RBM3 is associated with acute lung injury in septic mice and patients via the NF-κB/NLRP3 pathway.

Sepsis refers to host response disorders caused by infection, leading to life-threatening organ dysfunction. RNA-binding motif protein 3 (RBM3) is an important cold-shock protein that is upregulated in response to mild hypothermia or hypoxia. In this study, we aimed to investigate whether RBM3 is involved in sepsis-associated acute lung injury (ALI). Intraperitoneal injection of LPS (10 mg/kg) was performed in wild type (WT) and RBM3 knockout (KO, RBM3-/-) mice to establish an in vivo sepsis model. An NLRP3 inflammasome inhibitor, MCC950 (50 mg/kg), was injected intraperitoneally 30 min before LPS treatment. Serum, lung tissues, and BALF were collected 24 h later for further analysis. In addition, we also collected serum from sepsis patients and healthy volunteers to detect their RBM3 expression. The results showed that the expression of RBM3 in the lung tissues of LPS-induced sepsis mice and the serum of patients with sepsis was significantly increased and positively correlated with disease severity. In addition, RBM3 knockout (KO) mice had a low survival rate, and RBM3 KO mice had more severe lung damage, inflammation, lung cell apoptosis, and oxidative stress than WT mice. LPS treatment significantly increased the levels of nucleotide binding and oligomerization domain-like receptor family 3 (NLRP3) inflammasomes and mononuclear cell nuclear factor-κB (NF-κB) in the lung tissues of RBM3 KO mice. However, these levels were only slightly elevated in WT mice. Interestingly, MCC950 improved LPS-induced acute lung injury in WT and RBM3 KO mice but inhibited the expression of NLRP3, caspase-1, and IL-1ß. In conclusion, RBM3 was overexpressed in sepsis patients and LPS-induced mice. RBM3 gene deficiency aggravated sepsis-associated ALI through the NF-κB/NLRP3 pathway.

Correction to: Nomogram predicting cancer-specific mortality in early-onset rectal cancer: a competing risk analysis.

The original version of this article, unfortunately, contained errors.

Nomogram predicting cancer-specific mortality in early-onset rectal cancer: a competing risk analysis.

BACKGROUND: The incidence of rectal cancer has meaningfully increased in young patients. However, quantitative evaluation for the competing data of early-onset rectal cancer is lacking. So, we performed a competing risk analysis to calculate the cumulative incidence of death for patients with early-onset rectal cancer and developed a nomogram to predict the probability of cancer-specific mortality for these patients. METHODS: We abstracted data of patients with early-onset rectal cancer between 2004 and 2016 by using the Surveillance, Epidemiology, and End Results program database. The cumulative incidence function was used to calculate the crude cancer-specific mortality of early-onset rectal cancer. Fine and Gray's proportional sub-distribution hazard model was adopted to explore the risk factors of cancer-specific death. Then, we establish a nomogram to predict their 3-, 5-, and 10-year probabilities. RESULTS: We identified 9917 patients with early-onset rectal cancer, and they were randomly divided into training (n = 6941) and validation (n = 2976) cohorts. In the training cohort, the 3-, 5-, and 10-year cumulative incidences of cancer-specific death after diagnosis for early-onset rectal cancer were 11.4%, 19.9%, and 28.8%, respectively. Fine and Gray's model showed that sex, race, marital status, histology, T stage, N stage, M stage, examined lymph nodes, and pretreatment carcinoembryonic antigen were independently associated with cancer-specific mortality. Such factors were selected to develop a prognostic nomogram. CONCLUSION: The competing risk nomogram has an ideal performance for predictive cancer-specific mortality in early-onset rectal cancer.

Development and validation of the nasopharyngeal cancer scale among the system of quality of life instruments for cancer patients (QLICP-NA V2.0): combined classical test theory and generalizability theory.

