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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.
This study was aimed at determining the cause for the high incidence of tuberculosis (TB) reactivation occurring in males with a low body mass index (BMI). Current thinking about pulmonary TB describes infection in the lung apex resulting in cavitation after reactivation. A different hypothesis is put forward for TB infection, suggesting that this occurs in subclinical apical cavities caused by increased pleural stress due to a low BMI body habitus. A finite element analysis (FEA) model of a lung was constructed including indentations for the first rib guided by paramedian sagittal CT reconstructions, and simulations were conducted with varying antero‐posterior (AP) diameters to mimic chests with a different thoracic index (ratio of AP to the transverse chest diameters). A Pubmed search was conducted about gender and thoracic index, and the effects of BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung apex in low BMI chests, and a four‐fold increase with a low thoracic index, r2 = 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean thoracic index was statistically significantly lower in males, P = 0.001, and increased with age in both genders. This article is the first to suggest a possible mechanism linking pulmonary TB reactivation to low BMI due to the flattened thoracic wall shape of young male adults. The low thoracic index in young males may promote TB reactivation due to tissue destruction in the lung apex from high pleural stress levels. Clin. Anat. 28:614–620, 2015. © 2015 Wiley Periodicals, Inc.  相似文献   
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4.
The effects of 2,4-Dichlorophenoxyacetic acid on the growth rate, chemical composition, 14C-2,4-dichlorophenoxyacetic acid and 45Ca2+ uptake by Rhizobium sp. M 4 able to nodulate Arachis hypogaea were determined. Cellular growth was diminished by the presence of 10?3 M 2,4-dichlorophenoxyacetic acid in the medium. Alterations in cellular chemical composition, in 14C-2,4-dichlorophenoxyacetic acid and in 45Ca2+ uptake were found.  相似文献   
5.
Antioxidant defence during cardiopulmonary bypass surgery.   总被引:1,自引:0,他引:1  
OBJECTIVE: Cardiac surgery may lead to severe oxidative stress due to formation of oxidation products generated during ischemia and reperfusion. We investigated to which extent oxidative stress influences a number of endogenous antioxidants and markers of cellular activation. METHODS: At six time points blood was withdrawn from patients undergoing coronary artery bypass grafting, using the on-pump procedure. RESULTS: Both glutathione peroxidase and superoxide dismutase show a gradual and strong increase in activity during surgery (40 and 30%, respectively), returning to baseline values 24 h after surgery. The total antioxidant capacity has a maximum increase of 60%. Markers of cellular activation, such as eosinophil cationic protein and tryptase also increase during the procedure. CONCLUSION: Cardiac surgery results in systemic inflammation accompanied or caused by severe oxidative stress. The human body has a strong innate oxidative defence screen, which is probably not sufficient to fully compensate for the total amount of oxidative damage.  相似文献   
6.
The health status of many people in developing countries is often dismal compared with the norms in industrialized countries. Increasingly, medical practitioners in the United States and other industrialized countries have become interested in global health issues, an interest that often takes the form of short-term international medical trips. We discuss several ethical issues associated with participation in such trips and use our experiences in developing the Children's Health International Medical Project of Seattle (CHIMPS) to outline and illustrate a set of 7 guiding principles for making these trips. CHIMPS is a resident-run, faculty-supported international medical program founded in 2002 by pediatric residents at the University of Washington in Seattle. Members of CHIMPS work with a rural community in El Salvador to support ongoing public health interventions there and provide sustainable medical care in collaboration with the community and a local nongovernmental organization. The 7 principles developed as a result of this work-mission, collaboration, education, service, teamwork, sustainability, and evaluation-can be used as a model for health practitioners as they develop or select international medical trips. The importance of partnering with the community and working within the existing medical and public health infrastructure is emphasized. Many of the challenges of doing international medical work can be overcome when efforts are guided by a few specific principles, such as those we have outlined.  相似文献   
7.
A 13-item questionnaire was constructed to assess risk factors for HIV infection among 476 patients newly admitted over a one-year period to a state psychiatric hospital in New York City. Because psychopathology can affect patients' self-reports, the validity of the instrument was established by HIV antibody tests in a subset of 352 patients. Results of the questionnaire indicated that the 352 patients were almost equally divided between the high-risk and low-risk categories. HIV seroprevalence was .6 percent among the low-risk patients, but 14.4 percent among the high-risk patients. The findings suggest that a screening program to detect HIV-positive patients should be undertaken in this population, that it should be focused on the high-risk subgroup, and that the questionnaire can be used to define that subgroup. However, results of the study may not generalize to other geographic areas.  相似文献   
8.
