Outcome of Combination Chemotherapy with Docetaxel, Estramustine Phosphate, and Carboplatin after Docetaxel and Prednisolone Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer

We retrospectively reviewed the outcome of docetaxel, EMP, and carboplatin (DEC) as second-line chemotherapy in castration-resistant prostate cancer (CRPC) patients previously treated with docetaxel-prednisolone (DP). Nineteen patients pretreated with DP received a DEC regimen which consisted of a 28-day cycle of docetaxel [60 mg/m2 intravenously (IV) on day 1)], carboplatin (IV to an area under the curve of 5 on day 1), and EMP (560 mg orally daily). The DEC therapy was continued intermittently after two consecutive courses. End points were DEC effect on prostate-specific antigen (PSA), radiographic response, progression-free survival (PFS), and overall survival (OS). All patients received DP before DEC administration with a median of 6 cycles (range, 1 - 12). Mean follow-up duration was 19.0 months after starting DEC therapy;median total number of the therapy cycles was 2 (range, 1 - 11). Thirteen patients (68.4%) showed a PSA decrease;6 (31.6%) showed a decrease in the PSA level of ≥50%, including 4 with no PSA response to DP. Grade 3/4 neutropenia and febrile neutropenia were observed in 13 (68.4%) and 2 (10.5%) patients, respectively. The median PFS following DEC was 3.7 months. The median OS was 18.0 months. In univariate analyses, patients with ≤12 months from CRPC to DEC had shorter PFS and OS, whereas PSA response to DP was not associated with PFS or OS in CRPC patients treated with DEC after DP. In conclusion, DEC retains some clinical benefits for CRPC patients pretreated with DP, even in patients without any response to DP. Therefore, they may be an effective and feasible treatment option for CRPC patients after first-line docetaxel therapy, particularly for those deemed unfit for novel endocrine and chemotherapeutic drugs.

Effects of denosumab treatment in chronic liver disease patients with osteoporosis

BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)patients.Denosumab has been shown to increase bone mineral density(BMD)and decrease the risk of osteoporotic fracture in the general population.However,there are few reports evaluating the efficacy of denosumab in CLD patients.AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo.The study period for evaluating efficacy and safety was 12 mo.Changes from baseline in BMD at the lumbar spine,femoral neck,and total hip were evaluated at 12 mo of denosumab treatment.Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b(bone resorption marker),serum total procollagen type I N-terminal propeptide(bone formation maker),and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients,138(34.1%)patients were diagnosed with osteoporosis;among these,78 patients met the exclusion criteria and thus 60 patients were finally included in the present study.The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine,femoral neck,and total hip were+4.44%,+3.71%,and+4.03%,respectively.Denosumab significantly improved BMD,regardless of sex,patient age,and presence of liver cirrhosis.Serum tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P<0.001).Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P=0.010).No patients experienced fractures and moderate-to-severe adverse events,except for transient hypocalcemia.CONCLUSION Denosumab treatment was safe and increased BMD,suppressed bone turnover,and improved bone quality marker levels in CLD patients with osteoporosis,irrespective of differences in baseline characteristics.

New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide

Daily 20-mg and once-weekly 56.5-mg teriparatide（parathyroid hormone 1–34） treatment regimens increase bone mineral density（BMD） and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.

Bone Quality in Female Ballet Dancers: A Possible Determinant of Bone Health

Hypotheses:Values of serum markers related to bone quality are abnormal in young female ballet dancers. Methods: In 13 elite Japanese female ballet dancers (average age, 22 years), markers related to bone quality were investigated. These included: serum homocystein (HC), a marker of increased oxidative stress;pentosidine (Pent), a marker of glycation- or oxidation-induced non-enzymatic cross-links;markers of bone metabolism (bone alkaline phosphatase, BAP;tartrate-resistant acid phosphatase 5b, TRAP5b) and bone mineral density (BMD). It was determined whether there is a relationship between bone quality markers’ levels are related to amenorrhea and/or fatigue fractures. Results: Two dancers had fatigue fractures and 3 had a history of secondary amenorrhea. The average BMD was 1.305 ± 0.12 (g/cm2), in all these cases the Z-score was higher than -1.0. Although the serum levels of BAP, TRAP5b, and HC were normal in all examined dancers, in 2 out of 3 dancers with a history of secondary amenorrhea, pentosidine serum levels were increased. No relationship between bone quality markers’ levels and fatigue fractures was found. Conclusion: Latent deterioration of bone quality may occur in female athletes with secondary amenorrhea and otherwise normal BMD and calcium metabolism markers.

训练对蛙泳的划频、划距和速度的影响

游泳的推进力是由阻力和升力所构成。如果游泳运动员要以匀速游进,那么他的推进力必须与水的阻力相等,否则游速不是增加就是减低,二者必居其一。尽管游泳速度的提高与许多因素有关,如划手、蹬腿、手与腿的配合以及效率,但是平均速度则是由划频和划距的乘积所决定,即速度=划频×划距。

Use of Hi-resolution data for evaluating accuracy of traffic volume counts collected by microwave sensors

Over the past few years, the Utah Department of Transportation has developed the signal performance metrics （SPMs） system to evaluate the performance of signalized in- tersections dynamically. This system currently provides data summaries for several per- formance measures, one of them being turning movement counts collected by microwave sensors. As this system became public, there was a need to evaluate the accuracy of the data placed on the SPMs. A large-scale data collection was carried out to meet this need. Vehicles in the Hi-resolution data from microwave sensors were matched with the vehicles by ground-truth volume count data. Matching vehicles from the microwave sensor data and the ground-truth data manually collected required significant effort, A spreadsheet- based data analysis procedure was developed to carry out the task. A mixed model analysis of variance was used to analyze the effects of the factors considered on turning volume count accuracy. The analysis found that approach volume level and number of approach lanes would have significant effect on the accuracy of turning volume counts but the location of the sensors did not significantly affect the accuracy of turning volume counts. In addition, it was found that the location of lanes in relation to the sensor did not significantly affect the accuracy of lane-by-lane volume counts. This indicated that accu- racy analysis could be performed by using total approach volumes without comparing specific turning counts, that is, left-turn, through and right-turn movements. In general, the accuracy of approach volume counts collected by microwave sensors were within the margin of error that traffic engineers could accept. The procedure taken to perform the analysis and a summary of accuracy of volume counts for the factor combinations considered are presented in this paper.