Voided Urine Samples Research Articles

Detection of urinary Chlamydia trachomatis, Mycoplasma genitalium and human papilloma virus in the first trimester of pregnancy by PCR method

BackgroundMiscarriage and preterm delivery are the most important challenges of pregnancy. Different bacterial and viral infection may cause miscarriage and preterm delivery. Among bacterial factors, Mycoplasma genitalium and Chlamydia trachomatis have the most important role and human papilloma virus (HPV) is the leading viral factor in this regard.MethodsFirst void urine samples were collected from 119 pregnant women who visited health centers for routine first-trimester screening (12–14 weeks gestation). About 10 ml of the sample was centrifuged at 3000×g for 20 min and 1–2 ml of the sediment was transferred to sterile microfuges and stored at − 20 °C until analysis. DNA extraction was conducted using A101211 kits imported by Pars Tous Biotechnology Company. The following commercial kits, imported by Pars Tous Biotechnology, were used for PCR.ResultsThere is no significant association between urinary isolation of C. trachomatis and miscarriage (P = 0.93) and there is no significant association between urinary isolation of M. genitalium and miscarriage (P = 0.80). Regarding HPV, since all urine samples were PCR-negative, comparison was not possible. C. trachomatis was isolated from the urine samples of 6.72% of the pregnant women who underwent first-trimester screening in health centers using PCR. Previous studies reported a mean chlamydia isolation rate of 3% from urine specimens collected from pregnant women in general. T test showed no significant difference between the two groups (P = 0.10). Based on present study the mycoplasma isolation rate was 17.65% using PCR. Previous studies reported a mean mycoplasma isolation rate of 10% from urine specimens collected from pregnant women in general. T-test showed a significant difference between the two groups (P = 0.03).DiscussionFirst void urine samples in pregnant women may be an appropriate sample for detection of C. trachomatis and M. genitalium; however, it is not a good method for HPV isolation therefore vaginal or cervical discharge specimens should be used instead for detection of HPV.

Health Risk Assessment and Urinary Excretion of Children Exposed to Arsenic through Drinking Water and Soils in Sonora, Mexico.

Environmental arsenic exposure is associated with increased risk of non-cancerous chronic diseases and a variety of cancers in humans. The aims of this study were to carry out for the first time a health risk assessment for two common arsenic exposure routes (drinking water and soil ingestion) in children living in the most important agricultural areas in the Yaqui and Mayo valleys in Sonora, Mexico. Drinking water sampling was conducted in the wells of 57 towns. A cross-sectional study was done in 306 children from 13 villages in the valleys. First morning void urine samples were analyzed for inorganic arsenic (InAs) and monomethyl and dimethyl arsenic (MMA and DMA) by HPLC/ICP-MS. The results showed a wide range of arsenic levels in drinking water between 2.7 and 98.7μg As/L. Arsenic levels in agricultural and backyard soils were in the range of < 10-27mg As/kg. The hazard index (HI) = ∑hazard quotient (HQ) for drinking water, agricultural soil, and backyard soil showed values > 1 in 100% of the study towns, and the carcinogenic risk (CR) was greater than 1E-04 in 85%. The average of arsenic excreted in urine was 31.7μg As/L, and DMA had the highest proportion in urine, with averages of 77.8%, followed by InAs and MMA with 11.4 and 10.9%, respectively, percentages similar to those reported in the literature. Additionally, positive correlations between urinary arsenic levels and HI values were found (r = 0.59, P = 0.000). These results indicated that this population is at high risk of developing chronic diseases including cancer.

Detection of urothelial carcinoma, upper tract urothelial carcinoma, bladder carcinoma, and urothelial carcinoma with gross hematuria using selected urine-DNA methylation biomarkers: A prospective, single-center study

