Urine-based Test Research Articles

Evaluation of N-NOSE as a surveillance tool for recurrence in gastric and esophageal cancers: a prospective cohort study

ObjectiveEarly detection of recurrent gastric and esophageal cancers remains a critical challenge. Innovative and non-invasive cancer screening technologies, such as N-NOSE, can improve early detection. N-NOSE is a urine-based scent test that leverages the olfactory abilities of the nematode C. elegans. For the first time, this prospective study evaluates the efficacy of the N-NOSE chemotaxis index as a novel biomarker for postoperative surveillance and recurrence in patients with upper gastrointestinal cancers.MethodsA two-year prospective cohort study was conducted at The University of Tokyo Hospital, involving 40 patients with gastric and esophageal cancers. Urine samples were collected pre- and postoperatively and analysed using the N-NOSE technique.ResultsIn cases of recurrence with vascular invasion, the chemotaxis index at 100-fold urine dilution was significantly elevated compared to the non-recurrence group.ConclusionThis study suggests the potential of N-NOSE as an effective follow-up tool for patients with upper gastrointestinal cancer, particularly those with vascular invasion. While N-NOSE has been validated to distinguish between cancer and non-cancer, and its performance compared to traditional markers has been proven, it has not been studied for recurrence. Our data highlights, for the first time, the capability of N-NOSE in the surveillance of cancer recurrence.

N-NOSE Proves Effective for Early Cancer Detection: Real-World Data from Third-Party Medical Institutions.

Cancer remains a leading cause of mortality in Japan, yet participation in conventional screening programs is low due to invasiveness, cost, and accessibility. Non-invasive, affordable, and accurate methods for early cancer detection in asymptomatic individuals are urgently needed. This opinion manuscript evaluates nematode cancer testing, a novel urine-based screening test using the nematode Caenorhabditis elegans, for its potential to improve early cancer detection rates, based on real-world data published in a Japanese journal. Nematode cancer testing leverages the nematode's ability to detect cancer-associated volatile compounds in urine, offering a highly sensitive, non-invasive screening approach. We analyzed data from a nationwide survey of PET-equipped medical institutions in Japan, comparing cancer discovery rates between nematode cancer testing-triggered and standard PET screenings. In nematode cancer testing-triggered PET screenings, the cancer discovery rate was 2.96%, significantly higher than the 1.31% observed in standard PET screenings. The apparent positive predictive value (PPV) of nematode cancer testing was calculated at 2.09%; when adjusted for PET/CT sensitivity, the actual PPV increased to approximately 11.7%. This reflects a screening efficiency 14.6 times higher than the general population's cancer incidence. These findings indicate that nematode cancer testing successfully detects cancer in high-risk individuals and may encourage participation in further diagnostic evaluations. The recently published nationwide survey of PET-equipped medical institutions in Japan highlights the good performance of nematode cancer testing in cancer detection. As an opinion-type manuscript based on real-world data from Japan, this paper shows that nematode cancer testing has substantial potential as a cost-effective, minimally invasive primary cancer screening tool for asymptomatic populations. By enhancing early detection rates and screening efficiency, it addresses the limitations of traditional screening methods. Implementing nematode cancer testing could lead to improved cancer outcomes, particularly in populations with low participation in standard screening programs and resource-limited settings.

A urine-based liquid biopsy for detection of upper tract urothelial carcinoma: a self-matched study

