Association of Urinary Cadmium Concentration With Cognitive Impairment in US Adults: A Longitudinal Cohort Study.

BACKGROUND AND OBJECTIVES: Studies have indicated that cadmium (Cd) exposure is associated with neurotoxicity. However, data linking Cd exposure to cognitive impairment are sparse. We aimed to investigate the association between urinary Cd concentration and cognitive impairment in US adults. METHODS: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is an ongoing population-based prospective cohort study that enrolled 30,239 Black and White US adults aged 45 years or older at baseline (2003-2007). In a randomly selected subcohort of REGARDS participants who were free of cognitive impairment or stroke at baseline, certain trace element concentrations, including urinary creatinine-corrected Cd, were measured using biospecimens collected and stored at baseline. During an average of 10 years of follow-up, global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment, including verbal learning, memory, and executive function, was evaluated every other year using the Enhanced Cognitive Battery. Multivariable-adjusted logistic regression models were used to examine the association between urinary Cd concentration and the odds of global or domain-based cognitive impairment. RESULTS: A total of 2,172 participants (mean age: 64.1 ± 9.0 years; female: 54.8%; Black participants: 38.7%) with available data on urinary Cd concentration, including 195 cases of global cognitive impairment and 53 cases of domain-based cognitive impairment, were included in the analyses. While there was no association between Cd and cognitive impairment in the full sample, there was a significant positive association of urinary Cd concentration with global cognitive impairment among White but not Black participants. The odds of cognitive impairment for White participants in the high urinary Cd concentration group (≥median) were doubled compared with those in the low urinary Cd group (odds ratio 2.07, 95% CI 1.18-3.64). Sex, age, region, smoking pack-years, alcohol consumption, and other related metals did not materially modify the associations of interest. DISCUSSION: Findings from this prospective cohort study suggest that urinary Cd concentrations are associated with global cognitive impairment among White but not Black individuals. Further studies with repeatedly measured Cd exposure, larger sample sizes, and longer duration are needed to confirm our findings and explore the potential explanations for the observed racial discrepancy, such as the impact of smoking.

Prediagnostic whole blood cadmium and molybdenum associated with pancreatic cancer in an American cohort.

Environmental exposures such as cadmium might be contributing to the increasing incidence of pancreatic cancer. Few prospective studies have examined the association between trace elements and pancreatic ductal adenocarcinoma (PDAC). We conducted a nested case-control study in participants aged 55-74 years at baseline from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort to examine the association between 12 trace elements measured in predignostic whole blood and PDAC. From May 1998 through December 2014, 318 incident PDAC cases were identified during follow-up to 16.7 years. Two controls (n = 636) alive when each case was diagnosed were selected and matched by age (+ 5 years), sex, calendar date of blood draw (2-month blocks), and race and ethnic group. We used multivariable adjusted conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Cadmium and molybdenum were associated with PDAC [highest compared to lowest quintile: cadmium OR=1.81; 95% CI: 01.12, 2.95; P-trend = 0.03; molybdenum OR=0.50; 95% CI: 0.32, 0.80; P-trend = 0.02]. The inverse molybdenum association was only observed among ever smokers (OR=0.31, 95% CI: 0.17, 0.58, P-trend= 0.003, P-interaction=0.03) with no association in never smokers. Lead, arsenic, and other trace elements were not associated with PDAC. Our results support that increasing prediagnostic whole blood cadmium increases while molybdenum reduces PDAC risk.

Regulation of SELENOF translation by eIF4a3: Possible role in prostate cancer progression.

