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1.

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   
2.
The presence of certain defects in both cellular and humoral immunity after thermal injury has been established. Likewise, the translocation of enteric bacteria to the mesenteric lymph nodes and to distant organs has also been observed following serious thermal injury. The effects of granulocyte colony-stimulating factor (G-CSF) on bacterial translocation, the small bowel mucosa, and cecal bacterial content were investigated in a rat model of burn wound sepsis in which albino Wistar rats were scalded over 30% of their bodies, after which the lesions were infected by 1×108 colony-forming units (cfu)Pseudomonas aeruginosa. The control group was treated with 5% dextrose solution subcutaneously starting 2 days preburn, while the treatment group received 100μg/kg human G-CSF subcutaneously. On the 4th day post burn all animals were killed to examine the bowel and culture of the mesenteric lymph nodes (MLN), livers, and spleens. No significant differences were observed between the groups regarding the cecal bacterial content and small bowel; however, a difference was seen in the ratio of translocation in the MLN liver and spleen and quantitative MLN cultures. Based on these findings, G-CSF was thus found to be significantly effective in reducing bacterial translocation due to burn wound sepsis.  相似文献   
3.
The prevalence of diagnosed diabetes among American Indians in New Mexico with varied genetic and cultural backgrounds is reported. Utilizing community-based registries, the prevalence in persons ages 35 years and older ranged from 9.8 percent among Jicarilla Apache Indians to 28.2 percent among Zuni Indians. All rates were significantly higher than the U.S. rate of 5.3 percent for the same age group. In addition, in three of the five tribal groups examined, the rates of diagnosed diabetes in Indians less than 35 years of age (range from 0.5 percent to 1.3 percent) were significantly higher than the U.S. rate of 0.4 percent for the same age group. The prevalence rates of diagnosed diabetes found in this study of American Indians in New Mexico were intermediate between those for the United States as a whole and the Pima Indians of southern Arizona. Reasons for the variations and the relative contribution of obesity, fitness, or genetic risk in the development of diabetes need further study.  相似文献   
4.
In vitro comparisons of induction of perforin (PFP), granzyme B (GRB), production of cytokines, and cell-mediated cytotoxicity by interleukin-2 (IL-2), interleukin-15 (IL-15), or combinational IL-2/IL-15-induced lymphokine-activated killer cells were studied in this study. Whereas IL-2-induction was associated with a decrease in cultured cell population over a 7-day period, IL-15 alone or in combination with IL-2 resulted in significant increase including cytotoxic T lymphocytes and subsets of CD56+ lymphocytes, particularly cytokine-induced killer and cytolytic natural killer-T lymphocytes. The overall PFP, GRB, and tumor necrosis factor-alpha expression in different subtypes were also significantly higher with IL-15 alone or in combination with IL-2 induction with resultant superior cytotoxicity compared to IL-2 treatment. There was no significant advantage of addition of IL-2 over IL-15 induction. These results offer further information on the cytotoxic potency of these cytokines and their mechanisms of action implicating potential use of IL-15 as part of cytokine adoptive immunotherapy.  相似文献   
5.
This experimental study was designed to investigate the effects of vitamin E supplementation, especially on lipid peroxidation and antioxidant status elements 3/4 namely, glutathione (GSH), CuZn superoxide dismutase (CuZn SOD), and glutathione peroxidase (GSH Px), both in blood and liver tissues of streptozotocin (STZ) diabetic rats. The extent to which blood can be used to reflect the oxidative stress of the liver is also investigated. In diabetic rats, plasma lipid peroxide values were not significantly different,from control,whereas erythrocyte CuZn SOD (p < 0.01), GSH Px (p < 0.001) activities and plasma vitamin E levels (p < 0.001), were significantly more elevated than controls. Vitamin E supplementation caused significant decreases of erythrocyte GSH level (p < 0.01) in control rats and of erythrocyte GSH Px activity (p < 0.05) in diabetic rats. Liver findings revealed significantly higher lipid peroxide (p < 0.001) and vitamin E (p < 0.01) levels and lower GSH (p < 0.001), CuZn SOD (p < 0.001) and GSH Px (p < 0.01) levels in diabetic rats. A decreased hepatic lipid peroxide level (p < 0.01) and increased vitamin E/lipid peroxide ratio (p < 0.001) were observed in vitamin E supplemented, diabetic rats. A vitamin E supplementation level which did not cause any increase in the concentration of the vitamin in the liver or blood, was sufficient to lower lipid peroxidation in the liver. Vitamin E/lipid peroxide ratio is suggested as an appropriate index to evaluate the efficiency of vitamin E activity,independent of tissue lipid values. Further, the antioxidant components GSH, GSH Px and CuZn SOD and the relationships among them, were affected differently in the liver and blood by diabetes or vitamin E supplementation.  相似文献   
6.
