Zanetta S. Lamar

Higher Risk of Severe Drug-Induced Liver Injury among Hispanic HIV-Infected Patients after Initiation of Highly Active Antiretroviral Therapy

Background: Little is known about differences across ethnicities in the development of drug-induced liver injury (DILI) after highly active antiretroviral therapy (HAART) initiation. Methods: This is a retrospective, longitudinal, comparative, pilot study. DILI within the first year of HAART was evaluated in 50 HIV-infected Hispanics without viral hepatitis who initiated HAART between 2000 and 2009. It was compared to white and black patients (1:1:1) matched by age and CD4 counts. Results: HAART-related DILI of any grade occurred in 30 of 150 (20%) patients and was associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) use (OR 4.49 [95%CI 1.5-13.8]). Severe DILI was significantly more frequent among Hispanics compared to other groups (6% vs. 0%; P = .04). Of the 3 patients with severe DILI, 2 underwent liver imaging and had hepatic steatosis. Conclusions: Severe DILI within the first year of HAART initiation was infrequent and restricted to Hispanics. Additional studies are needed to determine if fatty liver is involved in the excess of severe DILI observed in this group.

Left Ventricular Mass Change After Anthracycline Chemotherapy

Background: Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment. Methods and Results: We performed blinded, serial assessments of body weight, LVEF and mass, LV-arterial coupling, aortic stiffness, and Minnesota Living with Heart Failure Questionnaire measures before and 6 months after initiating Anth-bC (n=61) and non–Anth-bC (n=15), and in 24 cancer-free controls using paired t and &khgr;2 tests and multivariable linear models. Participants averaged 51±12 years, and 70% were women. Cancer diagnoses included breast cancer (53%), hematologic malignancy (42%), and soft tissue sarcoma (5%). We observed a 5% decline in both LVEF (P<0.0001) and LV mass (P=0.03) in the setting of increased aortic stiffness and disrupted ventricular-arterial coupling in those receiving Anth-bC but not other groups (P=0.11–0.92). A worsening of the Minnesota Living with Heart Failure Questionnaire score in Anth-bC recipients was associated with myocardial mass declines (r=−0.27; P<0.01) but not with LVEF declines (r=0.11; P=0.45). Moreover, this finding was independent of LVEF changes and body weight. Conclusions: Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.

Hyperglycemia during first-line R-CHOP or dose adjusted R-EPOCH chemotherapy for non-Hodgkin lymphoma is prevalent and associated with chemotherapy alteration – a retrospective study

Abstract High-dose glucocorticoids such as prednisone are combined with cytotoxic chemotherapy in the R-CHOP or dose adjusted R-EPOCH regimens used for non-Hodgkin lymphoma (NHL). In this retrospective study, our primary objective was to evaluate the incidence of hyperglycemia during first-line R-CHOP or DA-EPOCH-R. The secondary objectives were to evaluate the incidence of chemotherapy alteration and overall survival in those with and without hyperglycemia. One hundred and sixty patients were eligible. We found that 47% of all patients had at least one hyperglycemic episode and hyperglycemia was associated with chemotherapy alteration (pu2009=u2009.028). Multivariate analysis revealed international prognostic index (IPI)u2009≥u20093 (pu2009=u2009.045) and chemotherapy alteration (pu2009=u2009.001) were associated with decreased overall survival. We conclude that hyperglycemia is common during first-line NHL treatment with R-CHOP or DA-EPOCH-R, even in the absence of known diabetes and is associated with alterations of chemotherapy. Baseline pre-PET scan fasting blood glucose of 100u2009mg/dL or higher may predict hyperglycemia during therapy.

A human bone marrow mesodermal-derived cell population with hemogenic potential

The presence, within the human bone marrow, of cells with both endothelial and hemogenic potential has been controversial. Herein, we identify, within the human fetal bone marrow, prior to establishment of hematopoiesis, a unique APLNR+, Stro-1+ cell population, co-expressing markers of early mesodermal precursors and/or hemogenic endothelium. In adult marrow, cells expressing similar markers are also found, but at very low frequency. These adult-derived cells can be extensively culture expanded in vitro without loss of potential, they preserve a biased hemogenic transcriptional profile, and, upon in vitro induction with Oct4, assume a hematopoietic phenotype. In vivo, these cells, upon transplantation into a fetal microenvironment, contribute to the vasculature, and generate hematopoietic cells that provide multilineage repopulation upon serial transplantation. The identification of this human somatic cell population provides novel insights into human ontogenetic hematovascular potential, which could lead to a better understanding of, and new target therapies for, malignant and nonmalignant hematologic disorders.

The Role of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in the Diagnosis and the Subtyping of Lymphoma in the Mediastinum

Endobronchial ultrasound-guided transbronchial needle aspiration is a commonly performed procedure in patients with mediastinal lymphadenopathy. Its role has been widely established in the diagnosis and the staging of lung cancer and other benign disease, but there is still debatable evidence regarding its role in the diagnosis, the subtyping, and the treatment of lymphoproliferative diseases. Consequently, there are no guidelines or statements to guide the choice of diagnostic modality in such cases. We review the available literature to evaluate the myth that endobronchial ultrasound-guided transbronchial needle aspiration does not provide sufficient diagnostic material for the accurate diagnosis and subtyping of mediastinal lymphoma.