METTL16 in human diseases: What should we do next?

METTL16 is a class-I methyltransferase that is responsible for depositing a vertebrate-conserved S-adenosylmethionine site. Since 2017, there has been a growing body of research focused on METTL16, particularly in the field of structural studies. However, the role of METTL16 in cell biogenesis and human diseases has not been extensively studied, with limited understanding of its function in disease pathology. Recent studies have highlighted the complex and sometimes contradictory role that METTL16 plays in various diseases. In this work, we aim to provide a comprehensive summary of the current research on METTL16 in human diseases.

Prognostic analysis of Yes-associated protein 1 in patients with colorectal cancer. A systematic review and meta-analsysis.

BACKGROUND: Colorectal cancer (CRC) is the most common carcinoma worldwide, but a lack of effective prognostic markers limits the clinical diagnosis and treatment. Yes-associated protein 1 (YAP1) is an effector of the HIPPO-pathway, which plays a critical role in cancer development and prognosis, including CRC. However, previous reports have suggested that it plays a dual role in CRC. METHODS: A meta-analysis using RevMan software 5.4 and Stata 14.0 was performed to evaluate the relationship between YAP1 and clinical outcomes of CRC, after searching for eligible studies from the PubMed, Web of Science and Embase databases. Online datasets GEPIA and LOGpc were also used to calculate survival results and compare with the meta-analysis results. Besides, "DESeq" packages was used for expression analysis of YAP1 from TCGA dataset. RESULTS: YAP1 was over expression in the tissue of cancers comparing to normal tissues in patients with CRC from TCGA database (p=0.000164) and GEPIA database. A total of 10 studies involving 2305 patients from literatures were selected. Pooled HR indicated that over-expression of YAP1 was associated with poor clinical outcomes (HR=1.70, 95% CI: 1.28-2.26, p=0.0003). Subgroup analysis showed a clear correlation between over-expression of YAP1 and worse survival rate in Chinese patients (HR=1.94, 95% CI: 1.40-2.69, p=0.0001), nuclear YAP1 over-expression (HR=2.07, 95% CI: 1.29-3.31, p=0.003), 60 months follow-up duration (HR=1.89, 95% CI: 1.30-2.73, p=0.0008), IHC test (HR=1.65, 95% CI: 1.17-2.33, p=0.005), IHC combined with other tests (HR=1.77, 95% CI: 1.13-2.77, p=0.01) and multivariate analysis (HR=1.70, 95% CI: 1.24-2.31, p=0.0009). Nevertheless, disease-free survival (DFS) did not show significant result in the patients with CRC in our meta-analysis (HR=1.38, 95% CI: 0.51-3.75, p=0.52) as well as in the GEPIA and LOGpc databases. Meanwhile, YAP1 over-expression was also significantly associated with worse overall survival (OS) in GSE17536, GSE40967, GSE29623 and GSE71187. CONCLUSION: YAP1 over-expression is common in CRC tissues. Over-expression of YAP1 in CRC patients, particularly in the nucleus, might be related to shorter OS, maybe in the early stages. YAP1 could serve as a potential predictor of poor prognosis in CRC.

The effects of Al-doped to cathode material based on hollow microspheres of nickel-manganese on sodium-ion batteries.

Sodium-ion batteries (SIBs) are expected to be a great substitute for lithium ion batteries. Although there are many difficulties to overcome, SIBs have become one of the most important research areas for large-scale energy storage equipment. The spherical particles are conducive to the contact between the cathode material and the electrolyte, which could increase the electrochemical reaction area, and improve the deintercalation rate of sodium ions during charging and discharging. In this paper, a precipitation method was used to prepare spherical MnCO3material as template and raw material. After all the raw materials were weighed with the molar ratios of Na0.67Mn0.67-0.75xNi0.33AlxO2, a series of hollow micro-spherical sodium-ion cathode materials were synthesized by the conventional high-temperature solid-state method. The effects of Al-doped on the structure and electrochemical performance of Na0.67Ni0.33Mn0.67O2was studied, and it was founded that the samples doped with Al had smaller particle size than that without Al. The electrochemical tests showed that Na0.67Mn0.595Ni0.33Al0.1O2(x= 0.1) exhibite superior high-rate capabilities and cyclic stability. And the hollow microsphere structure has a higher capacity, the first discharge capacity at 0.1C reach 128 mAh g-1.

