Influence of antimicrobial regimen on decreased in-hospital mortality of patients with MRSA bacteremia.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important causes of bacteremia. Recently, several epidemiological and microbiological changes have become evident in MRSA infections. The purposes of this study were to assess clinical characteristics of patients with MRSA bacteremia and microbiological changes in MRSA. We conducted a retrospective observational study on patients with MRSA bacteremia who were hospitalized between 2008 and 2011. We used univariate and multivariate analysis to evaluate the predictors associated with 30-day mortality. The 7-day and 30-day mortality rates were 12.0% and 25.3%, respectively. According to multivariate analysis, the independent predictors that associated with 30-day mortality were leukopenia, low serum albumin, high sequential organ failure assessment (SOFA) score, and quinolone use within 30 days. Compared to previous data (2003-2007), the SOFA score of the new data set remained unchanged, but in-hospital mortality decreased significantly. In particular, the mortality associated with use of vancomycin (VCM) was significantly lower. Although the minimum inhibitory concentration of VCM required to inhibit the growth of 90% of organisms (MIC90) had not changed, the trough value of VCM changed significantly; a VCM trough value of 10 or greater was significantly higher compared to previous data. Of the staphylococcal cassette chromosome mec (SCCmec) types, SCCmec II values decreased significantly, and SCCmec I and IV values increased significantly. Our results indicate that changes in VCM usage might contribute to decreased in-hospital mortality.

Influenza virus M2e with additional cysteine residues shows enhanced immunogenicity and protection against lethal virus challenge.

The amino acid sequence of the extracellular domain of matrix protein 2 (M2e) is conserved among all subtypes of influenza A viruses. Therefore, the M2e peptide can be considered as a target antigen for the development of a universal influenza vaccine. We evaluated the effects of adding cysteine residues to a peptide of amino acids 2-24 of M2e. Mice immunized with some of these peptides containing one, two, three, four, or five extra cysteines displayed enhanced antibody titers to M2e. In addition, immunization with a peptide containing three extra cysteines, along with an aluminum adjuvant, protected mice more effectively against a lethal influenza virus challenge than the original M2e peptide. These results indicated that an M2e peptide containing additional cysteine residues could be a universal influenza vaccine candidate even without the addition of strong adjuvants.

Amyloid beta peptides with an additional cysteine residue can enhance immunogenicity and reduce the amyloid beta burden in an Alzheimer's disease mouse model.

For the development of a safe vaccine for Alzheimer's disease (AD), we studied the immunogenicity of amyloid beta (Abeta) peptides without adjuvant. Addition of a cysteine residue (Cys) to Abeta peptides enhanced immunogenicity in mice compared to those without Cys. Vaccination with the Abeta-Cys peptides reduced Abeta deposits in AD model mice. From these results, the Abeta-Cys peptides, administered without adjuvant, are considered candidates for vaccine therapy for AD.

Significance of metastasis detected by molecular techniques in sentinel nodes of patients with gastrointestinal cancer.

The clinical significance of micrometastasis in sentinel nodes (SNs) may differ in various organs. In particular, the prognostic value of SN micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) is still controversial. We investigated the diagnostic and therapeutic significance of nodal molecular metastasis detected by nested RT-PCR for cytokeratin (CK) 19 mRNA in gastrointestinal cancer. In 51 cases with GI tract cancer treated by standard curative resection, SNs were identified by a radio-guided method. In 10 of 51 patients, 25 SNs and 3 non-SNs were histologically negative and RT-PCR positive. Three non-SNs with positive CK19 mRNA were randomly sampled from the same basin where histologically positive SNs were identified. Immunohistochemical analysis of six additional step sections obtained at 30- micro m intervals with use of an anticytokeratin antibody showed clearly recognizable histological metastases in 4 of 25 histologically negative/RT-PCR-positive SNs (16%). In one case of esophageal squamous cell carcinoma with nodal micrometastasis identified by CK19 RT-PCR, extranodal local recurrence in the SN basin (left supraclavicular basin) was observed 6 months postoperatively. These findings suggest that nodal micrometastasis detected by nested RT-PCR has some clinical significance in GI cancer. Molecular assessment of the SN may be a valuable tool to complement routine histological examination for GI cancers.

Intraoperative lymphatic mapping and sentinel lymph node sampling in esophageal and gastric cancer.

Recent studies for SN mapping of esophageal and gastric carcinoma show that the SN concept is valid even for upper GI cancers with multidirectional and complicated lymphatic flow. The relatively high incidence of anatomic skip metastasis can be attributed to aberrant distribution of SNs. An individualized and minimally invasive surgical approach can be applicable to management of esophageal and gastric carcinoma based on SN status. Although there are several issues to be resolved, this novel procedure has the potential for great benefit to improve quality control in the treatment of upper GI cancer. Well-designed clinical trials of lymphatic mapping for upper GI cancer will be essential to determine whether this technique is widely applicable in the management of these tumors.

Sentinel node mapping for colorectal cancer with radioactive tracer.

PURPOSE: The aim of this study was to test the feasibility and accuracy of radioactivity-guided mapping of the first lymph nodes found in draining the primary tumor site for colorectal cancer. METHODS: We enrolled 56 consecutive patients with preoperative diagnosis of curatively resectable colorectal cancer. Endoscopic injection of technetium Tc 99m-labeled tin colloid (15 MBq) was performed preoperatively, and radioactive sentinel nodes were identified intraoperatively with a gamma probe. Standard radical resection with lymph node dissection was performed in all patients, and all resected nodes were evaluated by routine histopathologic examination. RESULTS: Radioactivity-guided methods were used to detect sentinel nodes in 51 (91 percent) of 56 patients. The number of lymph nodes resected was 23.9 +/- 15.2 per case. The number of sentinel nodes was 3.5 +/- 2.1 (range, 0-8) per case. In 18 of 22 patients with lymph node metastasis, the sentinel node was positive. The incidence of metastasis in the sentinel node (22 percent) was significantly higher than that in nonsentinel nodes (3 percent, P < 0.01). Diagnostic accuracy according to sentinel node status was 92 percent (47/51). Four false-negative cases in this study were advanced cases with T3 primary tumors. The detection rate and diagnostic accuracy for patients with T1 or T2 primary tumors (29 cases) were 100 percent each. CONCLUSION: Intraoperative radioactivity-guided sentinel node mapping was accurate for patients with colorectal cancer with T1 or T2 tumors. The results suggest that sentinel node mapping and intraoperative biopsy may be a sensitive and specific diagnostic method for detecting metastasis in regional lymph nodes in patients with colorectal cancer.