Anal intraepithelial neoplasia and squamous cell carcinoma in HIV‐infected adults

Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults.     

INFLUENCE OF CONTEXTUAL FACTORS ON ACADEMIC PERFORMANCE IN A SAMPLE OF LATINO ADOLESCENTS: THE MODERATING ROLE OF SCHOOL ATTACHMENT

The present study further evaluated contextual factors (i.e., neighborhood violence and peer rejection) that contribute to academic performance by examining school attachment as a moderator of these associations in a sample of Latino high school students (N = 144, 54% male). Findings suggested that both neighborhood violence and peer rejection were negatively associated with academic performance. However, the influence of neighborhood violence depended on levels of school attachment, with neighborhood violence unrelated to poor academic performance when levels of school attachment were high. In contrast, peer rejection was robustly associated with poor academic performance, regardless of the level of school attachment. Implications of findings are discussed.     

THE ROLE OF SLEEP IN THE RELATION BETWEEN COMMUNITY VIOLENCE EXPOSURE AND DELINQUENCY AMONG LATINO ADOLESCENTS

Little is known about factors that account for the link between community violence exposure (CVE) and delinquency among adolescents. Sleep is one factor that warrants attention, given the poor sleep habits found among many adolescents and its relation to CVE and delinquent behaviors. Further, given the growing rate of Latino youth in the United States, and their risk for CVE, examining factors that account for this relation among Latino youth is essential for developing culturally sensitive interventions. This study evaluated whether sleep problems accounted for the link between CVE and delinquency among a sample of 144 Latino adolescents (54% male; ages 14­–19 years). CVE and sleep problems were uniquely related to delinquency. Further, Meeker's test of indirect effects indicated that sleep problems partially accounted for the relation between CVE and delinquency. Interventions targeting sleep problems in Latino adolescents may aid in reducing delinquency among Latino adolescents, particularly for those with CVE.     

Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization

Rationale and objectives. Severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are progressive allergic fungal lung diseases whose effective treatment remains to be established. Current treatment with itraconazole is associated with a 40% failure rate and adverse events (AEs). We assessed the effect of voriconazole or posaconazole as second- and third-line therapies. Methods. We conducted a retrospective review of adult asthmatic patients with either ABPA or SAFS receiving voriconazole or posaconazole. Clinical, radiological, and immunological evaluation was used to assess response. Results. There were 25 patients, ABPA (n = 20) or SAFS (n = 5), 10 males, median age = 58 years. All patients had failed itraconazole (n = 14) or developed AEs (n = 11). There were 33 courses of therapy analyzed, 24 with voriconazole and 9 with posaconazole. Clinical response to voriconazole was observed in 17/24 (70%) patients at 3 months, 15/20 (75%) at 6 months, and 12/16 (75%) at 12 months compared with 7/9 (78%) at 3, 6, and 12 months for posaconazole. Eighteen of 24 (75%) patients discontinued oral corticosteroids (OCS), 12 of them within 3 months of therapy. Asthma severity was downgraded from severe to moderate (n = 8) and moderate to mild (n = 1) asthma in 9 of 24 (38%) asthmatic patients. There was a marked reduction in OCS and short-acting beta-2 agonist use, health-care utilization due to asthma, and improvement in overall health status. Furthermore, there was a statistically significant reduction in immunological markers appearing at 9 months (p = .008) for total IgE and at 12 months for radioallergosorbent test IgE for Aspergillus fumigatus (p = .0056). Six of 23 (26%) patients on voriconazole had AEs requiring discontinuation before 6 months compared with none on posaconazole (p = .15). Four relapsed (57%), one at 3 months and three at 12 months after discontinuation. Conclusion. Both voriconazole and posaconazole are potentially effective alternative treatment options for SAFS and ABPA and may improve asthma control and reduce severity, though larger prospective studies are required to support these retrospective study findings.     

Acquired homozygosity of the rearranged bcr allele during the acute leukemic phase of a patient with Ph-negative chronic myeloid leukemia

A 45-year-old male patient with Ph-negative chronic myeloid leukemia (CML) had rearranged bcr-3' and bcr-5' gene regions in Southern blot studies when leukemia was diagnosed. During development of terminal blast crisis, successive blood samples showed a progressive decrease in the amount of germline bcr DNA and its complete loss by full blast crisis. There were also increased amounts of rearranged bcr DNA consistent with acquired homozygosity. A similar result was obtained with an IgV lambda probe and indicated homozygosity of a significant part of chromosome 22. The bcr-abl gene complex behaves as a somatic dominant in CML, and we suggest that its acquired homozygosity is a mechanism of bcr-abl amplification similar to duplication of the Ph chromosome commonly found in the blast crisis of CML.