Massive splenic infarction in an adolescent with hemoglobin S‐HPFH

Hemoglobin sickle‐hereditary persistence of fetal hemoglobin (S‐HPFH) is a condition in which there is compound heterozygosity for the Hb S mutation and the HPFH deletion. These patients have no anemia, little evidence of hemolysis and generally have a benign clinical course compared to other types of sickle cell anemia. We describe a 19‐year‐old male with HbS‐HPFH who had no history of anemia or vaso‐occlusive crisis, who presented with a massive splenic infarct. We conclude that patients with HbS‐HPFH can occasionally present with severe complications and require a high level of clinical suspicion for complications when presenting to the hospital. Pediatr Blood Cancer 2013; 60: E49–E51. © 2012 Wiley Periodicals, Inc.     

Individual,Psychosocial, and Social Correlates of Unprotected Anal Intercourse in a New Generation of Young Men Who Have Sex With Men in New York City

Objectives. We examined associations of individual, psychosocial, and social factors with unprotected anal intercourse (UAI) among young men who have sex with men in New York City.Methods. Using baseline assessment data from 592 young men who have sex with men participating in an ongoing prospective cohort study, we conducted multivariable logistic regression analyses to examine the associations between covariates and likelihood of recently engaging in UAI with same-sex partners.Results. Nineteen percent reported recent UAI with a same-sex partner. In multivariable models, being in a current relationship with another man (adjusted odds ratio [AOR] = 4.87), an arrest history (AOR = 2.01), greater residential instability (AOR = 1.75), and unstable housing or homelessness (AOR = 3.10) was associated with recent UAI. Although high levels of gay community affinity and low internalized homophobia were associated with engaging in UAI in bivariate analyses, these associations did not persist in multivariable analyses.Conclusions. Associations of psychosocial and socially produced conditions with UAI among a new generation of young men who have sex with men warrant that HIV prevention programs and policies address structural factors that predispose sexual risk behaviors.Young men who have sex with men (MSM) continue to be at increased risk for the acquisition and transmission of HIV. Nationally, among those aged 13 to 24 years, the estimate of new HIV infections attributed to male-to-male sexual contact increased from 61% in 2006 to 71% in 2009.1 In New York City between 2001 and 2008, 73% of HIV diagnoses among male adolescents and young adults were among young MSM.2 These national and local surveillance data confirm that a third generation of MSM, a generation that did not witness the heightened morbidity and mortality of the early AIDS epidemic, continue to bear a disproportionate burden of HIV/AIDS. In addition to these epidemiological trends, adolescents and young adults are at heightened risk for HIV/AIDS because the periods of adolescence and young adulthood are marked by a higher prevalence of HIV-related risk behaviors such as unprotected sex and illicit drug use.3,4 Moreover, these periods are often characterized by significant transitions and challenges for young MSM, specifically around the formation of sexual identity as well as coming out to family members and peers that may all coalesce to increase vulnerability for HIV.To date, research related to HIV risk among MSM, and more specifically young MSM, has generally focused on understanding the influence of individual-level characteristics on risk-taking behaviors. For example, it is well established that factors such as educational attainment,5 race/ethnicity,6–8 sexual orientation,9 age at sexual onset,8,10 and relationship status11,12 are associated with sexual risk-taking behaviors, such as engaging in unprotected anal intercourse (UAI). In addition, previous research indicates that those with a history of arrest and incarceration are more likely to engage in greater sexual risk behaviors than are those without such a history.13,14More recently, research efforts have moved beyond examining individual-level characteristics by considering both protective and harmful psychosocial states that may either buffer against or exacerbate vulnerabilities that function as drivers of HIV-related sexual risk behaviors.15,16 For instance, experiences of homophobia can often lead to discomfort with one’s sexual identity and may act as a significant psychosocial stressor linked to increased sexual risk taking.17,18 Conversely, young MSM with positive attitudes about homosexuality are less likely to have multiple sex partners and may be less likely to engage in UAI.19 Finally, gay community affiliation may function to either protect against or exacerbate the risk for HIV transmission and acquisition.Exposure and access to gay neighborhoods with norms promoting safer sexual behaviors may lead to safer sexual practices, such as consistent condom use, among MSM20 as well as greater awareness about HIV education and services available to MSM.21 However, higher gay community affinity among a younger generation of MSM may be associated with greater sexual risk taking in the absence of norms promoting safer sexual behaviors.22Increasingly, empirical research has examined the impact of social factors for their association with sexual risk taking among MSM overall.23 For example, several studies have linked poverty and economic disadvantage as socially produced risk factors associated with sexual risk taking among MSM.24,25 These associations may be more pronounced among individuals with higher levels of residential or housing instability or homelessness because they may engage in sex work to secure vital material resources and therefore be at an increased risk for HIV transmission and acquistion.24,26–28 Because of the need to understand the effect of individual, psychosocial, and social factors on HIV risk among young MSM, we sought to characterize how these factors influence sexual risk behaviors, specifically UAI, in a sample of young MSM. These findings have the potential to inform novel HIV/AIDS-related prevention and intervention efforts for this new generation of men.     

