Extracorporeal shockwave therapy of the perineum for male patients with chronic pelvic pain syndrome: a pilot study.

Background: Chronic pelvic pain syndrome (CPPS) is a complex condition that is often difficult to treat and may sometimes require a multidisciplinary team. Among the wide array of treatment options is extracorporeal shockwave therapy (ESWT). However, its role in CPPS remains controversial. The purpose of our study is to assess the efficacy and safety of ESWT of the perineum in male patients with CPPS. Methods: Fourteen patients aged between 21 and 85 years were recruited in this single-center, single-arm prospective trial from October 2018 to October 2020. ESWT was delivered to the perineum weekly for up to 8 weeks. Assessment was done via International Index for Erectile Function, International Prostate Symptom Score, King's Health Questionnaire, National Institutes of Health - Chronic Prostatitis Symptom Index, Visual Analogue Scale, Analgesic Questionnaire, and UPOINT (urinary symptoms [U], psychosocial dysfunction [P], organ-specific symptoms [O], infection-related symptoms [I], neurological/systemic conditions [N], tenderness of skeletal muscles [T]) phenotype system. The parameters are assessed before the start and end of treatment as well as at regular time points on follow-up appointments up to 20 weeks. Results: Thirteen patients completed the study. There was improvement in the Visual Analogue Scale pain score, Tenderness domain on UPOINT, King's Health Questionnaire, and National Institutes of Health - Chronic Prostatitis Symptom Index scores. In terms of erectile function, improvement in the erectile function domain of International Index for Erectile Function was observed. There was also significant improvement in lower urinary tract symptoms assessed on International Prostate Symptom Score. There were no adverse events reported post treatment and during the follow-up period. Conclusions: ESWT improved pain and quality of life of male patients with CPPS. It can be a safe and effective treatment modality in the armamentarium of CPPS.

The impact of body mass index on oncological and surgical outcomes of patients undergoing nephrectomy: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis to evaluate the impact of body mass index (BMI) on oncological (primary) and surgical (secondary) outcomes of patients who underwent nephrectomy, as obesity or high BMI is a known risk factor for renal cell carcinoma (RCC) and predictor of poorer outcomes. METHODS: Studies were identified from four electronic databases from database inception to 2 June 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. The review protocol was registered in the International Prospective Register of Systematic Reviews with the identification number: CRD42021275124. RESULTS: A total of 18 studies containing 13 865 patients were identified for the final meta-analysis. Regarding oncological outcomes, higher BMI predicted higher overall survival (BMI >25 vs BMI <25 kg/m2 : hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.58-0.85), cancer-specific survival (BMI >25 vs BMI <25 kg/m2 : HR 0.60, 95% CI 0.50-0.73; BMI 25-30 vs BMI <25 kg/m2 : HR 0.46, 95% CI 0.23-0.95; BMI >30 vs BMI <25 kg/m2 : HR 0.50, 95% CI 0.36-0.69), and recurrence-free survival rates (BMI >25 vs BMI <25 kg/m2 : HR 0.72, 95% CI 0.63-0.82; BMI 25-30 vs BMI <25 kg/m2 : HR 0.59, 95% CI 0.42-0.82). Those with a lower BMI fared better in surgical outcomes, such as operation time and warm ischaemic time, although the absolute difference was minimal and unlikely to be clinically significant. There was no difference between groups for length of hospital stay, intraoperative or postoperative complications, blood transfusion requirements, and conversion to open surgery. CONCLUSION: Our study suggests that a higher BMI is associated with improved long-term oncological survival and similar perioperative outcomes as a lower BMI. More research into the underlying biological and physiological mechanisms will enable better understanding of the effect of BMI, beyond mere association, on post-nephrectomy outcomes.

Author Correction: Clinical Validation of Targeted and Untargeted Metabolomics Testing for Genetic Disorders: A 3 Year Comparative Study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinical Validation of Targeted and Untargeted Metabolomics Testing for Genetic Disorders: A 3 Year Comparative Study.

