In patients with acute coronary syndromes, cardiac troponin I levels provide useful prognostic information and permit the early identification of patients with an increased risk of death.

Background Sickle cell anaemia (SCA) is associated with significant morbidity from acute complications and organ dysfunction beginning in the first year of life. In the first multicenter randomised double-blinded trial in very young children with SCA, the impact of hydroxyurea (hydroxycarbamide) therapy on organ dysfunction, clinical complications, and laboratory findings, and its toxicity, were examined. Methods Eligible subjects had HbSS or Sβ0thalassaemia, were age 9–18 months at randomisation, and were not selected for clinical severity. Subjects received liquid hydroxyurea, 20 mg/kg/day, or placebo for two years. Primary study endpoints were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate by 99mTc-DTPA clearance). Additional evaluations included: blood counts, HbF, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every two to four weeks. Findings Ninety-six subjects received hydroxyurea and 97 placebo; 86% completed the study. Significant differences were not seen for the primary endpoints, but suggestive benefit was noted in quantitative measures of spleen function. Hydroxyurea significantly decreased pain and dactylitis with trends for decreased acute chest syndrome, hospitalisation and transfusion. Hydroxyurea increased haemoglobin and HbF and decreased WBC count. Toxicity was limited to mild-moderate neutropaenia. Interpretation Although hydroxyurea treatment did not reduce splenic and renal dysfunction assessed by primary endpoint measures, it resulted in major clinical benefit because of diminished acute complications, favorable haematologic results, and a lack of unexpected toxicities. Based on the safety and efficacy data from this trial, hydroxyurea can now be considered for all very young children with SCA.

Sarcoidosis is a granulomatous disorder of unknown etiology, associated with an accumulation of CD4+ T cells and a TH1 immune response. Since previous studies of HLA associations with sarcoidosis were limited by serologic or low-resolution molecular identification, we performed high-resolution typing for the HLA-DPB1, HLA-DQB1, HLA-DRB1, and HLA-DRB3 loci and the presence of the DRB4 or DRB5 locus, to define HLA class II associations with sarcoidosis. A Case Control Etiologic Study of Sarcoidosis (ACCESS) enrolled biopsy-confirmed cases (736 total) from 10 centers in the United States. Seven hundred six (706) controls were case matched for age, race, sex, and geographic area. We studied the first 474 ACCESS patients and case-matched controls. The HLA-DRB1 alleles were differentially distributed between cases and controls (P<.0001). The HLA-DRB1*1101 allele was associated (P<.01) with sarcoidosis in blacks and whites and had a population attributable risk of 16% in blacks and 9% in whites. HLA-DRB1-F(47) was the amino acid residue most associated with sarcoidosis and independently associated with sarcoidosis in whites. The HLA-DPB1 locus also contributed to susceptibility for sarcoidosis and, in contrast to chronic beryllium disease, a non-E(69)-containing allele, HLA-DPB1*0101, conveyed most of the risk. Although significant differences were observed in the distribution of HLA class II alleles between blacks and whites, only HLA-DRB1*1501 was differentially associated with sarcoidosis (P<.003). In addition to being susceptibility markers, HLA class II alleles may be markers for different phenotypes of sarcoidosis (DRB1*0401 for eye in blacks and whites, DRB3 for bone marrow in blacks, and DPB1*0101 for hypercalcemia in whites). These studies confirm a genetic predisposition for sarcoidosis and present evidence for the allelic variation at the HLA-DRB1 locus as a major contributor.

The Pediatric Hydroxyurea Phase 3 Clinical Trial (BABY HUG) was a phase 3 multicenter, randomized, double-blind, placebocontrolled clinical trial of hydroxyurea in infants (beginning at 9-18 months of age) with sickle cell anemia. An important secondary objective of this study was to compare clinical events between the hydroxyurea and placebo groups. One hundred and ninetythree subjects were randomized to hy- Continuing Medical Education onlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™ . Physicians should claim only the credit commensurate with the extent of their participationin the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 4448. Disclosures The authors, the Associate Editor Narla Mohandas, and CME questions author Laurie Barclay, freelance writer and reviewer, Medscape, LLC, declare no competing financial interests. Learning objectivesUpon completion of this activity, participants will be able to:1. Describe the effect of hydroxyurea on rates of sickle cell complications for infants with sickle cell anemia (SCA) on the basis of a phase 3, multicenter, randomized trial.2. Describe the effect of hydroxyurea on rates of hospitalizations and transfusions for infants with SCA on the basis of a phase 3, multicenter, randomized trial.3. Describe the safety of hydroxyurea for infants with SCA on the basis of a phase 3, multicenter, randomized trial.