OBJECTIVES: This research was designed to develop a nasopharyngeal cancer (NPC) scale based on quality of life (QOL) instruments for cancer patients (QLICP-NA). This scale was developed by using a modular approach and was evaluated by classical test and generalizability theories. METHODS: Programmed decision procedures and theories on instrument development were applied to create QLICP-NA V2.0. A total of 121 NPC inpatients were assessed using QLICP-NA V2.0 to measure their QOL data from hospital admission until discharge. Scale validity, reliability, and responsiveness were evaluated by correlation, factor, parallel, multi-trait scaling, and t test analyses, as well as by generalizability (G) and decision (D) studies of the generalizability theory. RESULTS: Results of multi-trait scaling, correlation, factor, and parallel analyses indicated that QLICP-NA V2.0 exhibited good construct validity. The significant difference of QOL between the treated and untreated NPC patients indicated a good clinical validity of the questionnaire. The internal consistency (α) and test-retest reliability coefficients (intra-class correlations) of each domain, as well as the overall scale, were all >0.70. Ceiling effects were not found in all domains and most facets, except for common side effects (24.8 %) in the domain of common symptoms and side effects, tumor early symptoms (27.3 %) and therapeutic side effects (23.2 %) in specific domain, whereas floor effects did not exist in each domain/facet. The overall changes in the physical and social domains were significantly different between pre- and post-treatments with a moderate effective size (standard response mean) ranging from 0.21 to 0.27 (p < 0.05), but these changes were not obvious in the other domains, as well as in the overall scale. Scale reliability was further confirmed by G coefficients and index of dependability, with more exact variance components based on generalizability theory. CONCLUSIONS: QLICP-NA V2.0 exhibited reasonable degrees of validity, reliability, and responsiveness. However, this scale must be further improved before it can be used as a practical instrument to evaluate the QOL of NPC patients in China.

Association of heme oxygenase-1 polymorphisms with cancer risk: A systematic review and meta-analysis.

PURPOSE: Observational studies have recently focused on the association between heme oxygenase-1 (HMOX1) gene promoter polymorphisms and cancer risk. However, conflicting results have been obtained. To derive a precise estimate of the association, a systematic review and meta-analysis were conducted. METHODS: This study followed the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Medline, Embase and Web of Knowledge were systematically searched for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the allelic and genotypic comparisons according to the homozygous, heterozygous, dominant, and recessive genetic models. Between-study heterogeneity was quantified through I2 statistics, and publication bias was appraised by using funnel plots. Sensitivity analyses were conducted to evaluate the robustness of the meta-analysis findings. RESULTS: Meta-analysis of 9 studies involving 2491 cases and 3380 controls did not reveal any significant association of the HMOX-1 (GT)n and 413A>T polymorphisms with cancer risk. Stratified analysis by ethnicity showed a statistically significant association between (GT)n repeat length variant and susceptibility to cancer for the heterozygous genetic model among Asian populations (OR=1.42, 95% CI: 1.04-1.95, Pheterogeneity=0.218), which is a robust finding according to sensitivity analysis. Funnel plot inspection did not reveal any publication bias. CONCLUSION: In conclusion, this study comprehensively examined the available literature on the association of HMOX-1 (GT)n and 413A>T polymorphisms with cancer risk. Meta-analysis results suggest (GT)n repeat length polymorphism as a potential susceptibility variant for cancer in Asians. Additional large-scale and well-designed studies are needed to confirm these results.

Metastasis-associated protein 1 as a new prognostic marker for solid tumors: a meta-analysis of cohort studies.

