Using high titer West Nile intravenous immunoglobulin from selected Israeli donors for treatment of West Nile virus infection.

BACKGROUND: West Nile Virus (WNV) is endemic in Israel and a significant level of antibodies is present in the population due to natural exposure. Anecdotal cases suggested that the presence of anti-WNV antibodies in intravenous immunoglobulin (IVIG) from Israeli donors (IVIG-IL) assisted the recovery of patients with severe WNV infection. METHODS: To enhance the therapeutic efficacy of IVIG-IL against WNV infection, OMRIX Biopharmaceuticals, Israel, have developed a strategy for selection of plasma units from a 10% fraction of Israeli blood donors with anti-WNV antibodies. Positive units were processed into pharmaceutical grade WNV IVIG (WNIG). Following inoculation with WNV, mice received i.p. injections of different doses (0.01-8 mg/mouse) of IVIG-IL or WNIG, according to the specific experimental protocol. RESULTS: WNIG was about 10 times more potent (per gr of IgG) than was regular IVIG-IL when tested by ELISA and neutralization assays. In a mouse lethal WNV infection model, prophylactic treatment with WNIG was at least 5-10-fold more potent as compared to treatment with IVIG-IL. Treatment with WNIG during active encephalitis, three or four days following WNV infection, had a significant protective effect. WNIG was also very effective in protecting immunosuppressed mice. Indeed, treatment of dexamethasone-immunosuppressed mice with 0.2 or 1.0 mg WNIG 4 h after virus infection, led to 100% survival. CONCLUSION: IVIG produced from selected plasma donated in WNV endemic regions can be used to produce WNV IVIG with superior activity for therapeutic and prophylactic measures.

The ability of the wide range CRP assay to classify individuals with low grade inflammation into cardiovascular risk groups.

BACKGROUND: High sensitivity C-reactive protein (hsCRP) has become a routine assessment tool to discriminate between patients at low, intermediate or high risk for cardiovascular events using the threshold values of 1 and 3mg/L, respectively. Over the past years, several studies have proposed the wide range C-reactive protein (wrCRP) as an alternative to the hsCRP in various clinical scenarios. However, the potential use of wrCRP in assessing the cardiovascular risk has not yet been evaluated. METHODS: Both wrCRP and hsCRP were evaluated in 15,780 apparently healthy individuals who underwent a routine annual checkup in the Tel Aviv Sourasky Medical Center. Individuals with CRP levels >5mg/L were excluded. Agreement between the two methods was observed using the Bland-Altman method and the concordance correlation coefficient. Deming regression was used to build a calibration equation. Reclassification of individuals' risk level was observed and Cohen's kappa was used to evaluate risk agreement. RESULTS: A high correlation (r=0.98) along with a significant difference (p<0.001) between hsCRP and wrCRP raised the need for calibration. A simple calibration equation (Adjusted wrCRP=0.3136+0.8803×wrCRP) led to high agreement which enabled 8.4% reclassification of the risk group. A change in the intermediate risk threshold value from 1 to 0.9mg/L led to an almost perfect agreement (kappa=0.87, p<0.001) and a low reclassification rate (7.6%), with under 0.05% of the population undergoing a major reclassification (from high to low risk or vice versa). CONCLUSIONS: In the era of limited financial resources, wrCRP assay may be used as a reasonable routine assay to evaluate the cardiovascular risk in patients undergoing a routine annual checkup.

Once a cesarean always a cesarean? A computer-assisted decision analysis.

OBJECTIVE: A previous decision analysis models for two strategic choices for trial of labor or repeated cesarean after prior cesarean concluded that the degree of wish for an additional future pregnancy appeared to be a major determinant for choice between the two strategic options. We had extended the analysis model to stillbirth and hypoxic-ischemic encephalopathy in addition to placental complications while updating most of the outcomes in the decision tree. STUDY DESIGN: A model was formulated using a decision tree based on reported probabilities for various outcomes and estimated utilities. The question asked was should trial of labor or repeated cesarean be performed after a prior cesarean, with a varying desire for an additional pregnancy. The highest expected outcome determines the preference of our model. RESULTS: Our model favors repeated elective cesarean (0.9947) over trial of labor (0.9917) after a previous cesarean and is the preferred approach. This approach was preferable irrespective of the probability of additional pregnancy. CONCLUSION: In contrary to previous models, when taking into account the occurrence of a live infant birth, birth of an infant with hypoxic-ischemic encephalopathy stillbirth, neonatal death, abnormal placental implantation, hysterectomy and maternal death the preferred approach for women with previous cesarean is an elective repeated cesarean rather than trial of vaginal delivery.