Citations

Abstract With recent approval of the first dendritic cell (DC) vaccine for patient use, many other DC vaccine approaches are now being tested in clinical trials. Many of these DC vaccines employ tumor cell lysates (TL) generated from cells cultured in atmospheric oxygen (∼20% O2) that greatly exceeds levels found in tumors in situ. In this study, we tested the hypothesis that TLs generated from tumor cells cultured under physiologic oxygen (∼5% O2) would be more effective as a source for DC antigens. Gene expression patterns in primary glioma cultures established at 5% O2 more closely paralleled patient tumors in situ and known immunogenic antigens were more highly expressed. DCs treated with TLs generated from primary tumor cells maintained in 5% O2 took up and presented antigens to CD8 T cells more efficiently. Moreover, CD8 T cells primed in this manner exhibited superior tumoricidal activity against target cells cultured in either atmospheric 20% O2 or physiologic 5% O2. Together, these results establish a simple method to greatly improve the effectiveness of DC vaccines in stimulating the production of tumoricidal T cells, with broad implications for many of the DC-based cancer vaccines being developed for clinical application. Cancer Res; 71(21); 6583–9. ©2011 AACR.

Abstract To test recommended anticoagulation measures as predictors of 180-day venous thromboembolism (VTE) recurrence, we identified all Olmsted County, MN residents with incident VTE over the 14-year period of 1984-1997, and followed each case (N = 1166) forward in time for VTE recurrence. We tested the activated partial thromboplastin time (APTT), international normalized ratio (INR), and other measures of heparin and warfarin anticoagulation as predictors of VTE recurrence while controlling for baseline and time-dependent characteristics using Cox proportional hazards modeling. Overall, 1026 (88%) and 989 (85%) patients received heparin and warfarin, respectively, and 85 (8%) developed VTE recurrence. In multivariable analyses, increasing proportions of time on heparin with an APTT ≥ 0.2 anti-Xa U/mL and on warfarin with an INR ≥ 2.0 were associated with significant reductions in VTE recurrence, while the hazard with active cancer was significantly increased. Time from VTE onset to heparin start, duration of overlapping heparin and warfarin, and inferior vena cava (IVC) filter placement were not independent predictors of recurrence. At a heparin dose ≥ 30 000 U/d, the median proportion of time with an APTT ≥ 0.2 anti-Xa U/mL was 92%, suggesting that routine APTT monitoring and heparin dose adjustment may be unnecessary. In summary, lower-intensity heparin and standard-intensity warfarin anticoagulation are effective in preventing VTE recurrence.

A newly identified gene fusion defines the vascular cancer epithelioid hemangioendothelioma and encodes a chimeric transcription factor.

The role of surgery in continuous spike wave in slow-wave sleep has not been robustly explored. The authors present a case of an 11-year-old boy with refractory partial seizures and continuous spike wave in slow-wave sleep who was treated with an anterior temporal lobectomy. His presurgical brain magnetic resonance imaging revealed right basal ganglia and thalamic infarcts and right mesial temporal sclerosis. Following surgery, he achieved seizure freedom, cessation of continuous spike wave in slow-wave sleep, and improved cognition. This case provides further evidence that epilepsy syndromes with generalized electrographic discharges can be secondary to focal pathology and potentially cured with resective surgery. The normalization of his sleep electroencephalogram following the anterior temporal lobectomy suggests that temporal lobe structures may be involved in the seizure network needed to generate continuous spike wave in slow-wave sleep.

Digital replantation has become a well-established technique among reconstructive hand surgeons. Numerous replantation centers around the world have published series with impressive survival rates. The ultimate goal of replantation is the restoration of normal hand or digital function; thus, replantation success is not solely related to the outcome of the microvascular anastomosis, but also to the adequacy of bone, tendon, skin, and nerve repairs. In this manuscript, we review the literature on upper extremity and digital replantation from its historical background to current surgical outcomes, outlining surgical indications and contraindications, and the preoperative, operative, and postoperative management of these patients.

Better tools for assessing cognitive impairment in the early stages of Alzheimer's disease (AD) are required to enable diagnosis of the disease before substantial neurodegeneration has taken place and to allow for detection of subtle changes in the early stages of progression of the disease. The National Institute on Aging and the Alzheimer's Association convened a meeting to discuss state‐of‐the art methods for cognitive assessment, including computerized batteries, as well as new approaches in the pipeline. Speakers described research using novel tests of object recognition, spatial navigation, attentional control, semantic memory, semantic interference, prospective memory, false memory, and executive function as among the tools that could provide earlier identification of individuals with AD. In addition to early detection, there is a need for assessments that reflect real‐world situations so as to better assess functional disability. It is especially important to develop assessment tools that are useful in ethnically, culturally, and linguistically diverse populations as well as in individuals with neurodegenerative disease other than AD.