PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome. 相似文献
Over the past decade, treatment options for patients with multiple myeloma (MM) have improved substantially, resulting in
better response rates and prolonged overall survival (OS). Nevertheless, MM remains a challenging disease, especially if renal
insufficiency (RI) or extensive pre-treatment aggravates the assignment of the optimal treatment schedule. In this retrospective
study, we analyzed the outcome of lenalidomide plus dexamethasone in 167 patients with relapsed or refractory MM with focus
on RI. The baseline creatinine clearance (CLCr) was normal in 94 patients (CLCr ≥ 80 ml/min), while RI was observed in 73 patients, including 40 patients with mild RI (50 ≤ CLCr < 80 ml/min) and 33 patients with moderate or severe RI (CLCr < 50 ml/min). Response rates declined depending on the severity of RI, being 67% among patients with normal kidney function,
60% among patients with mild RI and 49% among patients with moderate or severe RI. Time to progression (TTP) was significantly
reduced in patients with severe RI and in case of >2 previous treatment lines. OS was not significantly different between
patients with normal and impaired renal function. In contrast, the number of previous treatment lines (2 vs. <2) and the use
of novel agents like bortezomib or thalidomide prior to lenalidomide plus dexamethasone therapy had a more adverse effect
on OS. In conclusion, lenalidomide plus dexamethasone is an effective regimen for relapsed or refractory patients with MM
complicated by RI with manageable toxicity. 相似文献
A causal treatment for traumatic Spinal Cord Injury (SCI) is the goal of the charitable Wings for Life Spinal Cord Research Foundation, located in Salzburg. In order realize this ambitioned endeavour, since 2004 Wings for Life competitively funds selected scientific projects aiming at the neurobiological repair of the injured spinal cord.An international Medical/Scientific Board and independent Peer Review Panel composed of more than 200 renowned Scientists and Clinicians (Wings for Life-?Faculty“) specialized on Spinal Cord Injury support the Executive board selecting the most promising projects within a 2 step ?Peer Review“ procedure. To date, Wings for Life funds more than 55 research projects. The projects range from basic science (target finding), applied basic and preclinical research (target validation) to clinical trials.In collaboration with twelve respected, specialized ?non-governmental organisations“ (NGOs), Wings for Life forms the umbrella organisation ICCP (International Campaign for Cures of Spinal Cord Injury) a world-wide network which develops synergies for responsible and effective translational research in spinal cord injury. 相似文献
This study aimed at evaluating the marginal and internal adaptation of low-viscosity bulk-fill composites to enamel and dentin using a self-etch or an etch-and-rinse adhesive without and with artificial ageing. Hundred and twenty-eight MOD cavities in extracted molars were assigned to eight groups (n = 16), restored with the adhesives OptiBond FL (OFL) or Xeno V+ (X) and two low-viscosity bulk-fill composites SDR or x-tra base, covered with Premise. Tetric EvoCeram Bulk Fill and Premise served as a control. n = 8 per group were subjected to prolonged water storage (180 days) and thermocycling (2500×). Scanning electron microscopy was used to determine marginal gaps (MG) and interfacial adhesive defects (IAD). There were no significant differences between composite types in 44 out of 48 (MG) or 43/48 (IAD) comparisons. More MG were observed with X than with OFL (14 out of 16 comparisons, two significant), while in 16 of 16 comparisons with X more IAD were observed (14 significant). After artificial ageing, MG generally increased (9/16 significant), compared to IAD (one significant). The performance of the investigated composite types concerning the integrity of the tooth-composites interface was comparable. Compared to the 1-step self-etch system, the bond with the 3-step etch-and-rinse adhesive was raised.
