Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study.

PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Use of Cotton Balls in Diapers for Collection of Urine Samples Impacts the Analysis of Routine Chemistry Tests: An Evaluation of Cotton Balls, Diapers, and Chemistry Analyzers.

OBJECTIVE: To evaluate the suitability of urine samples collected with cotton balls placed into diapers for routine laboratory chemistry analyses. STUDY DESIGN: Twenty pools of residual unpreserved urine samples were separated into control and treated aliquots. The treated samples were absorbed into 2 different brands of cotton balls, wrapped in 3 different brands of diapers, and incubated at 37°C for 1 hour. The urine-soaked cotton balls were placed into a syringe and expressed via plunger depression. Urine sodium, potassium, creatinine, urea, calcium, magnesium, inorganic phosphorus, albumin, and total protein were measured on all samples on 5 automated clinical chemistry platforms: Ortho Vitros 4600, Siemens Dimension Vista 500, Beckman Coulter AU5822, Roche Cobas 6000, and Abbott Architect c8000 at 5 separate hospital laboratories. Criteria used to exclude the presence of significant effects of urine from presoaked cotton balls in a diaper on the measurement of chemistry laboratory tests were R2 >0.95, slope of 0.9-1.1, and mean bias within ±10%. RESULTS: Albumin and total protein measurements demonstrated significant negative bias in urine from both brands of presoaked cotton balls with all brands of diapers on all 5 chemistry platforms compared with the control urine. We did not observe a significant effect of presoaking urine in cotton balls in a diaper on the measurement of sodium, inorganic phosphorus, and urea. The remaining tests demonstrated significant effects when measured in urine from presoaked cotton balls and/or diapers that were specific to the chemistry analyzer platform or diaper. CONCLUSIONS: Diaper and cotton ball-based urine collection significantly impacts the measurement of several common chemistry assays.

Validity of predictive equations for 24-h urinary sodium excretion at the population and individual levels among Chinese adults aged 18-69 years.

Spot urine (SU) collection is a convenient method commonly used for sodium estimation, but its validity in predicting 24-h urinary sodium (24-hUNa) excretion has not been thoroughly evaluated among the general population. The aim of this study was to comprehensively assess the validity of eight existing methods in predicting 24-hUNa excretion by using SU samples among Chinese adults. We analyzed 1424 representative individuals aged 18 to 69 years. We compared the measured and estimated measurements of 24-hUNa at the population level by examining bias, the correlation, intraclass correlation coefficients (ICCs), receiver operating characteristic (ROC) curves and Bland-Altman plots and analyzed the relative and absolute differences and misclassification at the individual level. The bias for all methods was significant (all p < 0.001), among which the smallest bias was - 7.9 mmol for the Toft formula and the largest bias was - 53.8 mmol for the Mage formula. Correlation coefficients were all less than 0.380, all formulas exhibited an area under the ROC curve below 0.683, and the Bland-Altman plots indicated slightly high dispersion of the estimation biases at higher sodium levels regardless of the formula. The proportions of relative differences > 40% for the eight methods were all over one-third, the proportions of absolute differences > 51.3 mmol/24 h (3 g/day NaCl) were all over 40%, and the misclassification rates (7, 10, and 13 g/day NaCl as cutoff points) were all over 65%. Caution remains due to poor validity between estimated and actual measurements when using the eight formulas to obtain a plausible estimation for surveillance of the Chinese population sodium excretion, and the results do not support the application of SU to estimate sodium intake at the individual level due to its poor performance with respect to classification.

Prevalence, antimicrobial susceptibility pattern and associated risk factors for urinary tract infections in pregnant women attending ANC in some integrated health centers in the Buea Health District.

