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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 purpose of this study was to compare averaged visual evoked potentials AVEPs) in normal subjects and in schizophrenics off and on phenothiazine medication. Flashes of 4 intensities were used. Ss were tested 3 times within a 1 month period. Measures of maximum amplitude (Am), frequency of peaks I FOP), and variability (V) were obtained- With increases in stimulus intensity all Ss showed increases in Ams and decreases in FOPs and V. Schizophrenics had smaller Ams. greater FOPs, and grear V than normals. Schizoprenies on phenothiazines generally had less FOPs initially and after 1 wk mi medication but not after about I month on medication. There was no consistently significant effect of phenothiazines on maximum amplitude. NO drug effect on variability was observed. Schizophrenics showed a decrease in FOPs over time while normals showed an increase. A relationship was found between variability and overall thought disturbance. Changes in clinical condition over a month were not associated with discernible AVEP changes. Relationships between Am, FOP, unit V are presented.  相似文献   
3.
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   
4.
The aim of the present study was to examine subpreputial bacteriology and to compare it with the urine cultures of healthy male children. Seventy-two male children were divided into two groups as A and B according to age. In both groups preputial sac and urine cultures were taken simultaneously. Gram (+) enteric cocci were the most common isolated pathogens from the preputial sac in group B. Enterobacter, E. coli and staphylococci species were isolated from the urine cultures of three patients in group B. We could not find any difference between the preputial sac swabs of group A and B patients, but the isolation rate of urine cultures of group A patients was significantly higher than group B (p < 0.05). The findings of the present study support a potential role of the prepuce acting as a reservoir of faecal bacteria in the pathogenesis of UTI in male infants, especially in the first year of life. Improved penile hygiene after the first year of life does not alter the subpreputial bacteriology, but significantly decreases the contamination of urine. This revised version was published online in August 2006 with corrections to the Cover Date.  相似文献   
5.
NAMI-A is a ruthenium complex endowed with a selective effect on lung metastases of solid metastasizing tumors. The aim of this study is to provide evidence that NAMI-A's effect is based on the selective sensitivity of the metastasis cell, as compared with other tumor cells, and to show that lungs represent a privileged site for the antimetastatic effects. The transplantation of Lewis lung carcinoma cells, harvested from the primary tumor of mice treated with 35 mg/kg/day NAMI-A for six consecutive days, a dose active on metastases, shows no change in primary tumor take and growth but a significant reduction in formation of spontaneous lung metastases. Transmission electron microscopy examination of lungs and kidney shows NAMI-A to selectively bind collagen of the lung extracellular matrix and also type IV collagen of the basement membrane of kidney glomeruli. The half lifetime of NAMI-A elimination from the lungs is longer than for liver, kidney, and primary tumor. NAMI-A bound to collagen is active on tumor cells as shown in vitro by an invasion test, using a modified Boyden chamber and Matrigel, and it inhibits the matrix metallo-proteinases MMP-2 and MMP-9 at micromolar concentrations, as shown in vitro by a zimography test. These data show NAMI-A to significantly affect tumor cells with metastatic ability. Binding to collagen allows NAMI-A to exert its selective activity on metastatic cells during dissemination and particularly in the lungs. These data also stress the wide spectrum of daily doses and treatment schedules at which NAMI-A is active against metastases.  相似文献   
6.
