Stereotactic radiosurgery for cavernous malformations

OBJECT: The use of stereotactic radiosurgery to treat cerebral cavernous malformations (CMs) is controversial. To evaluate the efficacy and safety of CM radiosurgery, the authors reviewed the experience at the Mayo Clinic during the past 10 years. METHODS: Seventeen patients underwent radiosurgery for high-surgical-risk CMs in the following sites: thalamus/basal ganglia (four patients), brainstem (12 patients), and corpus callosum (one patient). All patients had experienced at least two documented hemorrhages before undergoing radiosurgery. Stereotactic magnetic resonance (MR) imaging was used for target localization in all cases. The median margin radiation dose was 18 Gy and the median maximum dose was 32 Gy. The median length of follow-up review following radiosurgery was 51 months. The annual hemorrhage rate during the 51 months preceding radiosurgery was 40.1%, compared with 8.8% in the first 2 years following radiosurgery and 2.9% thereafter. In 10 patients (59%) new neurological deficits developed that were associated with regions of increased signal on long-repetition time MR imaging performed a median of 8 months (range 5-16 months) after radiosurgery. Three patients recovered, giving the group a permanent radiation-related morbidity rate of 41%. Compared with 31 patients harboring arteriovenous malformations (AVMs) of sizes and in locations similar to those of the aforementioned CMs, who underwent radiosurgery during the same time period, the patients with CMs were more likely to experience radiation-related complications (any complication, 59% compared with 10%; p < 0.001; permanent complication, 41% compared with 10%; p = 0.02). CONCLUSIONS: It is impossible to conclude that radiosurgery protects patients with CMs against future hemorrhage risk based on the available data, although it appears that some reduction in the bleeding rate occurs after a latency interval of several years. The risk of radiation-related complications after radiosurgery to treat CMs is greater than that found after radiosurgery in AVMs, even when adjusting for lesion size and location and for radiation dose.     

Identification of HLA-DRB1*1501-restricted T-cell epitopes from prostate-specific antigen.

The development of immunotherapy for prostate cancer based on the induction of autoimmunity to prostate tissue is very attractive because prostate is not a vital organ beyond the reproductive years. CD4 T cells play an important role in the development of antitumor immune responses, yet the identification of naturally processed MHC Class II-restricted epitopes derived from prostate differentiation antigens has not been described. To facilitate the search for prostate-specific antigen (PSA)-derived MHC class II-restricted peptides, we immunized mice transgenic for HLA-DRB1*1501 with human PSA and showed a robust dose-dependent immune response to the antigen. Screening a library of overlapping 20-mer peptides that span the entire PSA sequence identified two 20-mer peptides, PSA(171-190) and PSA(221-240), which were responsible for this reactivity. Immunization of DR2b transgenic mice with these peptides induced specific responses to the peptide and whole PSA. Identified peptides were used to stimulate CD4 T cells from HLA-DRB1*1501+ patients with a rare condition, granulomatous prostatitis, and who seem to have a preexisting immune response directed against the prostate gland. We previously showed a linkage of granulomatous prostatitis to HLA-DRB1*1501, suggesting that this disease may have an autoimmune etiology. Peptide-specific CD4 T-cell lines were generated from the peripheral blood of these patients as well as one patient with prostate cancer. These lines also recognized whole, processed PSA in the context of HLA-DRB1*1501. This study will be instrumental in understanding the interaction between circulating self-reactive T cells, organ-specific autoimmunity, and antitumor immune response. The use of these peptides for the immunotherapy of prostate cancer is under investigation.     

Modeling the cost of management options for stage I nonseminomatous germ cell tumors: a decision tree analysis.

PURPOSE: Patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) have been managed with surveillance, chemotherapy, or retroperitoneal lymphadenectomy (RPLND) with similar survival outcomes. Cost factors influencing the choice of therapy were evaluated using computer-based decision analysis. METHODS: A detailed model was developed that integrates projected costs for more than 60 possible treatment outcomes. It incorporates primary, adjuvant, and salvage chemotherapy, primary and post-chemotherapy RPLND, and both laparoscopic and open surgical approaches. Starting values and probabilities were derived from a comprehensive meta-analysis of the last 25 years of testes cancer literature. Hypothesis testing was performed using sensitivity analysis. RESULTS: The model predicts a cost premium for both primary chemotherapy (18.7%) and RPLND (51.7%) compared with surveillance. If laparoscopic RPLND was practiced, the cost premium for primary surgery (29.1%) approached that of chemotherapy (26.4%). Open RPLND was 1.25x as costly as laparoscopic RPLND, primarily because of longer hospitalization. The choice of open RPLND yielded a 6.9% cost premium for a surveillance program in this model. For such a program, primary chemotherapy became cost advantageous when the probability of recurrence during surveillance was more than 46%. CONCLUSION: This model allows a variety of treatment cost hypotheses to be tested. Primary RPLND is never cost advantageous over surveillance or primary chemotherapy. Surgical costs can significantly increase the overall cost of a surveillance program. In stage I patients with high-risk tumor characteristics, primary chemotherapy may have a cost advantage over surveillance.     

