Effect of the synthetic retinoid fenretinide on circulating free prostate-specific antigen, insulin-like growth factor-I, and insulin-like growth factor binding protein-3 levels in men with superficial bladder cancer.

PURPOSE: Fenretinide (4-HPR) is a synthetic retinoid that has shown a preventive activity in prostate cancer animal models. EXPERIMENTAL DESIGN: We measured the changes in total and free prostate-specific antigen (PSA) and its association with insulin-like growth factor I (IGF-I) and IGFBP-3 levels after 1 year of treatment in 24 subjects given 4-HPR and 24 control subjects enrolled in a randomized bladder cancer prevention trial. RESULTS: No significant effect of 4-HPR was observed on total and free fraction of PSA levels. The median percentage [95 confidence interval (95% CI)] change for % free PSA and total PSA in the 4-HPR and the control group were, respectively, 7.6 (95% CI, -4.0 to 69.3) versus 5.1 (95% CI, -21.4 to 59.8) and -7.8 (95% CI, -18.2 to 52.5) versus -12.3 (95% CI, -44.6 to 9.6). However, in patients ages <60 years, there was a trend to an increase of total free PSA and % free PSA after treatment with 4-HPR that was different from a trend to a decrease in the control group (P = 0.002 and 0.052, respectively). The interaction between age and treatment was statistically significant on free PSA (P = 0.001). A similar pattern was noted with smoking status (P = 0.011 for the interaction on free PSA). No association was observed between PSA levels and IGF-I or IGFBP-3 levels. CONCLUSIONS: We conclude that 4-HPR has no significant effect on circulating PSA, but it increases significantly free PSA levels in subjects younger than 60 years and in nonsmokers. These effects might support an activity in prostate cancer prevention but further studies are required.     

Radioquimioterapia de la enfermedad limitada del carcinoma pulmonar de célula pequeña. ¿Tratamiento concomitante en protocolos asistenciales?

Purpose We retrospectively reviewed our institution’s database to investigate the outcome and impact of combined radiochemotherapy (RT/CT; concomitant or in sequence) in localised small-cell lung cancer (L-SCLC). Material and methods Between January 1995 to November 1999, 79 patients with L-SCLC received combined RT/CT at our Institution. RT was delivered concurrently or sequentially following the CT. Patients with treatment response received additional prophylactic cranial irradiation (PCI). Results Of the patients treated, 54% had received concurrent CT/RT compared to 46% receiving RT following the CT. PCI was administered to 80% of the patients. Complete response was observed in 66% of patients. With a median follow up of 30 months, median overall survival was 15.9 months; 14.3 months for patients who received RT following CT and 21.6 months for those receiving concurrent CT/RT. The type of schedule of combined radiochemotherapy was an independent prognostic factor for survival free of local recurrence, as was additional PCI for distant metastasis-free survival. Conclusions Our results are similar to those reported previously in the literature. The main point of interest is that our patients were non-selected. We strongly support the use of concurrent CT/RT so as to achieve results comparable to the best in the literature.

     

Análisis coste-efectividad de samario-153 (Quadramet®) en el tratamiento del dolor en pacientes con cáncer de próstata y metástasis óseas

Objective. To evaluate the cost-effectiveness of samarium [¹⁵³Sm-EDTMP] (Quadramet®) compared to conventional therapy in the treatment of pain in patients with prostate cancer and bone metastases. Method. A decision tree model for the treatment of bone pain due to metastases was adapted to the Spanish context. The model represents the standard treatment patterns in Spain for the study population. The time-course of the model is 4 months and it computes an estimate for the cost of pain control per patient. The effectiveness data for the model derive from a randomised trial. The current treatment patterns have been established according to the consensus opinions of a group of medical experts. Results. The cost of pain control per patient is ? 12,515.39 for conventional therapy and ? 5,595.52 for samarium-153 (Quadramet®) therapy. The incremental cost-effectiveness analysis shows that samarium-153 (Quadramet®) is a dominant therapy. It presents lower costs and higher efficacy than the conventional strategy. The sensitivity analyses showed these results to be robust. Conclusion. Samarium-153 (Quadramet®) is costeffective in treating pain in patients with prostate cancer and bone metastases.     

Desempenho Diagnóstico da Angiotomografia Computadorizada e da Avaliação Seriada de Troponina Cardíaca Sensível em Pacientes com Dor Torácica e Risco Intermediário para Eventos Cardiovasculares

BackgroundCoronary tomography angiography (CTA) has been mainly used for chest pain evaluation in low-risk patients, and few data exist regarding patients at intermediate risk.ObjectiveTo evaluate the performance of serial measures of sensitive troponin and CTA in intermediate-risk patients.MethodsA total of 100 patients with chest pain, TIMI risk scores of 3 or 4, and negative troponin were prospectively included. All patients underwent CTA and those with coronary stenosis ≥ 50% were referred to invasive coronary angiography. Patients with coronary lesions <50% were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Outcomes were hospitalization, death, and myocardial infarction at 30 days. The comparison between methods was performed by Kappa agreement test. The performance of troponin measures and CTA for detecting significant coronary lesions and clinical outcomes was calculated. Results were considered statistically significant when p < 0.05.ResultsCoronary stenosis ≥ 50% on CTA was found in 38% of patients and significant coronary lesions on coronary angiography were found in 31 patients. Two clinical events were observed. Kappa agreement analysis showed low agreement between troponin measures and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The performance of CTA for detecting significant coronary lesions on coronary angiography or for predicting clinical events at 30 days was better than sensitive troponin measures (accuracy of 91% versus 60%).ConclusionCTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.     

A scoring system for AML patients aged 70 years or older,eligible for intensive chemotherapy: a study based on a large European data set using the DATAML,SAL, and PETHEMA registries

In a context of therapeutic revolution in older adults with AML, it is becoming increasingly important to select patients for the various treatment options by taking account of short-term efficacy and toxicity as well as long-term survival. Here, the data from three European registries for 1,199 AML patients aged 70 years or older treated with intensive chemotherapy were used to develop a prognostic scoring system. The median follow-up was 50.8 months. In the training set of 636 patients, age, performance status, secondary AML, leukocytosis, and cytogenetics, as well as NPM1 mutations (without FLT3-ITD), were all significantly associated with overall survival, albeit not to the same degree. These factors were used to develop a score that predicts long-term overall survival. Three risk-groups were identified: a lower, intermediate and higher-risk score with predicted 5-year overall survival (OS) probabilities of ≥12% (n = 283, 51%; median OS = 18 months), 3–12% (n = 226, 41%; median OS = 9 months) and <3% (n = 47, 8%; median OS = 3 months), respectively. This scoring system was also significantly associated with complete remission, early death and relapse-free survival; performed similarly in the external validation cohort (n = 563) and showed a lower false-positive rate than previously published scores. The European Scoring System ≥70, easy for routine calculation, predicts long-term survival in older AML patients considered for intensive chemotherapy.Subject terms: Acute myeloid leukaemia, Risk factors     

Über Die SystematIk von 18 aus verschiedenen Krankheitsprozessen der menschlichen Haut gewonnenen Sprosspilzen

Ohne ZusammenfassungD 5.Bei Vollendung meiner Arbeit möchte ich meinem sehr verehrten Lehrer, Herrn Prof. Dr.Grütz, Direktor der Dermatologischen Universitätsklinik Bonn, meinen besten Dank aussprechen für die überlassung des Themas und seinen mir jederzeit freundlich gewährten Rat.     

Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood

Nicotinamide riboside, an NAD⁺ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD⁺ decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.