IntroductionHematuria is the most common symptom of urothelial carcinomas (UC) but is often idiopathic. Cystoscopy is expensive which involves considerable patient discomfort, and conventional urine cytology for noninvasive UC detection and disease monitoring suffers from poor sensitivity. We aim to evaluate the performance of genes selected from a previous study in detecting UC, especially among patients with gross hematuria, as well as upper tract urothelial carcinoma (UTUC) and bladder carcinoma separately, in voided urine samples. MethodsUsing methylation-specific polymerase chain reaction, we examined the promoter methylation status of 10 genes in voided urine samples among 473 patients at our institution, including 217 UC patients and 256 control subjects. ResultsThe final combination of VIM, CDH1, SALL3, TMEFF2, RASSF1A, BRCA1, GDF15, and ABCC6 identified UC with a sensitivity of 0.83 and a specificity of 0.60. Additionally, a panel of selected genes (CDH1, HSPA2, RASSF1A, TMEFF2, VIM, and GDF15) identified UTUC with a sensitivity of 0.82 and a specificity of 0.68, while a panel of selected genes (VIM, RASSF1A, GDF15, and TMEFF2) identified bladder carcinoma with a sensitivity of 0.82 and a specificity of 0.53. Remarkably, a different panel (CDH1, SALL3, THBS1, TMEFF2, VIM, and GDF15) identified UC in patients with gross hematuria with 0.89 sensitivity and 0.74 specificity, and sensitivity (0.91) and specificity (0.92) could be achieved when cytology was included. ConclusionsThe selected urine-DNA methylation biomarkers are reliable, noninvasive, and cost-effective diagnostic tools for bladder carcinoma and UTUC, especially among patients with gross hematuria.

Prospective long-term evaluation of parenteral hydroxocobalamin supplementation in juvenile beagles with selective intestinal cobalamin malabsorption (Imerslund-Gräsbeck syndrome).

BackgroundProspective studies on maintenance treatment for Beagles with hereditary selective cobalamin (Cbl) malabsorption (Imerslund‐Gräsbeck syndrome, IGS) are lacking. In our experience, measurement of methylmalonic acid (MMA), a Cbl‐dependent metabolite, seems more helpful to monitor Cbl status as compared with serum Cbl concentrations.ObjectivesTo evaluate a standardized Cbl supplementation scheme in Beagles with IGS. We hypothesized that a single parenteral dose of 1 mg hydroxocobalamin (OH‐Cbl) would maintain clinical and metabolic remission for up to 2 months.AnimalsSix client‐owned juvenile Beagles with genetically confirmed IGS and 28 healthy control dogs.MethodsProspective study. Monthly IM OH‐Cbl (1 mg) supplementation was done over a median of 9 months (range, 6‐13) in 6 dogs, followed by bimonthly (every 2 months) injections in 5 dogs over a median of 6 months (range, 3‐10). Health status was assessed by routine clinical examinations at injection time points and owner observations. Voided urine samples were collected immediately before OH‐Cbl injections for measurement of MMA‐to‐creatinine concentrations using a gas‐liquid chromatography‐tandem mass spectrometry (GC‐MS) method.ResultsAll dogs were clinically healthy while receiving monthly and bimonthly OH‐Cbl supplementation. Urinary MMA results in healthy dogs ranged from 1.3 to 76.5 mmol/mol creatinine (median, 2.9). Median urinary MMA concentrations did not differ between dogs with IGS receiving monthly (n = 49; 5.3 mmol/mol creatinine; range, 2.3‐50.4) and bimonthly (n = 31; 5.3 mmol/mol creatinine; range, 1.6‐50) injections.Conclusions and Clinical ImportanceA maintenance parenteral dose of 1 mg OH‐Cbl monthly or bimonthly appears adequate in Beagles with IGS monitored by metabolic testing.

The Effect of Urine Concentration and pH on the Growth of Escherichia Coli in Canine Urine In Vitro.

BackgroundLower urinary tract infections are common in dogs, and Escherichia coli is the most common bacterial pathogen isolated. The literature has conflicting evidence regarding the inhibitory effects of urine concentration and pH on E. coli growth.Hypothesis/ObjectivesTo determine the effect of different pH and urine concentrations on E. coli growth in vitro.AnimalsVoided urine samples from 10 apparently healthy spayed female dogs were used.MethodsA matrix of 9 urine specific gravity (USG; 1.010, 1.020, and 1.030) and pH (5.5, 7.0, and 8.5) combinations was prepared by diluting and titrating filtered voided urine samples. Three E. coli isolates were obtained from urine of female dogs with signs of lower urinary tract infection and cultured at different urine pH and USG combinations in wells of a microtiter plate. The number of E. coli colony‐forming units (CFU) per mL of urine was calculated after aerobic incubation of the urine at 37°C for 18 hours, and statistically compared.ResultsSignificant differences were identified in the mean log CFU/mL among different combinations of pH and USG. The lowest log CFU/mL were observed in alkaline concentrated urine (pH 8.5 and USG 1.030).Conclusions and Clinical Importance Escherichia coli in vitro growth was higher in neutral to acidic and diluted urine compared to alkaline and concentrated urine. The impact of non‐alkalizing diluting diets on the incidence of E. coli lower urinary tract infections should be further explored.