Systematic evaluation of the diagnostic approach of inflammatory bowel disease guidelines.

OBJECTIVE: To collect and evaluate the diagnostic approach of inflammatory bowel disease (IBD) guidelines and provide useful feedback for guideline developers and evidence-based clinical information to help physicians make decisions. METHODS: Diagnostic guidelines for IBD were retrieved by performing systemic and manual searches. Qualified clinical practice guidelines (CPGs) were included and then evaluated by four well-trained evaluators using the AGREE II instrument. To reduce the bias generated in this process, we used the Measurement Scale of Rate of Agreement (MSRA) tool to interpret the results. Guidelines with good recommendation distributions among the diagnostic field were further reclassified and evaluated. RESULTS: Fifteen diagnostic CPGs for IBD were identified and evaluated, and 70.3% (11/15) of the CPGs were above the recommended level. We observed heterogeneity among the diagnostic CPGs for IBD and discrepancies among different domains in one specific guideline. Potential improvements were identified in the fields of stakeholder involvement, rigour of development and applicability. By further analysing the heterogeneity of the recommendations and evidence in 5 UC-CPGs, we found the following issues: no discussion of diagnosing severe complications of UC, disputed significance of serologic and genetic diagnoses of UC, insufficient attention towards medical histories/physical examinations/differential diagnoses and discrepancy in classification criteria. CONCLUSION: The included diagnostic CPGs for IBD were generally of good quality, but heterogeneity was identified. Addressing these issues will provide useful feedback for the guideline updating process, and it will also benefit current clinical practice and eventually patient outcome.

Identification immunophenotyping of lung adenocarcinomas based on the tumor microenvironment.

The tumor immune microenvironment is heterogeneous, and its impact on treatment responses is not well understood. It is still a challenge to analyze the interaction between malignant cells and the tumor microenvironment to apply suitable immunotherapy in lung adenocarcinoma. We performed the nonnegative matrix factorization method to 513 messenger RNA expression profiles of lung adenocarcinomas (LUADs) from The Cancer Genome Atlas (TCGA) to obtain an immune-related expression pattern. Subsequently, we characterized the immune-related gene signatures and clinical and survival characteristics. We used 576 patients from Gene Expression Omnibus to confirm our findings. Of the patients in the training cohort, 51% had a high immune enrichment score, high expression of immune cell signaling, cytolytic activity, and interferon (IFN)-related signatures (all P < .05). We denoted these as the Immune Class. We further subdivided the Immune Class into two subclasses based on the tumor microenvironment. These were denoted the Active Immune Class and Exhausted Immune Class. The former showed significant IFN, T-cells, M1 macrophage signatures, and better prognosis (all P < .05), while the latter presented an exhausted immune response with activated stromal enrichment, M2 macrophage signatures, and immunosuppressive factors such as WNT/transforming growth factor-ß (all P < .05). Furthermore, we predicted the response of our immunophenotypes to immunological checkpoint inhibitors (P < .05). Our findings provide a novel insight into the immune-related state of LUAD and can identify the patients who will be receptive to suitable immunotherapeutic treatments.

Proteobacteria Acts as a Pathogenic Risk-Factor for Chronic Abdominal Pain and Diarrhea in Post-Cholecystectomy Syndrome Patients: A Gut Microbiome Metabolomics Study.

BACKGROUND Laparoscopic cholecystectomy (LC) is regarded as the criterion standard for gallstone therapy, but post-cholecystectomy syndrome (PCS) is a common complication. This study aimed to analyze and identify differences in gut microbiome in PCS patients. MATERIAL AND METHODS This study involved 8 PCS patients (RS1), 8 asymptomatic PCS patients (RS2), and 8 healthy individuals (RS3). Genomic DNA of gut microbiome was extracted and amplified with CTAB method. PCR products were sequenced with Illumina High-Through Sequencing. Sequencing data were analyzed with QIIME software. Effective sequence of bacterial 16S-rRNA gene was clustered into OTUs using UPARSE software. Species annotations were evaluated using Mothur software. QIIME software was used to conduct complexity analysis and calculate UniFrac distances. R software was used to generate PCoA plots. RESULTS Bacterial 16S-rDNA gene sequences showed that the effective species annotative data were more than 97%. According to Ternary plot, Firmicutes and Bacteroidetes had similar abundance and contents among the 3 groups. Contents of Proteobacteria in RS1 were higher compared to RS2 and RS3. Bacterial genomic DNAs samples were clustered together in the same group; however, distances were relative far between different groups. RS1 illustrated significantly higher abundance of Proteobacteria colonies compared to healthy people (p<0.05), and illustrated higher abundance of Verrucomicrobia and lower abundance of Bacteroidetes and Firmicutes, but without significant differences (p>0.05). CONCLUSIONS Gut microbiome of PCS patients was dominated by Proteobacteria in feces and contained little Firmicutes and Bacteroidetes. The enhanced abundance of Proteobacteria might be the highly pathogenic risk factor for chronic abdominal pain and diarrhea in PCS patients.