Metastasis-associated protein 1 (MTA1) is a molecular marker in various solid tumors that has recently been investigated. The prognostic significance of MAT1 expression remains controversial. In this work, we aimed to determine the relationship between immunohistochemistry-detected MAT1 expression and survival of patients with solid tumors by conducting a meta-analysis of cohort studies. Relevant studies were identified via an electronic database search updated on October 28, 2013. We included cohort studies that reported hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) to determine the association of high MTA1 expression with overall survival (OS) and clinicopathological characteristics. Heterogeneity was quantified using I (2) statistics, and publication bias was evaluated using funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. We identified 16 cohort studies that focused on MTA1 overexpression and prognosis involving 2,253 cancer patients. Overall, the combined HR for OS was 1.85 (95 % CI: 1.55-2.28, P<0.001). Omission of any single study had no significant effect on the pooled HR estimate. When the studies were stratified by tumor type, similar results of poor prognosis were observed in non-small cell lung cancer (HR=2.05, 95 % CI: 1.14-3.68, P=0.016) and esophageal squamous cell carcinoma (HR=1.86, 95 % CI: 1.44-2.39, P<0.001). Moreover, multivariate survival analysis showed that MTA1 overexpression was an independent predictor of poor prognosis (HR=1.90, 95 % CI: 1.53-2.37, P<0.001). In addtional, MTA1 overexpression was significantly associated with tumor size (OR=2.72, 95 % CI=1.44-5.14, P=0.002), tumor stage (OR=2.44, 95 % CI=1.67-3.57, P<0.001), depth of invasion (OR=2.63, 95 % CI=1.74-3.97, P<0.001), and lymph node metastasis (OR=2.57, 95 % CI=1.57-4.19, P<0.001). However, when age, sex, and tumor differentiation were considered, no obvious association was observed. This study provides a comprehensive examination of the literature available on the association of MTA1 overexpression with OS and some clinicopathological features in solid tumors. Meta-analysis results provide evidence that MTA1 may be a new indicator of poor cancer prognosis. Considering the limitations of the eligible studies, other large-scale prospective trials must be conducted to clarify the prognostic value of MTA1 in predicting cancer survival.

Proton pump inhibitors may increase the risk of cisplatin-induced acute kidney injury in patients with nasopharyngeal carcinoma: a prospective cohort study.

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280-6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC.

Exploration of the methods of establishing the minimum clinical important difference based on anchors and their applications in the quality of life measurement scale QLICP-BR (V2.0) for breast cancer.

Objective: The measurement of the quality of life (QOL) in patients with breast cancer can evaluate the therapeutic effects of medical treatments and help to provide reference for clinical decisions. The minimum clinically important difference (MCID) can be better used in clinical interpretation than the traditional statistical significance. Based on the anchors, a variety of ways including traditional and updated anchor-based methods were used to explore most suitable MCID, so that to find better interpretation on scores of the scale QLICP-BR(V2.0) (Quality of Life Instruments for Cancer Patients-Breast cancer). Methods: According to the investigation data of breast cancer patients before and after treatment, the most relevant indicators in various domains of QLICP-BR (V2.0) was found as an anchor to statistically analyze the value of MCID, and three analysis methods of anchors were used: Traditional anchor-based method, ROC curve method, multiple linear regression model analysis. Anchors are divided into four standards according to the degree of change in the treatment effect: one grade difference (Standard A), at least one grade difference (Standard B), one grade better (Standard C), better (Standard D). The final MCID value is selected from different statistical methods and classification standards that are most suitable for clinicians to use. Results: Using Q29 of the EORTC QLQ-C30 as an anchor has the highest correlation with each domain of QLICP. The order of magnitude of MCID values among the four standard groups is: standard A< Standard C< Standard B< Standard D. The MCID value obtained by the ROC curve method is the most stable and is least affected by the sample size, and the MCID value obtained by the multiple linear regression model is the least. After comparisons and discussions, Standard C in the multiple linear regression model is used to determine the final MCID, which is the closest to other methods. After integer the MCID values of Physical domain (PHD), Psychological domain (PSD), Social domain (SOD), Common symptoms and side effect domain (SSD), Core/general module (CGD), Specific domain (SPD), Total score(TOT) can be taken as 15,10, 10, 11, 10, 9 and 9, respectively. Conclusion: In the evaluation of the QOL of breast cancer patients, although the results of MCID values produced by different methods are different, the results are relatively close. The anchor-based methods make the results of MCID more clinically interpretable by introducing clinical variables, and clinicians and researchers can choose the appropriate method according to the research purpose.