Global untargeted metabolomics (GUM) has entered clinical diagnostics for genetic disorders. We compared the clinical utility of GUM with traditional targeted metabolomics (TM) as a screening tool in patients with established genetic disorders and determined the scope of GUM as a discovery tool in patients with no diagnosis under investigation. We compared TM and GUM data in 226 patients. The first cohort (n = 87) included patients with confirmed inborn errors of metabolism (IEM) and genetic syndromes; the second cohort (n = 139) included patients without diagnosis who were undergoing evaluation for a genetic disorder. In patients with known disorders (n = 87), GUM performed with a sensitivity of 86% (95% CI: 78-91) compared with TM for the detection of 51 diagnostic metabolites. The diagnostic yield of GUM in patients under evaluation with no established diagnosis (n = 139) was 0.7%. GUM successfully detected the majority of diagnostic compounds associated with known IEMs. The diagnostic yield of both targeted and untargeted metabolomics studies is low when assessing patients with non-specific, neurological phenotypes. GUM shows promise as a validation tool for variants of unknown significance in candidate genes in patients with non-specific phenotypes.

Consolidation of vitamin A and E methods onto a multiplexing liquid chromatography tandem mass spectrometry platform simplifies laboratory workflow.

BACKGROUND: Vitamin A and E are routinely monitored to assess nutritional status. The most commonly used approach for their measurement involves laborious liquid-liquid extraction followed by high-performance liquid chromatography (HPLC) analysis on dedicated instrumentation. We describe a simple, rapid protocol for measurement of vitamin A and E and their integration into an existing online sample preparation liquid chromatography tandem mass spectrometry (SPLC-MS/MS) workflow. METHODS: We performed a method comparison between the SPLC-MS/MS and HPLC methods for vitamin A and E by measuring patient specimens across the concentration range 11-81 µg/dL for vitamin A and 1-18 mg/L for vitamin E. The analysis times on each platform were also compared. RESULTS: SPLC-MS/MS and HPLC methods were comparable with regards to analytical performance; mean bias across the measured range was 2.54% (95% CL: -11.56-16.64%) for vitamin A and -2.04% (95% CL: -18.20-14.12%) for vitamin E. Total analysis times were 7 min and 15 min for SPLC-MS/MS and HPLC respectively. CONCLUSIONS: The development of a simplified sample preparation protocol and the use of multiplexing SPLC-MS/MS have reduced sample analysis times for vitamin A and E. This method has also optimized clinical workflow through consolidation of previously independent benches.

Toxicants in folk remedies: implications of elevated blood lead in an American-born infant due to imported diaper powder.

Though most childhood lead exposure in the USA results from ingestion of lead-based paint dust, non-paint sources are increasingly implicated. We present interdisciplinary findings from and policy implications of a case of elevated blood lead (13-18 mcg/dL, reference level <5 mcg/dL) in a 9-month-old infant, linked to a non-commercial Malaysian folk diaper powder. Analyses showed the powder contains 62 % lead by weight (primarily lead oxide) and elevated antimony [1000 parts per million (ppm)], arsenic (55 ppm), bismuth (110 ppm), and thallium (31 ppm). These metals are highly bioaccessible in simulated gastric fluids, but only slightly bioaccessible in simulated lung fluids and simulated urine, suggesting that the primary lead exposure routes were ingestion via hand-mouth transmission and ingestion of inhaled dusts cleared from the respiratory tract. Four weeks after discontinuing use of the powder, the infant's venous blood lead level was 8 mcg/dL. Unregulated, imported folk remedies can be a source of toxicant exposure. Additional research on import policy, product regulation, public health surveillance, and culturally sensitive risk communication is needed to develop efficacious risk reduction strategies in the USA. The more widespread use of contaminated folk remedies in the countries from which they originate is a substantial concern.

Improved separation and analysis of plasma amino acids by modification of the MassTrak™ AAA Solution Ultraperformance® liquid chromatography method.

BACKGROUND: Ultraperformance® Liquid Chromatography (UPLC) is increasingly used for quantitative amino acid screening. The Waters MassTrak™ UPLC Amino Acid Analysis (AAA) Solution kit offers rapid analysis with minimal sample preparation. We describe a simple modification of this method enabling enhanced chromatographic separation of previously problematic analytes with improvements in quantification. METHODS: The commercial UPLC method was compared with our modified version of the same method. The modification incorporates eluent buffer of increased organic content run at reduced column temperature. UPLC methods were compared by analyzing amino acids from 57 plasma samples. A comparison (n=131) between the modified UPLC method and ion-exchange chromatography was also carried out. RESULTS: The commercial method produced a large negative bias for Tyrosine (-22.72%±14.10) and ornithine (-15.02%±10.07). Assay imprecision of Tyrosine using the commercial method (mean Tyrosine: 72.58 and 31.17µmol/l) produced values of 10.86% and 21.12% respectively, compared with the modified method (3.39% and 4.47%). The comparison of modified UPLC and ion-exchange methods was favorable, validating the improvements observed in amino acid quantification. CONCLUSION: The modified UPLC method has eliminated significant bias associated with the commercially available method. The modification is simple, robust and readily adaptable to the current MassTrak™ AAA Solution kit for clinical applications.