Comparison of the Glasgow-Blatchford and Rockall Scores for prediction of nonvariceal upper gastrointestinal bleeding outcomes in Chinese patients.

The Glasgow-Blatchford scores (GBS) and Rockall scores (RS) are commonly used for stratifying patients with nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Although predictive value of these scoring methods has been extensively validated, their clinical effectiveness remains unclear. The following study evaluated the GBS and RS scoring system with reference to bleeding, needs for further surgery, endoscopic intervention and death, in order to verify their effectiveness and accuracy in clinical application.Patients who presented with NVUGIH, or who were consequently diagnosed with the disease (by endoscopy examination) between January 1, 2008, and December 31, 2012 were enrolled in the study. GBS and RS scores were compared to predict bleeding, the needs for further surgery, endoscopic intervention, death by ROC curves and AUC value.Among 2977 patients, the pre-endoscopic RS and complete RS score (CRS) were superior to the GBS score (AUC: 0.842 vs 0.804 vs 0.622, respectively) for predicting the mortality risk in patients. The pre-endoscopic RS score predicting re-bleeding was significantly higher than the CRS and the GBS score (AUC: 0.658 vs 0.548 vs 0.528, respectively). In addition, the 3 scoring systems revealed to be poor predictors of surgical operation effectiveness (AUC: 0.589 vs 0.547 vs 0.504, respectively).Our data demonstrated that the GBS and RS scoring systems could be used to predict outcomes in patients with nonvariceal upper gastrointestinal bleeding.

miR-338-3p regulates the proliferation, apoptosis and migration of SW480 cells by targeting MACC1.

The mortality and incidence rates of colorectal cancer (CRC) vary widely worldwide. miR-338-3p inhibits tumor cell proliferation in several types of cancer, however, the role of miR-338-3p on CRC remains unknown. The aim of the current study was to investigate the cellular function of miRNA-338-3p (miR-338-3p) in CRC, the malignant behavior of CRC cells and the interaction between miR-338-3p and metastasis-associated in colon cancer-1 (MACC1). miR-338-3p expression was significantly decreased in CRC tissue compared with adjacent normal tissue. In the CRC cell line SW480, miR-338-3p overexpression suppressed cell proliferation and migration and induced G1/S cell cycle arrest and apoptosis. By contrast, miR-338-3p knockdown significantly enhanced cell proliferation and migration, and suppressed G1/S cell cycle arrest and apoptosis. Furthermore, the dual-luciferase reporter assay confirmed MACC1 as a direct target of miR-338-3p. In addition, miR-338-3p overexpression reduced the level of MACC1 protein expression and MACC1 expression was significantly upregulated in CRC tissue samples. MACC1 siRNA significantly reduced CRC cell proliferation and migration, whilst cell apoptosis was significantly increased. In conclusion, miR-338-3p expression was decreased in CRC. miR-338-3p regulated the proliferation, apoptosis and migration of CRC cells by targeting MACC1.

Colorectal follicular lymphoma: A case report.