The levels of the SELENOF selenoprotein are dramatically reduced in prostate cancer compared to adjacent benign tissue and reducing SELENOF in prostate epithelial cells results in the acquisition of features of the transformed phenotype. It was hypothesized that the aberrant increase in the eiF4a3 translation factor, which has an established role in RNA splicing and the regulation of selenoprotein translation, contributes to the lower levels of SELENOF. Using the available databases, eIF4a3 messenger RNA (mRNA) levels are elevated in prostate cancer compared to normal tissue as is the hypomethylation of the corresponding gene. Using a prostate cancer tissue microarray, we established that eiF4a3 levels are higher in prostate cancer tissue. Ectopic expression of eIF4a3 in prostate cancer cells reduced SELENOF levels and attenuated the readthrough of the UGA codon using a specialized reporter construct designed to examine UGA decoding, with the opposite effects observed using eIF4a3 knock-down constructs. Direct binding of eIF4a3 to the regulatory regions of SELENOF mRNA was established with pull-down experiments. Lastly, we show that an eIF4a3 inhibitor, eIF4a3-IN-2, increases SELENOF levels, UGA readthrough, and reduces binding of eIF4a3 to the SELENOF mRNA 3'-UTR in exposed cells. These data establish eIF4a3 as a likely prostate cancer oncogene and a regulator of SELENOF translation.

Polymeric Interlayer Strengthening with Boron Neutron Capture Radiation Treatment for Laminated Glass.

Polymer interlayer materials are utilized in laminated glass systems to provide increased resilience from blast incidents. The polymer chains within the interlayer material can benefit from material modifications that increase the crosslinking between adjacent chains. One theorized method of targeted crosslinking is made possible through a boron neutron capture process. This process utilizes neutron radiation that bombards boron material, thus producing emissions of highly energetic particles into the polymer. The method has been experimentally utilized for bulk material processing as well as surface treatment. The surface treatment process has been extensively investigated in this study to manipulate polymers commonly used as interlayer material. Comparison evaluation tests have been completed to show the material behavior change through static tensile loading, dynamic tensile loading, indentation testing, and scratch resistance testing. Results present the specific material behavior changes, effects on different interlayer material, and optimizations for the treatment processes. Data resulting from these tests will expand the understanding of the material behavior changes from treatment techniques and show evidence of the expected crosslinking. This understanding will lead to a quantifiable application of system capacities to improve the future designs of the window and building systems and lead to a safer, more secure, and resilient infrastructure. Polymer treatment by boron neutron capture radiation has produced polymer interlayers with the potential of increased resilience to blast. The research to date has evaluated treated polymers and shown that the hardening and increased elasticity of the material can be initiated through treatment, thus indicating crosslinking behavior. These results show distinct changes in the material behavior, particularly with the EVA interlayer material. The harder surface of the interlayer may resist the cutting of the interlayer surface by glass shards. Scratch resistance was 30% higher and the measured hardness was 100% on treated surfaces. Treated EVA exhibited a 40% higher stress capacity, a 35% higher toughness, and a 40% increase in the elasticity of the material. The overall toughness increase of the treated polymer material allows for a higher energy absorption, and an overall improvement of window performance in blast conditions. The treatment technique can be applied to a variety of window interlayer products for optimal material performance in blast conditions.

Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology.

Cortical iron has been shown to be elevated in Alzheimer's disease (AD), but the impact of the directly measured iron on the clinical syndrome has not been assessed. We investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD, its severity, and the rate of cognitive decline in the 12 years prior to death in subjects from the Memory and Aging Project (n = 209). Iron was elevated (ß [SE] = 9.7 [2.6]; P = 3.0 × 10-4) in the inferior temporal cortex only in subjects who were diagnosed with clinical AD during life and had a diagnosis of AD confirmed post-mortem by standardized criteria. Although iron was weakly associated with the extent of proteinopathy in tissue with AD neuropathology, it was strongly associated with the rate of cognitive decline (e.g., global cognition: ß [SE] = -0.040 [0.005], P = 1.6 × 10-14). Thus, cortical iron might act to propel cognitive deterioration upon the underlying proteinopathy of AD, possibly by inducing oxidative stress or ferroptotic cell death, or may be related to an inflammatory response.

Methylmercury exposure, genetic variation in metabolic enzymes, and the risk of glioma.