Association of CYP1A1 polymorphisms with prostate cancer risk: an updated meta-analysis.

Epidemiological studies have evaluated the association between 3801T>C and 2455A>G polymorphisms of cytochrome P450 1A1 (CYP1A1) and prostate cancer risk. However, controversy exists regarding the role of these polymorphisms. In this work, a meta-analysis was performed to derive a more precise estimation of the relationship. PubMed and ISI Web databases were searched for all cases dated until March 2012. Crude odds ratios with 95 % confidence intervals were used to assess the strength of the association between CYP1A1 polymorphisms and prostate cancer risk. Sensitivity analysis, excluding the studies that deviated from the Hardy-Weinberg equilibrium (HWE), was performed. A total of 17 studies fulfilled our inclusion criteria in this meta-analysis, 12 of which were eligible (1,645 cases and 1,801 controls) for 3801T>C, and eleven (1,640 cases and 1,959 controls) were eligible for 2455A>G. Overall, the 2455A>G polymorphism resulted in a significantly increased susceptibility to prostate cancer. In addition, no significant associations between 3801T>C polymorphism and prostate cancer susceptibility were found in all genetic models. Only an elevated risk was observed for TC versus CC in Asian studies. However, no relationship was found in the Asian group for TC versus CC after excluding the studies that deviated from HWE. Thus, this meta-analysis finds the 2455A>G allele to be a risk factor for prostate cancer, whereas the 3801T>C status does not seem to be capable of modifying prostate cancer risk.

Secular Trends in the Incidence of Migraine in China from 1990 to 2019: A Joinpoint and Age-Period-Cohort Analysis.

BACKGROUND: Migraine is a common disorder of the nervous system in China, imposing heavy burdens on individual and societies. Optimal healthcare planning requires understanding the magnitude and changing the trend of migraine incidence in China. However, the secular trend of migraine incidence in China remains unclear. METHODS: Data were collected from the Global Burden of Disease Study 2019 in China from 1990 to 2019 to investigate changes in the incidence rate of migraine. The average annual percent change and the relative risk were calculated using the joinpoint regression model and the age-period-cohort model, respectively. RESULTS: From 1990 to 2019, the age-standardized incidence rates of migraine in China increased by 0.26% (95% CI: 0.22 to 0.31) and 0.23% (95% CI: 0.19 to 0.28) per year in males and females, respectively. Age effects exerted the most significant impact on migraine incidence. Period effects showed a slightly decreasing trend in the incidence of migraine. In terms of cohort effects, people born after the 1960s presented a higher risk of migraine as compared with the total cohort, with the incidence risk of migraine increasing with birth cohorts. CONCLUSION: Migraine incidence shows an overall increasing trend in China, with a significant gender difference. A comprehensive understanding of the risk characteristics and disease pattern of migraine could allow the early detection of persons with a high risk of developing migraine and promote the development of timely intervention measures to relieve this burden effectively.

Trends in the Incidence and DALYs of Urolithiasis From 1990 to 2019: Results From the Global Burden of Disease Study 2019.

Objectives: To provide a comprehensive assessment of the estimated burden and trend of urolithiasis at the global, regional, and national levels. Methods: The age-standardized rates (ASRs) of the incidence and disability-adjusted life years (DALYs) of urolithiasis from 1990 to 2019 were obtained from the Global Burden of Disease Study 2019 database. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in urolithiasis burden. Results: In 2019, the ASRs of the incidence and DALYs were 1,394.03/100,000 and 7.35/100,000, respectively. The ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019 with EAPCs of -0.83 and -1.77, respectively. Males had a higher burden of urolithiasis than females. In 2019, the highest burden of urolithiasis was observed in regions with high-middle sociodemographic index (SDI), particularly in Eastern Europe, Central Asia, and Southeast Asia. The burden of urolithiasis increased in most countries or territories. The burden of urolithiasis and SDI had a non-linear relationship, and the estimated value of urolithiasis burden was the highest when the SDI value was ~0.7. Conclusion: Globally, the ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019, but an increasing trend was observed among many countries. More effective and appropriate medical and health policies are needed to prevent and early intervene in urolithiasis.