Quantitative prediction of unbound drug fraction (fu) is essential for scaling pharmacokinetics through physiologically based approaches. However, few attempts have been made to evaluate the projection of fu values under pathological conditions. The primary objective of this study was to predict fu values (n = 105) of 56 compounds with or without the information of predominant binding protein in patients with varying degrees of hepatic insufficiency by accounting for quantitative changes in molar concentrations of either the major binding protein or albumin plus alpha 1-acid glycoprotein associated with differing levels of hepatic dysfunction. For the purpose of scaling, data pertaining to albumin and α1-acid glycoprotein levels in response to differing degrees of hepatic impairment were systematically collected from 919 adult donors. The results of the present study demonstrate for the first time the feasibility of physiologically based scaling fu in hepatic dysfunction after verifying with experimentally measured data of a wide variety of compounds from individuals with varying degrees of hepatic insufficiency. Furthermore, the high level of predictive accuracy indicates that the inter-relation between the severity of hepatic impairment and these plasma protein levels are physiologically accurate. The present study enhances the confidence in predicting fu in hepatic insufficiency, particularly for albumin-bound drugs. 相似文献
IntroductionErectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging males and frequently occur together. Tadalafil has demonstrated efficacy in treating both conditions.AimThe study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men. We also assessed relationships of baseline disease severity and prostate specific antigen (PSA) to outcomes.MethodsData were pooled from four multinational, randomized studies of men ≥45 years with LUTS/BPH, with analyses restricted to sexually active men with ED. Randomization (baseline) followed a 4‐week placebo run‐in; changes from baseline were assessed vs. placebo using analysis of covariance.Main Outcome MeasuresInternational Prostate Symptom Score (IPSS), IPSS subscores, Quality‐of‐Life Index (IPSS‐QoL), BPH Impact Index (BII), and International Index of Erectile Function‐Erectile Function (IIEF‐EF) Domain score were used in this study.ResultsTadalafil (N = 505) significantly improved total IPSS vs. placebo (N = 521); mean changes from baseline were ?6.0 and ?3.6, respectively (P < 0.001). Improvements in IIEF‐EF Domain score (tadalafil, 6.4; placebo, 1.4) were also significant vs. placebo, as were the IPSS storage and voiding subscores, IPSS‐QoL, and BII (all P < 0.001).No significant impact of baseline ED severity or PSA category on IPSS response was observed (interaction P values, 0.463 and 0.149, respectively). Similarly, improvement in IIEF‐EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category (interaction P values, 0.926 and 0.230, respectively). Improvements in IPSS and IIEF‐EF Domain score during treatment were weakly correlated (r = ?0.229). Treatment‐emergent adverse events were consistent with previous reports.ConclusionsTadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions. Improvements in both conditions were significant regardless of baseline severity. Improvements in the total IPSS and the IIEF‐EF Domain score were weakly correlated. Porst H, Roehrborn CG, Secrest RJ, Esler A, and Viktrup L. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia and on erectile dysfunction in sexually active men with both conditions: Analyses of pooled data from four randomized, placebo‐controlled tadalafil clinical studies. J Sex Med 2013;10:2044–2052.相似文献
Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. In many children and adolescents, JIA is successfully treated with non-steroidal anti-inflammatory drugs (NSAID) and physiotherapy. However, in a significant number of cases the disease is resistant to this therapy, and treatment with second line disease-modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as first-choice second-line agent for the treatment of JIA. To increase drug safety, the Working Groups for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and Pediatric Rheumatology Austria have initiated the formulation of evidence-based recommendations. Evidence is based on consensus expert meetings, a MEDLINE search with the key words Methotrexate and juvenile arthritis limited to age 0–18 years, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases (Deutsches Rheumaforschungszentrum Berlin DRFZ), experience with MTX in adults with rheumatoid arthritis (RA), and recommendations of the German Society of Rheumatology (DGRh). Based on these data, evidence and recommendations are graded, and evidence-based recommendations for the use of MTX in children and adolescents with rheumatic disease are presented.Section Pharmacotherapy of the Working Group Pediatric Rheumatology Germany and Austria: I. Foeldvari; J.P. Haas, A. Haeffner, D. Hobusch,G. Horneff, A. Hospach, R. Keitzer, G. Klaus, M. Metzler, H. Michels, T. Niehues, I. Pilz, M. Sailer Höck, M. Schöntube, L. Schuchmann, K. Schumacher, H.W. Seyberth, E. Siemers, A. Urban, E. Weißbarth-Riedl. Working Group Pediatric Rheumatology North-Rhine-Westfalia: S. Benseler, G. Bürk, S. Fahl, I. Foeldvari, D. Föll, M. Frosch, G. Ganser, S. Kastner, I. Kleine, E. Lainka, K. Mönkemöller, J. Neubert, U. Neudorf, T. Niehues, J. Roth, S. Seeliger, N. Wagner, R. Wieland, H. Winowski. 相似文献