Methylmercury (MeHg) is an environmental neurotoxin with human exposure mainly from dietary intake of contaminated fish. Exposure to MeHg has been implicated in neurological damage, but research on its role in cancers, specifically glioma, is limited. In a glioma case-control study, we examined associations between toenail mercury (Hg) and glioma risk. We also examined genetic polymorphisms in 13 genes related to MeHg metabolism for association with glioma risk; genetic associations were also studied in the UK Biobank cohort. Median toenail Hg in cases and controls, respectively, was 0.066 µg/g and 0.069 µg/g (interquartile range (IQR): 0.032-0.161 and 0.031-0.150 µg/g). Toenail Hg was not found to be significantly associated with glioma risk (Odds Ratio: 1.02; 95% Confidence Interval: 0.91, 1.14; p = 0.70 in analysis for ordinal trend with increasing quartile of toenail MeHg). No genetic variant was statistically significant in both of the studies; one variant, rs11859163 (MMP2) had a combined p-value of 0.02 though it was no longer significant after adjustment for multiple testing (Bonferroni corrected p = 1). This study does not support the hypothesis that exposure to MeHg plays a role in the development of glioma at levels of exposure found in this study population.

Urinary cadmium concentration and the risk of ischemic stroke.

OBJECTIVES: To examine the association between urinary cadmium levels and the incidence of ischemic stroke and to explore possible effect modifications. METHODS: A case-cohort study was designed nested in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including 680 adjudicated incident cases of ischemic stroke and 2,540 participants in a randomly selected subcohort. Urinary creatinine-corrected cadmium concentration was measured at baseline. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated with the Barlow weighting method for the Cox proportional hazards regression model. RESULTS: The median urinary cadmium concentration was 0.42 (interquartile range 0.27-0.68) µg/g creatinine. After adjustment for potential confounders, urinary cadmium was associated with increased incidence of ischemic stroke (quintile 5 vs quintile 1: HR 1.50, 95% CI 1.01-2.22, p for trend = 0.02). The observed association was more pronounced among participants in the lowest serum zinc tertile (tertile 3 vs tertile 1: HR 1.82, 95% CI 1.06-3.11, p for trend = 0.004, p for interaction = 0.05) but was attenuated and became nonsignificant among never smokers (tertile 3 vs tertile 1: never smokers: HR 1.27, 95% CI 0.80-2.03, p for trend = 0.29; ever smokers: HR 1.60, 95% CI 1.06-2.43, p for trend = 0.07, p for interaction = 0.51). CONCLUSIONS: Findings from this study suggest that cadmium exposure may be an independent risk factor for ischemic stroke in the US general population. Never smoking and maintaining a high serum zinc level may ameliorate the potential adverse effects of cadmium exposure.

Toenail selenium, genetic variation in selenoenzymes and risk and outcome in glioma.

BACKGROUND: Selenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse. METHODS: In a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival. A total of 423 genetic variants in 29 candidate genes in the selenoenzyme pathway were studied in 1547 glioma cases and 1014 healthy controls. Genetic associations were also examined in the UK Biobank cohort comprised of 313,868 persons with 322 incident glioma cases. Toenail selenium was measured in a subcohort of 300 glioma cases and 300 age-matched controls from the case-control study. RESULTS: None of the 423 variants studied were consistently associated with glioma risk in the case-control and cohort studies. Moreover, toenail selenium in the case-control study had no significant association with glioma risk (p trend = 0.70) or patient survival among 254 patients with high grade tumors (p trend = 0.70). CONCLUSION: The present study offers no support for the hypothesis that selenium plays a role in the onset of glioma or patient outcome.

Demonstration of the bactericidal effects of the boron neutron capture reaction.

This pilot study represents a paradigm shift, using BNCT for the treatment of bacterial overgrowth on surgically implanted medical devices. In this study, titanium diboride disks were inoculated with S. aureus and irradiated in a thermal neutron beam. After a delivery of 2.6 × 1012 n/cm2 the surviving fraction of S. aureus on an irradiated disk was 3.1 × 10-5 when compared with non-irradiated controls. This pilot study demonstrates proof of principle of boron neutron capture therapy for infection control (BNCIC).