Temporal trends of phthalate exposures during 2007-2010 in Swedish pregnant women.

The general population is exposed to phthalates, a group of chemicals with strong evidence for endocrine disrupting properties, commonly used in a large number of consumer products. Based on published research and evidence compiled by environmental agencies, certain phthalate applications and products have become restricted, leading to an increasing number of "new generation compounds" coming onto the market during recent years replacing older phthalates. Some examples of such newer compounds are di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP), and most recently di-isononyl-cyclohexane-1,2-dicarboxylate (DiNCH). In order to evaluate temporal trends in phthalate exposure, first trimester urinary biomarkers of phthalates were measured in the Swedish SELMA study over a period of 2.5 years (2007-2010). We collected first morning void urine samples around week 10 of pregnancy from 1651 pregnant women. Spot samples were analyzed for 13 phthalate metabolites and one phthalate replacement and least square geometric mean (LSGM) levels of the metabolites were compared between the sampling years when adjusted for potential confounders. All 14 metabolites were detectable in more than 99% of the SELMA subjects. The levels were generally comparable to other studies, but the SELMA subjects showed slightly higher exposure to butyl-benzyl phthalate (BBzP) and di-butyl phthalate (DBP). Di-ethyl-hexyl phthalate (DEHP) metabolites levels decreased while DiNP, DiDP/di-2-propylheptyl phthalate (DPHP), and DiNCH metabolites levels increased during the sampling period. Urinary metabolite levels of the older phthalates and more recently introduced phthalate replacement compound changed during the short sampling period in this Swedish pregnancy cohort. Our results indicate that replacement of phthalates can make an impact on human exposure to these chemicals. During this particularly vulnerable stage of life, phthalate exposures are of particular concern as the impacts, though not immediately noticeable, may increase the risk for health effects later in life.

Promoter methylation of DNA damage repair (DDR) genes in human tumor entities: RBBP8/CtIP is almost exclusively methylated in bladder cancer

BackgroundGenome-wide studies identified pan-cancer genes and shared biological networks affected by epigenetic dysregulation among diverse tumor entities. Here, we systematically screened for hypermethylation of DNA damage repair (DDR) genes in a comprehensive candidate-approach and exemplarily identify and validate candidate DDR genes as targets of epigenetic inactivation unique to bladder cancer (BLCA), which may serve as non-invasive biomarkers.MethodsGenome-wide DNA methylation datasets (2755 CpG probes of n = 7819 tumor and n = 659 normal samples) of the TCGA network covering 32 tumor entities were analyzed in silico for 177 DDR genes. Genes of interest were defined as differentially methylated between normal and cancerous tissues proximal to transcription start sites. The lead candidate gene was validated by methylation-specific PCR (MSP) and/or bisulfite-pyrosequencing in different human cell lines (n = 36), in primary BLCA tissues (n = 43), and in voided urine samples (n = 74) of BLCA patients. Urines from healthy donors and patients with urological benign and malignant diseases were included as controls (n = 78). mRNA expression was determined using qRT-PCR in vitro before (n = 5) and after decitabine treatment (n = 2). Protein expression was assessed by immunohistochemistry (n = 42). R 3.2.0. was used for statistical data acquisition and SPSS 21.0 for statistical analysis.ResultsOverall, 39 DDR genes were hypermethylated in human cancers. Most exclusively and frequently methylated (37%) in primary BLCA was RBBP8, encoding endonuclease CtIP. RBBP8 hypermethylation predicted longer overall survival (OS) and was found in 2/4 bladder cancer cell lines but not in any of 33 cancer cell lines from entities with another origin like prostate. RBBP8 methylation was inversely correlated with RBBP8 mRNA and nuclear protein expression while RBBP8 was re-expressed after in vitro demethylation. RBBP8 methylation was associated with histological grade in primary BLCA and urine samples. RBBP8 methylation was detectable in urine samples of bladder cancer patients achieving a sensitivity of 52%, at 91% specificity.ConclusionsRBBP8 was identified as almost exclusively hypermethylated in BLCA. RBBP8/CtIP has a proven role in homologous recombination-mediated DNA double-strand break repair known to sensitize cancer cells for PARP1 inhibitors. Since RBBP8 methylation was detectable in urines, it may be a complementary marker of high specificity in urine for BLCA detection.