Past research suggests that environmental factors may be associated with sarcoidosis risk. We conducted a case control study to test a priori hypotheses that environmental and occupational exposures are associated with sarcoidosis. Ten centers recruited 706 newly diagnosed patients with sarcoidosis and an equal number of age-, race-, and sex-matched control subjects. Interviewers administered questionnaires containing questions regarding occupational and nonoccupational exposures that we assessed in univariable and multivariable analyses. We observed positive associations between sarcoidosis and specific occupations (e.g., agricultural employment, odds ratio [OR] 1.46, confidence interval [CI] 1.13-1.89), exposures (e.g., insecticides at work, OR 1.52, CI 1.14-2.04, and work environments with mold/mildew exposures [environments with possible exposures to microbial bioaerosols], OR 1.61, CI 1.13-2.31). A history of ever smoking cigarettes was less frequent among cases than control subjects (OR 0.62, CI 0.50-0.77). In multivariable modeling, we observed elevated ORs for work in areas with musty odors (OR 1.62, CI 1.24-2.11) and with occupational exposure to insecticides (OR 1.61, CI 1.13-2.28), and a decreased OR related to ever smoking cigarettes (OR 0.65, CI 0.51-0.82). The study did not identify a single, predominant cause of sarcoidosis. We identified several exposures associated with sarcoidosis risk, including insecticides, agricultural employment, and microbial bioaerosols.

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Data from 2543 HIV-infected women were analyzed to correlate antiretroviral therapy (ART) used during pregnancy with maternal and pregnancy outcomes. ART was analyzed according to class of agents used and according to monotherapy versus combination ART containing neither protease inhibitors (PIs) nor nonnucleoside reverse transcriptase inhibitors versus highly active ART. Timing of ART was classified according to early (recorded at or before 25-week gestation study visit) and late (recorded at 32-week gestation or delivery visit) use. Maternal outcomes assessed included hematologic, gastrointestinal, neurologic, renal, and dermatologic complications; gestational diabetes; lactic acidosis; and death. Adverse pregnancy outcomes assessed included hypertensive complications; pre-term labor or rupture of membranes; preterm delivery (PTD); low birth weight; and stillbirth. Logistic regression analyses controlling for multiple covariates revealed ART to be independently associated with few maternal complications: ART use was associated with anemia (odds ratio [OR] = 1.6, 95% confidence interval [CI]: 1.1-2.4), and late use of ART was associated with gestational diabetes (OR = 3.5, 95% CI: 1.2-10.1). Logistic regression analyses revealed an increase in PTD at <37 weeks for 10 women with late use of ART not containing zidovudine (ZDV; OR = 7.9, 95% CI: 1.4-44.6) and a decrease in adverse pregnancy outcomes as follows: late use of ART containing ZDV was associated with decreased risk for stillbirth and PTD at <37 weeks (OR = 0.06, 95% CI: 0.02-0.18; OR = 0.5, 95% CI: 0.3-0.8, respectively), and ART containing nucleoside reverse transcriptase inhibitors but not ZDV during early and late pregnancy was associated with decreased risk for PTD at <32 weeks (OR = 0.3, 95% CI: 0.2-0.7). Benefits of ART continue to outweigh observed risks.

Rationale: Prior studies comparing abnormalities in pulmonary function between HIV-infected and HIV-uninfected persons in the current era are limited. Objectives: To determine the pattern and severity of impairment in pulmonary function in HIV-infected compared to HIV-uninfected individuals. Methods: Cross-sectional analysis of 300 HIV-infected and 289 HIV-uninfected men enrolled from 2009-2011 in two clinical centers of the Lung HIV Study. Participants completed pre- and post-bronchodilator spirometry, diffusing capacity (DLCO) measurement, and standardized questionnaires. Results: Most participants had normal airflow; 18% of HIV-infected and 16% of HIV-uninfected men had airflow obstruction. The mean percent predicted DLCO was 69% in HIV-infected vs. 76% in HIV-uninfected men (p<0.001). A moderately to severely reduced DLCO of ≤60% was observed in 30% of HIV-infected compared to 18% of HIV-uninfected men (p<0.001), despite the fact that 89% of those with HIV were on antiretroviral therapy. A reduced DLCO was significantly associated with HIV and CD4 cell count in linear regression adjusting for smoking and other confounders. The DLCO was lowest in HIV-infected men with CD4 cell counts <200 compared to those with CD4 cell counts ≥200 and to HIV-uninfected men. Respiratory symptoms of cough, phlegm and dyspnea were more prevalent in HIV-infected patients particularly those with abnormal pulmonary function compared to HIV-uninfected patients. Conclusions: HIV infection is an independent risk factor for reduced DLCO, particularly in individuals with a CD4 cell count below 200. Abnormalities in pulmonary function among HIV-infected patients manifest clinically with increased respiratory symptoms. Mechanisms accounting for the reduced DLCO require further evaluation.