BACKGROUND: Urinary tract infections (UTIs) are the second most frequent infections after respiratory tract infections that affect humans, with over 150 million cases per year. The anatomy of the female urinary tract predisposes them to UTIs than men. More so, physiological and hormonal changes during pregnancy put pregnant woman at risk of UTIs. Untreated UTI(s) in pregnancy can be detrimental to both the mother and child causing preterm labour, low birth weight and pyelonephritis. The situation is worrisome because the infection can be asymptomatic. This study investigated the prevalence and risk factors for UTIs, diagnostic potential of dipstick analyses and antimicrobial susceptibility of uropathogens from pregnant women attending ANC in some Integrated Health Centers (IHCs) in Buea Health District (BHD). METHODS: A structured questionnaire was administered to consenting pregnant women at participating IHCs to collect data on demographic characteristics, risk factors and symptoms of UTI. Urine samples were collected for dipstick analysis and culture. Antibiograms were performed on the isolates by the disc diffusion method. A bivariate analysis was performed to investigate the association of the risk factors to UTI. Chi square (χ2) test, odds ratios with corresponding 95% confidence intervals were used to compare statistics and test for associations at a significant level of p ≤ 0.05. RESULTS: Of the 287 participants recruited, 89(31%) were positive for UTI. There were 150 women with no symptoms of which 43(28.7%) were positive for UTI. E. coli was the most frequent (43.2%) of the organisms implicated in bacteriuria. There was no significant association between the risk factors studied and UTI. Isolates were most sensitive to ciprofloxacin (73.5%) and gentamycin (73.5%) and resistant to ceftriaxone (70.6%) and tetracycline (64.7%). Nitrite test was highly specific (100%) for the diagnosis of UTI while leucocyte esterase was more sensitive (48.3%) than specific (44.9%). CONCLUSIONS: The prevalence of UTI in BHD was high. In conformity with previous findings in same area, there were no risk factors associated with UTI. We recommended a longitudinal study with a larger sample size to follow up the women to term in order to determine the gravity of this infection on pregnancy outcomes.

Caffeine-induced hypokalemia: a case report.

BACKGROUND: With an increase in the global popularity of coffee, caffeine is one of the most consumed ingredients of modern times. However, the consumption of massive amounts of caffeine can lead to severe hypokalemia. CASE PRESENTATION: A 29-year-old man without a specific past medical history was admitted to our hospital with recurrent episodes of sudden and severe lower-extremity weakness. Laboratory tests revealed low serum potassium concentration (2.6-2.9 mmol/L) and low urine osmolality (100-130 mOsm/kgH2O) in three such prior episodes. Urinary potassium/urinary creatinine ratio was 12 and 16 mmol/gCr, respectively. The patient was not under medication with laxatives, diuretics, or herbal remedies. Through an in-depth interview, we found that the patient consumed large amounts of caffeine-containing beverages daily, which included > 15 cups of coffee, soda, and various kinds of tea. After the cessation of coffee intake and concomitant intravenous potassium replacement, the symptoms rapidly resolved, and the serum potassium level normalized. CONCLUSIONS: An increased intracellular shift of potassium and increased loss of potassium in urine due to the diuretic action have been suggested to be the causes of caffeine-induced hypokalemia. In cases of recurring hypokalemia of unknown cause, high caffeine intake should be considered.

Mass spectrometry-based urinary metabolomics for exploring the treatment effects of Radix ginseng-Schisandra chinensis herb pair on Alzheimer's disease in rats.

Herb pairs are the unique combinations of two relatively fixed herbs, intrinsically convey the basic idea of traditional Chinese medicine prescriptions. The compatibility of Radix ginseng and Schisandra chinensis has been used in traditional Chinese medicine for treating Alzheimer's disease for many years. However, there are few studies on Radix ginseng-Schisandra chinensis herb pair, and the underlying action mechanism is still unclear. In this study, the mechanism of Radix ginseng-Schisandra chinensis herb pair on Alzheimer's disease was investigated by using the mass spectrometry-based urinary metabolomics method. Sixteen urinary endogenous metabolites were identified as potential biomarkers. Meanwhile, 10 biomarkers were quantified with tandem mass spectrometry. The study result showed that the brain pathologic symptoms of model rats were improved and the potential biomarkers were adjusted backward significantly after the herb pair administration. The metabolic pathways linked to the herb pair-regulated endogenous biomarkers included phenylalanine and tyrosine metabolism, tryptophan metabolism, purine metabolism, and so on. The above metabolic pathways reflected that Radix ginseng-Schisandra chinensis herb pair mainly regulates abnormal energy metabolism, reduces inflammation, and regulates gut microbiota and neurotransmitters in the treatment of Alzheimer's disease.