A genome-scale DNA methylation study in women with interstitial cystitis/bladder pain syndrome.

To assess the feasibility of using voided urine samples to perform a DNA methylation study in females with interstitial cystitis/bladder pain syndrome (IC/BPS) as compared to age- and race-matched controls. A unique methylation profile could lead to a non-invasive, reproducible, and objective biomarker that would aid clinicians in the diagnosis of IC/BPS. Nineteen IC/BPS patients and 17 controls were included. IC/BPS patients had an Interstitial Cystitis Symptom Index score of >8; controls had no bladder symptoms. DNA was extracted from pelleted urine sediment. Samples with >500 ng of genomic DNA underwent quantitative DNA methylation assessment using the Illumina Infinium MethylationEPIC BeadChip. Age- and race-matching was applied prior to analysis. Linear regression models were used to compare average methylation between IC/BPS cases and controls at each cytosine guanine dinucleotide site (loci where methylation can occur). Sixteen participants (eight IC/BPS age- and race-matched to eight controls) had adequate DNA for methylation analysis. The median age was 43.5 years (interquartile range 33.8, 65.0), the median BMI was 27.1 (IQR 22.7, 31.4), and 14 were Caucasian (87.5%). A total of 688 417 CpG sites were analyzed. In exploratory pathway analysis utilizing the top 1000 differentially methylated CpG sites, the mitogen-activated protein kinase (MAPK) pathway was overrepresented by member genes. The results demonstrate the feasibility of using voided urine specimens from women with IC/BPS to perform DNA methylation assessments. Additionally, the data suggest genes within or downstream of the MAPK pathway exhibit altered methylation in IC/BPS.

Positive urinary fluorescence in situ hybridization indicates poor prognosis in patients with upper tract urothelial carcinoma.

Here, we evaluated the potential contribution of fluorescent in situ hybridization (FISH) as a prognostic risk factor of bladder recurrence and survival in patients with upper tract urothelial carcinoma (UTUC). A total of 159 UTUC patients were enrolled in this study from January 2012 to May 2016. The 159 voided urine samples before surgery were analyzed using the UroVysion® kit to detect the copy numbers of chromosomes 3, 7, 17 and 9p21 (p16). Patients were classified using an optimal cutoff value of chromosomes 3, 7, 17, and 9p21. Cox's proportional hazards regression model was used to assess the prognostic value of FISH for bladder recurrence and survival. We found that 27 (17.6%) patients experienced bladder recurrence and 26 (16.4%) patients died from cancer, with a median follow-up of 27 months. The patients with positive FISH result were more likely to present bladder recurrence (p = 0.077). However, positive FISH was not associated with cancer specific-free survival (CSS) (p = 0.944). Tumor multifocality, the percentage of abnormal chromosome 3 > 5%, chromosome 7 > 6%, chromosome 17 > 11% and deletion of p16 > 4% were significant prognostic risk factors for BRFS in univariate analysis. In multivariate analysis, only tumor multifocality (hazard ratio [HR] = 3.487, 95%CI: 1.605–7.576, p = 0.002) and the percentage of p16 loss > 4% were both prognostic risk factors for bladder recurrence (HR = 3.487, 95%CI: 1.605–7.576, p = 0.002). These data consider that the urinary FISH test could be a powerful tool in predicting the risk of bladder recurrence in patients with UTUC.

Validation of Urine-based Gene Classifiers for Detecting Bladder Cancer in a Chinese Study.

