Hooverbridges1425

Frontobasal fractures occur in up to 24% of head injuries and often require a multidisciplinary approach. Besides the common bone fractures, the complex anatomy can cause damage to the sense of vision and smell. Further possibly lethal complications such as cerebrospinal fluid leak followed by meningitis or internal carotid bleeding can follow. Diagnostic and treatment options are reviewed with a focus on the endoscopic endonasal approach.Optimal management of patients with traumatic brain injury (TBI) remains a challenge, despite significant improvements in pathophysiologic understanding and treatment strategies in recent decades. Because primary brain injury sustained at the time of trauma is irreversible, the TBI management mainly aims for early detection and treatment of secondary brain injury such as space-occupying intracerebral hematomas and brain edema. Prevention of secondary brain injury requires a high standard of care and understanding of both medical and surgical treatment modalities. This review focuses on practical recommendations for neurosurgical and intensive care management in patients with severe TBI.Airway management in craniofacial trauma patients is a challenge for an anesthetist. Treating these patients requires a close interdisciplinary communication and cooperation. Maintaining the airway and oxygenation of the patient is the initial challenge in craniofacial trauma patients. The management of the difficult airway is facilitated and patient's safety improved by following one of several published difficult airway algorithms. We describe the St. Gallen difficult airway algorithm for the management of difficult airway in general and the airway in facial trauma patients in particular. Whenever possible, the airway should be secured in a conscious and spontaneously breathing patient. It is important to be familiar with different techniques and to change the approach after two unsuccessful attempts with one technique. Once the airway is established, all available preventive measures should be used to avoid losing the airway. A tracheotomy has its place in a significant number of patients in whom an immediate postoperative or a delayed extubation appears unfeasible.

Identifying patients who will experience lung cancer recurrence after surgery remains a challenge. We aimed to evaluate whether mutant forms of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (mEGFR and mKRAS) are useful biomarkers in resected non-small cell lung cancer (NSCLC).

We retrospectively reviewed data from 841 patients who underwent surgery and molecular testing for NSCLC between 2007 and 2012.

mEGFR was observed in 103 patients (12.2%), and mKRAS in 265 (31.5%). The median overall survival (OS) and time to recurrence (TTR) were significantly lower for mKRAS (OS 43 months; TTR 19 months) compared with mEGFR (OS 67 months; TTR 24 months) and wild-type patients (OS 55 months; disease-free survival (DFS) 24 months). Patients with KRAS G12V exhibited worse OS and TTR compared with the entire cohort (OS KRAS G12V 26 months vs

60 months; DFS KRAS G12V 15 months vs

24 months). These results were confirmed using multivariate analyses (non-G12V status, hazard ratio (HR) 0.43 (confidence interval 0.28-0.65), P<0.0001 for OS; HR 0.67 (0.48-0.92), P=0.01 for TTR). Risk of recurrence was significantly lower for non-KRAS G12V (HR 0.01, (0.001-0.08), P<0.0001).

mKRAS and mEGFR may predict survival and recurrence in early stages of NSCLC. Patients with KRAS G12V exhibited worse OS and higher recurrence incidences.

mKRAS and mEGFR may predict survival and recurrence in early stages of NSCLC. Patients with KRAS G12V exhibited worse OS and higher recurrence incidences.

There is currently no standard second-line treatment for metastatic pancreatic adenocarcinoma (MPA), and progression-free survival is consistently <4 months in this setting. The aim of this study was to evaluate the efficacy and tolerability of Nab-paclitaxel plus gemcitabine (A+G) after Folfirinox failure in MPA.

From February 2013 to July 2014, all consecutive patients treated with A+G for histologically proven MPA after Folfirinox failure were prospectively enrolled in 12 French centres. A+G was delivered as described in the MPACT trial, until disease progression, patient refusal or unacceptable toxicity.

Fifty-seven patients were treated with Nab-paclitaxel plus gemcitabine, for a median of 4 cycles (range 1-12). The disease control rate was 58%, with a 17.5% objective response rate. Median overall survival (OS) was 8.8 months (95% CI 6.2-9.7) and median progression-free survival was 5.1 months (95% CI 3.2-6.2). Since the start of first-line chemotherapy, median OS was 18 months (95% CI 16-21). selleck compound No toxic deaths occurred. Grade 3-4 toxicities were reported in 40% of patients, consisting of neutropenia (12.5%), neurotoxicity (12.5%), asthenia (9%) and thrombocytopenia (6.5%).

A+G seems to be effective, with a manageable toxicity profile, after Folfirinox failure in patients with MPA.

A+G seems to be effective, with a manageable toxicity profile, after Folfirinox failure in patients with MPA.

Recently, many studies have suggested a possible adjuvant role of aspirin in colorectal cancer, reporting a positive prognostic effect with its use in patients with established disease. The aim of this study was to investigate the anticancer effect of aspirin use during preoperative chemoradiation for rectal cancer.

Two hundred and forty-one patients with stage II-III rectal cancer and candidates for chemoradiation (CRT) were selected and assigned to two groups group 1, patients taking aspirin at the time of diagnosis, and group 2, all others. Treatment and oncological outcomes were explored.

