Do etoricoxib and indometacin have similar effects and safety for gouty arthritis? A meta-analysis of randomized controlled trials

Tzu-Min Lin,1,2,* Jia-En Chi,1,3,* Chi-Ching Chang,2,4,* Yi-No Kang1 1Center for Evidence-Based Medicine, Department of Education, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China; 2Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China; 3School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China; 4Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China *These authors contributed equally to this work Background: Gout, a common medical condition that causes pain, can be treated by painkillers and anti-inflammatories. Indometacin and etoricoxib are two such drugs. However, no synthesized evidence exists comparing etoricoxib with indometacin in treating patients with gout.Methods: We searched PubMed, Embase, Ovid MEDLINE, Web of Science, ScienceDirect, and the Cochrane Library without restrictions on language or publication date for potential randomized clinical trials comparing etoricoxib with indometacin for gout. The meta-analysis was conducted using a random-effects model.Results: Search results yielded 313 references from six electronic databases, four of which met the eligibility criteria. These four were randomized clinical trials, and they involved a total of 609 patients with gouty arthritis. No significant differences were observed in pain score change, tenderness, or swelling between etoricoxib and indometacin; the mean differences were −0.05 (95% CI, −0.21 to 0.10), −0.06 (95% CI, −0.18 to 0.05), and −0.04 (95% CI, −0.17 to 0.09). However, the pooled data revealed that significantly fewer overall adverse events occurred in the etoricoxib group (n=105, 33.5%) than in the indometacin group (n=130, 44.1%) and the risk ratio was 0.77 (95% CI, 0.62–0.94).Conclusion: Our meta-analysis revealed that etoricoxib and indometacin have similar effects on pain relief. However, etoricoxib has a significantly lower risk of adverse events than does indometacin, especially digestive system-related adverse events. Keywords: gout, etoricoxib, indometacin&nbsp

Seronegative Herpes simplex Associated Esophagogastric Ulcer after Liver Transplantation

Herpes simplex infection is characterized by acute or subacute infection, often followed by a chronic carrier state. Consecutive recurrences may flare up if immunocompromise occurs. Herpes simplex associated esophagitis or duodenal ulcer have been reported in immunocompromised patients due to neoplasm, HIV/AIDS or therapeutically induced immune deficiency. Here we report the case of an HSV-DNA seronegative patient who developed grade III dysphagia 13 days after allogeneic liver transplantation. Endoscopy revealed an esophageal-gastric ulcer, and biopsy histopathology showed a distinct fibroplastic and capillary ulcer pattern highly suspicious for viral infection. Immunohistochemistry staining revealed a distinct nuclear positive anti-HSV reaction. Antiviral therapy with acyclovir and high-dose PPI led to a complete revision of clinical symptoms within 48 h. Repeat control endoscopy after 7 days showed complete healing of the former ulcer site at the gastroesophageal junction. Although the incidence of post-transplantation Herpes simplex induced gastroesophageal disease is low, the viral HSV ulcer may be included into a differential diagnosis if dysphagia occurs after transplantation even if HSV-DNA PCR is negative

Long-term prognosis of symptomatic isolated middle cerebral artery disease in Korean stroke patients

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the long-term mortality and recurrence rate of stroke in first-time stroke patients with symptomatic isolated middle cerebral artery disease (MCAD) under medical management.</p> <p>Methods</p> <p>We identified 141 first ever stroke patients (mean age, 64.4 ± 12.5 years; 53% male) with symptomatic isolated MCAD. MCAD was defined as significant stenosis of more than 50% or occlusion of the MCA as revealed by MR angiography. The median follow-up was 27.7 months. We determined a cumulative rate of stroke recurrence and mortality by Kaplan-Meier survival analyses and sought predictors using the Cox proportional hazard model.</p> <p>Results</p> <p>The cumulative composite outcome rate (stroke recurrence or any-cause death) was 14%, 19%, 22%, and 28% at years 1, 2, 3, and 5, respectively. The annual recurrence rate of stroke was 4.1%. The presence of diabetes mellitus was the only significant independent predictor of stroke recurrence or any cause of death in multivariate analyses of Cox proportional hazard model adjusted for any plausible potential confounding factors.</p> <p>Conclusions</p> <p>We estimated the long-term prognosis of stroke patients with isolated symptomatic MCAD under current medical management in Korea. Diabetes mellitus was found to be a significant predictor for stroke recurrence and mortality.</p

The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis

BACKGROUND: The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. RESULTS: Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. CONCLUSION: Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes

Where It’s at Really Matters: In Situ In Vivo Vascular Endothelial Growth Factor Spatially Correlates with Electron Paramagnetic Resonance pO2 Images in Tumors of Living Mice

Purpose: Tumor microenvironments show remarkable tumor pO_{2} heterogeneity, as seen in prior EPR pO_{2} images (EPROI). pO_{2} correlation with hypoxia response proteins is frustrated by large rapid pO2 changes with position. Procedures: To overcome this limitation, biopsies stereotactically located in the EPROI were used to explore the relationship between vascular endothelial growth factor A (VEGF) concentrations in living mouse tumors and the local EPROI pO_{2}. Results: Quantitative ELISA VEGF concentrations correlated (p = 0.0068 to 0.019) with mean pO_{2}, median pO_{2}, and the fraction of voxels in the biopsy volume with pO_{2} less than 3, 6, and 10 Torr. Conclusions: This validates EPROI hypoxic fractions at the molecular level and provides a new paradigm for the assessment of the relationship, in vivo, between hypoxia and hypoxia response proteins. When translated to human subjects, this will enhance understanding of human tumor pathophysiology and cancer response to therapy