Variation in clinical vitamin D status by DiaSorin Liaison and LC-MS/MS in the presence of elevated 25-OH vitamin D2.

BACKGROUND: We compared total 25-OH vitamin D status measured by DiaSorin Liaison and tandem mass spectrometry (LC-MS/MS) among patients with high and low 25-OH vitamin D(2). METHODS: Total 25-OH vitamin D was measured in plasma containing high (>25 nmol/l or >50%, n=26) and low (<2.5 nmol/l, n=29) 25-OH vitamin D(2) using DiaSorin Liaison and an LC-MS/MS method using NIST 972-verified calibrators. Samples were classified as vitamin D adequate (total 25-OH vitamin D ≥50 nmol/l), and inadequate or deficient (<50 nmol/l) by each method. Deming and multiple linear regression were used to compare methods. RESULTS: Samples were significantly more likely to be classified as inadequate or deficient by DiaSorin Liaison (36%) vs LC-MS/MS (9%). This increased in the presence of high 25-OH vitamin D2 (42% vs 0%). Total 25-OH vitamin D by DiaSorin Liaison was 26.0 nmol/l lower than LC-MS/MS, which increased to 34.1 nmol/l among samples with high 25-OH vitamin D(2). This was attributed to lower recovery of 25-OH vitamin D(2) (proportional bias=0.64 nmol/l) by DiaSorin Liaison, independent of D(3) (proportional bias=0.86 nmol/l). CONCLUSIONS: Patients were more likely to be classified as vitamin D inadequate or deficient by DiaSorin Liaison compared to an LC-MS/MS method, which was in part due to the presence of 25-OH vitamin D(2).

Lead poisoning from use of bronze drinking vessels during the late Chinese Shang dynasty: an in vitro experiment.

INTRODUCTION: Bronze drinking vessels famous for their intricate carvings and used by the aristocracy in the Chinese Shang dynasty (1555-1145 BCE) are known to have been fabricated with alloys containing soft metallic lead. The contribution of lead leaching from such vessels into the fermented grain wines drunk by the Chinese nobility in ancient times has not been previously estimated. METHODS: Three bronze vessels containing 8% lead by weight were fabricated to resemble the late Shang bronze goblets. Shaoxing drinking rice wine was purchased locally and placed in the vessels, using a white grape wine and water as comparisons. Sampling was performed at baseline, 2 min, and then at days 1, 2, 4, and 7. Lead concentrations in the liquid matrix were measured using atomic absorption spectroscopy. RESULTS: Significant amounts of lead leached into the liquid within one day: 13,900 µg/L in water, 45,900 µg/L in rice wine, and 116,000 µg/L in white wine. Lead continued to leach into both the grape and rice wines with the passage of time. DISCUSSION: Significant lead contamination of Shaoxing rice wine was detected when it was left in bronze goblets fabricated to resemble the Shang dynasty vessels. If a liter of contaminated wine was drunk daily, the daily intake of lead could have been as high as 85 mg. Such a high degree of contamination could cause chronic lead poisoning, affecting the health of the Shang nobility who used bronze beverage containers, before lead was excluded from the manufacture of bronze.

Liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for monitoring methotrexate in the setting of carboxypeptidase-G2 therapy.

Medications that have a narrow therapeutic window must be regularly monitored to assist in clinical dosing. Methotrexate (MTX) is one such chemotherapeutic agent that is closely monitored using various standard assays. Patients who have renal failure and who are treated using high-dose protocols are often given carboxypeptidase-G2 (CPDG(2)) as a chemoprotective agent. In this setting an inactive metabolite of MTX, 2, 4-diamino-N(10)-methylpteroic acid (DAMPA) is produced. DAMPA cross-reacts with MTX in most immunoassays, thus making them unsuitable for the monitoring of MTX in the setting of CPDG(2) therapy. We describe a rapid LC-MS-MS method that can be used to determine MTX levels in these cases.

