Matching risk and resources in high-risk pregnancies.

OBJECTIVE: To evaluate the joint impact of pregnancy risk and the timing of referral of high-risk pregnancies from obstetricians to maternal fetal medicine (MFM) sub-specialists on gestational age (GA) at delivery. METHODS: For the period 1992-2002, 2567 consecutive deliveries from pregnancies of at least 23 weeks gestational age (GA) from a community-level sub-specialty perinatal center were studied. A multiple regression model was developed specifying the impact of various risk factors and referral timing. RESULTS: Prior pregnancy risk was inversely related to GA at birth. Referral timing, operationalized as a continuous variable, did not have a significant additive impact on GA at birth, but several dummy-variable interaction effects combining risk factors and referral before 20 weeks as a dichotomy were significant. CONCLUSION: There are identifiable risks that occur either before the pregnancy or early into it that should lead to early referral to a sub-specialist because of their impact on GA at birth. Early referral is an important tactic in a larger preterm prevention strategy, but it needs to be embedded in a broader maternal-fetal health initiative in which both generalists and sub-specialists play important roles.     

Inhibition of glioblastoma angiogenesis and invasion by combined treatments directed against vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and vascular endothelial-cadherin.

PURPOSE: Inhibition of angiogenesis can influence tumor cell invasion and metastasis. We previously showed that blockade of vascular endothelial growth factor receptor-2 (VEGFR-2) with the monoclonal antibody DC101 inhibited intracerebral glioblastoma growth but caused increased tumor cell invasion along the preexistent vasculature. In the present study, we attempted to inhibit glioma cell invasion using a monoclonal antibody against the epidermal growth factor receptor (EGFR), which in the context of human glioblastomas, has been implicated in tumor cell invasion. In addition, we analyzed whether blockade of vascular endothelial (VE)-cadherin as a different antiangiogenic target could also inhibit glioblastoma angiogenesis and growth. EXPERIMENTAL DESIGNS: Nude mice who received intracerebral glioblastoma xenografts were treated using monoclonal antibodies against VEGFR-2 (DC101), EGFR (C225), and VE-cadherin (E4G10) either alone or in different combinations. RESULTS: Increased tumor cell invasion provoked by DC101 monotherapy was inhibited by 50% to 66% by combined treatment with C225 and DC101. C225 inhibited glioblastoma cell migration in vitro, but had no effect on the volume of the main tumor mass or on tumor cell proliferation or apoptosis in vivo, either alone or in combination with DC101. The anti-VE-cadherin monoclonal antibody E4G10 was a weaker inhibitor of tumor angiogenesis and growth than DC101, and also caused a weaker increase in tumor cell invasion. CONCLUSIONS: Inhibition of angiogenesis achieved by blocking either VEGFR-2 or VE-cadherin can cause increased glioma cell invasion in an orthotopic model. Increased tumor cell invasion induced by potent inhibition of angiogenesis with DC101 could be inhibited by simultaneous blockade of EGFR.     

Screening for avascular necrosis of the hip with rapid MRI: preliminary experience

PURPOSE: The purpose of this work was to compare rapidly acquired MR images with routinely employed SE and turbo SE (TSE) images in screening for hip avascular necrosis (AVN). METHOD: Twelve patients with findings suspicious for radiographically occult AVN of one or both hips were studied with our routine screening protocol (imaging time >7 min) and similarly weighted, rapidly acquired MR sequences (imaging time <1 min). RESULTS: The rapidly acquired MR images were judged to be similar to the routine protocol in demonstrating marrow edema, irregular lines within the femoral head characteristic of AVN, and osteoarthritis. CONCLUSION: The rapidly acquired MR sequences that we studied reliably revealed the presence or absence of AVN, marrow edema, and osteoarthritis of the hip in our sample population when compared with SE and TSE sequences that we routinely perform. Further investigation of rapidly acquired MR sequences is warranted, as imaging time may be dramatically reduced and patient throughput increased.     

Measurement of aggregate risk with copulas

Summary When aggregating financial risk on a portfolio level, the specification of the dependence structure between the risk factors plays an important role. Promising parametric models are often based on a so-called copula approach. Case studies of market crashes suggest the application of concepts allowing for extremal dependence. We present a transformed copula as a new model that both fits the data and allows for exact prediction in the tails. It turns out that the new model improves benchmark models like the t- or Clayton copula with respect to risk measures like VaR or Expected Shortfall. By performing different goodness-of-fit tests, the quality of the estimation is examined.     

