Surgical site infection in spinal metastasis: risk factors and countermeasures.

金沢大学附属病院整形外科STUDY DESIGN: A retrospective review (phase 1) and prospective clinical study (phase 2). OBJECTIVES: To identify independent risk factors for surgical site infection (SSI) and to evaluate the positive effect of prostaglandin E1 (PGE1) to decrease the risk of SSI in patients with spinal metastasis. SUMMARY OF BACKGROUND DATA: Surgery for spinal metastasis is associated with an increased risk of SSI. Although previous reports have evaluated risk factors of SSI for spinal metastasis, most of the studies lack multivariate analysis. A recent study demonstrated the utility of PGE1 in decreasing wound complications in patients with prior irradiation. The role of PGE1 in surgery for spinal metastasis has not been previously evaluated. METHODS: One hundred ten patients with spinal metastasis were retrospectively reviewed (phase 1). Risk factors for SSI were analyzed using logistic regression. Phase 2 was a prospective clinical trial investigating the utility of PGE1 at reducing the rate of SSI. Ninety-four patients with spinal metastasis were treated at our institute. The infection rate and risk factors identified in phase 1 and 2 were compared. RESULTS: The rate of SSI during phase 1 was 7.1%. Independent risk factors identified by multivariate logistic regression were diabetes, and preoperative irradiation. The rate of SSI for patients who had irradiation before surgery was 32%, whereas the rate for patients without irradiation was 1.1%. This difference was statistically significant. The rate of SSI in phase 2 was 3.1%. In phase 2 patients who received preoperative irradiation, the rate of SSI was 4.5%. The difference between phase 1 and phase 2 was statistically significant. CONCLUSION: This study identified diabetes and preoperative irradiation to be independent risk factors for SSI in patients with spinal metastasis. PGE1 administration was found to significantly decrease the incidence of SSI in patients with spinal metastasis who underwent preoperative irradiation.全文公開2010031

Neoadjuvant chemotherapy with docetaxel, nedaplatin, and fluorouracil for resectable esophageal cancer : A phase II study

Cisplatin plus 5‐fluorouracil is regarded as standard neoadjuvant chemotherapy for esophageal squamous cell carcinoma (ESCC) in Japan, but the prognosis remains poor. We have previously described how definitive chemoradiotherapy with docetaxel, nedaplatin, and 5‐fluorouracil (DNF) led to a very high response rate and promising survival times. We therefore undertook a phase II trial to evaluate the feasibility and efficacy of neoadjuvant DNF. The study included patients with clinical stage Ib‐III ESCC. Chemotherapy consisted of i.v. docetaxel (30 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 8, and a continuous infusion of 5‐fluorouracil (400 mg/m2/day) on days 1‐5 and 8‐12, every 3 weeks. After three courses of chemotherapy, esophagectomy was carried out. The primary end‐point was the completion rate of the protocol treatment. Twenty‐eight patients were enrolled (cStage Ib/II/III, 2/3/23) and all received at least two cycles of chemotherapy. Twenty‐five patients underwent surgery, all of whom achieved an R0 resection, leading to a completion rate of 89.3%. The overall response rate was 87.0%. A pathological complete response was confirmed in eight (32.0%) cases. Grade 3/4 adverse events included leukopenia (32.1%), neutropenia (39.3%), febrile neutropenia (10.7%), thrombocytopenia (10.7%), and diarrhea (14.3%), but were manageable. Treatment‐related deaths and major surgical complications did not occur. Estimated 2‐year progression‐free and overall survival rates were 70.4% and 77.2%, respectively. Thus, DNF therapy was well tolerated and deemed feasible, with a strong tumor response in a neoadjuvant setting for ESCC. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014305)

Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: an open-label, single-arm, multicenter, pilot study