Antiurolithic efficacy of a phenolic rich ethyl acetate fraction of the aerial parts of Aerva lanata (Linn) Juss. ex Schult. in ethylene glycol induced urolithic rats.

OBJECTIVES: The study was carried out to evaluate the in vivo antiurolithic efficaciousness of an ethyl acetate fraction of Aerva lanata (EAFAL) derived from the hydromethanolic extract of its aerial parts (HMEAL). METHODS: In vivo pharmacological potency of EAFAL was assessed by ethylene glycol (EG) induced urolithiasis model in male Wistar albino rats. Urine samples of the animals were analysed for physical parameters, stone promoters, inhibitors along with an evaluation of the biochemical parameters of serum and kidneys. Histopathological investigation of the kidneys was done. The fraction was further subjected to LC-MS and HPLC for its phytochemical evaluation. KEY FINDINGS: EAFAL demonstrated a significant antiurolithic effect by a restoration of the balance between urinary promoters and inhibitors along with an amelioration of the urinary pH. The abnormally elevated levels of serum nitrogenous substances, calcium, albumin, globulin, total protein along with altered renal calcium, oxalate and uric acid were also alleviated significantly followed by an improvement of the histopathological aberrancies. Phytochemical analysis showed evidence of phenolic components and flavonoids. CONCLUSIONS: The current findings prove the beneficial role of phenolic and flavonoid rich EAFAL in ameliorating urolithiasis induced abnormalities of urine, serum and kidneys.

Metabolites of 2- and 3-Monochloropropanediol (2- and 3-MCPD) in Humans: Urinary Excretion of 2-Chlorohydracrylic Acid and 3-Chlorolactic Acid after Controlled Exposure to a Single High Dose of Fatty Acid Esters of 2- and 3-MCPD.

SCOPE: Fatty acid esters of 2-monochloropropane-1,3-diol (2-MCPD) and 3-monochloropropane-1,2-diol (3-MCPD) are formed during the deodorization of vegetable oils. After lipase-catalyzed hydrolysis in the intestine, 2- and 3-MCPD are absorbed, but their ensuing human metabolism is unknown. METHODS AND RESULTS: The compounds 2-chlorohydracrylic acid (2-ClHA) and 3-chlorolactic acid (3-ClLA) resulting from oxidative metabolism of 2-MCPD and 3-MCPD, respectively, are identified and quantified in human urine samples. An exposure study with 12 adults is conducted to determine the urinary excretion of 2-ClHA and 3-ClLA. The participants eat 12 g of hazelnut oil containing 24.2 mg kg-1 2-MCPD and 54.5 mg kg-1 3-MCPD in the form of fatty acid esters. Average daily amounts of "background" excretion before the exposure are 69 nmol 2-ClHA and 3.0 nmol 3-ClLA. The additional mean excretion due to the uptake of the hazelnut oil amounts to 893 nmol 2-ClHA (34.0% of the 2-MCPD dose) and 16.4 nmol 3-ClLA (0.28% of the 3-MPCD dose). CONCLUSIONS: The products of oxidative metabolism of 2- and 3-MCPD, 2-ClHA, and 3-ClLA, are described for the first time in humans. Due to the lack of specificity, the metabolites may not be used as exposure biomarkers to low doses of bound 2- and 3-MCPD, respectively.

Urinary Tract Infection in Outpatient Children and Adolescents: Risk Analysis of Antimicrobial Resistance.

