Attribution of ghrelin to cancer; Attempts to unravel an apparent controversy

Ghrelin is an endogenous peptide hormone mainly produced in the stomach. It has been known to regulate energy homeostasis, stimulate secretion of growth hormone, and mediate many other physiologic effects. Various effects attributed to ghrelin contribute to many aspects of cancer development and progression. Accordingly, a large body of evidence has emerged about the association of ghrelin with several types of cancer in scales of cell-line, animal, and human studies. However, existing data are controversial. This controversy occurs in two main domains: one is the controversial results in local effects of ghrelin on different types of human cancer cell-lines; the second is the apparent disagreement in the results o

Prognostic significance of matrix metalloproteinase-7 in gastric cancer survival: a meta-analysis.

The prognostic role of matrix metalloproteinase-7 in gastric cancer survival has been widely evaluated. However, the results are controversial. We aimed to set up a meta-analysis to reach a conclusion on the prognostic significance of metalloproteinase-7 in gastric cancer survival as well as its association with clinicopathological parameters. We searched popular databases from 1988 until October 2014 to gather eligible peer-reviewed papers addressing the prognostic effect of matrix metalloproteinase-7 in gastric cancer patients' survival. The CASP check list was used for quality appraisal. Pooled hazard ratio (HR) for survival and odds ratio (OR) for association with their 95% confidence interval (CI) were considered as summary measurements. Finally, 1208 gastric cancer patients from nine studies were included in the meta-analysis. Pooled HR estimate for survival was 2.01 (95% CI = 1.62 - 2.50, P < 0.001), which indicated a significant poor prognostic effect for matrix metalloproteinase-7. Sensitivity analysis detected no dominancy for any study. No publication bias was detected according to Egger's and Begg's tests. Clinicopathological assessment revealed that higher matrix metalloproteinase-7 expression is associated with deeper invasion (pooled OR = 3.20; 95% CI = 1.14 - 8.96; P = 0.026), higher TNM stage (pooled OR = 3.67; 95% CI = 2.281-5.99; P<0.001), lymph node metastasis (pooled OR = 2.84; 95% CI = 1.89 - 4.25; P<0.001), and distant metastasis (pooled OR = 3.68; 95% CI = 1.85 - 7.29; P<0.001), but not with histological grade. This meta-analysis indicated a significant poor prognostic effect of matrix metalloproteinase-7 in gastric cancer survival. Additionally it was associated with aggressive tumor phenotype

Single-step transepithelial photorefractive keratectomy in high myopia: qualitative and quantitative visual functions

AIM: To investigate quantitative and qualitative optical outcomes of single-step transepithelial photorefractive keratectomy (TransPRK) in high myopia. METHODS: In a prospective interventional case-series, 30 eyes with high myopia (-6.00 to -8.75 D) with (up to -3.00 D) or without astigmatism were enrolled from Bina Eye Hospital, Tehran, Iran. One-step TransPRK was performed with aberration-free aspherical optimized profile and SCHWIND AMARIS 500 laser. One-year follow-up results for refraction, visual acuities, vector analysis, ocular wave-front (OWF) and corneal wave-front (CWF) higher order aberrations (HOA), contrast sensitivity (CS), and post-operative haze were assessed. RESULTS: After the surgery, both photopic and mesopic CSs significantly improved (both P<0.001). We detected significant induction of OWF coma and trefoil (P<0.001 for both) HOAs; CWF coma (P=0.002), spherical (P<0.001), and tetrafoil (P=0.003) HOAs in 6 mm analysis diameter; and CWF trefoil (P=0.04) HOA in 4 mm analysis diameter. The range of mean induction observed for various HOAs was 0.005-0.11 µm. The 86.7% of eyes reached an uncorrected distance visual acuity of 20/20 or better; 96.7% of eyes were within ±0.5 D of targeted spherical refraction. In vector analysis, mean correction index value was 1.03 and mean index of success was 0.22. By 12mo after the operation, no eye lost any number of corrected distance visual acuity lines. We detected no corneal haze greater than 1+ throughout the follow-up. CONCLUSION: Our findings show promising effects of single-step TransPRK on quality of vision in high myopic eyes. It also improves refraction and visual acuity

Flow diagram for study selection process.

<p>The figure demonstrates how finally included studies were selected from primary search records.</p

Meta-analysis of MMP7 overexpression association with clinicopathological parameters in included studies.

<p><i>OR</i>: pooled odds ratio; <i>CI</i>: confidence interval; <i>Z</i>: test value for fixed/random effect model; <i>P</i>_<i>Z</i>: statistical <i>P value</i> for Z test; <i>P</i>_<i>Q</i>: statistical <i>P value</i> for heterogeneity Q test. <i>I</i>^<i>2</i><i>%</i>: quantitative metric I²test.</p><p>^a Fixed effect model OR (95% CI)</p><p>^b random effect model OR (95% CI)</p><p>Meta-analysis of MMP7 overexpression association with clinicopathological parameters in included studies.</p

Subgroup meta-analysis results for MMP7 impact on Gastric Cancer survival.