Background: Glutathione plays crucial roles in the detoxification and antioxidant systems of cells and has been used to treat acute poisoning and chronic liver diseases by intravenous injection. This is a first study examining the therapeutic effects of oral administration of glutathione in patients with nonalcoholic fatty liver disease (NAFLD). Methods: The study was an open label, single arm, multicenter, pilot trial. Thirty-four NAFLD patients diagnosed using ultrasonography were prospectively evaluated. All patients first underwent intervention to improve their lifestyle habits (diet and exercise) for 3 months, followed by treatment with glutathione (300 mg/day) for 4 months. We evaluated their clinical parameters before and after glutathione treatment. We also quantified liver fat and fibrosis using vibration-controlled transient elastography. The primary outcome of the study was the change in alanine aminotransferase (ALT) levels. Results: Twenty-nine patients finished the protocol. ALT levels significantly decreased following treatment with glutathione for 4 months. In addition, triglycerides, non-esterified fatty acids, and ferritin levels also decreased with glutathione treatment. Following dichotomization of ALT responders based on a median 12.9% decrease from baseline, we found that ALT responders were younger in age and did not have severe diabetes compared with ALT non-responders. The controlled attenuation parameter also decreased in ALT responders. Conclusions: This pilot study demonstrates the potential therapeutic effects of oral administration of glutathione in practical dose for patients with NAFLD. Large-scale clinical trials are needed to verify its efficacy. Trial registration: UMIN000011118 (date of registration: July 4, 2013)

Mutagenesis Objective Search and Selection Tool (MOSST): an algorithm to predict structure-function related mutations in proteins

<p>Abstract</p> <p>Background</p> <p>Functionally relevant artificial or natural mutations are difficult to assess or predict if no structure-function information is available for a protein. This is especially important to correctly identify functionally significant non-synonymous single nucleotide polymorphisms (nsSNPs) or to design a site-directed mutagenesis strategy for a target protein. A new and powerful methodology is proposed to guide these two decision strategies, based only on conservation rules of physicochemical properties of amino acids extracted from a multiple alignment of a protein family where the target protein belongs, with no need of explicit structure-function relationships.</p> <p>Results</p> <p>A statistical analysis is performed over each amino acid position in the multiple protein alignment, based on different amino acid physical or chemical characteristics, including hydrophobicity, side-chain volume, charge and protein conformational parameters. The variances of each of these properties at each position are combined to obtain a global statistical indicator of the conservation degree of each property. Different types of physicochemical conservation are defined to characterize relevant and irrelevant positions. The differences between statistical variances are taken together as the basis of hypothesis tests at each position to search for functionally significant mutable sites and to identify specific mutagenesis targets. The outcome is used to statistically predict physicochemical consensus sequences based on different properties and to calculate the amino acid propensities at each position in a given protein. Hence, amino acid positions are identified that are putatively responsible for function, specificity, stability or binding interactions in a family of proteins. Once these key functional positions are identified, position-specific statistical distributions are applied to divide the 20 common protein amino acids in each position of the protein's primary sequence into a group of functionally non-disruptive amino acids and a second group of functionally deleterious amino acids.</p> <p>Conclusions</p> <p>With this approach, not only conserved amino acid positions in a protein family can be labeled as functionally relevant, but also non-conserved amino acid positions can be identified to have a physicochemically meaningful functional effect. These results become a discriminative tool in the selection and elaboration of rational mutagenesis strategies for the protein. They can also be used to predict if a given nsSNP, identified, for instance, in a genomic-scale analysis, can have a functional implication for a particular protein and which nsSNPs are most likely to be functionally silent for a protein. This analytical tool could be used to rapidly and automatically discard any irrelevant nsSNP and guide the research focus toward functionally significant mutations. Based on preliminary results and applications, this technique shows promising performance as a valuable bioinformatics tool to aid in the development of new protein variants and in the understanding of function-structure relationships in proteins.</p

Chapter 21: Metals and Ceramics

and nickel show large µ values (between 4 and 5), which means adhesion is stronger in the inert gases than in air. The high friction of pure metals shown in Abrasive wear resistance of such pure metals linearly increases with hardness as shown in Soft Metals and Soft Bearing Alloys When hard metals such as steels slide on themselves without lubricants, high friction, gross seizure, and severe wear take place in air or vacuum. A soft-metal thin film at the sliding interface between hard materials can reduce friction to the level of µ = 0.1 to 0.2. Gold, silver, lead, and indium are representative soft metals whose hardness values vary from about 0.3 GPa to about 0.5 GPa. In practical cases of soft metal-lubricated tribosystems, sliding velocities are relatively small and soft metals are not expected to work in the molten state