BACKGROUND: Urinary tract infection (UTI) is a common bacterial infection in children. ​​​​​​​Early treatment may prevent renal damage in pyelonephritis. The choice of empiric antibiotic treatment is based on knowledge of the local susceptibility of urinary bacteria to antibiotics. In Israel the recommended empiric oral antibiotic treatment are First or second generation cephalosporin, trimethoprim-sulfamethoxazole or amoxicillin-clavulanic acid. OBJECTIVES: To describe resistance rates of urine bacteria isolated from children with UTI in the community settings. Identify risk factors for resistance. METHODS: A retrospective cross-sectional study of UTI in children aged 3 months to 18 years diagnosed with UTI and treated as outpatients in a large community clinic between 7/2015 and 7/2017 with a diagnosis of UTI. RESULTS: A total of 989 urinary samples were isolated, 232 were included in the study. Resistance rates to cephalexin, cefuroxime, ampicillin/clavulanate and Trimethoprim-Sulfamethoxazole were 9.9%, 9.1%, 20.7%, and 16.5%, respectively. Urinary tract abnormalities and recurrent UTI were associated with an increase in antibiotic resistance rates. Other factors such as age, fever, and previous antibiotic treatment were not associated with resistance differences. CONCLUSIONS: Resistance rates to common oral antibiotics were low compared to previous studies performed in Israel in hospital settings. First generation cephalosporins are the preferred empiric antibiotics for febrile UTI for outpatient children. Amoxicillin/clavulanate is not favorable due to resistance of over 20% and the broad spectrum of this antibiotic. Care should be taken in children with renal abnormalities as there is a worrying degree of resistance rates to the oral first line antibiotic therapy.

Estimating 24-Hour Sodium Excretion from Spot Urine Samples in Chinese Adults: Can Spot Urine Substitute 24-Hour Urine Samples?

Several estimating equations for predicting 24-h urinary sodium (24-hUNa) excretion using spot urine (SU) samples have been developed, but have not been readily available to Chinese populations. We aimed to compare and validate the six existing methods at population level and individual level. We extracted 1671 adults eligible for both 24-h urine and SU sample collection. Mean biases (95% CI) of predicting 24-hUNa excretion using six formulas were 58.6 (54.7, 62.5) mmol for Kawasaki, -2.7 (-6.2, 0.9) mmol for Tanaka, -24.5 (-28.0, -21.0) mmol for the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) with potassium, -26.8 (-30.1, -23.3) mmol for INTERSALT without potassium, 5.9 (2.3, 9.6) mmol for Toft, and -24.2 (-27.7, -20.6) mmol for Whitton. The proportions of relative difference >40% with the six methods were nearly a third, and the proportions of absolute difference >51.3 mmol/24-h (3 g/day salt) were more than 40%. The misclassification rate were all >55% for the six methods at the individual level. Although the Tanaka method could offer a plausible estimation for surveillance of the population sodium excretion in Shandong province, caution remains when using the Tanaka formula for other provincial populations in China. However, these predictive methods were inadequate to evaluate individual sodium excretion.

[What To Do In Case Of Hematuria? - Step By Step]. / Was tun bei Hämaturie? ­ Schritt für Schritt.

Hematuria is a common clinical finding and has a wide spectrum of possible causes. Erythrocytes can originate from any part of the genitourinary tract. An urine dipstick test is the first step in diagnostic approach. Medical history may help to narrow down the range of causes: arterial hypertension or a family history of renal disease may indicate a renal disease. Risk factors for an urinary tract malignoma point to an urological origin. If the microscopy shows more than 5 % acanthocytes in the urine sediment, a glomerular cause can be assumed. Normal erythrocytes suggest a non-glomerular cause. A nephrologist should be consulted if urine sediment microscopy and other clinical features (e. g. clinically relevant proteinuria, elevated serum creatinine) indicate a renal disease. In this case, a renal biopsy should be considered to confirm the diagnosis of glomerulopathy and to develop a treatment plan. If an urological pathology is suspected, sonography should be complemented by a multi-phasic computed tomography. Based on the imaging results, a retrograde ureteroscopy should be considered. Repeated urinalysis on an annual basis for two consecutive years is recommended, if no diagnosis can be established.

