Publications

BACKGROUND

The incidence of non-Hodgkin lymphoma (NHL) in human immunodeficiency virus (HIV)-infected patients remains high despite treatment with antiretroviral therapy (ART).

METHODS

We evaluated NHL incidence in HIV-infected patients followed in the Centers for AIDS Research Network of Integrated Clinical Systems who started combination ART and achieved suppression of HIV. We estimated the hazard ratio for NHL by time-varying HIV viremia categories, accounting for time-varying CD4 cell count using marginal structural models.

RESULTS

We observed 37 incident NHL diagnoses during 21 607 person-years of follow-up in 6036 patients (incidence rate, 171 per 100 000 person-years; 95% confidence interval [CI], 124-236). NHL incidence was high even among patients with nadir CD4 cell count >200 cells/µL (140 per 100 000 person-years [95% CI, 80-247]). Compared with ≤50 copies/mL, hazard ratios (HRs) for NHL were higher among those with HIV viremia of 51-500 copies/mL (HR current = 1.66 [95% CI, .70-3.94]; HR 3-month lagged = 2.10 [95% CI, .84-5.22]; and HR 6-month lagged = 1.46 [95% CI, .60-3.60]) and >500 copies/mL (HR current = 2.39 [95% CI, .92-6.21]; HR 3-month lagged = 3.56 [95% CI, 1.21-10.49]; and HR 6-month lagged = 2.50 [95% CI, .91-6.84]). Current HIV RNA as a continuous variable was also associated with NHL (HR = 1.42 per log10 copies/mL [95% CI, 1.05-1.92]).

CONCLUSIONS

Our findings demonstrate a high incidence of NHL among HIV-infected patients on ART and suggest a role of HIV viremia in the pathogenesis of NHL. Earlier initiation of potent ART and maximal continuous suppression of HIV viremia may further reduce NHL risk.

PURPOSE

To develop a method for high-resolution cardiac T1 mapping.

METHODS

A new method, accelerated and navigator-gated look-locker imaging for cardiac T1 estimation (ANGIE), was developed. An adaptive acquisition algorithm that accounts for the interplay between navigator gating and undersampling patterns well-suited for compressed sensing was used to minimize scan time. Computer simulations, phantom experiments, and imaging of the left ventricle (LV) were used to optimize and evaluate ANGIE. ANGIE's high spatial resolution was demonstrated by T1 mapping of the right ventricle (RV). Comparisons were made to modified Look-Locker imaging (MOLLI).

RESULTS

Retrospective reconstruction of fully sampled datasets demonstrated the advantages of the adaptive algorithm. For the LV, ANGIE measurements of T1 were in good agreement with MOLLI. For the RV, ANGIE achieved a spatial resolution of 1.2 × 1.2 mm(2) with a scan time of 157 ± 53 s per slice, and measured RV T1 values of 980 ± 96 ms versus 1076 ± 157 ms for lower-resolution MOLLI. ANGIE provided lower intrascan variation in the RV T1 estimate compared with MOLLI (P < 0.05).

CONCLUSION

ANGIE enables high-resolution cardiac T1 mapping in clinically reasonable scan times. ANGIE opens the prospect of quantitative T1 mapping of thin cardiovascular structures such as the RV wall.

A 70-year-old female Eritrean immigrant living in the USA presented with classic findings of genitourinary (GU) tuberculosis (TB), including risk of tuberculosis exposure based on country of origin, chronic urinary tract symptoms and persistent sterile pyuria despite antibacterial therapy. Furthermore, this patient had the hallmark radiographical findings of ureteral stricture, a dilated pelvic calyceal system, hydroureteronephrosis and bladder wall thickening, as well as a bladder wall biopsy that revealed granulomatous disease. The patient was evaluated multiple times over the course of 3 years in outpatient and inpatient medical settings before a diagnosis was made and appropriate treatment initiated. As with many cases of GU TB, a protracted diagnosis allowed for advanced disease progression and significant morbidity from obstructive uropathy and chronic kidney disease.

BACKGROUND

Estimating the burden of disease attributable to long-term exposure to fine particulate matter (PM2.5) in ambient air requires knowledge of both the shape and magnitude of the relative risk (RR) function. However, adequate direct evidence to identify the shape of the mortality RR functions at the high ambient concentrations observed in many places in the world is lacking.

OBJECTIVE

We developed RR functions over the entire global exposure range for causes of mortality in adults: ischemic heart disease (IHD), cerebrovascular disease (stroke), chronic obstructive pulmonary disease (COPD), and lung cancer (LC). We also developed RR functions for the incidence of acute lower respiratory infection (ALRI) that can be used to estimate mortality and lost-years of healthy life in children < 5 years of age.

METHODS

We fit an integrated exposure-response (IER) model by integrating available RR information from studies of ambient air pollution (AAP), second hand tobacco smoke, household solid cooking fuel, and active smoking (AS). AS exposures were converted to estimated annual PM2.5 exposure equivalents using inhaled doses of particle mass. We derived population attributable fractions (PAFs) for every country based on estimated worldwide ambient PM2.5 concentrations.

RESULTS

The IER model was a superior predictor of RR compared with seven other forms previously used in burden assessments. The percent PAF attributable to AAP exposure varied among countries from 2 to 41 for IHD, 1 to 43 for stroke, < 1 to 21 for COPD, < 1 to 25 for LC, and < 1 to 38 for ALRI.

CONCLUSIONS

We developed a fine particulate mass-based RR model that covered the global range of exposure by integrating RR information from different combustion types that generate emissions of particulate matter. The model can be updated as new RR information becomes available.

Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-γ, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-γ signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.