Serial bedside B-type natriuretic peptide strongly predicts prognosis in acute coronary syndrome independent of echocardiographic abnormalities.

BACKGROUND: Elevated levels of B-type natriuretic peptide (BNP) are associated with adverse clinical outcomes in acute coronary syndrome (ACS), but several questions remain outstanding. Firstly, it has not yet been determined whether an additional BNP sample at 7 weeks post ACS would enhance risk prediction. Secondly, we assessed whether the prognostic potential of BNP in ACS could be explained by echocardiographic abnormalities such as left ventricular hypertrophy (LVH). METHODS: We measured bedside BNP levels in 443 consecutive patients presenting with ACS and at 7 weeks outpatient follow-up. Main outcome measure was either all-cause mortality, readmission with ACS, or congestive heart failure) at 10 months from presentation. RESULTS: Of the 443 patients, 120 patients presented with ST-elevation myocardial infarction (27%). There were 90 cardiovascular (CV) events at 10 months. Adjusting for age, sex, hypertension, diabetes mellitus, smoking status, renal dysfunction, left ventricular ejection fraction, and echocardiographic LVH elevated near patient BNP levels (>80 pg/mL) were still associated with subsequent CV events when measured on admission (adjusted relative risk [RR] 2.63 [95% CI 1.34-5.19)] and also at 7 weeks post ACS (adjusted RR 4.12 [95% CI 1.58-10.72]). Patients with persistent BNP elevation at 7 weeks were also at an increased risk of CV events compared to those with an initial high BNP which then fell (unadjusted RR 4.04 [95% CI 1.24-13.15]). CONCLUSION: In ACS, bedside BNP levels predict CV events at 10 months, independent of many echocardiographic abnormalities including LVH. Furthermore, our study suggests that an additional 7 weeks post ACS BNP enhances risk stratification over and above a one-off high BNP at baseline.

Biomarkers in Osteosarcoma.

Osteosarcoma is the most common primary tumor of bone and accounts for approximately 19% of all malignant tumors of bone. It is the third most common malignant tumor in teenagers. More than twenty years ago, the advent of a multidisciplinary approach that combined multi-agent chemotherapy and limb-sparing surgery greatly improved the survival rate of patients with osteosarcoma. Unfortunately, since that time, survival rates have not dramatically improved. To date, the most powerful predictors of outcome have remained the ability to detect metastatic disease at diagnosis and the histopathologic response of the tumor to preoperative chemotherapy. Presently, 80% of patients who do not have distant metastases at initial diagnosis will become long-term survivors. Unfortunately, this means that approximately 20% of patients who do not present with metastases at diagnosis will not survive. This group of patients appears to be resistant to current treatment as attempts to intensify therapy after surgery for patients with a poor histopathologic response has not significantly improved survival rates. It is these patients that are in the greatest need of additional clinically relevant markers for prognosis and who can be most helped by molecular analysis. While steady progress has been made in the identification of genetic alterations in osteosarcoma, no individual molecular marker has thus far been demonstrated to have a better prognostic significance in the treatment of osteosarcomas than the current clinical markers. Thus there is clearly a need to employ new comprehensive analysis technologies to develop significantly more informative classification systems and to identify new therapeutic targets.

Molecular characterization of subject-specific oral microflora during initial colonization of enamel.

The initial microbial colonization of tooth surfaces is a repeatable and selective process, with certain bacterial species predominating in the nascent biofilm. Characterization of the initial microflora is the first step in understanding interactions among community members that shape ensuing biofilm development. Using molecular methods and a retrievable enamel chip model, we characterized the microbial diversity of early dental biofilms in three subjects. A total of 531 16S rRNA gene sequences were analyzed, and 97 distinct phylotypes were identified. Microbial community composition was shown to be statistically different among subjects. In all subjects, however, 4-h and 8-h communities were dominated by Streptococcus spp. belonging to the Streptococcus oralis/Streptococcus mitis group. Other frequently observed genera (comprising at least 5% of clone sequences in at least one of the six clone libraries) were Actinomyces, Gemella, Granulicatella, Neisseria, Prevotella, Rothia, and Veillonella. Fluorescence in situ hybridization (FISH) confirmed that the proportion of Streptococcus sp. sequences in the clone libraries coincided with the proportion of streptococcus probe-positive organisms on the chip. FISH also revealed that, in the undisturbed plaque, not only Streptococcus spp. but also the rarer Prevotella spp. were usually seen in small multigeneric clusters of cells. This study shows that the initial dental plaque community of each subject is unique in terms of diversity and composition. Repetitive and distinctive community composition within subjects suggests that the spatiotemporal interactions and ecological shifts that accompany biofilm maturation also occur in a subject-dependent manner.