Association of Tumor Size With Prognosis in Patients With Resectable Endometrial Cancer: A SEER Database Analysis.

This study aimed to explore the relationship between tumor size (Ts) and prognosis in endometrial cancer (EC). A total of 52,208 patients with EC who underwent total hysterectomy were selected from the Surveillance, Epidemiology, and End Results Program database. Overall survival (OS) and endometrial cancer-specific survival (ESS) were chosen as survival outcomes. The Cox proportional hazards model was used to explore the effect of Ts on prognosis. The restricted cubic splines based on the Cox regression model were used to determine the nonlinear relationship between Ts and survival. When Ts was analyzed as a categorical variable, the risk of death increased with Ts, with the highest risk in patients with Ts > 9 cm with regard to all-cause death (ACD) (hazard ratio [HR] 1.317; 95% confidence interval [CI], 1.196-1.450; P < 0.001) and endometrial cancer-specific death (ESD) (HR, 1.378; 95% CI, 1.226-1.549; P < 0.001). As a continuous variable, Ts showed a nonlinear relationship with ACD (HR, 1.061; 95% CI, 1.053-1.069; P < 0.001) and ESD (HR, 1.062; 95% CI, 1.052-1.073; P < 0.001). The risk of mortality increased quickly with Ts when Ts was less than 7.5 cm and then leveled off when Ts was larger than 7.5 cm in all patients. Among patients with lymph node metastasis, the risk of poor prognosis decreased rapidly with Ts when Ts was less than 3.5 cm, and subsequently increased sharply with Ts when Ts ranged from 3.5 cm to 7.5 cm, and then increased slowly when Ts was larger than 7.5 cm (P < 0.001 for nonlinearity). There was a nonlinear relationship between Ts and prognosis in patients with EC. Clinicians should not ignore the impact of small tumors on prognosis in EC patients with lymph node metastasis.

Development and validation of a nomogram for predicting long-term overall survival in nasopharyngeal carcinoma: A population-based study.

We aimed to develop a nomogram based on a population-based cohort to estimate the individualized overall survival (OS) for patients with nasopharyngeal carcinoma (NPC) and compare its predictive value with that of the traditional staging system.Data for 3693 patients with NPC were extracted from the Surveillance, Epidemiology, and End Results dataset and randomly divided into two sets: training (n = 2585) and validation (n = 1108). On the basis of multivariate Cox regression analysis, a nomogram was constructed to predict the 3-, 5-, and 10-year survival probability for a patient. The performance of the nomogram was quantified with respect to discrimination, calibration, and clinical utility.In the training set, age, sex, race, marital status, histological type, T stage, N stage, M stage, radiotherapy, and chemotherapy were selected to develop a nomogram for predicting the OS probability based on the multivariate Cox regression model. The nomogram was generally more discriminative compared with the American Joint Committee on Cancer 7th staging system. Calibration plots exhibited an excellent consistency between the observed probability and the nomogram's prediction. Categorical net classification improvement and integrated discrimination improvement suggested that the predictive accuracy of the nomogram exceeded that of the classic staging system. With respect to decision curve analyses, the nomogram exhibited preferable net benefit gains than the staging system across a wide range of threshold probabilities.This proposed nomogram exhibits an excellent performance with regard to its predictive accuracy, discrimination capability, and clinical utility, and thus can be used as a convenient and reliable tool for prognosis prediction in patients with NPC.

Pretreatment Aspartate Aminotransferase-to-Alanine Aminotransferase (De Ritis) Ratio Predicts the Prognosis of Nonmetastatic Nasopharyngeal Carcinoma.

