Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

Decompressive craniectomy for the treatment of refractory high intracranial pressure in traumatic brain injury

Abstract: Background High intracranial pressure (ICP) is the most frequent cause of death and disability after a severe traumatic brain injury (TBI) High ICP is usually treated with general maneuvers (normothermia, sedation, etc) and a set of first-line therapeutic measures (moderate hypocapnia, mannitol, etc) When these measures fail to control high ICP, second-line therapies are initiated Of these, barbiturates, hyperventilation, moderate hypothermia, or removal of a variable amount of skull bone (decompressive craniectomy) are used Objectives To assess the effects of secondary decompressive craniectomy on outcomes and quality of life for patients with severe TBI in whom conventional medical therapeutic measures have failed to control a raised ICP Search methods We searched the following electronic databases: Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, PubMed, EMBASE, ZETOC, CINAHL, and Controlled Trials metaRegister (wwwcontrolled-trialscom/mrct/search) We searched the Internet using Google Scholar (http://scholargooglecom) and handsearched relevant conference proceedings We also contacted experts in the field and authors of included studies The searches were last conducted in May 2008 Selection criteria Randomized or quasi-randomized studies assessing patients over the age of 12 months with severe TBI who underwent decompressive craniectomy to control ICP refractory to conventional medical treatments Data collection and analysis The electronic search and handsearching results were examined for reports of potentially relevant trials, which were then retrieved in full The selection criteria were applied, data extraction performed, and studies assessed for methodological quality Main results We found only one trial with 27 participants, conducted in a pediatric population Decompressive craniectomy was associated with a risk ratio (RR) for death of 054 (95% CI 017 to 172) and a RR of 054 (95% CI 029 to 101) for an unfavorable outcome (death, vegetative status, or severe disability 6 to 12 months after injury) To date, no results are available to confirm or refute the effectiveness of decompressive craniectomy in adults Authors' conclusions There is no evidence from randomized controlled trials that supports the routine use of secondary decompressive craniectomy to reduce unfavorable outcomes in adults with severe TBI and refractory high ICP In the study with a pediatric population, decompressive craniectomy reduced the risk of death and unfavorable outcomes Despite the wide CI for death and the small sample size of this one identified study, the treatment may be justified in patients below the age of 18 years when maximal medical treatment has failed to control ICP There are two ongoing randomized controlled trials of decompressive craniectomy (RescueICP and DECRA) that will allow further conclusions on the efficacy of this procedure in adults

Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAFV600E-Mutant Colorectal Cancer

Abstract: Although BRAF inhibitor monotherapy yields response rates >50% in BRAFV600-mutant melanoma, only ~5% with BRAFV600E colorectal cancer (CRC) respond. Preclinical studies suggest that lack of efficacy in BRAFV600E CRC is due to adaptive feedback reactivation of MAPK signaling, often mediated by EGFR. This clinical trial evaluated BRAF and EGFR inhibition with dabrafenib (D) + panitumumab (P) ± MEK inhibition with trametinib (T) to achieve greater MAPK suppression and improved efficacy in 142 patients with BRAFV600E CRC. Confirmed response rates for D+P, D+T+P, and T+P were 10%, 21%, and 0%, respectively. Pharmacodynamic analysis of paired pre- and on-treatment biopsies found that efficacy of D+T+P correlated with increased MAPK suppression. Serial cell-free DNA analysis revealed additional correlates of response and emergence of KRAS and NRAS mutations on disease progression. Thus, targeting adaptive feedback pathways in BRAFV600E CRC can improve efficacy, but MAPK reactivation remains an important primary and acquired resistance mechanism.

The role of VEGF and EGFR inhibition : Implications for combining anti-VEGF and anti-EGFR agents

Abstract: Multiple cellular pathways influence the growth and metastatic potential of tumors. This creates heterogeneity, redundancy, and the potential for tumors to bypass signaling pathway blockade, resulting in primary or acquired resistance. Combining therapies that inhibit different signaling pathways has the potential to be more effective than inhibition of a single pathway and to overcome tumor resistance. Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors have become key therapies in several tumor types. Close relationships between these factors exist: VEGF signaling is up-regulated by EGFR expression and, conversely, VEGF up-regulation independent of EGFR signaling seems to contribute to resistance to EGFR inhibition. Therefore, inhibition of both pathways could improve antitumor efficacy and overcome resistance to EGFR inhibition. Preclinical studies have shown that VEGF and EGFR inhibitors can have additive effects and that combined inhibition is effective in EGFR inhibitor-resistant cell lines. Clinical trials have also produced promising data: combining the anti-VEGF monoclonal antibody bevacizumab with the anti-EGFR antibody cetuximab or the EGFR tyrosine kinase inhibitor erlotinib increases benefit compared with either of these anti-EGFR agents alone or combined with chemotherapy. The potential of this novel approach to anticancer therapy will be elucidated by large, ongoing clinical trials.