Untargeted UPLC-MS metabolomics reveals multiple changes of urine composition in healthy adult volunteers after consumption of curcuma longa L. extract.

Curcuma longa L. is used as food supplement to prevent diseases, although limited studies have been performed on healthy subjects up to now. In the present work, an untargeted UPLC-MS metabolomics approach was applied to study the changes of 24-hours urinary composition on healthy volunteers due to a 28-days daily consumption of a dried C. longa extract containing a standardized amount of curcuminoids. Changes in the excretion of different metabolites were observed after supplementation. Curcumin and two metabolic derivatives (hexahydrocurcumin and dihydrocurcumin) were detected in urine, indicating the absorption of the main curcuminoid from the extract and its further metabolism by liver and gut microbiota. For the first time ar-turmerone, the main apolar constituent of curcuma, was detected in urine in intact form, and its presence was confirmed by a targeted GC-MS analysis. The increase of tetranor-PGJM and tetranor-PGDM, two prostaglandin-D2 metabolites, was observed, being related to the anti-inflammatory effect exerted by curcuma. The variation of the amounts of HPAG, PAG, proline-betaine and hydroxyphenyllactic acid indicate that the supplementation induced changes to the activity of gut microbiota. Finally, the reduced excretion of niacin metabolites (nicotinuric acid, trigonelline and 2PY) and medium- and short-chain acylcarnitines suggests that curcuma could induce the mitochondrial ß-oxidation of fatty acids for energy production in healthy subjects. Overall, the results indicate that a prolonged daily consumption of a dried curcuma extract exerts multiple effects on healthy subjects, furthermore they show the opportunity offered by untargeted metabolomics for the study of the bioactivity of natural extracts in healthy human volunteers.

The clinical rate of antibiotic change following empiric treatment for suspected urinary tract infections.

PURPOSE: To determine the rate of antibiotic change in an outpatient setting following empiric treatment of culture proven UTI and to identify risk factors associated with change. METHODS: Patients with suspected UTI and urine culture were reviewed (January 2016-June 2016). Those with a positive culture were categorized by whether or not they were treated empirically. Empiric treatment was evaluated for associations with clinical-demographic data, symptoms and urinalysis (UA). Antibiotic change was evaluated with clinical-demographic data, urine culture, and resistance patterns. RESULTS: 916 urine cultures (636 patients) were included. 391 (43%) cultures were positive, and 164 (42%) were treated empirically. Clinical-demographic data did not differ between groups. Those treated empirically had more documented UTI symptoms (93 vs 58%, P < 0.001), and UA abnormalities including positive nitrites (51 vs 29%, P < 0.001), 3 + leukocyte esterase (27 vs 19%, P = 0.002) and 3 + blood (13 vs 4%, P = 0.005). Of those treated empirically, 42/164 (26%) required an antibiotic change, and this was associated with immunosuppression (12 vs 2%, P = 0.027) resistance to > 3 antibiotics (33 vs 20%, P = 0.039) and also resistance to fluoroquinolone (50 vs 30%, P = 0.016), monobactam (19 vs 7% P = 0.042) and TMP-SMX (52 vs 19%, P < 0.001). CONCLUSIONS: Almost one-quarter of patients treated empirically required antibiotic change. This was driven largely by bacterial resistance. New technologies allowing rapid bacterial identification and sensitivity may improve patient care.

Discovering Cross-Reactivity in Urine Drug Screening Immunoassays through Large-Scale Analysis of Electronic Health Records.

