Effect of Bevacizumab Plus Temozolomide-Radiotherapy for Newly Diagnosed Glioblastoma with Different MGMT Methylation Status: A Meta-Analysis of Clinical Trials.

BACKGROUND MGMT methylation status can influence the therapeutic effect and prognosis of glioblastoma (GBM). There are conflicting results from studies evaluating the efficacy of bevacizumab (BV) when it is combined with temozolomide (TMZ) and radiotherapy (RT) in patients diagnosed with GBM with different MGMT methylation status. MATERIAL AND METHODS Data were extracted from publications in PubMed, Embase, and The Cochrane Library, with the last search performed March 23, 2016. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained. RESULTS Data from 3 clinical trials for a total of 1443 subjects were used for this meta-analysis. MGMT methylated and unmethylated patients showed improved PFS in the BV group (pooled HRs, 0.769, 95% CIs 0.604-0.978, P=0.032; 0.675, 95%CIs 0.466-0.979, P=0.038). For patients with either type of GBM, BV did not improve the OS based on the pooled HRs 1.132 (95% CIs 0.876-1.462; P=0.345) for methylated and 1.018 (95% CIs 0.879-1.179; P=0.345) for unmethylated. CONCLUSIONS Bevacizumab combined with temozolomide-radiotherapy correlated with improved PFS for treatment of patients with different MGMT methylation status of newly diagnosed GBM. There was insufficient evidence to determine the synergistic effects of combining BV with TMZ and RT on improving survival in patients with different MGMT methylation status.

Effect of metformin on serum interleukin-6 levels in polycystic ovary syndrome: a systematic review.

BACKGROUND: Most women with polycystic ovary syndrome (PCOS) have insulin resistance, hyperinsulinemia, and elevated serum IL-6 levels. These elevated IL-6 levels may have links with insulin resistance and hyperandrogenism. Metformin may have beneficial effects on the chronic low-grade inflammatory background associated with PCOS. METHODS: A systematic review was performed via PUBMED, EMBASE, and The Cochrane Library on PCOS studies published through November 30, 2013. Studies were selected that evaluated the effect of metformin on IL-6 levels in PCOS patients. Studies not containing adequate diagnosis information about PCOS or not excluding of other causes of hyperandrogenism were excluded. RESULTS: Five studies met the inclusion criteria. Of these, one study reported a significant decrease in IL-6 levels after metformin treatment in women with PCOS. Two studies reported that treatment-related reductions in IL-6 levels were significantly correlated with insulin metabolism. In the remaining two studies, plasma IL-6 levels did not change following metformin treatment. CONCLUSIONS: Serum IL-6 levels of PCOS patients may be influenced by metformin. Early application of metformin therapy may relieve chronic low-grade inflammation in women with PCOS. However, further investigations with larger samples are needed to better understand the effects of metformin on IL-6 levels and chronic inflammation in PCOS.

An examination of the protective effects and molecular mechanisms of curcumin, a polyphenol curcuminoid in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and is an enormous burden on both patients and society. There is an urgent need for effective alternative therapeutic strategies for the treatment of DN, as medical treatment is currently limited. The anti-inflammatory, antioxidative, anti-apoptotic, and anti-fibrosis properties of curcumin, a polyphenol curcuminoid, have been demonstrated in research on diabetic nephropathy. The clinical and preclinical trials and mechanisms by which curcumin affects DN have been discussed in this review. A deeper understanding of the pharmacological effects of curcumin on diabetic nephropathy may provide new therapies to improve the development and occurrence of diabetic nephropathy.

Rapid Recovery of Spontaneous Spinal Epidural Hematoma without Surgical Treatment: Case Report and Literature Review.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is a relatively uncommon yet potentially disabling neurologic emergency. The classical presentation includes a severe acute attack, sometimes radiating pain at the back, interscapular, or neck areas, followed by neurologic deficits. The main treatment is surgical, and self-healing cases are rare. CASE DESCRIPTION: A 17-year-old female was admitted to the neurosurgery department with neck pain, myasthenia of the limbs, and difficulty moving. Mild neck pain had developed 1 week prior with no obvious predisposing causes. The patient had suddenly suffered severe neck pain during normal walking and developed rapid paralysis of her limbs. There was no recent history of trauma, infection, or drug administration. Magnetic resonance imaging performed 1 hour after the onset of limb paralysis demonstrated a large spinal epidural hematoma that extended from C4 to C6. However, 9 hours after the initial onset of severe neck pain, her symptoms completely ceased. Magnetic resonance imaging demonstrated that the SSEH had nearly dissipated. CONCLUSIONS: Most cases of SSEH with spontaneous resolution are located on the upper thoracic and cervical spine. Surgery is the standard of care for these patients but can occasionally be deferred if the patient demonstrates significant rapid improvement.