Effect of a Radical Cystectomy Care Pathway on Postoperative Length of Stay and Outcomes.

OBJECTIVE: To determine whether an enhance recovery protocol for radical cystectomy patient affected the length of stay or the number and type of readmissions that occurred after hospital discharge. MATERIALS AND METHODS: We prospectively assessed 152 cystectomy patients after initiation of the pathway. These patients were compared with the previous 147 patient operated on before the pathway initiation. Eligible patients were those undergoing radical cystectomy with any diversion at our institution. Univariate tests were performed using Wilcoxon sum-rank and chi-square tests. Multivariate analyses were performed using logistic regression models to assess for patient factors related to readmissions. RESULTS: With institution of the pathway, length of stay decreased from 10 to 7.1 days. Our readmission rates did not change significantly. Patients were readmitted for different reasons after pathway implementation, with the rate of urinary tract infection-related readmissions increasing from 14.3% to 40.4%, but with a concomitant decrease in the rate of readmissions for wound and deep space infections from 42.9% to 23.4%. Our venous thromboembolism rate decreased from 6.8% to 3.3% with implementation of the protocol. CONCLUSION: Implementation of a cystectomy care pathway significantly decreased length of stay without an increased rate of readmissions at 30 days. No patient factors predisposed to an increased rate of readmission. Pathway implementation led to a decrease in wound and deep space infection readmissions, but was associated with an increase in urinary tract infection readmissions. Further studies are examining if early intervention can further decrease readmission rates.

The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is characterized by an enlarged prostate, lower urinary tract symptoms (LUTS), and a decreased urinary flow rate. Common in older men, BPH is a progressive disease that can eventually lead to complications including acute urinary retention (AUR) and the need for BPH-related surgery. Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone (DHT), which is formed from testosterone under the influence of 5-alpha reductase. Thus, 5-alpha reductase inhibitors (5-ARIs) effectively reduce the serum and intraprostatic concentration of DHT, causing an involution of prostate tissue. Two 5-ARIs are currently available for the treatment of BPH-finasteride and dutasteride. Both have been demonstrated to decrease prostate volume, improve LUTS and urinary flow rates, which ultimately reduces the risk of AUR and BPH-related surgery. Therefore, either alone or in combination with other BPH medications, 5-ARIs are a mainstay of BPH management.

Cross sectional study of serum selenium concentration and esophageal squamous dysplasia in western Kenya.

BACKGROUND: Low serum selenium status has been associated with increased risk of esophageal squamous cell carcinoma (ESCC). East Africa is a region of high ESCC incidence and is known to have low soil selenium levels, but this association has not previously been evaluated. In this study we assessed the association of serum selenium concentration and the prevalence of esophageal squamous dysplasia (ESD), the precursor lesion of ESCC, in a cross-sectional study of subjects from Bomet, Kenya. METHODS: 294 asymptomatic adult residents of Bomet, Kenya completed questionnaires and underwent endoscopy with Lugol's iodine staining and biopsy for detection of ESD. Serum selenium concentrations were measured by instrumental neutron activation analysis. Odds ratios (OR) and confidence intervals (95% CI) for associations between serum selenium and ESD were calculated using unconditional logistic regression. RESULTS: The mean serum selenium concentration was 85.5 (±28.3) µg/L. Forty-two ESD cases were identified (14% of those screened), including 5 (12%) in selenium quartile 1 (Q1), 5 (12%) in Q2, 15 (36%) in Q3, and 17 (40%) in Q4. Higher serum selenium was associated with prevalence of ESD (Q4 vs Q1: OR: 3.03; 95% CI: 1.05-8.74) and this association remained after adjusting for potential confounders (Q4 vs Q1: OR: 3.87; 95% CI: 1.06-14.19). CONCLUSION: This is the first study to evaluate the association of serum selenium concentration and esophageal squamous dysplasia in an African population at high risk for ESCC. We found a positive association between higher serum selenium concentration and prevalence of ESD, an association contrary to our original hypothesis. Further work is needed to better understand the role of selenium in the etiology of ESCC in this region, and to develop effective ESCC prevention and control strategies.