Background: Current standard methods used to detect and monitor bladder cancer (BC) are invasive or have low sensitivity. We have previously reported in an international European study four non-invasive tests for BC diagnosis based on the gene expression patterns of urine.Objective: to validate the tests in an independent Asian cohort.Design, setting and participants: Prospective blinded study in which consecutive voided urine samples from BC patients and controls (n=520) were collected in the Fudan University Shanghai Cancer Center from 2014-2016. Gene expression values were quantified using TaqMan Arrays. The same cut-off as previously reported for discrimination between tumours and controls was used in this validation study.Results and limitations: Finally, a total of 257 tumour and 132 control urine samples were analysed. We found a high accuracy for the four gene classifiers in this independent Asian set, the classifiers composed of 5 and 10 genes achieved the best sensitivity (80.54% and 81.32%, respectively) maintaining a high specificity (91.67% and 85.61%, respectively). Sensitivity of 5-gene (GS_D5) and 10-gene (GS_D10) expression classifiers in recurrent BC cases (78 and 79%, respectively) is comparable to that of primary BC cases (82%). Cytology and NMP22 identified 67% and 40%, respectively, of tumours that have been diagnosed with our tests. In addition, influence of each studied gene was analyzed and showed similar gene rank between Chinese and Caucasian population.Conclusions: Our study proves that our non-invasive diagnostic BC tests can be reproduced in independent cohorts and in an external laboratory. All the four gene classifiers have shown equal or superior performance to the current gold standard in the present and previously reported validation studies. Consequently, they may be taken for consideration as molecular tests applicable to clinical practice in the management of BC.Patient summary: Our gene classifiers achieve sensitivities up to 90% in HR NMIBC and MIBC patients, while this achievement is comparatively lower in LR NMIBC ones.

Chlamydia trachomatis urogenital infection and associated risk factors among university students in Croatia

O bjective − The study aimed to determine the prevalence of Chlamydia trachomatis infection among university students in Croatia and to determine risk factors associated with chlamydia infection. M aterial and methods − The study was conducted as an opportunistic screening of asymptomatic sexually active students attending routine health examinations during their first year of studying. The first void urine samples from males, cervical swab or first void urine samples from females and data regarding life style, sexual and other health-risk behaviour were collected and analysed. R esults − Overall prevalence of chlamydia infection was 4.9%, with the testing response rate of 29.5%. The only identified risk factor was female sex. Female students preferred urine sample over cervical swab sample and avoided gynaecologist examination. Conclusion − Opportunistic screening is a feasible strategy to diagnose asymptomatic chlamydia infection among university students in Croatia. Results may contribute to decision making on the form of chlamydia control policy, including choice of screening settings and specimens suitable for target population.

Urinary carbohydrate antigen 19-9/creatinine ratio: A non-invasive marker for follow-up of unilateral ureteropelvic junction obstruction in children

Ureteropelvic junction obstruction (UPJO) is the most common cause of hydronephrosis in children. One major challenge in the management of UPJO is to select the patients that must be subjected to early obstruction relief. Currently, there is no gold standard for this assessment. Therefore, the aim of the present study was to evaluate the urinary levels of carbohydrate antigen (CA) 19-9 and normalized CA 19-9 (Ca 19-9/Cr ratio) in UPJO patients before and after surgery and compare them with a control group to assess their potential clinical application as an assisting tool in diagnosis of UPJO patients. From Jan 2013 to Jun 2016, 30 children with history of inguinal hernia, circumcision, hydrocele, and undescended testis as the control group (group 1) and 30 children with unilateral congenital UPJO (group 2) were enrolled in the study. Random CA 19-9 and random creatinine were measured in the voided urine samples of control group and proven congenital UPJO group preoperatively (group 2A) and at 6 months after dismembered pyeloplasty (group 2B). In addition, the random urinary CA 19-9/CR ratio was evaluated as a marker to normalized urinary CA 19-9. The urinary CA 19-9/Cr ratio was significantly greater in the UPJO group than in the control group. The urinary CA 19-9 also was more in group 2A than in group 1; however, it was not statistically significant. The urinary CA 19-9/Cr ratio and renal pelvis anteroposterior diameter decreased significantly in the group 2B 6 month after complete relief of obstruction in comparison with group 2A preoperatively. Urinary CA 19-9 also decreased in 2B group though it was not significant. Urinary CA 19-9/Cr ratio is suggested as a non-invasive marker that can assist in diagnosis and long-term follow-up of UPJO patients. This ratio is superior to urinary CA 19-9 as it is more strongly correlated with UPJ obstruction.

