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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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Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Objective

To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies.

Design, setting, and participants

A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified.

Outcome measurements and statistical analyses

Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated.

Results and limitations

Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC).

Conclusions

Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting.

Patient summary

We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI.  相似文献   
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OBJECTIVES: The aim of this study is to evaluate the effect of ZnSO(4) addition to a conventional glass ionomer and a resin-modified glass ionomer on solubility, flexural strength, zinc and fluoride (F) release, and Streptococcus mutans growth inhibition. METHODS: 5 or 10% ZnSO(4) was added to Vitremer and Ketac-Fil powders. Solubility test was performed based on ISO 7489. Flexural strength was determined by 3-point bending test based on ISO 4049. Zn release/uptake was determined by atomic emission spectrometry; F release/uptake was measured using a F-specific electrode. Both release measurements were performed for 15 d before and 15 d after recharging. Antibacterial test was conducted according to agar plate methods against S. mutans, by measuring the inhibition halos in 1-h and 15-d specimens. Data were analyzed by ANOVA. RESULTS: Solubility increased with higher ZnSO(4) content, but remained below the ISO 7489 limit. Flexural strength was not affected by ZnSO(4) addition, and Vitremer performed better than Ketac-Fil. The control materials released no zinc. Vitremer with 10% ZnSO(4) released the highest amount of zinc. Fluoride release was similar for Ketac-Fil and Vitremer. In both cases, the highest amounts were released in the first 24 h. The growth inhibition halo of S. mutans was similar for both materials with highest content of ZnSO(4) and occurred only with 1-h specimens. SIGNIFICANCE: Zinc addition decreased microorganisms growth and improved fluoride release, without significantly affecting the materials' flexural strength and solubility.  相似文献   
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BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study.   总被引:7,自引:0,他引:7  
After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk. INTRODUCTION: Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly. MATERIALS AND METHODS: Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight. RESULTS: Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups. Conclusions: In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis.  相似文献   
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BACKGROUND: The activity and isoenzyme composition of N-acetyl-beta-D-hexosaminidase (EC.3.2.1.52) in seminal plasma of fertile and infertile men have been evaluated. However, no data are available on the isoenzyme content in seminal plasma from patients with secretory azoospermia. METHODS: The activity and isoenzyme composition of seminal plasma from 15 normozoospermic controls and 18 patients with secretory azoospermia were determined by fluorimetric methods. 4-Methylumbelliferil-2-acetamido-2-deoxy-beta-D-glucopyranoside and 4-methylumbelliferil-2-acetamido-2-deoxy-beta-D-glucopyranoside-6-sulfate were used as fluorigenic substrates. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficiency of the assays. RESULTS: No significant difference was found in total enzyme activity between the two groups, while isoenzyme A activity was significantly lower (p=0.004) and the ratio between total enzyme activity and isoenzyme A activity was significantly higher (p=0.04) in azoospermic patients compared to controls. The diagnostic efficiency of these evaluations was low (< or =75.7%). CONCLUSIONS: Our findings show that the isoenzyme composition of N-acetyl-beta-D-hexosaminidase in seminal plasma from patients with secretory azoospermia is significantly different from controls, but this difference does not represent a useful marker of secretory azoospermia. The fluorimetric assays are simple and rapid methods for evaluating the isoenzyme composition.  相似文献   
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The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline. Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group. Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25-3.20; excess net change 2.8%, 0.4-5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males. The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.  相似文献   
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Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded.  相似文献   
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