7.
A total of 5,366 pregnant Turkish women were screened for hepatitis B surface antigen (HBsAg) and 225 (4.2%) of them were found to be positive. Hepatitis B e antigen (HBeAg) was detected in 6.2% of HBsAg-positive pregnant women. The overall prevalence of HBsAg and antibody to HBsAg (anti-HBs) among the spouses, previous children, mothers and first degree relatives of the HBsAg-positive pregnant women was 56%, 49%, 79% and 74% respectively. The prevalence of HBsAg is thus high in pregnant Turkish women with familial clustering of hepatitis B virus infection.  相似文献   
8.
The purpose of this investigation was to describe the neural constraints on three-dimensional (3-D) orientations of the eye in space (Es), head in space (Hs), and eye in head (Eh) during visual fixations in the monkey and the control strategies used to implement these constraints during head-free gaze saccades. Dual scleral search coil signals were used to compute 3-D orientation quaternions, two-dimensional (2-D) direction vectors, and 3-D angular velocity vectors for both the eye and head in three monkeys during the following visual tasks: radial to/from center, repetitive horizontal, nonrepetitive oblique, random (wide 2-D range), and random with pin-hole goggles. Although 2-D gaze direction (of Es) was controlled more tightly than the contributing 2-D Hs and Eh components, the torsional standard deviation of Es was greater (mean 3.55 degrees ) than Hs (3.10 degrees ), which in turn was greater than Eh (1.87 degrees ) during random fixations. Thus the 3-D Es range appeared to be the byproduct of Hs and Eh constraints, resulting in a pseudoplanar Es range that was twisted (in orthogonal coordinates) like the zero torsion range of Fick coordinates. The Hs fixation range was similarly Fick-like, whereas the Eh fixation range was quasiplanar. The latter Eh range was maintained through exquisite saccade/slow phase coordination, i.e., during each head movement, multiple anticipatory saccades drove the eye torsionally out of the planar range such that subsequent slow phases drove the eye back toward the fixation range. The Fick-like Hs constraint was maintained by the following strategies: first, during purely vertical/horizontal movements, the head rotated about constantly oriented axes that closely resembled physical Fick gimbals, i.e., about head-fixed horizontal axes and space-fixed vertical axes, respectively (although in 1 animal, the latter constraint was relaxed during repetitive horizontal movements, allowing for trajectory optimization). However, during large oblique movements, head orientation made transient but dramatic departures from the zero-torsion Fick surface, taking the shortest path between two torsionally eccentric fixation points on the surface. Moreover, in the pin-hole goggle task, the head-orientation range flattened significantly, suggesting a task-dependent default strategy similar to Listing's law. These and previous observations suggest two quasi-independent brain stem circuits: an oculomotor 2-D to 3-D transformation that coordinates anticipatory saccades with slow phases to uphold Listing's law, and a flexible "Fick operator" that selects head motor error; both nested within a dynamic gaze feedback loop.  相似文献   
9.
One hundred and forty-four patients with apparently benign gastric ulcer were endoscopically followed up in order to evaluate the outcome of the lesion. Particular attention was given to: (a) detect possible delay in diagnosing gastric cancer; (b) ascertain the frequency of association with epithelial dysplasia; (c) establish the role of markers, such as serum pepsinogen group I (PGI), and gastric juice CEA in predicting gastric ulcer evolution. Endoscopic and bioptic check-ups were carried out during the first year at 3, 6 and 12 months after endoscopic healing of the ulcer, and then at every symptomatic recurrence. Ten patients (6.9%) were found to present histological evidence of malignancy (within 3 months in six cases, between 6 and 12 months in three cases, and after 41 months in the rest). Four cases were early gastric cancers, and six had shown dysplastic changes of the mucosa at the edge or scar of the ulcer. Serum PGI levels were not significantly different in gastric cancer patients, while gastric juice CEA levels were sharply increased compared to those of gastric ulcer patients: nine out of ten patients had values above normal range. These data suggest that: (a) there may be some delay in diagnosing gastric carcinoma, and gastric ulcer patients should be controlled routinely more than once; (b) the presence of dysplasia indicates the need for prolonged follow-up, because of the high risk of association with or evolution into gastric cancer, and because of the higher number of early gastric cancer detections that this protocol allows; (c) further support in monitoring patients "at risk" may be afforded by gastric juice CEA determination.  相似文献   
10.
Journal of Public Health - Because an increasing number of patients travel internationally to seek medical care, Turkey offers comprehensive and outstanding services under extraordinary conditions...  相似文献   
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