Aspirin use was associated with a higher rate of tumour downstaging (67.6% vs 43.6%, P=0.01), good pathological response (46% vs 19%; P<0.001), and a slightly, although not significant, higher rate of complete pathological response (22% vs 13%; P=0.196). Aspirin use was also associated with a better 5-year progression-free survival (86.6% vs 67.1%; hazard rate (HR)=0.20; 95% CI=0.07-0.60) and overall survival (90.6% vs 73.2%; HR=0.21; 95% CI=0.05-0.89). Although chance of local relapse was similar (HR=0.6; 95% CI=0.06-4.5), aspirin use was associated with a lower risk of developing metastasis (HR=0.30; 95% CI=0.10-0.86).

Aspirin might have anticancer activity against rectal cancer during preoperative CRT. This finding could be clinically relevant and should be further investigated with randomised trials.

Aspirin might have anticancer activity against rectal cancer during preoperative CRT. This finding could be clinically relevant and should be further investigated with randomised trials.

Renal cell carcinoma is one of the most chemoresistant cancers, and its metastatic form requires administration of targeted therapies based on angiogenesis or mTOR inhibitors. Understanding how these treatments impact the human metabolism is essential to predict the host response and adjust personalised therapies. We present a metabolomic investigation of serum samples from patients with metastatic RCC (mRCC) to identify metabolic signatures associated with targeted therapies.

Pre-treatment and serial on-treatment sera were available for 121 patients participating in the French clinical trial TORAVA, in which 171 randomised patients with mRCC received a bevacizumab and temsirolimus combination (experimental arm A) or a standard treatment either sunitinib (B) or interferon-α+bevacizumab (C). Metabolic profiles were obtained using nuclear magnetic resonance spectroscopy and compared on-treatment or between treatments.

Multivariate statistical modelling discriminates serum profiles before and after several weeks of treatment for arms A and C. The combination A causes faster changes in patient metabolism than treatment C, detectable after only 2 weeks of treatment. Metabolites related to the discrimination include lipids and carbohydrates, consistently with the known RCC metabolism and side effects of the drugs involved. Comparison of the metabolic profiles for the three arms shows that temsirolimus, an mTOR inhibitor, is responsible for the faster host metabolism modification observed in the experimental arm.

In mRCC, metabolomics shows a faster host metabolism modification induced by a mTOR inhibitor as compared with standard treatments. These results should be confirmed in larger cohorts and other cancer types.

In mRCC, metabolomics shows a faster host metabolism modification induced by a mTOR inhibitor as compared with standard treatments. These results should be confirmed in larger cohorts and other cancer types.

The human epidermal growth factor receptor (EGFR) is an important target for cancer treatment. Currently, only the EGFR antibodies cetuximab and panitumumab are approved for the treatment of patients with colorectal cancer. However, a major clinical challenge is a short-term response owing to development of acquired resistance during the course of the treatment.

In this study, we investigated the molecular mechanisms underlying development of acquired resistance in DiFi colorectal cancer cells to the anti-EGFR mAb ICR62 (termed DiFi62) and to the small molecule tyrosine kinase inhibitor (TKI) gefitinib (termed DiFiG) using a range of techniques.

Compared with the findings from parental DiFi and DiFiG cells, development of acquired resistance to anti-EGFR mAb ICR62 in DiFi62 cells was accompanied by an increase in cell surface EGFR and increased phosphorylation of HER-2 and HER-3. Interestingly, DiFi62 cells also acquired resistance to treatment with anti-EGFR mAbs cetuximab and ICR61, which bind to other distinct epitopes on the extracellular domain of EGFR, but these cells remained equally sensitive as the parental cells to treatment with pan-HER inhibitors such as afatinib.

Our results provide a novel mechanistic insight into the development of acquired resistance to EGFR antibody-based therapy in colorectal cancer cells and justify further investigations on the therapeutic benefits of pan-HER family inhibitors in the treatment of colorectal cancer patients once acquired resistance to EGFR antibody-based therapy is developed.

Our results provide a novel mechanistic insight into the development of acquired resistance to EGFR antibody-based therapy in colorectal cancer cells and justify further investigations on the therapeutic benefits of pan-HER family inhibitors in the treatment of colorectal cancer patients once acquired resistance to EGFR antibody-based therapy is developed.We examined the effects of Cd on growth, lipid peroxidation, reactive oxygen species (ROS) accumulation, antioxidant enzymatic activity, and lignin content in the roots of two varieties of Vicia sativa. Treatment with Cd decreased plant growth and increased ROS and lipid peroxidation levels to a greater extent in the Cd-sensitive variety ZM than in the Cd-tolerant variety L3. Most hydrogen peroxide (H2O2) and superoxide anion (O2(•-)) were accumulated in the cell walls and extracellular spaces in response to Cd treatments. Chemical assays and experiments using inhibitors showed that larger increases in H2O2 and O2(•-) production in ZM than in L3 were probably attributed to elevated Cd-induced nicotinamide adenine dinucleotide-peroxidase (NADH-POD) activity. Cd treatment increased the accumulation of lignin and the guaiacol peroxidase (GPOD) activities in the apoplast more significantly in ZM root than in L3. Howerver, root laccase activity was higher in L3 than in ZM. Thus Cd toxicity induced significant lignification in the roots of V.