Rituximab decreases the risk of lymphoma in patients with HIV-associated multicentric Castleman disease

HIV-associated multicentric Castleman disease (MCD) is associated with a high risk of developing non-Hodgkin lymphoma (NHL). Rituximab is effective in HIV-MCD, but its impact on NHL incidence remains unknown. From a single-center prospective cohort, 113 patients were identified with a diagnosis of HIV-MCD for the present study. To compare the incidence of NHL between patients who had received a rituximab-based treatment (R+ group) and those who had not (R- group), data were analyzed before and after matching on propensity scores and after multiple imputation. The mean follow-up was 4.2 years. In the R- group (n = 65), 17 patients developed NHL (incidence, 69.6 of 1000 person years). In the R+ group (n = 48), only 1 patient developed NHL (incidence, 4.2 of 1000 person years). Based on the propensity score-matching method, a significant decrease in the incidence of NHL was observed in patients who had been treated with rituximab (hazard ratio, 0.09; 95% confidence interval, 0.01-0.70). Ten Kaposi sarcoma (KS) exacerbations and 1 newly diagnosed KS were observed in 9 patients after rituximab therapy. Rituximab was associated with an 11-fold lower risk of developing lymphoma. KS exacerbation was the most challenging adverse event after rituximab therapy.     

Fiblast (trafermin) in acute stroke: results of the European-Australian phase II/III safety and efficacy trial

BACKGROUND: Trafermin (basic fibroblast growth factor) has been shown to reduce infarct volume in acute ischemic stroke models, and to promote functional recovery and new synapse formation when given to animals with completed cerebral infarction. A previous study in acute stroke patients suggested that trafermin was safe and well tolerated when given over a 3-hour period over a wide dose range. METHODS AND RESULTS: Double-blind, parallel group, placebo-controlled trial of a single 24-hour intravenous infusion of trafermin. Patients having onset of stroke symptoms within 6 h and a baseline score of >/=7 on the NIH Stroke Scale (>/=2 motor) were randomized to receive 5 or 10 mg of trafermin or placebo intravenously infused over 24 h. The primary efficacy outcome was a categorized combination of the Barthel and Rankin scales assessed at 90 days. A total of 286 patients had been enrolled at 55 sites in 11 countries when the sponsor directed that enrollment be stopped because an interim analysis of efficacy data predicted too small a chance of demonstrating a statistically significant benefit after recruitment of the planned 900 patients. The 5-mg group showed a slight but nonsignificant advantage over placebo (OR 1.2, 95% CI 0.72-2.00, p = 0.48); the 10-mg group showed a nonsignificant disadvantage (OR 0.74, 95% CI 0.44-1.22, p = 0.24). Mortality rates at 90 days were 17% in the 5-mg group, 24% in the 10-mg group and 18% in the placebo group. Treatment with trafermin was associated with an increased leukocytosis and a decrease in blood pressure: mean decrease in systolic blood pressure from baseline was 19 mm Hg in the 5-mg group, 22 mm Hg in the 10-mg group and 8 mm Hg in the placebo group. In a post hoc subgroup analysis, patients in the 5-mg group treated more than 5 h after the onset of symptoms showed an apparent advantage over placebo (OR 2.1, 95% CI 1.00-4.41, p = 0.044; after age adjustment: OR 1.9, 95% CI 0.91-4.13, p = 0.08). CONCLUSIONS: With the proper treatment regimen, trafermin can likely be given safely to stroke patients. The 5-mg dose showed a trend toward a treatment advantage. The ideal time window for this agent may exceed 5 h. This may open new avenues for acute stroke therapy, aiming at enhancing recovery mechanisms rather than immediate neuroprotection.     

Medical decision assistance. Logical method and application to thyroid diseases (author's transl)]

Medical diagnosis assistance is described in terms of step by step logical reasoning methods. Boolean functions, possibly connected with phi-fuzzy functions, and a theorem proving algorithm may be used at each step. The choice merely depends on the accuracy of diagnosis at a given step. Numerical results based on a study of patients with thyroid diseases are presented.     

High levels of interferon gamma in the plasma of children with complete interferon gamma receptor deficiency

We have found that children with complete interferon gamma (IFNgamma) receptor deficiency, unlike patients with other genetic defects predisposing them to mycobacterial diseases, have very high levels of IFNgamma in their plasma. This unexpected observation provides a simple and accurate diagnostic method for complete IFNgamma receptor deficiency in children with clinical disease caused by bacille Calmette-Guérin vaccines or environmental nontuberculous mycobacteria.