BACKGROUND: The pretreatment aspartate aminotransferase-to-alanine aminotransferase (De Ritis) ratio is reportedly valuable in prognosis prediction of various malignancies. However, its value in the prognosis of nasopharyngeal carcinoma (NPC) has not yet been reported. This study aimed to evaluate the effect of the De Ritis ratio on the survival outcomes of patients with nonmetastatic NPC. METHODS: We retrospectively reviewed the medical data of 1023 patients with nonmetastatic NPC admitted between 2009 and 2013 at a single center. The Fine and Gray competing risk regression model was used to analyze the associations between the De Ritis ratio and the survival outcomes of cancer-specific survival (CSS) and progression-free survival (PFS) by using the subdistribution hazard ratio (SHR) and 95% confidence interval (CI) as size effects. The Cox proportional hazard model was used to evaluate the correlation between the De Ritis ratio and overall survival (OS) by using hazard ratio (HR) and 95% CI as size effects. RESULTS: Patients were divided into two groups in accordance with the pretreatment De Ritis ratio by using an optimal cutoff value of 1.65. Compared with the patients with low De Ritis ratio (< 1.65), those with elevated De Ritis ratio (≥ 1.65) had poorer prognosis with regard to CSS, PFS, and OS. Notably, multivariate analyses showed that high De Ritis ratio was independently associated with poor CSS (SHR = 1.64, 95% CI: 1.25-2.16), PFS (SHR = 1.69, 95% CI: 1.30-2.19), and OS (HR = 1.81, 95% CI: 1.39-2.40). CONCLUSION: Pretreatment De Ritis ratio can be an independent prognostic predictor for patients with nonmetastatic NPC.

Neutrophil-to-lymphocyte ratio predicts diagnosis and prognosis of idiopathic sudden sensorineural hearing loss: A systematic review and meta-analysis.

BACKGROUND: Chronic inflammation has been regarded as one of the causes of idiopathic sudden sensorineural hearing loss (ISSHL). Several individual studies have reported the association between neutrophil-to-lymphocyte ratio (NLR) and ISSHL. However, the findings have been inconsistent, and these data have not been systematically evaluated. Thus, we conducted this meta-analysis to further explore the predictive value of NLR on formation and prognosis of ISSHL. METHODS: A comprehensive literature search was performed to identify eligible studies based on PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. The Standardized mean deviation (SMD) with its 95% confidence interval (CI) was applied to be the effect size estimate. RESULTS: A total 10 papers with 15 retrospective case-control studies, which included 1029 ISSHL patients (the case group) and 1020 healthy people (the control group), were selected for the meta-analysis of the relationship between NLR and onset of ISSHL. The NLR levels in the case group were observed to be higher than the control group (SMD = 1.65, 95% CI = 1.20-2.09, P < .001). The pooled results did not significantly change by the subgroup analyses based on study region, baseline matching, and laterality. Moreover, 9 publications with 12 retrospective cohort studies, which included 590 recovered ISSHL patients and 438 unrecovered ISSHL patients, explored the association between NLR and ISSHL prognosis, and the combined data showed that the NLR value was much higher in unrecovered patients rather than recovered patients (SMD = 1.27, 95% CI: 0.62-1.92, P < .001). The subgroup analyses based on study region, laterality, type of steroid, medication administration, maintenance treatment, follow-up period, and definition of "recovered" further supported these results. CONCLUSION: The results of this meta-analysis suggest that NLR might be a useful biomarker to determine the onset and prognosis of ISSHL.

Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis.