A number of studies have shown that chemical stimulation (using N-methyl-D-aspartate (NMDA) infusions) or electrical stimulation of the ventral hippocampus (VH) elicits locomotor activation and sustained increases in nucleus accumbens (NAc) dopamine (DA) levels in rodents. How DA neurotransmission in NAc is involved in these effects has also been well established. However, the modulatory role of the DA receptors located in VH is not yet fully understood. The purpose of this study was to characterize the role played by VH D1 and D2 subtype receptors in both the locomotor activation and NAc DA increases induced by NMDA stimulation of the VH. This was assessed by studying how retrodialysis application of NMDA (50 mM, 10 min) affects motor activity and NAc DA levels during simultaneous retrodialysis administration of the D1/D5 receptor antagonist SCH 23390 (100 and 250 microM, 60 min) or the D2 receptor antagonist raclopride (100 and 250 microM, 60 min). SCH 23390 attenuated or completely abolished NMDA-evoked locomotor activation and the concurrent increase in NAc DA levels. On the other hand, raclopride was initially able to attenuate the effects of VH NMDA stimulation. However, in the last phase of the experiments, animals showed an important increase in clonic seizure activity with a simultaneous and dramatic increase in NAc DA levels. Our results show that the NMDA receptor-mediated effects in the VH require both D1 and, probably, D2 receptors and suggest that DA in VH strongly modulates the excitatory outputs from this brain area.  相似文献   
7.
Hypoxia treatment of normal peritoneal fibroblasts results in alterations that are characteristic for fibroblasts obtained from postoperative peritoneal adhesion tissue. In this study, we have shown that hypoxia treatment enhances normal peritoneal fibroblast elimination by lymphokine-activated killer cells to the level of adhesion tissue fibroblasts, suggesting a pivotal role of hypoxia in the adhesion development.  相似文献   
8.
9.
Background: The present research aimed to evaluate the effect on outcomes of immunonutrition (IMN) enteral formulas during the intensive care unit (ICU) stay. Methods: A multicenter prospective observational study was performed. Patient characteristics, disease severity, nutritional status, type of nutritional therapy and outcomes, and laboratory parameters were collected in a database. Statistical differences were analyzed according to the administration of IMN or other types of enteral formulas. Results: In total, 406 patients were included in the analysis, of whom 15.02% (61) received IMN. Univariate analysis showed that patients treated with IMN formulas received higher mean caloric and protein intake, and better 28-day survival (85.2% vs. 73.3%; p = 0.014. Unadjusted Hazard Ratio (HR): 0.15; 95% CI (Confidence Interval): 0.06–0.36; p < 0.001). Once adjusted for confounding factors, multivariate analysis showed a lower need for vasopressor support (OR: 0.49; 95% CI: 0.26–0.91; p = 0.023) and continuous renal replacement therapies (OR: 0.13; 95% CI: 0.01–0.65; p = 0.049) in those patients who received IMN formulas, independently of the severity of the disease. IMN use was also associated with higher protein intake during the administration of nutritional therapy (OR: 6.23; 95% CI: 2.59–15.54; p < 0.001), regardless of the type of patient. No differences were found in the laboratory parameters, except for a trend toward lower triglyceride levels (HR: 0.97; 95% CI: 0.95–0.99; p = 0.045). Conclusion: The use of IMN formulas may be associated with better outcomes (i.e., lower need for vasopressors and continuous renal replacement), together with a trend toward higher protein enteral delivery during the ICU stay. These findings may ultimately be related to their modulating effect on the inflammatory response in the critically ill. NCT Registry: 03634943.  相似文献   
10.
ObjectiveTo determine how many dispensary drugs should be in the safety stock in a tertiary hospital in accordance with the risk level and the number of days that the hospital is able to withstand a stockout.MethodsWe statistically analysed the infliximab order recorded over a period of 120 days. This drug is relevant for this study as it is costly and is immediately supplied to the clinic. Using the data records for purchasing and dispensing in our department, we created a table to compare the level of risk assumed with the number of units in stock and the number of days that the safety stock should last. In addition, we calculated how much stock there should be in accordance with different heuristic rules used by pharmacy departments.ResultsIn the period being studied, the daily order was 11.4 ± 14.8 units of infliximab. Using the methodology proposed, we discovered that there should be 79 units in the safety stock. Other hospital rules determine values of 47 and 119 units.ConclusionsThe method proposed allows us to discover the risk level that is assumed when selecting the safety stock. Therefore, we are able to design a safety stock policy consistent with the risk level adopted. Under certain assumptions the safety stock quota provided by this method could be reduced. Lastly, there is a notable difference between the safety stock values suggested by different rules, as it has been shown in this article.  相似文献   
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