BackgroundTo establish the pathological diagnosis of UTUC before treatment is profitable. At present, the conventional pathological diagnostic methods have certain problems. Besides, the urine-based DNA methylation test have been already utilized to detect bladder cancer.ObjectiveTo evaluate the sensitivity and specificity of DNA methylation plus 17 genes mutation test and compare the combined test with cytology.Materials and methodsWe included 45 patients from April 2019 to May 2022, all of whom underwent radical nephroureterectomy (RNU), nephrectomy, diagnostic ureteroscopy or tissue biopsy. Before surgery, the urine samples were collected for DNA methylation plus 17 genes mutation test and cytology. The test performance was calculated, and comparative ROC curves were drawn.ResultsThe median age of the patients was 67 years. The Kappa value of the DNA methylation plus 17 genes mutation test and tissue pathology was 0.59 (p<0.001). The sensitivity/specificity/PPV/NPV of DNA methylation plus 17 genes mutation test was 86/80/94/62% compared with 29/100/100/29% for cytology. The AUC of DNA methylation plus 17 genes mutation test was 0.829 (p<0.001).The mutated gene proportion of UTUC patients was 51.43% for TERT and 25.71% for TP53.ConclusionThe test performance of DNA methylation plus 17 genes mutation test was satisfactory, which may replace cytology in the future. Further multicenter studies with larger samples are needed to confirm the clinical value of this promising method.Novelty & impact statementsWe evaluated the diagnostic efficacy of a urine-based liquid biopsy for the detection of UTUC and compared the combined test with cytology. We found satisfactory results and concluded that the test could partly replace cytology. Further studies are needed.

1973P Urine-based molecular testing identifies FGFR alteration-positive patients for treatment with TAR-210

1973P Urine-based molecular testing identifies FGFR alteration-positive patients for treatment with TAR-210

Abstract A001: Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients

Abstract One commonly employed management strategy for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy followed by radical cystectomy (RC) and urinary diversion. Approximately 35% of patients achieve a pathologic complete response (pCR) when evaluated from RC specimens. RC with urinary diversion is a life-altering operation with high complication rates and therefore determining who are complete responders would improve quality of life and could decrease costs and still achieve a high cure rate via RC avoidance. Unfortunately, current methods cannot accurately identify complete responders. Our lab has developed a urine-based liquid biopsy test in which DNA isolated from urine and germline is isolated and subjected to panel exome sequencing for enumeration of somatic variants. This occurs under the premise that tumor DNA identified (as mutant alleles) is a marker of residual disease while the absence of tumor DNA (meaning the absence of mutant alleles) can indicate a pCR. A 60 gene panel was designed to be used for exonic sequencing of urinary DNA (uDNA) to identify mutations indicative of bladder cancer or therapeutic targets. We have shown that most mutations in tumor tissue (Mt) are detectable as mutations in urine (Mu). We also showed that the presence or absence of residual Mu after completion of chemotherapy strongly associates with residual disease or pCR at the time of RC, respectively. Therefore, this test could be used after neoadjuvant therapy to better identify patients for RC avoidance. We optimized this test by studying pre-analytical factors affecting the yield, purity, and integrity of uDNA and the quality of sequencing data using prospectively collected samples from patients with MIBC. We are also in the process of testing commercial and novel preservatives to optimize DNA integrity, yield, and mutation detection accuracy to enable temporary ambient temperature storage without compromising mutation detection, permitting shipping/centralized testing. Lastly, we are comparing two library preparation approaches. Study of these preanalytical factors has increased the number of Mu that can be detected and were applied to a cohort of patients who underwent bladder sparing curative-intent treatment in a prospective clinical trial. Studies described herein will enable liquid biopsy tests to accurately identify patients with pCR after neoadjuvant therapy and might safely avoid radical cystectomy. Citation Format: Philip H. Abbosh, Henkel Valentine, Rhea Arya. Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A001.

EarlyTect BCD, a Streamlined PENK Methylation Test in Urine DNA, Effectively Detects Bladder Cancer in Patients with Hematuria

The current noninvasive diagnostic approaches for detecting bladder cancer (BC) often exhibit limited clinical performance, especially for the initial diagnosis. This study aims to evaluate the validity of a streamlined urine-based PENK methylation test called EarlyTect BCD in detecting BC in patients with hematuria scheduled for cystoscopy in Korean and American populations. The test seamlessly integrates two steps, linear target enrichment and quantitative methylation-specific PCR within a single closed tube. The detection limitation of the test was approximately two genome copies of methylated PENK per milliliter of urine. In the retrospective training set (n=105), an optimal cutoff value was determined to distinguish BC from non-BC, resulting in a sensitivity of 87.3% and a specificity of 95.2%. In the prospective validation set (n=210, 122 Korean and 88 American patients), the overall sensitivity for detecting all stages of BC was 81.0%, with a specificity of 91.5% and an area under the curve value of 0.889. There was no significant difference between the two groups. The test achieved a sensitivity of 100% in detecting high-grade Ta and higher stages of BC. The negative predictive value of the test was 97.7%, and the positive predictive value was 51.5%. The findings of this study demonstrate that EarlyTect BCD is a highly effective noninvasive diagnostic tool for identifying BC among patients with hematuria.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective, cross-sectional, diagnostic accuracy study

Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART). 897 ART-initiators were recruited irrespective of symptoms and sputum induction offered. For triage (n=800), we evaluated point-of-care blood-based CRP testing, compared with the WHO-recommended four-symptom screen (W4SS). For sputum-based confirmatory testing (n=787), we evaluated Xpert Ultra versus Xpert MTB/RIF (Xpert). For urine-based confirmatory testing (n=732), we evaluated Xpert Ultra and LF-LAM. We used a sputum culture reference standard. 463 (52%) of 897 participants were female. The areas under the receiver operator characteristic curves for CRP was 0·78 (95% CI 0·73-0·83) and for number of W4SS symptoms was 0·70 (0·64-0·75). CRP (≥10 mg/L) had similar sensitivity to W4SS (77% [95% CI 68-85; 80/104] vs 77% [68-85; 80/104]; p>0·99] but higher specificity (64% [61-68; 445/696] vs 48% [45-52; 334/696]; p<0·0001]; reducing unnecessary confirmatory testing by 138 (95% CI 117-160) per 1000 people and number-needed-to-test from 6·91 (95% CI 6·25-7·81) to 4·87 (4·41-5·51). Sputum samples with Xpert Ultra, which required induction in 49 (31%) of 158 of people (95% CI 24-39), had higher sensitivity than Xpert (71% [95% CI 61-80; 74/104] vs 56% [46-66; 58/104]; p<0·0001). Of the people with one or more confirmatory sputum or urine test results that were positive, the proportion detected by Xpert Ultra increased from 45% (26-64) to 66% (46-82) with induction. Programmatically done haemoglobin, triage test combinations, and urine tests showed comparatively worse results. CRP is a more specific triage test than W4SS in those initiating ART. Sputum induction improves diagnostic yield. Sputum samples with Xpert Ultra is a more accurate confirmatory test than with Xpert. South African Medical Research Council, EDCTP2, US National Institutes of Health-National Institute of Allergy and Infectious Diseases.

Large-scale Prospective Validation Study of a Multiplex RNA Urine Test for Noninvasive Detection of Upper Tract Urothelial Carcinoma

BackgroundCurrent approaches for diagnosis and monitoring of upper tract urothelial carcinoma (UTUC) are often invasive, costly, and not efficient for early-stage and low-grade tumors. ObjectiveTo validate a noninvasive urine-based RNA test for accurate UTUC diagnosis. Design, setting, and participantsUrine samples were prospectively collected from 61 patients with UTUC and 99 controls without urothelial carcinomas, in five clinical centers between October 2022 and August 2023 prior to any invasive test (cystoscope or ureteroscope) or treatment. All samples were analyzed with a urine-based RNA test composed of eight genes (CA9, CCL18, ERBB2, IGF2, MMP12, PPP1R14D, SGK2, and SWINGN). The test results were presented with a risk score for each participant, which was applied to categorize patients into low- or high-risk groups. Outcome measurements and statistical analysisThe diagnosis of UTUC was based mainly on preoperative radiological examination criteria and confirmed by postoperative pathological results. The recursive feature elimination and support vector machine algorithms, χ2, and Student t test were used. Results and limitationsThe eight-gene urine test accurately detected UTUC patients and controls with an area under the curve (AUC) of 0.901 in a single-center testing cohort (n = 93) and an AUC of 0.926 in a multicenter clinical validation cohort (n = 66). In the merged validation cohort, the eight-gene urine test achieved high sensitivity of 90.16%, specificity of 88.89%, and overall accuracy of 89.38%. Remarkably, excellent performance was achieved in 11 low-grade UTUC patients with accuracy of 100%. However, this study collected the urine of UTUC patients only at a single preoperative time point and did not perform continuous tests during the pathological process of UTUC in the surveillance population. ConclusionsOur results demonstrated that the eight-gene urine test can differentiate accurately between UTUC and other urological diseases with high sensitivity and specificity. In clinical practice, it may be used for identifying UTUC patients effectively, leading to reduced reliance on ureteroscopy and blind surgery. Patient summaryIn this study, we investigated a multiplex RNA urine test for noninvasive upper tract urothelial carcinoma (UTUC) diagnosis before treatment. We found that the risk scores derived from the multiplex RNA urine test differed significantly between UTUC patients and corresponding controls.