Diagnostic and prognostic role of urinary collagens in primary human bladder cancer.

Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of fragments of cytokeratin‐19 (CYFRA21‐1), nuclear matrix protein 22 (NMP‐22), and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Protein levels of COL4A1, COL13A1, CYFRA21‐1, and NMP‐22 in urine supernatants were measured using enzyme‐linked immunosorbent assays. Diagnostic performance and optimal cut‐off values were determined by receiver operating characteristic analysis. Urine levels of COL4A1, COL13A1, the combined values of COL4A1 and COL13A1 (COL4A1 + COL13A1), and CYFRA21‐1 were significantly elevated in urine from patients with BCa compared to the controls. Among these biomarkers, the optimal cut‐off value of COL4A1 + COL13A1 at 1.33 ng/mL resulted in 57.4%, 83.7%, 56.1%, 80.7%, and 91.7% sensitivity for low‐grade tumors, high‐grade tumors, Ta, T1, and muscle invasive disease, respectively. We evaluated the prognostic value of preoperative urine levels in 130 non‐muscle invasive BCa samples after the initial transurethral surgery. A high urinary COL4A1 + COL13A1 was found to be an independent risk factor for intravesical recurrence. Although these data need to be externally validated, urinary COL4A1 and COL13A1 could be a potential diagnostic and prognostic biomarker for BCa. This easy‐to‐use urinary signature identifies a subgroup of patients with a high probability of recurrence and progression in non‐muscle invasive and muscle invasive BCa.

RETENTION OF 7Be IN THE LUNGS FOLLOWING INTAKE BY INHALATION.

Several workers were internally exposed to 7Be particles following their dispersion in air from a damaged electrodeposited source. A series of in vivo measurements performed with one worker up to 108 days post exposure determined that retention of 7Be in the thoracic region of the respiratory tract was best described by a two-component exponential function with half-lives of ~0.4 and ~109 days. The initial deposition in the thoracic region was estimated to be 6.8 kBq. The concentration of 7Be in single void urine samples collected from this worker up to 3 days post intake ranged from 1 to 10 Bq/l. In the absence of specific knowledge about the physical and chemical characteristics of the inhaled particles, the committed effective dose was estimated to be 0.3 μSv.

Spectrophotometric photodynamic detection involving extracorporeal treatment with hexaminolevulinate for bladder cancer cells in voided urine.

To evaluate the feasibility of hexaminolevulinate (HAL) for the photodynamic detection of cancer cells in voided urine. This study included 50 patients with bladder cancer that was confirmed histologically after transurethral resection (bladder cancer group) and 50 outpatients without a history of urothelial carcinoma or cancer-related findings (no malignancy group). One third of the voided urine samples were incubated with aminolevulinic acid (ALA-treated samples), one third were incubated with HAL (HAL-treated samples), and the remaining samples were incubated without treatment (untreated samples). For detecting cellular protoporphyrin IX levels, the intensity of the samples at the excitation wavelength of 405nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated or HAL-treated samples and the untreated samples at 635nm was calculated. HAL-induced fluorescence cytology (HFC) showed that the difference was significantly higher in patients with high-grade tumors than in those with low-grade tumors (p=0.0003) and the difference was significantly higher in patients with low-grade tumors than in those without a history of urothelial carcinoma or cancer-related findings (p=0.021). The areas under the receiver operating characteristic curves of ALA-induced fluorescence cytology (AFC) and HFC were 0.77 and 0.81, respectively. The AUC of HFC was significantly higher than that of AFC (p<0.0001). The overall sensitivity values for conventional cytology, AFC, and HFC were 49, 74, and 74%, respectively. The overall specificity values for AFC and HFC were 70 and 94%, respectively. Spectrophotometric photodynamic detection involving extracorporeal treatment with HAL for bladder cancer cells in voided urine showed high accuracy. This bladder cancer detection method is easy and cost-effective, and has the potential for clinical use.

Are Demographic, Psychosocial, and Behavioral Factors Associated with Urinary Salt Excretion in Japanese Workers?

