Radiotherapy in langerhans cell histiocytosis - a rare indication in a rare disease

Introduction: Langerhans Cell Histiocytosis (LCH) represents a rare benign disorder, previously designated as “Histiocytosis X”, “Type II Histiocytosis” or “Langerhans Cell Granulomatosis”. Clinical presentation includes osteolysis, ulcerations of skin and soft tissues but also involvement of the CNS is described. Because treatment concepts are not well defined the German Cooperative Group on Radiotherapy for Benign Diseases performed a retrospective analysis. Methods and material: Eight closely cooperating centres collected patients’ data of the past 45 years. As study endpoints disease free survival, recurrent disease, death and therapy related side effects were defined. Results: A total of 80 patients with histologically proven LCH were irradiated within the past 45 years. According to the LCH classification of Greenberger et al. 37 patients had stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb and the median age was 29 years. The median Follow up was 54 months (range 9–134 months). A total of 39 patients had a surgical intervention and 23 patients a chemotherapy regimen. Radiation treatment was carried out with a median total dose of 15 Gy (range 3–50.4 Gy). The median single fraction was 2 Gy (range 1.8-3 Gy). Overall, 77% patients achieved a complete remission and 12.5% achieved a partial remission. The long-term control rate reached 80%. Within an actuarial overall 5-year survival of 90% no radiogenic side and late effects ≥EORTC/RTOG II° were observed. Conclusion: In the present study a large collective of irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe treatment option and even low RT doses show sufficient local control.<br

Putting theory oriented evaluation into practice

Evaluations of gaming simulations and business games as teaching devices are typically end-state driven. This emphasis fails to detect how the simulation being evaluated does or does not bring about its desired consequences. This paper advances the use of a logic model approach which possesses a holistic perspective that aims at including all elements associated with the situation created by a game. The use of the logic model approach is illustrated as applied to Simgame, a board game created for secondary school level business education in six European Union countries

Excess cardiovascular mortality associated with cold spells in the Czech Republic

<p>Abstract</p> <p>Background</p> <p>The association between cardiovascular mortality and winter cold spells was evaluated in the population of the Czech Republic over 21-yr period 1986–2006. No comprehensive study on cold-related mortality in central Europe has been carried out despite the fact that cold air invasions are more frequent and severe in this region than in western and southern Europe.</p> <p>Methods</p> <p>Cold spells were defined as periods of days on which air temperature does not exceed -3.5°C. Days on which mortality was affected by epidemics of influenza/acute respiratory infections were identified and omitted from the analysis. Excess cardiovascular mortality was determined after the long-term changes and the seasonal cycle in mortality had been removed. Excess mortality during and after cold spells was examined in individual age groups and genders.</p> <p>Results</p> <p>Cold spells were associated with positive mean excess cardiovascular mortality in all age groups (25–59, 60–69, 70–79 and 80+ years) and in both men and women. The relative mortality effects were most pronounced and most direct in middle-aged men (25–59 years), which contrasts with majority of studies on cold-related mortality in other regions. The estimated excess mortality during the severe cold spells in January 1987 (+274 cardiovascular deaths) is comparable to that attributed to the most severe heat wave in this region in 1994.</p> <p>Conclusion</p> <p>The results show that cold stress has a considerable impact on mortality in central Europe, representing a public health threat of an importance similar to heat waves. The elevated mortality risks in men aged 25–59 years may be related to occupational exposure of large numbers of men working outdoors in winter. Early warnings and preventive measures based on weather forecast and targeted on the susceptible parts of the population may help mitigate the effects of cold spells and save lives.</p

A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis

BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118

Selenium supplementation in radiotherapy patients: do we need to measure selenium levels in serum or blood regularly prior radiotherapy?

Considering the review by Puspitasari and colleagues, an additional discussion of the endpoints of the Se supplementation studies described would be helpful. In our view, selenium can safely be given to selenium-deficient cancer patients prior to and during radiotherapy. Therefore, in order to help the radiation oncologist in decision making, we strongly advocate to determine the selenium status prior to and during a potential adjuvant selenium supplementation, e.g. when trying to ease the side-effects of radiation treatment or in the aftercare situation when the selenium status may become insufficient

Magnetoliposomes as Contrast Agents for Longitudinal in vivo Assessment of Transplanted Pancreatic Islets in a Diabetic Rat Model

Magnetoliposomes (MLs) were synthesized and tested for longitudinal monitoring of transplanted pancreatic islets using magnetic resonance imaging (MRI) in rat models. The rat insulinoma cell line INS-1E and isolated pancreatic islets from outbred and inbred rats were used to optimize labeling conditions in vitro. Strong MRI contrast was generated by islets exposed to 50 µg Fe/ml for 24 hours without any increased cell death, loss of function or other signs of toxicity. In vivo experiments showed that pancreatic islets (50-1000 units) labeled with MLs were detectable for up to 6 weeks post-transplantation in the kidney subcapsular space. Islets were also monitored for two weeks following transplantation through the portal vein of the liver. Hereby, islets labeled with MLs and transplanted under the left kidney capsule were able to correct hyperglycemia and had stable MRI signals until nephrectomy. Interestingly, in vivo MRI of streptozotocin induced diabetic rats transplanted with allogeneic islets demonstrated loss of MRI contrast between 7-16 days, indicative of loss of islet structure. MLs used in this study were not only beneficial for monitoring the location of transplanted islets in vivo with high sensitivity but also reported on islet integrity and hereby indirectly on islet function and rejection.status: publishe