Abstract 3701: Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients

Abstract The gold standard therapy for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy followed by radical cystectomy (RC) and urinary diversion. Some patients may have their disease completely eradicated by chemotherapy as ~35% of patients achieve a pathologic complete response (pCR) when evaluated from RC specimens. RC with urinary diversion is a life-altering operation with high complication rates and therefore determining who are complete responders would improve quality of life and could decrease costs and still achieve a high cure rate via RC avoidance. Unfortunately, current methods cannot accurately identify complete responders. Our lab has developed a urine-based liquid biopsy test in which DNA isolated from urine and germline is isolated and subjected to panel exome sequencing for enumeration of somatic variants. This occurs under the premise that tumor DNA identified (as mutant alleles) is a marker of residual disease while the absence of tumor DNA (meaning the absence of mutant alleles) can indicate a pCR. A 55 gene panel was designed to be used for exonic sequencing of urinary DNA (uDNA) to identify mutations indicative of bladder cancer or therapeutic targets. We have shown that most mutations in tumor tissue are detectable as mutations in urine (Mu). We also showed that the presence or absence of residual Mu after completion of chemotherapy strongly associates with residual disease or pCR at the time of RC, respectively. Therefore, this test could be used after neoadjuvant therapy to better identify patients for RC avoidance. To optimize this test, we are currently evaluating pre-analytical factors affecting the yield, purity, and integrity of uDNA and the quality of sequencing data using prospectively collected samples from patients with MIBC. We are also testing commercial and novel preservatives to identify one that maintains cell-free DNA integrity, yield, and mutation detection accuracy to enable temporary ambient temperature storage without compromising mutation detection, permitting shipping/centralized testing. Lastly, we are comparing two library preparation approaches: classical hybrid capture-based (Agilent SureSelect XTHS) and amplicon+hybrid capture-based (Agilent HaloPlexHS) to determine which performs the best for identifying the variants in a sample. Our results showed that both sequencing depth and the quality bases mapped was higher when utilizing the SureSelect XTHS kit as compared to HaloPlexHS using approximately the same number of reads. This improvement may also increase the power to detect rare alleles. Studies described herein will enable liquid biopsy tests to accurately identify patients with pCR after neoadjuvant therapy and might safely avoid radical cystectomy. Citation Format: Rhea Arya, Henkel Valentine, Uttam Satyal, Raju Chelluri, Mengmeng Li, Philip Abbosh. Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3701.

Evaluation of the efficacy of urine-based lipoarabinomannan antigen test in the diagnosis of pulmonary tuberculosis