RATIONALE: Considering the low incidence of colorectal follicular lymphoma (FL) and its clinical features in endoscopic views, only a few studies have described the pathological diagnosis and treatment of this disease. This study aimed to reveal the overall process of clinical diagnosis and treatment of colorectal FL by conducting a case review. PATIENT CONCERNS: A 27-year-old female presented to our department because of "severe bloody stool" lasting for more than 1 month. Her primary symptom was melena. Colonoscopy revealed widespread flat polyps with various immunophenotypes (CD10+, BCL2+, BCL6+, cyclin D1-, CD5-) in the colorectal area. DIAGNOSIS: In accordance with manifestations on positron emission tomography-computed tomography (PET/CT), the patient was diagnosed with stage IV colorectal FL. INTERVENTIONS: PET/CT reexamination after 2 courses of rituximab, cyclophosphamide, liposomal doxorubicin, vincristine sulfate, and hydroprednisone (R-CHOP) regimen and 3 courses of R-CHOP plus etoposide regimen for chemotherapy indicated a significant reduction in tumor burden. Subsequently, rituximab was administered alone in 2 treatment courses. OUTCOMES: Lesions on PET/CT disappeared after reexamination. No recurrence was observed within the 12-month follow-up period. LESSONS: Colorectal FL is a rare disease with an inert clinical course and is common in the ileocecal area. Endoscopic views show multiple polyps. Interventional treatment is usually provided after observation of clinical symptoms or during disease progression. The disease has a relatively good prognosis.

Peptic Ulcer Is the Most Common Cause of Non-Variceal Upper-Gastrointestinal Bleeding (NVUGIB) in China.

BACKGROUND This study aimed to discover the common cause of non-variceal upper-gastrointestinal bleeding (NVUGIB) by conducting a multi-center retrospective study from 2008 to 2012. MATERIAL AND METHODS Hospitalized patients ages ≥18 years old, from 8 hospitals in China, diagnosed with NVUGIB by endoscopy from 1 January 2008 to 31 December 2012 were enrolled. Questionnaires were developed and a data-entry graphical user interface was designed by using EpiData software. RESULTS Total of 2977 hospitalized patients from 8 medical centers were included. A total of 95.47% (2842/2977) of patients were admitted to a general ward, 3.53% (105/2977) were admitted to an emergency ward, and 1.00% (31/2977) were admitted to an intensive care unit. Peptic ulcer remained the most common cause of NVUGIB (73.26%), but there was a declining trend in its constituent ratio, from 2008 to 2012. A total of 14.41% (429/2977) of patients had co-morbid conditions, 92.85% (2764/2977) used proton-pump inhibitors (PPIs) prior to endoscopic treatment, 19.65% (585/2977) underwent emergency endoscopy, and 23.45% (698/2977) received a transfusion of red blood cell suspensions. A total of 5.34% (159/2977) underwent endoscopic therapy, with a treatment rate of 16.9% in high-risk peptic ulcer patients (96/568). A total of 7.69% (237/2977) were administered aspirin, of whom 32.50% (77/237) resumed aspirin intake after gastrointestinal bleeding was controlled. The median length of hospitalization was 8 days (IQR, 5-11) and the mortality rate was 1.71% (51/2977). CONCLUSIONS Peptic ulcer was still the most common cause of NVUGIB in China. The proportion of patients with high-risk peptic ulcer bleeding who received endoscopic therapy was 16.9%. Only 19.65% of NVUGIB patients underwent emergency endoscopy.

Identification of pathway-based recurrence-associated signatures in optimally debulked patients with serous ovarian cancer.

Serous ovarian cancer (SOC) is the most common form of the histological subtype of epithelial ovarian cancer, with the worst clinical outcome. Despite improvements in surgery and chemotherapy, most patients with SOC experience recurrence within 12-18 months of first-line treatment. Current studies are unable to robustly predict the recurrence of SOC, and more accurate predictive models are urgently required. We have, therefore, developed a novel pathway-structured model to predict the recurrence of SOC. We trained the model on a set of 333 patients and validated it in 3 diversified validation datasets of 403 patients. Genes significantly associated with recurrence within each pathway were identified using a Cox proportional hazards model based on LASSO estimation in the training dataset. Next, a pathway-structured scoring matrix was obtained after computation of the prognostic score for each pathway by fitting to the Cox proportional hazards model. With the pathway-structure scoring matrix as an input, the pathway-based recurrent signatures were identified using the Cox proportional hazards model based on LASSO estimation and the significant pathway-based signatures were externally validated in 3 independent datasets. Meanwhile, our pathway-structured model was compared with a commonly used gene-based model. Our results revealed that our 12 pathway-based signatures successfully predicted the recurrence of SOC with high accuracy in the training dataset and in the 3 validation datasets. Moreover, our pathway-structured model was superior to the gene-based model in 4 datasets. The pathways selected in our study will provide new insights into the pathogenesis and clinical treatments of SOC.