BACKGROUND: Exposure to drugs of abuse is frequently assessed using urine drug screening (UDS) immunoassays. Although fast and relatively inexpensive, UDS assays often cross-react with unrelated compounds, which can lead to false-positive results and impair patient care. The current process of identifying cross-reactivity relies largely on case reports, making it sporadic and inefficient, and rendering knowledge of cross-reactivity incomplete. Here, we present a systematic approach to discover cross-reactive substances using data from electronic health records (EHRs). METHODS: Using our institution's EHR data, we assembled a data set of 698651 UDS results across 10 assays and linked each UDS result to the corresponding individual's previous medication exposures. We hypothesized that exposure to a cross-reactive ingredient would increase the odds of a false-positive screen. For 2201 assay-ingredient pairs, we quantified potential cross-reactivity as an odds ratio from logistic regression. We then evaluated cross-reactivity experimentally by spiking the ingredient or its metabolite into drug-free urine and testing the spiked samples on each assay. RESULTS: Our approach recovered multiple known cross-reactivities. After accounting for concurrent exposures to multiple ingredients, we selected 18 compounds (13 parent drugs and 5 metabolites) to evaluate experimentally. We validated 12 of 13 tested assay-ingredient pairs expected to show cross-reactivity by our analysis, discovering previously unknown cross-reactivities affecting assays for amphetamines, buprenorphine, cannabinoids, and methadone. CONCLUSIONS: Our findings can help laboratorians and providers interpret presumptive positive UDS results. Our data-driven approach can serve as a model for high-throughput discovery of substances that interfere with laboratory tests.

Prevalence of twenty-four hour urine testing in Veterans with urinary stone disease.

OBJECTIVE: The American Urological Association guidelines recommend 24-hour urine testing in patients with urinary stone disease to decrease the risk of stone recurrence; however, national practice patterns for 24-hour urine testing are not well characterized. Our objective is to determine the prevalence of 24-hour urine testing in patients with urinary stone disease in the Veterans Health Administration and examine patient-specific and facility-level factors associated with 24-hour urine testing. Identifying variations in clinical practice can inform future quality improvement efforts in the management of urinary stone disease in integrated healthcare systems. MATERIALS AND METHODS: We accessed national Veterans Health Administration data through the Corporate Data Warehouse (CDW), hosted by the Veterans Affairs Informatics and Computing Infrastructure (VINCI), to identify patients with urinary stone disease. We defined stone formers as Veterans with one inpatient ICD-9 code for kidney or ureteral stones, two or more outpatient ICD-9 codes for kidney or ureteral stones, or one or more CPT codes for kidney or ureteral stone procedures from 2007 through 2013. We defined a 24-hour urine test as a 24-hour collection for calcium, oxalate, citrate or sulfate. We used multivariable regression to assess demographic, geographic, and selected clinical factors associated with 24-hour urine testing. RESULTS: We identified 130,489 Veterans with urinary stone disease; 19,288 (14.8%) underwent 24-hour urine testing. Patients who completed 24-hour urine testing were younger, had fewer comorbidities, and were more likely to be White. Utilization of 24-hour urine testing varied widely by geography and facility, the latter ranging from 1 to 40%. CONCLUSIONS: Fewer than one in six patients with urinary stone disease complete 24-hour urine testing in the Veterans Health Administration. In addition, utilization of 24-hour urine testing varies widely by facility identifying a target area for improvement in the care of patients with urinary stone disease. Future efforts to increase utilization of 24-hour urine testing and improve clinician awareness of targeted approaches to stone prevention may be warranted to reduce the morbidity and cost of urinary stone disease.

Urinary tract infections in a university hospital: pathogens and antibiotic susceptibility.