Although high salt intake is a major public health problem, little is known about the predictors of salt intake in Japanese. The present study aims to investigate the association of demographic, psychosocial, and behavioral factors with urinary salt excretion in Japanese workers. From September to November 2014, a self-administered questionnaire was completed by Japanese workers at 8 workplaces in Niigata, Japan. Demographic factors (shift work, household income, family structure, the person responsible for cooking, and smoking habit) were assessed by questionnaire. Psychosocial factors (self-efficacy, perceived social support, and knowledge) were measured using a scale similar to items from an existing scale. Behavioral factors (intake frequency of foods and alcohol, and general dietary behavior) were assessed using a validated, brief-type self-administered diet history questionnaire. Estimated 24-hour urinary salt excretion was calculated from sodium and creatinine concentrations in second morning void or spot urine samples. Analysis of covariance was used to examine the association of factors with urinary salt excretion while adjusting for age and body mass index. Of 457 respondents, 406 participants’ data were analyzed. Urinary salt excretion was not associated with any demographic and psychosocial factors. The intake frequency of pickled vegetables and buckwheat noodles, and the amount of soup consumed with noodles were significantly and positive association with urinary salt excretion in women. Conversely, amount of soy sauce and Worcestershire sauce used at the table was significantly and negative association with urinary salt excretion in men. The association with salt intake was found only behavioral factors in Japanese workers.

Diagnostic value of DNA aneuploidy for urothelial carcinoma.

e16007 Background: The incidence and mortality of urologic cancer are increasing in China and worldwide. Early diagnosis is the key to improve survival. DNA-Image-Cytometry (DNA-ICM) is to assist in the early microscopical diagnosis and grading of various types of tumors, measuring the DNA-contents of their cells. This study investigates the role of DNA aneuploidy in improving diagnostic sensitivity and specificity for urothelial carcinoma. Methods: 274 voided urine samples (204 cases from patients with urothelial carcinomas and 70 cases from patients with benign urinary system diseases) were analyzed with DNA-ICM and liquid-based cytology (LBC) .Fresh urine samples were collected in the morning of the analysis. Sedimented cell-preparations were obtained through centrifugation (cytospins) for DNA-ICM. The sensitivity and specificity of DNA ICM and LBC were calculated by comparing with the pathology in cells with moderate and severe dysplasia. Results: Sensitivity of DNA-ICM was 70.3% which was much higher than that of liquid-based cytology (27.2%)(P &lt; 0.01). Specificity of DNA-ICM was 100% while specificity of LBC was 98.6%. The sensitivity of DNA-ICM in upper urinary tract urothelial cell carcinoma(UTCUs) were 68.75%, lower than 75.00% in bladder urothelial cell carcinomas, there was no significant differences between them(P &gt; 0.01). Conclusions: DNA single cell cytometry represents a highly relevant tool in the objective identification of urothelial carcinoma with a sufficient sensitivity and specificity. Enhancing its extended use as an adjuvant strategy for the early screening of the urothelial carcinoma during routine analyses is benefical. DNA-ICM is an effective screening method for urothelial cancer. Its use to monitor the treatment should be further validated in larger series.