Sites of distant metastases and overall survival in ovarian cancer: A study of 1481 patients.

OBJECTIVE: To assess the association between patterns of distant metastases and overall survival in metastatic ovarian cancer and identify prognostic factors for site-specific distant metastases. METHODS: Data was obtained from the SEER database between 2010 and 2014. Univariate and multivariate Cox proportional hazard models were used to identify variables associated with overall survival. Survival times between different groups were compared using Kaplan-Meier analysis and log-rank tests. RESULTS: We analyzed 1481 patients. The most common distant metastatic site was liver, followed by distant lymph nodes, lung, bone, and brain. The site of distant metastases was an independent prognostic factor for overall survival. Using liver metastases as reference, overall survival was lower for lung metastases (p = 0.0297) and higher for distant lymph node metastases (p = 0.0006). Using distant lymph nodes as reference, distant metastases to the liver (p = 0.0006), lung (p < 0.0001), brain (p = 0.0455), and bone (p = 0.0138) were all associated with worse overall survival. The number of metastatic sites did not affect overall survival. We also found that surgery and chemotherapy affected overall survival for patients with distant lymph node metastases only; age, histological subtype, surgery, and chemotherapy affected overall survival for patients with liver metastases only, while histological subtype and chemotherapy affected overall survival for patients with lung metastases only. CONCLUSIONS: The site of distant metastases affected overall survival in metastatic ovarian cancer. Patients with specific distant metastatic sites should receive special treatment and management. The identified prognostic factors can help clinician evaluate the prognosis for ovarian cancer patients with distant metastases.

Expression of annexin II in gastric carcinoma and its role in gastric cancer metastasis.

AIM: To investigate the expression of annexin II in gastric carcinoma and its role in the metastasis of gastric cancer. METHODS: The expression of annexin II in 51 cases of gastric carcinoma and 24 cases of adjacent tissues was detected by immunohistochemistry. The relationship between annexin II and clinical features of gastric cancer was analyzed. Annexin II specific siRNA was used to inhibit the expression of annexin II in gastric cancer HGC-27 cells, and the effects of annexin II on the migration and secretion of matrix metalloproteinases (MMPs) were observed. RESULTS: The positive rate of annexin II protein was 82.4% in gastric cancer tissues and 37.5% in adjacent tissues. There was significant difference between the two groups (P < 0.01); and the positive expression of annexin II was not related to the sex and age of the patients (P > 0.05). The expression of annexin II protein was correlated with tumor size, histological differentiation, TNM stage, Lymph node metastasis and other clinical features were significantly correlated, the difference was statistically significant (P < 0.05). Inhibition of annexin II expression, gastric cancer HGC-27 cells migration and secretion of MMPs were significantly decreased, the difference was statistically significant (P < 0.05). CONCLUSION: Annexin II is highly expressed in gastric cancer tissues, annexin II protein expression is related to tumor size, histological differentiation, TNM staging, lymph node metastasis and other clinical features were significantly correlated. Annexin II high expression can promote the invasion and metastasis of gastric cancer.

Dataset of integrin-linked kinase protein: Protein interactions in cardiomyocytes identified by mass spectrometry.

Using hearts from mice overexpressing integrin linked kinase (ILK) behind the cardiac specific promoter αMHC, we have performed immunoprecipitation and mass spectrometry to identify novel ILK protein:protein interactions that regulate cardiomyocyte activity and calcium flux. Integrin linked kinase complexes were captured from mouse heart lysates using a commercial antibody, with subsequent liquid chromatography tandem mass spectral analysis. Interacting partners were identified using the MASCOT server, and important interactions verified using reverse immunoprecipitation and mass spectrometry. All ILK interacting proteins were identified in a non-biased manner, and are stored in the ProteomeXchange Consortium via the PRIDE partner repository (reference ID PRIDE: PXD001053). The functional role of identified ILK interactions in cardiomyocyte function and arrhythmia were subsequently confirmed in human iPSC-cardiomyocytes.

YAP/TAZ Are Mechanoregulators of TGF-ß-Smad Signaling and Renal Fibrogenesis.