BACKGROUND: A substantial group of patients visit the emergency department (ED) with complaints of urinary tract infections (UTI). Treatment advice is based on national and local public health surveillance data. It is unclear whether this advice is adequate for hospitals with selected patient populations, such as university hospitals. METHODS: We performed a retrospective study on patients visiting the ED of the Erasmus University Medical Center (Erasmus MC) in the Netherlands from January 1st, 2013 until December 31st, 2014 with a suspected complicated UTI (cUTI) and positive urinary cultures. Patient data, data concerning the ED visit and microbiological data were analysed. RESULTS: 439 patients visited the ED, of whom 429 had a cUTI. Our results were compared with NethMap data. Distribution of uropathogens was comparable with the overall distribution in the Netherlands. Antibiotic susceptibility was comparable for intravenous antibiotics, but was lower for oral antibiotics. Susceptibility for empiric antibiotic therapy (i.e., cefuroxime and gentamyicin) was 96.2%. Pathogens differed from the index culture in 56.2% 104/185) of the urinary cultures available from the previous year. Using logistic regression, we found that a shorter time between last admission to the initiated antibiotic regimen was associated with lower susceptibility of cultured uropathogens. CONCLUSION: The distribution and antibiotic susceptibility of uropathogens for intravenous antibiotics in a Dutch university hospital is comparable with overall distribution in the Netherlands. Empiric antibiotic therapy in our local guideline appears to be an adequate antibiotic regimen for cUTI and we therefore recommend treating patients accordingly. Extension of the chosen regimen based on earlier cultured pathogens is advised, and narrowing of the antibiotic regimen strongly discouraged.

The first method for determination of lipoyllysine in human urine after oral lipoic acid supplementation.

Aim: The first method on urinary excreted amounts of lipoyllysine (LLys) after lipoic acid (LA) supplementation was developed and validated. The suggested procedure allowed simultaneous determination of LLys and LA. Methodology & results: After the conversion of analytes into their reduced forms with tris(2-carboxyethyl)phosphine and derivatization via thiol group with 1-benzyl-2-chloropyridinium bromide, separation of analytes derivatives was performed on C18 column using a gradient mobile phase consisting of acetic acid and acetonitrile. The calibration curves for LA and LLys were linear (R2 > 0.999) in the range of 0.4-12 µM concentration and all validation results were acceptable, according to the US FDA bioanalytical method guidelines. Conclusion: This method was effectively applied for LA and LLys quantification in human urine after oral LA supplementation.

New Advances in Amino Acid Profiling in Biological Samples by Capillary Electrophoresis-Mass Spectrometry.

Capillary electrophoresis-mass spectrometry (CE-MS) offers a high efficiency microseparation platform for amino acid profiling when analyzing volume-restricted biological samples, such as a dried blood spot punch. Direct analysis of amino acids and their analogs is routinely achieved using strongly acidic buffer conditions under positive-ion mode detection with a coaxial sheath liquid interface for electrospray ionization (ESI). New advances in online sample preconcentration, pre-column chemical derivatization, and/or low flow/sheathless CE-MS interface designs can further improve sensitivity while allowing for resolution of amino acid stereoisomers and labile aminothiols with low nanomolar detection limits. Additionally, multiplexed separations in CE-MS based on serial injection of seven or more samples within a single run greatly boosts sample throughput (<2-3 min/sample) without added infrastructure costs while allowing for stringent quality control and signal batch correction. Accurate prediction of the electromigration behavior of amino acids and their analogs offers a convenient approach for structural elucidation that is complementary to high-resolution MS and MS/MS. Simultaneous analysis of amino acids together with other classes of ionic metabolites by CE-MS allows for comprehensive metabolomic screening as required for new advances in clinical medicine, nutritional sciences, and population health.

MEASUREMENT OF URANIUM IN URINE, HAIR AND NAILS IN SUBJECTS OF NISKA BANJA TOWN, A HIGH NATURAL BACKGROUND RADIATION AREA OF SERBIA.

Urine, hair and nail samples were collected from a population of both sex aged from 40 to 87 years in Niska Banja (227 km south of Belgrade, Serbia) with a high level of natural radioactivity (HLNRA). To assess and monitor the public exposure, urine samples for each subject (24 h period) were collected and concentration of uranium (U) was analysed using alpha-particle spectrometry. Human hair and nails considered as bio-indicators of the public exposure to radionuclides over a long period of months or even years and concentration of U was determined using inductively coupled plasma-mass spectrometry. The mean concentrations of U in urine, hair and nail were 123 ng/L, 17 ng/g and 8 ng/g, respectively. There was a large variation and may be due to geological origin.