Direct Measurement of B(D0->phiX0) and B(D+->phiX+)

The first measurement of B(0->phi X0) and an upper limit for B(D+->phi X+) are determined from 22.3 pb-1 of e+e- annihilation data at a C. M. energy of 4.03 GeV. The data were recorded by the Beijing Spectrometer (BES) at BEPC. A recoil charge method is applied for the first time to charm threshold data to determine the charge of the D meson in the recoil from 9054+-309+-416 reconstructed D0, D+ mesons. The branching fractions B(D->phiX0) =(1.71+0.76-0.71+-0.17)%, and B(D+->phiX+) <1.8% are determined from 10 events with a reconstructed D and a recoiling phi. In addition, a 90% C.L. upper limit of B(D+->phi e+X0)<1.6% is determined from a search for semileptonic decays of the D+.Comment: Submitted to Phys. Rev.

Suppression of TGFβ-Induced Epithelial-Mesenchymal Transition Like Phenotype by a PIAS1 Regulated Sumoylation Pathway in NMuMG Epithelial Cells

Epithelial-mesenchymal-transition (EMT) is a fundamental cellular process that is critical for normal development and tumor metastasis. The transforming growth factor beta (TGFβ) is a potent inducer of EMT like effects, but the mechanisms that regulate TGFβ-induced EMT remain incompletely understood. Using the widely employed NMuMG mammary epithelial cells as a model to study TGFβ-induced EMT, we report that TGFβ downregulates the levels of the SUMO E3 ligase PIAS1 in cells undergoing EMT. Gain and loss of function analyses indicate that PIAS1 acts in a SUMO ligase dependent manner to suppress the ability of TGFβ to induce EMT in these cells. We also find that TGFβ inhibits sumoylation of the PIAS1 substrate SnoN, a transcriptional regulator that antagonizes TGFβ-induced EMT. Accordingly, loss of function mutations of SnoN sumoylation impair the ability of SnoN to inhibit TGFβ-induced EMT in NMuMG cells. Collectively, our findings suggest that PIAS1 is a novel negative regulator of EMT and reveal that inhibition of the PIAS1-SnoN sumoylation pathway represents a key mechanism by which TGFβ induces EMT, with important implications in normal development and tumor metastasis

Etiologic Diagnosis of Lower Respiratory Tract Bacterial Infections Using Sputum Samples and Quantitative Loop-Mediated Isothermal Amplification

Etiologic diagnoses of lower respiratory tract infections (LRTI) have been relying primarily on bacterial cultures that often fail to return useful results in time. Although DNA-based assays are more sensitive than bacterial cultures in detecting pathogens, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. Here we report a nationwide cohort study on 2986 suspected LRTI patients across P. R. China. We compared the performance of a DNA-based assay qLAMP (quantitative Loop-mediated isothermal AMPlification) with that of standard bacterial cultures in detecting a panel of eight common respiratory bacterial pathogens from sputum samples. Our qLAMP assay detects the panel of pathogens in 1047(69.28%) patients from 1533 qualified patients at the end. We found that the bacterial titer quantified based on qLAMP is a predictor of probability that the bacterium in the sample can be detected in culture assay. The relatedness of the two assays fits a logistic regression curve. We used a piecewise linear function to define breakpoints where latent pathogen abruptly change its competitive relationship with others in the panel. These breakpoints, where pathogens start to propagate abnormally, are used as cutoffs to eliminate the influence of contaminations from normal flora. With help of the cutoffs derived from statistical analysis, we are able to identify causative pathogens in 750 (48.92%) patients from qualified patients. In conclusion, qLAMP is a reliable method in quantifying bacterial titer. Despite the fact that there are always latent bacteria contaminated in sputum samples, we can identify causative pathogens based on cutoffs derived from statistical analysis of competitive relationship

Gas7-Deficient Mouse Reveals Roles in Motor Function and Muscle Fiber Composition during Aging

Background: Growth arrest-specific gene 7 (Gas7) has previously been shown to be involved in neurite outgrowth in vitro; however, its actual role has yet to be determined. To investigate the physiological function of Gas7 in vivo, here we generated a Gas7-deficient mouse strain with a labile Gas7 mutant protein whose functions are similar to wild-type Gas7. Methodology/Principal Findings: Our data show that aged Gas7-deficient mice have motor activity defects due to decreases in the number of spinal motor neurons and in muscle strength, of which the latter may be caused by changes in muscle fiber composition as shown in the soleus. In cross sections of the soleus of Gas7-deficient mice, gross morphological features and levels of myosin heavy chain I (MHC I) and MHC II markers revealed significantly fewer fast fibers. In addition, we found that nerve terminal sprouting, which may be associated with slow and fast muscle fiber composition, was considerably reduced at neuromuscular junctions (NMJ) during aging. Conclusions/Significance: These findings indicate that Gas7 is involved in motor neuron function associated with muscle strength maintenance