Like many organs, the kidney stiffens after injury, a process that is increasingly recognized as an important driver of fibrogenesis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are related mechanosensory proteins that bind to Smad transcription factors, the canonical mediators of profibrotic TGF-ß responses. Here, we investigated the role of YAP/TAZ in the matrix stiffness dependence of fibroblast responses to TGF-ß In contrast to growth on a stiff surface, fibroblast growth on a soft matrix led to YAP/TAZ sequestration in the cytosol and impaired TGF-ß-induced Smad2/3 nuclear accumulation and transcriptional activity. YAP knockdown or treatment with verteporfin, a drug that was recently identified as a potent YAP inhibitor, elicited similar changes. Furthermore, verteporfin reduced YAP/TAZ levels and decreased the total cellular levels of Smad2/3 after TGF-ß stimulation. Verteporfin treatment of mice subjected to unilateral ureteral obstruction similarly reduced YAP/TAZ levels and nuclear Smad accumulation in the kidney, and attenuated renal fibrosis. Our data suggest that organ stiffening cooperates with TGF-ß to induce fibrosis in a YAP/TAZ- and Smad2/3-dependent manner. Interference with this YAP/TAZ and TGF-ß/Smad crosstalk likely underlies the antifibrotic activity of verteporfin. Finally, through repurposing of a clinically used drug, we illustrate the therapeutic potential of a novel mechanointerference strategy that blocks TGF-ß signaling and renal fibrogenesis.

Recombinant N-Terminal Slit2 Inhibits TGF-ß-Induced Fibroblast Activation and Renal Fibrosis.

Fibrosis and inflammation are closely intertwined injury pathways present in nearly all forms of CKD for which few safe and effective therapies exist. Slit glycoproteins signaling through Roundabout (Robo) receptors have been described to have anti-inflammatory effects through regulation of leukocyte cytoskeletal organization. Notably, cytoskeletal reorganization is also required for fibroblast responses to TGF-ß Here, we examined whether Slit2 also controls TGF-ß-induced renal fibrosis. In cultured renal fibroblasts, which we found to express Slit2 and Robo-1, the bioactive N-terminal fragment of Slit2 inhibited TGF-ß-induced collagen synthesis, actin cytoskeletal reorganization, and Smad2/3 transcriptional activity, but the inactive C-terminal fragment of Slit2 did not. In mouse models of postischemic renal fibrosis and obstructive uropathy, treatment with N-terminal Slit2 before or after injury inhibited the development of renal fibrosis and preserved renal function, whereas the C-terminal Slit2 had no effect. Our data suggest that administration of recombinant Slit2 may be a new treatment strategy to arrest chronic injury progression after ischemic and obstructive renal insults by not only attenuating inflammation but also, directly inhibiting renal fibrosis.

PPI versus Histamine H2 Receptor Antagonists for Prevention of Upper Gastrointestinal Injury Associated with Low-Dose Aspirin: Systematic Review and Meta-analysis.

This study compared proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2RAs) for prevention of low-dose aspirin (LDA)-related gastrointestinal (GI) erosion, ulcer and bleeding. Electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Data were searched from the date of their establishment to December 31, 2013. Randomized controlled trials comparing PPIs and H2RAs for prevention of GI injury associated with low-dose aspirin (LDA) were collected. Two reviewers independently abstracted studies and patient characteristics and appraised study quality using the Cochrane risk-of-bias tool. Meta-analysis was performed using RevMan 5.1 software. We included nine RCTs involving 1047 patients. The meta-analysis showed that PPIs were superior to H2RAs for prevention of LDA-associated GI erosion/ulcer [odds ratio (OR=0.28, 95% confidence interval (CI): 0.16-0.50] and bleeding (OR=0.28, 95% CI: 0.14-0.59). In conclusion, PPIs were superior to H2RAs for prevention of LDA-related GI erosion/ulcer and bleeding. Higher quality, large, multicenter RCTs are needed to demonstrate the preventive effect of the two acid-suppressive drugs.

Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries.