Early-Life Colonization by Anelloviruses in Infants

Anelloviruses (AVs) are found in the vast majority of the human population and are most probably part of a healthy virome. These viruses infect humans in the early stage of life, however, the characteristics of the first colonizing AVs are still unknown. We screened a collection of 107 blood samples from children between 0.4 and 64.8 months of age for the presence of three AV genera: the Alpha-, Beta- and Gammatorquevirus. The youngest child that was positive for AV was 1.2 months old, and a peak in prevalence (100% of samples positive) was reached between the twelfth and eighteenth months of life. Intriguingly, the beta- and gammatorqueviruses were detected most at the early stage of life (up to 12 months), whereas alphatorqueviruses, the most common AVs in adults, increased in prevalence in children older than 12 months. To determine whether that order of colonization may be related to oral transmission and unequal presence of AV genera in breast milk, we examined 63 breast milk samples. Thirty-two percent of the breast milk samples were positive in a qPCR detecting beta- and gammatorqueviruses, while alphatorqueviruses were detected in 10% of the samples, and this difference was significant (p = 0.00654). In conclusion, we show that beta- and gammatorqueviruses colonize humans in the first months of life and that breastfeeding could play a role in AV transmission.     

FOLFOX 4 Combined with Herbal Medicine for Advanced Colorectal Cancer: A Systematic Review

This systematic review evaluates the clinical evidence for the addition of herbal medicines (HMs) to FOLFOX 4 for advanced colorectal cancer (ACRC) in terms of tumor response rate (tRR), survival, quality of life and reduction in adverse events (AEs). Seven electronic databases were searched for randomized controlled trials (RCTs) of FOLFOX4 combined with HMs compared to FOLFOX4 alone. Outcome data for 13 randomized controlled trials were analysed using Review Manager 5.1. Risk of bias for objective outcomes including tumor response and survival was judged as low. Publication bias was not evident. Meta‐analyses found the addition of HMs improved tRR (RR 1.25, 95%CI 1.06–1.47, I² = 0%), one year survival (RR 1.51, 95%CI 1.19–1.90, I² = 0%) and quality of life in terms of Karnofsky Performance Status (KPS) gained (RR 1.84, 95%CI 1.54‐2.19, I² = 0%); alleviated grade 3 and 4 chemotherapy‐related AEs for neutropenia (RR 0.33, 95%CI 0.18‐0.60, I² = 0%), nausea and vomiting (RR 0.34, 95%CI 0.17‐0.67, I² = 0%) and neurotoxicity (RR 0.39, 95%CI 0.15‐1.00, I² = 0%), compared to FOLFOX4 alone. The most frequently used herbs were Astragalus membranaceus, Panax ginseng, Atractylodes macrocephala, Poria cocos, Coix lachryma‐jobi and Sophora flavescens. In experimental studies, each of these herbs has shown actions that could have contributed to improved tumor response. Copyright © 2013 John Wiley & Sons, Ltd.     

Evaluation of adaptive spatial enhancement in suprathreshold visual field screening

Sixty-three normal subjects and 94 abnormal patients, most of whom had glaucoma, were tested in the central visual field using a threshold-related, eccentricity-compensated, spatially adaptive suprathreshold screening program and a full-threshold program on the Humphrey field analyzer. The initial stimulus locations on the screening test were identical to those of the threshold test; additional screening stimuli were presented surrounding each missed initial stimulus. Surprisingly, this spatial enhancement strategy did not improve sensitivity or specificity rates of the screening beyond that achieved by considering the initial stimulus locations alone. Points missed during screening often showed a depressed sensitivity rate (measured threshold greater than 6 dB below the age-corrected normal reference value) in the same area of the threshold field. This was true in fields from abnormal and normal subjects. This finding of persistent shallow defects in the same test session among otherwise normal persons has disturbing implications for the importance of "confirmed" defects in the diagnosis of disease.     

Clinical and serum lipid findings in a large family with autosomal dominant retinitis pigmentosa

Retinitis pigmentosa, of unknown cause, has recently been associated with decreased amounts of the polyunsaturated fatty acid, docosahexaenoic acid, in the plasma of affected as compared with unaffected relatives. It has been suggested that this finding may serve as a marker for the disease and might indicate alterations in photoreceptor cell metabolism. The authors studied 54 members of a family with dominantly inherited retinitis pigmentosa in five generations. In addition to the typical clinical findings of retinitis pigmentosa, eight persons also had a bull's eye maculopathy, and four persons had uni- or bilateral optic nerve drusen. When the authors determined the plasma fatty acid and lipid contents, they saw the expected age-related effect on cholesterol and triglycerides, but an unexpected, significant reduction in fatty acids in the unaffected controls as compared with persons with retinitis pigmentosa. The authors' results emphasize the heterogeneity of phenotypic expression of retinitis pigmentosa within a single family.     

Threshold Amsler grid testing in maculopathies

The Amsler grid is a suprathreshold target and thus may fail to detect relative scotomas. If the grid is viewed through two cross-polarizing filters creating low luminance conditions (threshold Amsler grid testing) the test is far more sensitive. Ten patients with disorders of the macula with normal standard white Amsler grid testing were studied with three other Amsler grid tests. Of the 15 involved eyes, 12 had visual field defects present with threshold Amsler grid testing. Tangent screen examination showed defects in 10 of these 12 eyes. The two red grids used were not as sensitive as the threshold grid. Three eyes had metamorphopsia with the white grid which became the site of a visual field defect with threshold testing. Threshold Amsler grid testing is a rapid and sensitive technique for the evaluation of the central 10 degrees of visual field in patients with maculopathies.