PD19-09 PERFORMANCE OF A NOVEL URINE-BASED BIOMARKER FOR THE MONITORING OF BLADDER CANCER RECURRENCE

You have accessJournal of UrologyBladder Cancer: Non-invasive II1 Apr 2017PD19-09 PERFORMANCE OF A NOVEL URINE-BASED BIOMARKER FOR THE MONITORING OF BLADDER CANCER RECURRENCE Ofer Nativ, Sarel Halachmi, Kohava Biton, Marina Zlotnik, Chen Yoffe, Noa Davis, Yael Glickman, and Jacob Bejar Ofer NativOfer Nativ More articles by this author , Sarel HalachmiSarel Halachmi More articles by this author , Kohava BitonKohava Biton More articles by this author , Marina ZlotnikMarina Zlotnik More articles by this author , Chen YoffeChen Yoffe More articles by this author , Noa DavisNoa Davis More articles by this author , Yael GlickmanYael Glickman More articles by this author , and Jacob BejarJacob Bejar More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.882AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The accurate detection of low-grade (LG) urothelial cell carcinoma (UCC) may be challenging, particularly in cases where cytomorphologic features overlap with those of non-neoplastic changes. CellDetect is a unique histochemical stain which enables color discrimination, in addition to morphological examination, for the differentiation between benign and malignant cells in urine specimens. A multi-institutional blinded study has recently shown that this color feature significantly improves the sensitivity for LG tumors when compared to standard urine cytology. The objective of the present study was to confirm this performance in an independent cytology laboratory. METHODS Voided urine samples were collected from a first cohort of patients undergoing routine cystoscopic surveillance. To enrich the study with positive cases, a second cohort of patients scheduled for transurethral resection (TURBT) was also enrolled. The patients from both cohorts had a documented history of bladder cancer. Urine samples were processed into two cytocentrifuge smears and each slide was stained with either CellDetect or standard cytology stain. Both specimens were observed by a cytopathologist blinded to the final diagnosis. The results were then compared to the gold standard (biopsy for positive cases and biopsy or cystoscopy for negative cases). RESULTS 73 patients were enrolled in this study, among which 51 were UCC-negative and 22 UCC-positive. The sensitivity of CellDetect was 82% compared to 59% for standard cytology (p<0.05) while the specificity was not significantly different (86% versus 94%). Moreover, the urine-based biomarker was able to detect 73% of the LG tumors compared to 45% by standard cytology. In addition, it correctly diagnosed 91% of the HG tumors compared to 73% for standard stain. CONCLUSIONS This study validates the usability of CellDetect in clinical settings. Particularly, it confirms its ability to accurately identify UCC recurrence throughout all cancer grades. This could be particularly useful in LG cases where cytomorphologic criteria overlap with benign reactive conditions. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e368 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ofer Nativ More articles by this author Sarel Halachmi More articles by this author Kohava Biton More articles by this author Marina Zlotnik More articles by this author Chen Yoffe More articles by this author Noa Davis More articles by this author Yael Glickman More articles by this author Jacob Bejar More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

UroMark\u2014a urinary biomarker assay for the detection of bladder cancer

BackgroundBladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity.ResultsWe defined a 150 CpG loci biomarker panel from a cohort of 86 muscle-invasive bladder cancers and 30 normal urothelium. Based on this panel, we developed the UroMark assay, a next-generation bisulphite sequencing assay and analysis pipeline for the detection of bladder cancer from urinary sediment DNA. The 150 loci UroMark assay was validated in an independent cohort (n = 274, non-cancer (n = 167) and bladder cancer (n = 107)) voided urine samples with an AUC of 97%. The UroMark classifier sensitivity of 98%, specificity of 97% and NPV of 97% for the detection of primary BC was compared to non-BC urine.ConclusionsEpigenetic urinary biomarkers for detection of BC have the potential to revolutionise the management of this disease. In this proof of concept study, we show the development and utility of a novel high-throughput, next-generation sequencing-based biomarker for the detection of BC-specific epigenetic alterations in urine.

Relation of renal dysfunction with incident atrial fibrillation and cardiovascular morbidity and mortality: The PREVEND study.

Renal dysfunction is a risk factor for cardiovascular disease, including atrial fibrillation (AF) and mortality. However, the exact pathobiology linking different renal dysfunction measures, such as albumin excretion or glomerular filtration rate (GFR), to cardiovascular- and AF risk are unclear. In this study, we investigated the association of several renal function measures and incident AF, and whether the relation between renal measures and outcomes is modified by AF. We examined 8265 individuals (age 49 ± 13 years, 50% women) included in the PREVEND study. We used albumin excretion (morning void and 24-h urine samples), serum creatinine, cystatin C, and Cystatin C-based, creatinine-based, and creatinine-cystatin C-based GFR as renal function measures; results: During a follow-up of 9.8 ± 2.3 years, 267 participants (3.2%) developed AF. In the multivariate-adjusted model, GFR, estimated by creatinine, cystatin C, or the combination was not associated with incident AF. However, increased albumin excretion was strongly associated with incident AF; urine albumin concentration and excretion (HRmorning void 1.10, P = 0.005 and HR24-hr collection 1.05, P = 0.033) and albumin creatinine ratio (HRmorning void 1.05, P = 0.010 and HR24-hr collection 1.06, P < 0.001). Interaction terms of incident AF and renal measures were not significant for incident cerebrovascular events, peripheral vascular events, ischemic heart disease, heart failure, and mortality. In this community-based cohort, increased albumin excretion, and not GFR, was associated with incident AF, independent of established cardiovascular risk factors. Incidence of AF did not largely alter the association of renal dysfunction and cardiovascular outcomes.