AIM: To determine the preventive effect and safety of proton pump inhibitors (PPIs) in low-dose aspirin (LDA)-associated gastrointestinal (GI) ulcers and bleeding. METHODS: We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to December 2013, and checked conference abstracts of randomized controlled trials (RCTs) on the effect of PPIs in reducing adverse GI events (hemorrhage, ulcer, perforation, or obstruction) in patients taking LDA. The preventive effects of PPIs were compared with the control group [taking placebo, a cytoprotective agent, or an H2 receptor antagonist (H2RA)] in LDA-associated upper GI injuries. The meta-analysis was performed using RevMan 5.1 software. RESULTS: We evaluated 8780 participants in 10 RCTs. The meta-analysis showed that PPIs decreased the risk of LDA-associated upper GI ulcers (OR = 0.16; 95%CI: 0.12-0.23) and bleeding (OR = 0.27; 95%CI: 0.16-0.43) compared with control. For patients treated with dual anti-platelet therapy of LDA and clopidogrel, PPIs were able to prevent the LDA-associated GI bleeding (OR = 0.36; 95%CI: 0.15-0.87) without increasing the risk of major adverse cardiovascular events (MACE) (OR = 1.00; 95%CI: 0.76-1.31). PPIs were superior to H2RA in prevention of LDA-associated GI ulcers (OR = 0.12; 95%CI: 0.02-0.65) and bleeding (OR = 0.32; 95%CI: 0.13-0.79). CONCLUSION: PPIs are effective in preventing LDA-associated upper GI ulcers and bleeding. Concomitant use of PPI, LDA and clopidogrel did not increase the risk of MACE.

Electrical stimulation therapy for slow transit constipation in children: a systematic review.

PURPOSE: Slow transit constipation is a common disorder in children, which often does not respond well to ordinary treatments. We have conducted a systematic review of reported studies in order to better define the current state of knowledge about electrical stimulation treatment of slow transit constipation in children. METHODS: We searched PubMed, Embase, Cochrane Library, BioMed Central, and ISI Web of Knowledge with relevant terms; six studies, all from one center, met the criteria for inclusion. Two trials were randomized clinical trials, and four were prospective studies. The number of subjects included in the studies was 8 to 39, with ages 3 to 18 years. RESULTS: Treatment sessions varied from 20 to 30 min 3 times per week to 1 h daily, and duration of therapy varied from 3 weeks to 6 months. Statistically significant improvements after electrical stimulation therapy were recorded in one to four outcome measures in each of the studies: frequency of defecation, soiling, Bristol Stool Scale, radionuclear transit studies, and quality of life; however, the improvements were of modest degree and of uncertain clinical significance. Quality assessment of the studies found various levels of bias, with attrition bias and reporting bias in all six. CONCLUSIONS: This systemic review found moderate support for the effectiveness of electrical stimulation therapy in slow transit constipation in children. However, better-designed studies, with larger and more diverse patient populations followed for longer time periods, will be needed in order to reliably determine the efficacy of electrical stimulation therapy in the treatment of this disorder.

Risk Factors Associated with Mortality and Increased Drug Costs in Nonvariceal Upper Gastrointestinal Bleeding.

BACKGROUND/AIMS: To determine risk factors associated with mortality and increased drug costs in patients with nonvariceal upper gastrointestinal bleeding. METHODOLOGY: We retrospectively analyzed data from patients hospitalized with nonvariceal upper gastrointestinal bleeding between January 2001-December 2011. Demographic and clinical characteristics and drug costs were documented. Univariate analysis determined possible risk factors for mortality. Statistically significant variables were analyzed using a logistic regression model. Multiple linear regression analyzed factors influencing drug costs. p < 0.05 was considered statistically significant. RESULTS: The study included data from 627 patients. Risk factors associated with increased mortality were age > 60, systolic blood pressure<100 mmHg, lack of endoscopic examination, comorbidities, blood transfusion, and rebleeding. Drug costs were higher in patients with rebleeding, blood transfusion, and prolonged hospital stay. CONCLUSION: In this patient cohort, re-bleeding rate is 11.20% and mortality is 5.74%. The mortality risk in patients with comorbidities was higher than in patients without comorbidities, and was higher in patients requiring blood transfusion than in patients not requiring transfusion. Rebleeding was associ-ated with mortality. Rebleeding, blood transfusion, and prolonged hospital stay were associated with increased drug costs, whereas bleeding from lesions in the esophagus and duodenum was associated with lower drug costs.