Sixteen subjects, affected by chronic tension-type headache (TTH) accordingly to the International Headache Society Classification (1988) criteria, in presence of tenderness in pericranial muscles,with a mean age of 37+/-11.8 years, and ten healthy volunteer subjects, age and sex matched, were submitted to postural analysis by Static Posturography (S.Ve.P. Amplaid). Aim of the study was to evaluate whether patients with TTH have disturbed postural control, as compared to normal subjects. Postural analysis considered all posturographic variables but focused on spectral frequency analysis of body sway. In both open (OE) and closed eyes (CE) condition, spectral frequency analysis showed a significantly increased body sway at low (OE= p < or = 0.01; CE= p < or = 0.01) and middle (OE= p < or = 0.01; CE= p < or = 0.01) frequencies on the antero-posterior (y) plane and at low frequencies (OE= p < or = 0.05; CE= p < or = 0.05) on the lateral (x) plane. Statistical analysis was performed using the Student's t test for unpaired data, p value 0.05 defined significant. The proprioceptive input seems to be predominant at middle and high frequencies in maintaining posture, our results seem then to suggest a proprioceptive disturbance in TTH patients. The disturbance is likely related to chronic pericranial muscle contraction and tenderness. Posturography and spectral analysis may help not only in the diagnosis of a postural disturbance but even more in the follow-up of TTH patients, during and after a medical and/or a rehabilitative treatment.  相似文献   
9.
In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg/m2; mean (SD)] with different levels of ordinary physical activity, but not performing upper-extremity training, we measured FMD at 1 min after reactive hyperemia, and pulmonary oxygen uptake (O2) at ventilatory anaerobic threshold (O2AT) and at peak effort (peak O2) during an incremental exercise on a treadmill. In our participants, FMD was 9.1 (3.4)%, O2AT was 40.72 (5.92) ml/kg per min, and peak O2 was 52.95 (8.13) ml/kg per min. Using bivariate Pearsons correlation, and in separate multivariate regression analyses, O2AT and peak VO2 showed a significant and reasonably good correlation with FMD (r=0.84, P<0.001 and r=0.77, P=0.001, respectively), independent of age, body mass index and serum total cholesterol (=0.77, P<0.001, R2 of the overall model=0.79 and =0.70, P<0.005, R2 of the overall model=0.69, respectively). Our data provide evidence suggesting that in young healthy men a higher submaximal and maximal aerobic exercise performance is associated with a greater FMD of peripheral conduit arteries.  相似文献   
10.
Previously, it was shown that type IVB pili encoded by the Salmonella enterica serovar Typhi pil operon are used to facilitate bacterial entry into human intestinal epithelial cells in vitro and that such entry is inhibited by purified prepilin (pre-PilS) protein (X.-L. Zhang, I. S. M. Tsui, C. M. C. Yip, A. W. Y. Fung, D. K.-H. Wong, X. Dai, Y. Yang, J. Hackett, and C. Morris, Infect. Immun. 68:3067-3073, 2000). The pil operon concludes with a simple shufflon, and a recombinase gene product (Rci) inverts DNA in the C-terminal region of the pilV gene to allow synthesis of two distinct PilV proteins, PilV1 and PilV2, which are presumptive minor pilus proteins. We show here that the type IVB pili mediate bacterial self-association, but only when the PilV1 and PilV2 proteins are not expressed. This may be achieved in wild-type serovar Typhi by rapid DNA inversion activity of the shufflon. We show that the inversion activity inhibits the expression of genes inserted between the 19-bp inverted repeats used for Rci-mediated recombination and that the activity of Rci increases when DNA is supercoiled. The data suggest that serovar Typhi self-associates under conditions (such as low oxygen tension in the gut) that favor DNA supercoiling. These results explain (i) the function of the serovar Typhi shufflon and (ii) why there are only two possible shufflon states, in contrast to the many possible states of other shufflon systems. The data further indicate that a very early step in serovar Typhi pathogenesis may be type IVB pilus-mediated self-association of bacteria in the anaerobic human small intestine prior to invasion of the human gut epithelium. The suggested type IVB pilus-dependent step in typhoid fever pathogenesis may partially explain the enhanced invasiveness of serovar Typhi for humans.  相似文献   
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