Several previous studies have reported the prognostic value of hexokinase 2 (HK2) in digestive system tumors. However, these studies were limited by the small sample sizes and the results were inconsistent among them. Therefore, we conducted a meta-analysis based on 15 studies with 1932 patients to assess the relationship between HK2 overexpression and overall survival (OS) of digestive system malignancies. The relationship of HK2 and clinicopathological features was also evaluated. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CI) were calculated to estimate the effect size. Positive HK2 expression showed poor OS in all tumor types (HR = 1.75 [1.41-2.18], P < 0.001). When stratified by tumor type, the impact of HK2 overexpression on poor prognosis was observed in gastric cancer (HR = 1.77 [1.25-2.50], P < 0.001), hepatocellular carcinoma (HR = 1.87 [1.58-2.21], P < 0.001), and colorectal cancer (HR = 2.89 [1.62-5.15], P < 0.001), but not in pancreatic ductal adencarcinoma (HR = 1.11 [0.58-2.11], P = 0.763). Furthermore, high HK2 expression was significantly associated with some phenotypes of tumor aggressiveness, such as large tumor size (OR = 2.03 [1.10-3.74], P = 0.024), positive lymph node metastasis (OR = 2.05 [1.39-3.02], P < 0.001), advanced clinical stage (OR = 2.17 [1.21-3.89], P = 0.009) and high alpha fetoprotein level (OR = 1.47 [1.09-2.02] P = 0.013). In summary, HK2 might act as a prognostic indicator and a potential therapeutic target of these digestive system cancers.

Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies.

PURPOSE: The expression of pyruvate kinase M2 (PKM2) has been linked to tumor formation and invasion. Specifically, the relationship between high PKM2 expression and prognosis has been evaluated in solid tumors of digestive system. However, the prognostic value of PKM2 remains controversial. METHODS: A literature search of PubMed, Embase, and Cochrane databases was conducted until October 2015. The end point focused on overall survival (OS). The pooled hazard ratio (HR) or odds ratio and the 95% confidence intervals were calculated to correlate PKM2 overexpression with OS and clinicopathological characteristics by employing fixed- or random-effects models, depending on the heterogeneity of the included studies. RESULTS: We identified 18 cohorts in 16 studies involving 2,812 patients for this meta-analysis. Overall, the combined HR for OS in all tumor types was 1.74 (1.44-2.11; P<0.001). When stratified by tumor type, the influence of PKM2 expression on poor prognosis was also found in gastric cancer (HR =1.54 [1.08-2.21], P=0.018), esophageal squamous cell carcinoma (HR =1.71 [1.38-2.12], P<0.001), hepatocellular cancer (HR =1.92 [1.52-2.42], P<0.001), biliary cancer (HR =2.11 [1.50-2.95], P<0.001), and oral cancer (HR =3.49 [1.97-6.18], P<0.001), but not in pancreatic ductal adenocarcinoma (HR =1.03 [0.28-3.76], P=0.968). Furthermore, PKM2 overexpression had a negative effect on the late clinical stage of all tumor types except for pancreatic ductal adenocarcinoma. The high density of PKM2 overexpression was significantly associated with some clinical characteristics in different cancer types, such as tumor stage, modal metastasis, and tumor size. CONCLUSION: Our findings revealed significant association of PKM2 overexpression with OS and certain clinicopathological features in solid tumors of digestive system, thereby suggesting that PKM2 might be an indicator of poor prognosis in digestive system cancers.

Prognostic value of rsf-1/hbxap in human solid tumors: a meta-analysis of cohort studies.

PURPOSE: Recent studies have investigated remodeling and spacing factor 1 (Rsf-1) as a molecular marker in various solid tumors. However, whether or not Rsf-1 exerts a negative or positive effect on the survival of patients with solid cancers remains controversial. Therefore, this study aims to determine whether or not Rsf-1 may be a predicative marker of poor prognosis and aggressive tumor progression. METHODS: We conducted a meta-analysis of 11 cohort studies (n = 1620 patients) to evaluate the relationship between Rsf-1 and clinical outcome. We included studies with data on overall survival (OS), disease-specific survival (DSS), recurrent-free survival (RFS), metastasis-free survival (MFS), and hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: High Rsf-1 expression was significantly associated with poor survival in solid tumors. Overall, the combined HR for OS was 1.49 (95% CI = 1.21-1.84, P < 0.001), DSS 3.07 (95% CI = 1.67-5.62, P < 0.001), RFS 2.51 (95% CI = 1.12-5.63, P = 0.025), and MFS 2.14 (95% CI = 1.49-3.06, P < 0.001). In addition, Rsf-1 overexpression was significantly associated with tumor stage (OR = 4.13, 95% CI = 2.84-6.00, P < 0.001), primary tumor (OR = 2.09, 95% CI = 1.58-2.75, P < 0.001), nodal status (OR = 1.95, 95% CI = 1.40-2.72, P < 0.001), and histological grade (OR = 3.09, 95% CI = 2.10-4.54, P < 0.001). CONCLUSIONS: Rsf-1 may be a predicative marker of poor prognosis and aggressive tumor progression.