A pilot genome-wide association study of early-onset breast cancer

High-density oligonucleotide microarrays containing a large number of single nucleotide polymorphisms (SNPs) have enabled genome-wide association (GWA) analysis to become a reality. We used the early access Affymetrix Mendel Nsp 250K chips in a GWA case–control pilot study to identify genomic regions associated with breast cancer. We included 30 randomly sampled incident invasive breast cancer cases aged <45 years without deleterious mutations in the BRCA1 or BRCA2 genes, and 30 population controls individually matched on age, ethnicity and geographical area. The overall genotype call rate was 97.13 ± 1.33% for controls and 97.48 ± 1.42% for cases. Comparison was made between cases and controls for 203,477 genotyped SNPs using (a) unconditional logistic regression (ULR), (b) conditional logistic regression (CLR) models with adjustment for the matched pairs, (c) allelic tests for single marker tests and (d) haplotype trend regression (HTR). Genomic control and EIGENSTRAT methods were used for correction of population stratification in appropriate models. We demonstrate the similarity and dissimilarity of results from different statistical analyses. We found several possible significant regions harboring biologically meaningful known candidate genes, such as genes encoding fibroblast growth factor, transforming growth factor, epidermal growth factor, and estrogen synthesis enzymes to be associated with early-onset breast cancer. In single marker analysis, none of the SNPs were statistically significant after correction for multiple testing. However, haplotype association tests, using 90730 tag-SNPs, suggested two regions in GLG1 and UGT1 genes retaining significance even after Bonferroni correction. Nevertheless, without systematic replication, findings from this pilot study, especially the associations of breast cancer in relation to specific SNPs, should be interpreted with great caution.     

Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: case study

Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide is an effective chemotherapeutic agent for patients with glioblastoma multiforme, but it induces significant lymphopenia. Although there is monthly fluctuation of the white blood cell count, specifically the CD4 and CD8 counts, there was no cumulative decline in the patient described in this case report. Depriving patients of this agent, in order to treat with immunotherapy, is controversial. Despite conventional dogma, we demonstrated that chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy. In fact, the temozolomide-induced lymphopenia may prove to be synergistic with a peptide vaccine secondary to inhibition of regulatory T cells or their delayed recovery.     

Non-aspirin non-steroidal anti-inflammatory drugs in colorectal cancer: a review of clinical studies

Colorectal cancer (CRC) chemoprevention is an area of interest. Non-steroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory agents which have been identified as cancer chemoprevention agents given that inflammation is thought to contribute to tumorigenesis. Most studies have demonstrated that the NSAID, aspirin, plays a beneficial role in the prevention of CRC and colonic adenomas. Non-aspirin NSAIDs (NA-NSAIDs) have also been studied in CRC chemoprevention. There is increasing literature around their role in pre-cancerous polyp prevention and in decreasing CRC incidence and CRC-related outcomes in certain high-risk subgroups. However, the use of NA-NSAIDs may be accompanied by increased risks of toxicity. Further studies are required to establish the associations between concurrent aspirin and NA-NSAID use, and CRC-related outcomes.Subject terms: Colorectal cancer, Cancer prevention     

Does a child's mid‐upper arm circumference‐for‐age z‐score represent another nutritional indicator of childhood malnutrition status?

Child wasting is defined as a weight‐for‐height/length z‐score (WLZ/WHZ) < −2, and this indicator of nutritional status is used worldwide. However, a precise measurement is required for the assessment of a child''s nutritional status, which may not always be possible due to expensive instruments, especially in poor resource settings. In some instances, mid‐upper arm circumference‐for‐age z‐score (MUACZ) is also being used for screening purposes, which is a simple and useful nutritional indicator. The objective of this paper is to identify the optimal cut‐off point for the MUACZ to identify wasted children, and also to determine if the same factors are associated with MUACZ and wasting. Data were derived from the Suchana evaluation data. The optimal cut‐off value was estimated via receiver operating characteristic (ROC) curve analysis using acute malnutrition as a gold standard with maximum sensitivity and specificity. Multiple logistic regression was used to assess the associated factors with the MUACZ. Using the gold standard indicator of nonwasting (WLZ ≥ −2), a positive outcome, the optimal cut‐off point for the MUACZ was −1.27. The area under the ROC curve was 0.88, indicating that the model had a power of 88% to differentiate between the positive and negative classes. It implies that a child''s MUACZ was correlated with WLZ, and a MUACZ below −1.27 appeared to accurately identify wasting among children aged 3–23 months. MUACZ < −1.27 might be another useful indicator of childhood wasting than a WLZ < −2.