Toenail mineral concentration and risk of esophageal squamous cell carcinoma, results from the Golestan Cohort Study.

Studies conducted in China linked selenium deficiency to higher risk of esophageal squamous cell carcinoma (ESCC), but this has not been widely tested outside that selenium-deficient region. The aim of this study was to investigate the association between selenium and other mineral concentrations in toenails and risk of ESCC in a region with high incidence rates. In this nested case-control study, we identified 222 cases of ESCC from the Golestan Cohort Study, Iran, which has followed up 50,045 participants since enrollment (2004-2008). We randomly selected one control for each case matched by age and sex, using incidence density sampling. We used toenail samples collected at baseline to measure the concentration of selenium, zinc, chromium, mercury, and scandium using instrumental neutron activation analysis. Multivariate adjusted logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals. Median nail selenium, zinc, chromium, and mercury levels were 1.01, 74.59, 0.77, and 0.018 µg/g in cases and 1.02, 75.71, 0.71, and 0.023 µg/g in controls, respectively. The adjusted odds ratios comparing each fourth quartile of mineral status versus the first quartile were as follows: selenium = 0.78 (95% CI, 0.41-1.49); zinc=0.80 (95% CI, 0.42-1.53); chromium = 0.91 (95% CI, 0.46-1.80); and mercury=0.61 (95% CI, 0.27-1.38), and all trend tests were non-significant. The nail selenium concentration in our controls reflects relatively high selenium status. No evidence of association between selenium or chromium concentrations in toenails and the risk of ESCC was detected in this population.

Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models.

Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. Mice were implanted with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the lipid bilayer and encapsulated Na3[1-(2`-B10H9)-2-NH3B10H8] within the liposomal core. Mice were irradiated 30 hours after the second injection in a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. Despite relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.

Prostate MRI: a national survey of Urologist's attitudes and perceptions.

INTRODUCTION: The use of multi-parametric (MP) MRI to diagnose prostate cancer has been the subject of intense research, with many studies showing positive results. The purpose of our study is to better understand the accessibility, role, and perceived accuracy of MP-MRI in practice by surveying practicing urologists. MATERIALS AND METHODS: Surveys were sent to 7,400 practicing American Urological Association member physicians with a current email address. The survey asked demographic information and addressed access, accuracy, cost, and role of prostate MRI in clinical practice. RESULTS: Our survey elicited 276 responses. Respondents felt that limited access and prohibitive cost of MP-MRI limits its use, 72% and 59% respectively. Academic urologists ordered more MP-MRI studies per year than those in private practice (43.3% vs. 21.1%; p<0.001). Urologists who performed more than 30 prostatectomies a year were more likely to feel that an MP-MRI would change their surgical approach (37.5% vs. 19.6%, p-value=0.002). Only 25% of respondents agreed or strongly agreed that MP-MRI should be used in active surveillance. For patients with negative biopsies and elevated PSA, 39% reported MP-MRI to be very useful. CONCLUSIONS: Our study found that MP-MRI use is most prominent among practitioners who are oncology fellowship-trained, practice at academic centers, and perform more than 30 prostatectomies per year. Limited access and prohibitive cost of MP-MRI may limit its utility in practice. Additionally, study participants perceive a lack of accuracy of MP-MRI, which is contrary to the recent literature.