Variation of Mean Absolute Relative Differences of Continuous Glucose Monitoring Systems Throughout the Day

Background:There is an increasing use of continuous glucose monitoring (CGM) by people with diabetes. Measurement performance is often characterized by the mean absolute relative difference (MARD). However, MARD is influenced by a number of factors and little is known about whether MARD is stable throughout the day.Material and Methods:A total of 24 participants with type 1 diabetes were enrolled in the study. The study was performed for seven in-patient days. Participants wore two CGM systems in parallel and performed additional frequent blood glucose (BG) measurements. On two days, glucose excursions were induced.MARD was calculated between pairs of CGM and BG values, with BG values serving as reference values. ARD values calculated from CGM-BG pairs were grouped by hour of the day. Results were analyzed separately for glucose excursion days and for regular days.Results:Total MARDs for the complete study duration were 12.5% ± 3.6% and 13.2% ± 2.4% (n = 24). Throughout the day marked variability of MARD was observed (8.0% ± 1.3%-16.3% ± 2.9% (G5); 9.1% ± 1.4%-16.3% ± 5.3% (FL), up to n = 157 each). Low(est) MARD values were observed before breakfast and dinner, when subjects were in or near a fasting state. Especially after breakfast and lunch, MARD values were higher than average.Conclusions:Analytical performance of the two CGM systems, assessed by MARD, was found to vary markedly throughout the day. Activities of daily life likely triggered these variations. An increasing number of CGM users base therapeutic decisions on CGM values, and they should be aware of these variations of performance throughout the day.     

Factors affecting adherence to a raw vegan diet

The purpose of this study was to evaluate adherence and identify predictors of adherence to a raw vegan diet (i.e., uncooked plant foods) following a stay at a raw vegan institute. In this cohort study of guests at a raw vegan institute, subjects completed written questionnaires upon arrival and 12 weeks later. Of 107 eligible guests, 84 participated. Mean age was 54 years, 23 were male, and 73 white. Fifty-one completed the 12-week follow-up. Eight (16%) reported their diet to be 80% raw vegan at baseline and 14 (28%) at follow-up. Based on a raw vegan dietary adherence score (range 0-42) created for this study, mean adherence (SD) increased from 15.1 (5.4) to 17.0 (5.8) over 12 weeks (p=0.03). Baseline predictors of adherence included: education (beta=0.95), severity of disease (beta=0.98), and self-efficacy to adhere (beta=0.72). Future interventions that evaluate this diet should address self-efficacy, an important, potentially remediable predictor of adherence.     

Bolus-chasing contrast-enhanced 3D MRA of the lower extremity. Comparison with intraarterial DSA

PURPOSE: To evaluate step-table 3D contrast-enhanced (CE) MRA with bolus chasing for the detection and grading of stenoses in patients with peripheral vascular disease (PVD) of the lower extremities. MATERIAL AND METHODS: Fifty patients were studied by step-table bolus-chasing 3D-CE-MRA and i.a. DSA within 24 h. After determination of the individual circulation time, CE-MRA was performed during power injection of 40 ml of Gd-DTPA. To cover the whole range between the renal arteries and the feet with three slab locations, the scanner table was manually advanced twice for 350 mm. Total imaging time was 1 min 23 s. The degree of stenosis and image quality of the images were evaluated by 2 observers. In addition, a treatment plan was established based on the 3D-CE-MRA and DSA investigations. RESULTS: In 44 of 50 patients (88%), the visualization of the arterial tree from the renal arteries to the foot was possible. Forty-six of 50 patients (92%) had good or very good image quality. In the calf, 3D-CE-MRA was superior to DSA in 6 patients. For the detection of stenosis >50%, sensitivity was 99.5%, specificity 98.8%, positive predictive value 95.6% and the negative predictive value 99.8%. Cohen's kappa for 3D-CE-MRA vs. DSA was 0.926; for interobserver agreement it was 0.96. CONCLUSION: Bolus-chasing 3D-CE-MRA with manual table movement is a simple, robust and easy to perform technique which provides high quality angiograms of the lower extremity arterial system and is comparable to, i.a., DSA for the diagnosis of PVD.