Occurrence and Positive Predictive Value of Additional Nonmass Findings for Risk Stratification of Breast Microcalcifications in Mammography

AbstractPurposeTo assess the occurrence and positive predictive value of additional nonmass findings to stratify the risk of breast microcalcifications.MethodsThis retrospective evaluation included 278 lesions with vacuum- or image-guided hook-wire biopsy for suspicious microcalcifications. The lesions were categorized into exclusive microcalcifications and microcalcifications with focal asymmetry, tubular density or architectural distortion (ie, nonmass findings). To evaluate the utility of additional nonmass findings for risk stratification, outcome variables were positive predictive values and odds ratios for malignancy and invasive carcinoma.ResultsForty-five of 278 microcalcification lesions (16%) were associated with nonmass findings: 28 focal asymmetries, 2 tubular densities, and 15 focal asymmetries in conjunction with tubular densities. Architectural distortion was observed in 28 of these cases. The odds ratio for additional nonmass findings relative to exclusive microcalcifications was 5.9 and was statistically significant (P < .00001). Architectural distortion was the most specific indicator for malignancy and invasiveness, with odds ratios of 6.5 (P = .0072) and 5.6 (P = .0214), respectively.ConclusionsMicrocalcifications with nonmass findings were less frequent than exclusive microcalcifications but were more predictive for malignancy. Architectural distortion demonstrated the highest risk of malignancy and invasiveness. Assessment of additional nonmass findings might be useful for further risk stratification of microcalcifications, indications for additional imaging, and pretreatment considerations

Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease - indication of an evolving epidemic in West Africa

<p>Abstract</p> <p>Background</p> <p>HIV-1 is one of the fastest evolving pathogens, and is distinguished by geographic and genetic variants that have been classified into different subtypes and circulating recombinant forms (CRFs). Early in infection the primary coreceptor is CCR5, but during disease course CXCR4-using HIV-1 populations may emerge. This has been correlated with accelerated disease progression in HIV-1 subtype B. Basic knowledge of HIV-1 coreceptor tropism is important due to the recent introduction of coreceptor antagonists in antiretroviral therapy, and subtype-specific differences regarding how frequently HIV-1 CXCR4-using populations appear in late-stage disease need to be further investigated. To study how frequently CXCR4-using populations appear in late-stage disease among HIV-1 subtype A and CRF02_AG, we evaluated the accuracy of a recombinant virus phenotypic assay for these subtypes, and used it to determine the HIV-1 coreceptor tropism of plasma samples collected during late-stage disease in Guinea-Bissau. We also performed a genotypic analysis and investigated subtype-specific differences in the appearance of CXCR4 tropism late in disease.</p> <p>Results</p> <p>We found that the recombinant virus phenotypic assay accurately predicted HIV-1 coreceptor tropism of subtype A and CRF02_AG. Over the study period (1997-2007), we found an increasing and generally high frequency of CXCR4 tropism (86%) in CRF02_AG. By sequence analysis of the V3 region of our samples we developed a novel genotypic rule for predicting CXCR4 tropism in CRF02_AG, based on the combined criteria of the total number of charged amino acids and net charge. This rule had higher sensitivity than previously described genotypic rules and may be useful for development of future genotypic tools for this CRF. Finally, we conducted a literature analysis, combining data of 498 individuals in late-stage disease, and found high amounts of CXCR4 tropism for all major HIV-1 subtypes (60-77%), except for subtype C (15%).</p> <p>Conclusions</p> <p>The increase in CXCR4 tropism over time suggests an evolving epidemic of CRF02_AG. The results of the literature analysis demonstrate the need for further studies investigating subtype-specific emergence for CXCR4-tropism; this may be particularly important due to the introduction of CCR5-antagonists in HIV treatment regimens.</p