No abstract

Elevated OEF in the deep white matter identifies a signature of metabolically stressed brain tissue at increased stroke risk in pediatric patients with SCD. We propose that border zone physiology, exacerbated by chronic anemic hypoxia, explains the high risk in this region.

Blood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO, thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric spin echo sequences measured CBF and OEF, respectively, which were compared pre- and posttransfusion. Volumes of tissue with OEF above successive thresholds (36%, 38%, and 40%), as a metric of regional metabolic stress, were compared pre- and posttransfusion. Transfusions increased hemoglobin (Hb; from 9.1 to 10.3 g/dL; < .001) and decreased Hb S (from 39.7% to 24.3%; < .001). Transfusions reduced CBF (from 88 to 82.4 mL/100 g per minute; = .004) and OEF (from 34.4% to 31.2%; < .001). At all thresholds, transfusions reduced the volume of peak OEF found in the deep white matter, a location at high infarct risk in SCA ( < .001). Reduction of elevated CBF and OEF, both globally and regionally, suggests that CTT mitigates infarct risk in pediatric SCA by relieving cerebral metabolic stress at patient- and tissue-specific levels.

BACKGROUND.Radioimmunotherapy with radiolabeled monoclonal antibodies to CD20 produces a high response rate in patients with recurring non‐Hodgkin lymphoma (NHL), but the durability of those remissions is not well defined.METHODS.Data on patients with recurring NHL treated with yttrium Y 90 ibritumomab tiuxetan in 4 clinical trials were reviewed to identify patients with a long‐term response, defined as a time to progression of 12 months or longer.RESULTS.Long‐term responses were seen in 37% (78/211) of patients. At a median follow‐up of 53.5 months (range, 12.7–88.9) the median duration of response was 28.1 months and the median time to progression was 29.3 months. A third of these patients had been treated with at least 3 previous therapies, and 37% of them had not responded to their last therapy. The findings in patients with follicular lymphoma (n = 59) were similar to those in the overall population of long‐term responders. The estimated overall survival at 5 years was 53% for all patients treated with 90Y ibritumomab tiuxetan and 81% for long‐term responders.CONCLUSIONS.A single dose of 90Y ibritumomab tiuxetan can produce durable responses and prolonged overall survival in a substantial number of patients in whom previous therapies have failed. Cancer 2007. © 2007 American Cancer Society.

The purpose of this study was to explore the feasibility of obtaining magnetic resonance-measured cerebral metabolic rate of oxygen utilization (MR-CMRO(2)) in acute ischemic stroke patients. Seven stroke patients were serially imaged: 4.5 +/- 0.9 hours (tp1), 3 to 5 days (tp2), and 1 to 3 months (tp3) after symptom onset. Diffusion-weighted, perfusion-weighted, and multiecho gradient-echo/spin-echo images were acquired; cerebral blood flow and oxygen extraction fraction maps were obtained from which CMRO(2) was calculated as the product of cerebral blood flow and oxygen extraction fraction. The final infarct lesions obtained from tp3 T2-weighted images and the "penumbra" obtained from the tp1 perfusion-weighted image-defined lesion were coregistered onto tp1 CMRO(2) maps. CMRO(2) values in the region of brain that eventually infarcted were reduced to 0.40 +/- 0.24 of the respective region on the contralateral hemisphere. The "salvaged penumbra" defined by the area of mismatch between the final infarct and the tp1 perfusion-weighted lesion demonstrated an average CMRO(2) value of 0.55 +/- 0.11 of the contralateral hemisphere. Although our results are preliminary and require further evaluation, the ability to obtain in vivo measurements of MR-CMRO(2) noninvasively potentially can provide information for determining brain tissue viability in acute ischemic stroke patients.