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Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

Patients and Methods

We conducted a multicenter retrospective analysis in the Triveneto region of Italy.

Results

One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.

Conclusion

This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined.  相似文献   
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This study evaluated the effect of new motions of the motor TriAuto ZX2 on the cyclic fatigue of endodontic instruments. Vortex Blue 35.06 instruments were divided into four groups (n = 10) and tested for fatigue in a curved artificial canal (90° and 2 mm radius) using the following motions: continuous rotation (CR), Optimum Torque Reverse (OTR) set at 180° and the Optimum Glide Path (OGP), which was tested at 90° and 240°. The time to fracture (TTF) and the lengths of the fractured fragments were recorded. The mean TTF was significantly different among the groups (anova , P < 0.05): OGP 90° (213.39 ± 27.45), OTR 180° (121.24 ± 17.03), OGP 240° (45.24 ± 5.61) and CR (8.43 ± 1.27). Weibull analysis confirmed the shortest life expectancy for CR and the longest survival for OGP at 90°. The resistance to fatigue was affected by motions and pre‐set angles. The proprietary movements that are currently available for endodontic instruments were classified according to their kinematics.  相似文献   
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BACKGROUND: Low molecular weight heparins (LMWH) like dalteparin are increasingly used for anticoagulation during haemodialysis (HD). The available laboratory tests for monitoring LMWH anticoagulation are time-consuming and expensive, and the suitability of the conventional activated clotting time (ACT) is controversial. A simple and cheap bedside test would be useful. METHODS: We studied the factor Xa-activated whole blood clotting time (Xa-ACT) in vitro and in vivo in nine patients undergoing chronic HD with i.v. dalteparin bolus anticoagulation and compared it with the conventional ACT. Plasma anti-factor Xa (antiXa) activity was determined with a chromogenic assay. Thrombin-antithrombin complexes were measured to detect coagulation activation. RESULTS: Xa-ACT and ACT were prolonged with rising dalteparin concentration. In vitro, both clotting times were strongly correlated with the antiXa levels (r = 0.94 and 0.89, respectively). Nevertheless, compared with the ACT, the Xa-ACT was considerably more sensitive to the LMWH in vitro (healthy blood: Xa-ACT 90 s/U vs ACT 26 s/U; uraemic blood: Xa-ACT 96 s/U vs ACT 31 s/U) as well as in vivo (Xa-ACT 81 s/U vs ACT 22 s/U) and reflected different intensities of anticoagulation. An initial dalteparin bolus of 80+/-11 U/kg body weight was able to prevent coagulation activation for up to 4 h of HD. CONCLUSION: For monitoring LMWH anticoagulation the Xa-ACT was superior to the conventional ACT in vitro as well as in vivo during HD. The Xa-ACT can be useful as a LMWH bedside test. The ACT was not sensitive enough to serve as a LMWH monitoring tool.  相似文献   
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Neutrophil oxidative metabolism, C3d and beta 2 microglobulin levels, were assessed in nine consecutive patients undergoing cardiopulmonary bypass surgery with polypropylene hollow fiber oxygenators for open cardiac operations. Generation of oxygen free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and phorbol myristate acetate. A significant increase in light emission was detected by using both of the chemiluminescence stimulators. Moreover, a remarkable and significant increase in C3d levels was found already at 10 min. Conversely minimal changes in levels of beta 2 microglobulin were detected during cardiopulmonary bypass surgery. These data suggest that the impact of the patient blood with the foreign surface of cardiopulmonary bypass results in activation of phagocyte cells with increased potential in oxygen consumption. These effects could be partially complement-mediated.  相似文献   
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Thermal characterization was carried out on highly stereoregular and regioregular syndiotactic polypropene (sPP) obtained with isopropylidene(cyclopentadienyl)(9-fluorenyl)zirconium dichloride and methylaluminoxane. The influence of molecular weight and syndiotacticity degree on the thermodynamic melting point (T°m) of sPP were separately investigated by examining samples with a fully syndiotactic pentads content (rrrr) ranging from ca. 81% to ca. 94% and with an weight-average molecular weight (M?w) ranging from 9,6 · 104 to 17,3 · 104. Upon excluding any influence of the molecular weight, the correlation between the rrrr pentads content and the T°m of the samples led to the extrapolation of the thermodynamic melting point for a fully syndiotactic polypropene.  相似文献   
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Clinical trials have utilized intermittent diethylstilbestrol diphosphate (DES) therapy in advanced symptomatic prostatic carcinoma to diminish the morbidity of standard endocrine therapy. To determine the effect of intermittent DES administration on the Dunning R3327 rat prostatic adenocarcinoma 60 days following tumor implant, 6 groups were randomly assigned: control (N = 8), castrate (N = 10), high dose DES (N = 8, 1.6 micrograms/ml DES continuously in drinking water), low dose DES (N = 10, 0.4 microgram/ml continuously in drinking water), intermittent high dose DES (N = 10, 1.6 micrograms/ml DES in drinking water for 1 week, then off for 3 weeks), and intermittent low dose DES (N = 10, 0.4 microgram/ml DES for 1 week, then off for 3 weeks). Results indicate that low or high dose DES, and intermittent low or intermittent high dose DES during the week of administration were able to reduce serum testosterone to castrate levels (0.1 ng/ml). After withdrawal of intermittent DES, serum testosterone returned toward control levels (1.0 ng/ml). Initial mean tumor burden between control and treatment groups was not significantly different. All DES exposed rats had a tumor volume at death (range, 15.6-18.3 cm3) smaller than control (mean, 25.4 cm3) or castrate (mean, 40.8 cm3) rats. Despite this significant survival advantage from the time of randomization was achieved only in castrate (median survival, 331 days) or high dose DES (median survival, 359 days) groups compared to control (median survival, 225 days). Similarly, significant prolongation in tumor doubling time was achieved only by rats receiving castration or high dose DES. Intermittent DES administration controls tumor volume but does not provide a survival advantage. In this respect, intermittent DES is inferior to castration.  相似文献   
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