Accuracy of Presepsin in Sepsis Diagnosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: It's difficult to differentiate sepsis from non-sepsis, especially non-infectious SIRS, because no good standard exists for proof of infection. Soluble CD14 subtype (sCD14-ST), recently re-named presepsin, was identified as a new marker for the diagnosis of sepsis in several reports. However, the findings were based on the results of individual clinical trials, rather than a comprehensive and overall estimation. Thus, we conducted this systematic review and meta-analysis to estimate the pooled accuracy of presepsin in patients with sepsis suspect. METHODS: A comprehensive electronic search was performed via internet retrieval system up to 15 December 2014. Methodological quality assessment was applied by using the QUADAS2 tool. The diagnostic value of presepsin in sepsis was evaluated by using the pooled estimate of sensitivity, specificity, likelihood ratio, and diagnostic odds ratio, as well as summary receiver operating characteristics curve. RESULTS: Nine studies with 10 trials and 2159 cases were included in the study. Only two trials had low concerns regarding applicability, whereas all trials were deemed to be at high risk of bias. Heterogeneity existed in the non-threshold effect, but not in the threshold effect. The pooled sensitivity of presepsin for sepsis was 0.78 (0.76-0.80), pooled specificity was 0.83 (0.80-0.85), pooled positive likelihood ratio was 4.63 (3.27-6.55), pooled negative likelihood ratio was 0.22 (0.16-0.30), and pooled diagnostic odds ratio was 21.73 (12.81-36.86). The area under curve of summary receiver operating characteristics curve was 0.89 (95%CI: 0.84 to 0.94) and Q* index was 0.82 (95%CI: 0.77 to 0.87). CONCLUSION: This meta-analysis demonstrates that presepsin had some superiority in the management of patients, and may be a helpful and valuable biomarker in early diagnosis of sepsis. However, presepsin showed a moderate diagnostic accuracy in differentiating sepsis from non-sepsis which prevented it from being recommended as a definitive test for diagnosing sepsis in isolation, but the results should be interpreted cautiously.

16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reaction in the Diagnosis of Bloodstream Infections: A Systematic Review and Meta-Analysis.

OBJECTIVE: We aim to evaluate the accuracy of the 16S ribosomal ribonucleic acid (rRNA) gene polymerase chain reaction (PCR) test in the diagnosis of bloodstream infections through a systematic review and meta-analysis. METHODS: A computerized literature search was conducted to identify studies that assessed the diagnostic value of 16S rRNA gene PCR test for bloodstream infections. Study quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence intervals (95% CI) for each study. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Statistical analysis was performed in Meta-DiSc 1.4 and Stata/SE 12.0 software. RESULTS: Twenty-eight studies were included in our meta-analysis. Using random-effect model analysis, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.87 (95% CI, 0.85-0.89), 0.94 (95% CI, 0.93-0.95), 12.65 (95% CI, 8.04-19.90), 0.14 (95% CI, 0.08-0.24), and 116.76 (95% CI, 52.02-262.05), respectively. The SROC curve indicated that the area under the curve (AUC) was 0.9690 and the maximum joint sensitivity and specificity (Q*) was 0.9183. In addition, heterogeneity was statistically significant but was not caused by the threshold effect. CONCLUSION: Existing data suggest that 16S rRNA gene PCR test is a practical tool for the rapid screening of sepsis. Further prospective studies are needed to assess the diagnostic value of PCR amplification and DNA microarray hybridization of 16S rRNA gene in the future.