Abnormal Cerebral Perfusion Profile in Older Adults with HIV-Associated Neurocognitive Disorder: Discriminative Power of Arterial Spin-Labeling.

BACKGROUND AND PURPOSE: The aging HIV-infected (HIV+) population has increased vascular comorbidities, including stroke, and increased cognitive deficits compared with the general population. Arterial spin-labeling is a technique to measure cerebral blood flow and is more sensitive than regional volume loss in assessing neurodegenerative diseases and cognitive aging. Previous studies have found global cerebral perfusion abnormalities in the HIV+ participants. In this study, we evaluated the specific regional pattern of CBF abnormalities in older HIV+ participants using quantitative whole-brain arterial spin-labeling. MATERIALS AND METHODS: CBF data from the UCSF HIV Over 60 Cohort and the Alzheimer Disease Neuroimaging Initiative were retrospectively evaluated to identify 19 HIV+ older adults, all with plasma viral suppression (including 5 with HIV-associated neurocognitive disorder); 13 healthy, age-matched controls; and 19 participants with early mild cognitive impairment. CBF values were averaged by ROI and compared among the 3 groups using generalized linear models. RESULTS: When we accounted for age, education, sex, and vascular risk factors, the HIV+ participants demonstrated alterations in regional cerebral perfusion, including hypoperfusion of bilateral temporal, parietal, and occipital brain regions compared with both clinically healthy participants and those with mild cognitive impairment. Arterial spin-labeling showed reasonable test characteristics in distinguishing those with HIV-associated neurocognitive disorder from healthy controls and participants with mild cognitive impairment. CONCLUSIONS: This study found specific CBF patterns associated with HIV status despite viral suppression-data that should animate further investigations into the pathobiologic basis of vascular and cognitive abnormalities in HIV-associated neurocognitive disorders.

Sequential therapy combining clofarabine and T-cell-replete HLA-haploidentical haematopoietic SCT is feasible and shows efficacy in the treatment of refractory or relapsed aggressive lymphoma.

Prognosis is poor for patients with biologically aggressive Non-Hodgkin lymphoma (NHL), refractory to chemotherapy or relapsed after autologous transplantation, especially when no disease control before allogeneic transplantation is achieved. In 16 patients (median age 53, median prior regimes 5) with relapsed or refractory non-remission NHL, we analysed retrospectively the efficacy of a sequential therapy comprising clofarabine re-induction followed by a reduced-intensity conditioning with fludarabine, CY and melphalan, and T-cell-replete HLA-haploidentical transplantation. High-dose CY was utilized post-transplantation. All patients engrafted. Early response (day +30) was achieved in 94%. Treatment-related grade III-IV toxicity occurred in 56%, most commonly transient elevation of transaminases (36%), while there was a low incidence of infections (19% CMV reactivation, 19% invasive fungal infection) and GVHD (GVHD: acute III-IV: 6%; mild chronic: 25%). One-year non-relapse mortality was 19%. After a median follow-up of 21 months, estimated 1- and 2-year PFS was 56 and 50%, respectively, with 11 patients (69%) still alive after 2 years. In summary, sequential therapy is feasible and effective and provides an acceptable toxicity profile in high-risk non-remission NHL. Presumably, cytotoxic reinduction with clofarabine provides enough remission time for the graft-versus lymphoma effect of HLA-haploidentical transplantation to kick in, even in lymphomas that are otherwise chemo-refractory.

Multicenter validation of a bedside antisaccade task as a measure of executive function.

OBJECTIVE: To create and validate a simple, standardized version of the antisaccade (AS) task that requires no specialized equipment for use as a measure of executive function in multicenter clinical studies. METHODS: The bedside AS (BAS) task consisted of 40 pseudorandomized AS trials presented on a laptop computer. BAS performance was compared with AS performance measured using an infrared eye tracker in normal elders (NE) and individuals with mild cognitive impairment (MCI) or dementia (n = 33). The neuropsychological domain specificity of the BAS was then determined in a cohort of NE, MCI, and dementia (n = 103) at UCSF, and the BAS was validated as a measure of executive function in a 6-center cohort (n = 397) of normal adults and patients with a variety of brain diseases. RESULTS: Performance on the BAS and laboratory AS task was strongly correlated and BAS performance was most strongly associated with neuropsychological measures of executive function. Even after controlling for disease severity and processing speed, BAS performance was associated with multiple assessments of executive function, most strongly the informant-based Frontal Systems Behavior Scale. CONCLUSIONS: The BAS is a simple, valid measure of executive function in aging and neurologic disease.