Performance evaluation of a particle-enhanced turbidimetric cystatin C assay on the Hitachi 917 analyzer.

BACKGROUND: Human cystatin C is a low molecular weight protein that has been proposed as a new endogenous marker of glomerular filtration rate. We investigated the performance of the Genzyme cystatin C assay on the Hitachi 917 analyzer. METHODS: Imprecision, linearity, recovery, and interference studies were performed on the Hitachi 917 analyzer. For method comparison, split sample aliquots were assayed using the described method and 2 other commercially available cystatin C assays. RESULTS: The assay was linear from 0.24 to 6.36 mg/l. Within-run coefficient of variation (CV) was 4.2 and 0.8% at cystatin C concentrations of 0.50 and 2.00 mg/l, respectively. Between-run CV was 4.3 and 2.7% at the same concentrations. The average analytical recovery was 99%. Bilirubin (< or =30 mg/dl), triglycerides (< or =1000 mg/dl), intralipid (L index < or =1000), and rheumatoid factor (< or =1000 IU/ml) did not interfere with the assay. A >10% change in cystatin C level was observed when hemoglobin concentration was >800 mg/dl. The assay compared well with the Dade Behring immunonephelometric assay and the Dako immunoturbidimetric assay. CONCLUSION: The Genzyme cystatin C immunoassay is an acceptable method for the determination of cystatin C on the Hitachi 917 analyzer.

Interference by carbamazepine and oxcarbazepine with serum- and urine-screening assays for tricyclic antidepressants.

OBJECTIVE: The purpose of this work was to evaluate the potential cross-reactivity of 2 antiepileptic medications containing 3-ringed structures, namely, carbamazepine and oxcarbazepine, with screening assays for tricyclic antidepressants. METHODS: A cross-sectional study of 52 patients between 3 and 19 years of age who had been prescribed either carbamazepine or oxcarbazepine was conducted. A serum fluorescence-polarized immunoassay and a urine enzyme-linked immunoassay were used. The serum carbamazepine or oxcarbazepine level was measured. Gas chromatography/mass spectrometry, a confirmatory test for tricyclic antidepressant detection, was subsequently performed on the serum specimen. RESULTS: A linear dependency on medication level was observed with the serum fluorescence-polarized immunoassay assay. This relationship was stronger for carbamazepine (4.2 microg/L tricyclic antidepressant detected per microgram/liter of carbamazepine) than for oxcarbazepine (0.7 microg/L tricyclic antidepressant detected per milligram/liter). At higher carbamazepine levels (8.0-11.6 mg/L), 12 of 13 patients had a positive serum fluorescence-polarized immunoassay result; at lower levels (0.1-7.9 mg/L), only 1 of 20 had a positive result. None of the patients who were receiving oxcarbazepine showed significant tricyclic antidepressant activity on either assay. CONCLUSIONS: Carbamazepine interferes at a statistically significant level with serum fluorescence-polarized immunoassay assay and in a dose-dependent fashion. Neither carbamazepine nor oxcarbazepine exhibit significant tricyclic antidepressant activity on urine enzyme-linked immunoassay assay.

Measurement of whole blood sirolimus by an HPLC assay using solid-phase extraction and UV detection.

The authors developed an HPLC assay for determining blood sirolimus concentration using a relatively simple solid-phase extraction and UV detection. The retention times of sirolimus and the internal standard, 32-desmethoxyrapamycin, are 8.7 and 9.3 minutes, respectively. The assay possesses linearity up to 200 ng/mL, sensitivity to 2.0 ng/mL, and day-to-day reproducibility of 8.8, 9.8, 6.1, and 6.4% at sirolimus concentrations of 6, 10, 20, and 30 ng/mL, respectively. A patient correlation study using this HPLC method and an established LC/MS/MS assay revealed a slope of 0.982 and intercept of -0.021 ng/mL and a correlation coefficient of 0.99 (n = 37). Of the 31 different drugs tested none interfered with the measurement of the drug of interest, and a recovery study gave an overall mean recovery of 101.8%. The authors conclude that the method described here is suited for the therapeutic monitoring of blood sirolimus concentration.