis of cancer patients. However, the results were inconsistent. Methods: We searched the Web of Science, PubMed, Embase and Cochrane library databases to identify studies evaluating the prognostic value of IDO1 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using fixed-effects/random-effects models. Results: This systematic review and meta-analysis included 2706 patients from 24 articles. The results indicated a shorter overall survival in patients with high expression of IDO1 (hazard ratio [HR] = 2.03, 95% confidence interval [CI]: 1.56-2.63). Furthermore, disease-free survival was worse in patients with high expression of IDO1 (HR = 2.47, 95% CI: 1.46-4.20). Additionally, the pooled odds ratios (ORs) showed that increased IDO1 was significantly associated with tumor differentiation (OR = 1.81, 95% CI: 1.05-3.12), distant metastasis (OR = 1.45, 95% CI: 1.02-2.06), and poor clinical stage (OR = 1.89, 95% CI: 1.13-3.17). However, no significant correlation was observed of increased IDO1 expression with age, sex, lymph node metastasis, and tumor size. Conclusion: High expression of IDO1 is associated with poor clinical outcomes. IDO1 could serve as a biomarker of prognosis and a potential predictive factor of clinicopathology in various cancers. Further studies should be performed to verify the clinical utility of IDO1 in human solid tumors. [ABSTRACT FROM AUTHOR]