Association of ACVRL1 Genetic Polymorphisms with Arteriovenous Malformations: A Case-Control Study and Meta-Analysis.

OBJECTIVE: To investigate the association between polymorphisms in the gene encoding activin receptorlike kinase 1 (ACVRL1) with brain arteriovenous malformations (BAVMs) using a case-control study in a Chinese Han population, followed by a meta-analysis of the published literature. METHODS: This study focused on the genotypic analysis of 4 single nucleotide polymorphisms (SNPs; rs2071219, rs706819, rs2293094, and rs11169953) in 50 patients with BAVM and 120 healthy volunteers attending Provincial Hospital in China. A meta-analysis was subsequently conducted involving an extensive literature search for relevant studies. RESULTS: Our cohort study showed a significant association between ACVRL1 rs706819 and increased risk for BAVM. Reduced BAVM risk was correlated with the G allele of rs2293094 and the C allele of rs11169953. However, neither the genotype nor allele frequencies of rs2071219 were found to be significantly different between the BAVM and control groups. Meta-analysis further confirmed that no significant evidence of association was found between rs2071219 and BAVM risk. Haplotype analysis of rs706819, rs2293094, and rs11169953 showed that the GGT haplotype could reduce the risk of BAVM, whereas the GAC haplotype may increase the risk of BAVM. CONCLUSIONS: The present study indicates an association between 3 susceptibility SNPs, rs706819, rs2293094, and rs11169953, in the ACVRL1 gene and BAVM. Follow-up functional studies on the ACVRL1 gene are required to better understand its roles in BAVM development.

Association of VEGF genetic polymorphisms with recurrent spontaneous abortion risk: a systematic review and meta-analysis.

BACKGROUND: Studies of the associations between the genetic polymorphisms of the vascular endothelial growth factor (VEGF) gene and recurrent spontaneous abortion (RSA) have revealed conflicting results. The present meta-analysis was performed to provide a more precise estimation of these relationships and to explore potential sources of heterogeneity that may have influenced the reported disparities. METHODS: An extensive literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library through June 6, 2014. Crude odds ratio (OR) with 95% confidence intervals were calculated. RESULTS: 10 case-control studies including 1,832 RSA patients and 2,271 healthy controls were identified. Meta-analysis indicated that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms in the VEGF gene correlated with elevated RSA risk. The rs1570360 variant was statistically significantly relevant to RSA risk among non-Asian populations. Interestingly, the rs3025039 variant was statistically significantly relevant to RSA risk among Asian populations. CONCLUSIONS: The current meta-analysis indicates that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms increase RSA susceptibility. Moreover, rs1570360 and rs3025039 polymorphisms may play various roles in RSA susceptibility in various geographic groups.

c-Met expression is associated with time to recurrence in patients with glioblastoma multiforme.

The aim of this study was to explore the difference in c-Met expression between primary and recurrent glioblastoma multiforme (GBM), and to determine whether the dysregulation of c-Met expression has a role in the malignant progression of GBM. Paired primary and recurrent GBM specimens from the same patient were evaluated using immunohistochemical analysis. The association between c-Met expression and progression-free survival time (PFST) was analyzed. There was a significant difference in c-Met expression between primary and recurrent tumors (p=0.020), and patients with tumors expressing c-Met at a higher level had a significantly shorter PFST (6.1 months vs. 11.5 months; p=0.026). Our study indicates that recurrent GBM express c-Met at a higher level and that c-Met overexpression is associated with shorter PFST in patients with GBM. These findings suggest that c-Met potentially has an important role in the treatment of GBM.