Prostate MRI: a national survey of urologist's attitudes and perceptions

ABSTRACT Introduction The use of multi-parametric (MP) MRI to diagnose prostate cancer has been the subject of intense research, with many studies showing positive results. The purpose of our study is to better understand the accessibility, role, and perceived accuracy of MP-MRI in practice by surveying practicing urologists. Materials and Methods Surveys were sent to 7,400 practicing American Urological Association member physicians with a current email address. The survey asked demographic information and addressed access, accuracy, cost, and role of prostate MRI in clinical practice. Results Our survey elicited 276 responses. Respondents felt that limited access and prohibitive cost of MP-MRI limits its use, 72% and 59% respectively. Academic urologists ordered more MP-MRI studies per year than those in private practice (43.3% vs. 21.1%; p<0.001). Urologists who performed more than 30 prostatectomies a year were more likely to feel that an MP-MRI would change their surgical approach (37.5% vs. 19.6%, p-value=0.002). Only 25% of respondents agreed or strongly agreed that MP-MRI should be used in active surveillance. For patients with negative biopsies and elevated PSA, 39% reported MP-MRI to be very useful. Conclusions Our study found that MP-MRI use is most prominent among practitioners who are oncology fellowship-trained, practice at academic centers, and perform more than 30 prostatectomies per year. Limited access and prohibitive cost of MP-MRI may limit its utility in practice. Additionally, study participants perceive a lack of accuracy of MP-MRI, which is contrary to the recent literature.

The role of the assistant during robot-assisted partial nephrectomy: does experience matter?

The objective of this study was to evaluate surgical outcomes with respect to the experience level of the bedside assistant during robot-assisted partial nephrectomy. A retrospective review was conducted of a prospectively maintained database of 414 consecutive robot-assisted laparoscopic partial nephrectomies performed by experienced robotic surgeons at our institution from April 2011 to September 2014. A senior-level assistant was defined as a resident in his or her post-graduate year (PGY) 4 or 5, or a fellow. Junior-level assistants were considered to be PGY-2, PGY-3, or a nurse first assistant. Multivariate analyses were performed using linear, Poisson, and logistic regression models. There were 115 junior-level cases and 299 senior-level cases. On univariate analysis, the experience level of the assistant had no impact on operative time (168 for junior level vs. 163 min for senior level, p = 0.656). Likewise, there were no differences between the junior- and senior-level groups with regard to warm ischemia time (21.3 vs. 20.9 min, p = 0.843), negative margin status (111/115 (96.5 %) vs. 280/299 (93.6 %), p = 0.340), or postoperative complications (17/115 (14.8 %) vs. 35/299 (11.7 %), p = 0.408). After multivariate analysis, operative time was associated with increased body mass index and tumor size (both p < 0.001), but not with resident experience level (p = 0.051). Estimated blood loss and postoperative complications were also not associated with the PGY of the assistant (p = 0.488 and p = 0.916, respectively). Despite common concern, the PGY status of a physician trainee serving as the bedside assistant does not appear to influence the outcomes of robot-assisted partial nephrectomy at a high-volume center.

The Nail as a Biomonitor of Trace Element Status in Golestan Cohort Study.

BACKGROUND In the Golestan Cohort Study that was launched to investigate the causes of esophageal cancer, a complete biospecimen bank was established for storage of collected blood, urine, hair, and nail samples. The objective of this study was to evaluate the feasibility of nail samples as a biomarker of selected trace elements status. METHODS Thirty toenail samples were selected randomly from the participants of Golestan Cohort Study (GCS). The samples were cleaned and analyzed for selenium, mercury, chromium, iron, zinc, and scandium by instrumental neutron activation analysis at the University of Missouri Research Reactor Center. Pearson correlation coefficients were computed for selected trace elements concentration versus scandium concentration to assess terrestrial contamination. RESULTS The selenium, zinc, and mercury were not correlated with scandium, suggesting they were free from substantial contamination. The high correlations of scandium with iron and chromium suggest that the iron and chromium levels may be compromised by terrestrial contamination. The coefficients of variation for duplicate samples for selenium and zinc were 2.6% and 7.2%, respectively. CONCLUSION The nail samples from Golestan Cohort Study appears to be useable as a biomarker of selenium, zinc, and mercury and could be considered for use in future studies.

