Pure endoscopic endonasal odontoidectomy: anatomical study

Different disorders may produce irreducible atlanto-axial dislocation with compression of the ventral spinal cord. Among the surgical approaches available for a such condition, the transoral resection of the odontoid process is the most often used. The aim of this anatomical study is to demonstrate the possibility of an anterior cervico-medullary decompression through an endoscopic endonasal approach. Three fresh cadaver heads were used. A modified endonasal endoscopic approach was made in all cases. Endoscopic dissections were performed using a rigid endoscope, 4 mm in diameter, 18 cm in length, with 0 degree lenses. Access to the cranio-vertebral junction was possible using a lower trajectory, when compared to that necessary for the sellar region. The choana is entered and the mucosa of the rhinopharynx is dissected and transposed in the oral cavity in order to expose the cranio-vertebral junction and to obtain a mucosal flap useful for the closure. The anterior arch of the atlas and the odontoid process of C2 are removed, thus exposing the dura mater. The endoscopic endonasal approach could be a valid alternative to the transoral approach for anterior odontoidectomy

Early Events Associated with Infection of Epstein-Barr Virus Infection of Primary B-Cells

Epstein Barr virus (EBV) is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology) was used to introduce an expression cassette of green fluorescent protein (GFP) by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6–7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6–12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Different strategies for mechanical VENTilation during CardioPulmonary Bypass (CPBVENT 2014): Study protocol for a randomized controlled trial

Background: There is no consensus on which lung-protective strategies should be used in cardiac surgery patients. Sparse and small randomized clinical and animal trials suggest that maintaining mechanical ventilation during cardiopulmonary bypass is protective on the lungs. Unfortunately, such evidence is weak as it comes from surrogate and minor clinical endpoints mainly limited to elective coronary surgery. According to the available data in the academic literature, an unquestionable standardized strategy of lung protection during cardiopulmonary bypass cannot be recommended. The purpose of the CPBVENT study is to investigate the effectiveness of different strategies of mechanical ventilation during cardiopulmonary bypass on postoperative pulmonary function and complications. Methods/design: The CPBVENT study is a single-blind, multicenter, randomized controlled trial. We are going to enroll 870 patients undergoing elective cardiac surgery with planned use of cardiopulmonary bypass. Patients will be randomized into three groups: (1) no mechanical ventilation during cardiopulmonary bypass, (2) continuous positive airway pressure of 5 cmH2O during cardiopulmonary bypass, (3) respiratory rate of 5 acts/min with a tidal volume of 2-3 ml/Kg of ideal body weight and positive end-expiratory pressure of 3-5 cmH2O during cardiopulmonary bypass. The primary endpoint will be the incidence of a PaO2/FiO2ratio <200 until the time of discharge from the intensive care unit. The secondary endpoints will be the incidence of postoperative pulmonary complications and 30-day mortality. Patients will be followed-up for 12 months after the date of randomization. Discussion: The CPBVENT trial will establish whether, and how, different ventilator strategies during cardiopulmonary bypass will have an impact on postoperative pulmonary complications and outcomes of patients undergoing cardiac surgery. Trial registration: ClinicalTrials.gov, ID: NCT02090205. Registered on 8 March 2014

Gecko-inspired chitosan adhesive for tissue repair

The advent of nanotechnology has opened the possibility of fabricating nanoscopic pillars on the surface of polymeric films mimicking the Gecko\u27s foot, in an attempt to increase their adhesive capabilities enhanced by van der Waals forces. However, these forces are considerably weakened in a wet physiological environment. To circumvent this loss in force, current biocompatible adhesives with nanopillars require complex multiple-step fabrication, including an extra layer of adhesive coating to stabilize tissue bonding under physiological conditions. In this report, we describe a simple one-step fabrication process of a single-layer chitosan film that has pillars with base diameter in the range of 100-600 nm and a height of ~70 nm. The nanostructured adhesive is laser-bonded to tissue and does not require pillar coating to enhance bonding in water. In comparison with a \u27flat\u27 adhesive (without pillars), the nanostructured adhesive bonded significantly stronger to tissue under either stress or pressure. Atomic force spectroscopy also confirmed the superior bonding capability of the nanostructured adhesive. This study demonstrates a one-step fabrication technique to produce a monolayer gecko-inspired adhesive that is biocompatible and bonds effectively to tissue