<p><i>HR</i>: pooled hazard ratio; <i>CI</i>: confidence interval; <i>Z</i>: test value for fixed/random effect model; <i>P</i>_<i>Z</i>: statistical <i>P value</i> for Z test; <i>P</i>_<i>Q</i>: statistical <i>P value</i> for heterogeneity Q test.</p><p>^a Fixed effect model HR (95% CI)</p><p>^b random effect model HR (95% CI)</p><p>Subgroup meta-analysis results for MMP7 impact on Gastric Cancer survival.</p

New insights into physiopathology of immunodeficiency-associated vaccine-derived poliovirus infection; systematic review of over 5 decades of data.

International audienceWidespread administration of oral poliovirus vaccine (OPV) has decreased global incidence of poliomyelitis by ≈99.9%. However, the emergence of vaccine-derived polioviruses (VDPVs) is threatening polio-eradication program. Primary immunodeficiency (PID) patients are at higher risks of vaccine-associated paralytic poliomyelitis (VAPP) and prolonged excretion of immunodeficiency-associated VDPV (iVDPV). We searched Embase, Medline, Science direct, Scopus, Web of Science, and CDC and WHO databases by 30 September 2016, for all reports of iVDPV cases. Patient-level data were extracted form eligible studies. Data on immunization coverage and income-level of countries were extracted from WHO/UNICEF and the WORLD BANK databases, respectively. We assessed bivariate associations between immunological, clinical, and virological parameters, and exploited multivariable modeling to identify independent determinants of poliovirus evolution and patients' outcomes. Study protocol was registered with PROSPERO (CRD42016052931). 4329 duplicate-removed titles were screened. A total of 107 iVDPV cases were identified from 68 eligible articles. The majority of cases were from higher income countries with high polio-immunization coverage. 74 (69.81%) patients developed VAPP. Combined immunodeficiency patients showed lower rates of VAPP (p \textless .001) and infection clearance (p = .02), compared to humoral immunodeficiency patients. The rate of poliovirus genomic evolution was higher at early stages of replication, decreasing over time until reaching a steady state. Independent of replication duration, higher extent (p = .04) and rates (p = .03) of genome divergence contributed to a less likelihood of virus clearance. PID type (p \textless .001), VAPP occurrence (p = .008), and income-level of country (p = .04) independently influenced patients' survival. With the use of OPV, new iVDPVs will emerge independent of the rate of immunization coverage. Inherent features of PIDs contribute to the clinical course of iVDPV infection and virus evolution. This finding could shed further light on poliomyelitis pathogenesis and iVDPV evolution pattern. It also has implications for public health, the polio eradication effort and the development of effective antiviral interventions

Forrest plot of overall hazard ratio estimate for MMP7 impact on GC survival.

<p>The middle point of the diamond represents the pooled HR and its left and right corners represent 95% CI. Horizontal lines belong to individual studies; the middle point and line length represent the corresponding study`s extracted HR and 95% CI. The area of box tagged with each line represents the individual study`s weight of contribution to the meta-analysis.</p

Evidence-based prevention and treatment of osteoporosis after spinal cord injury: a systematic review

© 2017, Springer-Verlag Berlin Heidelberg. Purpose: Spinal cord injury (SCI) results in accelerated bone mineral density (BMD) loss and disorganization of trabecular bone architecture. The mechanisms underlying post-SCI osteoporosis are complex and different from other types of osteoporosis. Findings of studies investigating efficacy of pharmacological or rehabilitative interventions in SCI-related osteoporosis are controversial. The aim of this study was to review the literature pertaining to prevention and evidence-based treatments of SCI-related osteoporosis. Methods: In this systematic review, MEDLINE, EMBASE, PubMed, and the Cochrane Library were used to identify papers from 1946 to December 31, 2015. The search strategy involved the following keywords: spinal cord injury, osteoporosis, and bone loss. Results: Finally, 56 studies were included according to the inclusion criteria. Only 16 randomized controlled trials (involving 368 patients) were found. We found following evidences for effectiveness of bisphosphonates in prevention of BMD loss in acute SCI: very low-quality evidence for clodronate and etidronate, low-quality evidence for alendronate, and moderate-quality evidence for zoledronic acid. Low-quality evidence showed no effectiveness for tiludronate. In chronic SCI cases, we found low-quality evidence for effectiveness of vitamin D 3 analogs combined with 1-alpha vitamin D 2 . However, low-quality inconsistent evidence exists for alendronate. For non-pharmacologic interventions, very low-quality evidence exists for effectiveness of standing with or without treadmill walking in acute SCI. Other low-quality evidences indicated that electrical stimulation, tilt-table standing, and ultrasound provide no significant effects. Very low-quality evidence did not show any benefit for low-intensity (3 days per week) cycling with functional electrical stimulator in chronic SCI. Conclusions: No recommendations can be made from this review, regarding overall low quality of evidence as a result of high risk of bias, low sample size in most of the studies, and notable heterogeneity in type of intervention, outcome measurement, and duration of treatment. Therefore, future high-quality RCT studies with higher sample sizes and more homogeneity are strongly recommended to provide high-quality evidence and make applicable recommendations for prevention and treatment of SCI-related bone loss