Hemorrhagic Cystitis Requiring Bladder Irrigation is Associated with Poor Mortality in Hospitalized Stem Cell Transplant Patients

Purpose: To evaluate the overall prognosis of post-stem cell transplant inpatients who required continuous bladder irrigation (CBI) for hematuria. Materials and Methods: We performed a retrospective analysis of adult stem cell transplant recipients who received CBI for de novo hemorrhagic cystitis as inpatients on the bone marrow transplant service at Washington University from 2011-2013. Patients who had a history of genitourinary malignancy and/or recent surgical urologic intervention were excluded. Multiple variables were examined for association with death. Results: Thirty-three patients met our inclusion criteria, with a mean age of 48 years (23-65). Common malignancies included acute myelogenous leukemia (17/33, 57%), acute lymphocytic leukemia (3/33, 10%), and peripheral T cell lymphoma (3/33, 10%). Median time from stem cell transplant to need for CBI was 2.5 months (0 days-6.6 years). All patients had previously undergone chemotherapy (33/33, 100%) and 14 had undergone prior radiation therapy (14/33, 42%). Twenty-eight patients had an infectious disease (28/33, 85%), most commonly BK viremia (19/33, 58%), cytomegalovirus viremia (17/33, 51%), and bacterial urinary tract infection (8/33, 24%). Twenty-two patients expired during the same admission as CBI treatment (22/33 or 67% of total patients, 22/28 or 79% of deaths), with a 30-day mortality of 52% and a 90-day mortality of 73% from the start of CBI. Conclusions: Hemorrhagic cystitis requiring CBI is a symptom of severe systemic disease in stem cell transplant patients. The need for CBI administration may be a marker for mortality risk from a variety of systemic insults, rather than directly attributable to the hematuria.

Nomogram Predicting Prostate Cancer-specific Mortality for Men with Biochemical Recurrence After Radical Prostatectomy.

BACKGROUND: The natural history of prostate-specific antigen (PSA)-defined biochemical recurrence (BCR) of prostate cancer (PCa) after definitive local therapy is highly variable. Validated prediction models for PCa-specific mortality (PCSM) in this population are needed for treatment decision-making and clinical trial design. OBJECTIVE: To develop and validate a nomogram to predict the probability of PCSM from the time of BCR among men with rising PSA levels after radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Between 1987 and 2011, 2254 men treated by radical prostatectomy at one of five high-volume hospitals experienced BCR, defined as three successive PSA rises (final value >0.2 ng/ml), single PSA >0.4 ng/ml, or use of secondary therapy administered for detectable PSA >0.1 ng/ml. Clinical information and follow-up data were modeled using competing-risk regression analysis to predict PCSM from the time of BCR. INTERVENTION: Radical prostatectomy for localized prostate cancer and subsequent PCa BCR. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCSM. RESULTS AND LIMITATIONS: The 10-yr PCSM and mortality from competing causes was 19% (95% confidence interval [CI] 16-21%) and 17% (95% CI 14-19%), respectively. A nomogram predicting PCSM for all patients had an internally validated concordance index of 0.774. Inclusion of PSA doubling time (PSADT) in a nomogram based on standard parameters modestly improved predictive accuracy (concordance index 0.763 vs 0.754). Significant parameters in the models were preoperative PSA, pathological Gleason score, extraprostatic extension, seminal vesicle invasion, time to PCa BCR, PSA level at PCa BCR, and PSADT (all p<0.05). CONCLUSIONS: We constructed and validated a nomogram to predict the risk of PCSM at 10 yr among men with PCa BCR after radical prostatectomy. The nomogram may be used for patient counseling and the design of clinical trials for PCa. PATIENT SUMMARY: For men with biochemical recurrence of prostate cancer after radical prostatectomy, we have developed a model to predict the long-term risk of death from prostate cancer.