Objective: To analyze the diagnostic efficacy of urinary lipoarabinomannan (LAM) antigen detection method in tuberculosis patients, and to provide an experimental basis for the clinical application of urinary LAM kit in China. Methods: From March to May 2023, 228 patients with lung diseases [134 male, 94 female, age 20-82 (44.8±16.7) years] were prospectively collected in Beijing Chest Hospital, Capital Medical University, including 143 pulmonary tuberculosis patients and 85 non-tuberculosis patients. Urine and sputum samples from patients were collected for traditional etiological detection and urinary LAM antigen detection. The screening results of each positive detection combination were analyzed, and the difference analysis and regression analysis were performed. Results: The detection sensitivity and specificity of the urinary LAM kit were 46.2% (95%CI: 37.9%-54.7%) and 96.5% (95%CI: 89.3%-99.1%), respectively, with an overall coincidence rate of 64.9%. The detection rate of LAM antigen detection and GeneXpert MTB/RIF (Xpert) combined (60.8%, 87/143) was significantly higher than that of Xpert alone (49.7%, 71/143), and the difference was statistically significant (P<0.05). The results of risk factor analysis showed that the risk of negative urinary LAM antigen test results increased significantly as the bacterial load decreased. Conclusions: Urine LAM antigen detection method has a high specificity and can be combined with traditional methods to effectively improve the detection rate. Urinary LAM antigen detection method still has limitations, such as the influence of bacterial load and the inability to distinguish nontuberculosis mycobacteria samples, which needs further experimental verification.

Urine-Based Biomarker Test Uromonitor® in the Detection and Disease Monitoring of Non-Muscle-Invasive Bladder Cancer-A Systematic Review and Meta-Analysis of Diagnostic Test Performance.

Optimal urine-based diagnostic tests (UBDT) minimize unnecessary follow-up cystoscopies in patients with non-muscle-invasive bladder-cancer (NMIBC), while accurately detecting high-grade bladder-cancer without false-negative results. Such UBDTs have not been comprehensively described upon a broad, validated dataset, resulting in cautious guideline recommendations. Uromonitor®, a urine-based DNA-assay detecting hotspot alterations in TERT, FGFR3, and KRAS, shows promising initial results. However, a systematic review merging all available data is lacking. Studies investigating the diagnostic performance of Uromonitor® in NMIBC until November 2023 were identified in PubMed, Embase, Web-of-Science, Cochrane, Scopus, and medRxiv databases. Within aggregated analyses, test performance and area under the curve/AUC were calculated. This project fully implemented the PRISMA statement. Four qualifying studies comprised a total of 1190 urinary tests (bladder-cancer prevalence: 14.9%). Based on comprehensive analyses, sensitivity, specificity, positive-predictive value/PPV, negative-predictive value/NPV, and test accuracy of Uromonitor® were 80.2%, 96.9%, 82.1%, 96.6%, and 94.5%, respectively, with an AUC of 0.886 (95%-CI: 0.851-0.921). In a meta-analysis of two studies comparing test performance with urinary cytology, Uromonitor® significantly outperformed urinary cytology in sensitivity, PPV, and test accuracy, while no significant differences were observed for specificity and NPV. This systematic review supports the use of Uromonitor® considering its favorable diagnostic performance. In a cohort of 1000 patients with a bladder-cancer prevalence of ~15%, this UBDT would avert 825 unnecessary cystoscopies (true-negatives) while missing 30 bladder-cancer cases (false-negatives). Due to currently limited aggregated data from only four studies with heterogeneous quality, confirmatory studies are needed.

Urine-based testing for patient selection and genomic characterization of patients with FGFR alteration-positive non–muscle-invasive bladder cancer (NMIBC) treated with TAR-210.

676 Background: TAR-210 is an intravesical drug delivery system that is designed to provide local, continuous release of erdafitinib. Its safety and efficacy are being evaluated in a first-in-human clinical study (NCT05316155) of patients with bladder cancer whose tumors harbor select FGFR alterations (alt). Toovercome tissue-based challenges in identifying susceptible FGFRalt to select patients for treatment with TAR-210, Janssen partnered with Predicine to use a proprietary urine cell-free DNA diagnostic assay (PredicineCARE). Validation of the urine assay to detect FGFRalt was previously demonstrated using urine samples collected in a highly controlled manner via a collaboration with Stratifyer Molecular Pathology GmbH, Cologne, Germany (Kim et al. ASCO GU 2023). However, evaluation of the urine assay for diagnostic screening in a real-world setting is currently lacking. Here, we report preliminary results of the urine assay for patient selection. We also report on the characterization of the urine-defined genomic landscape in screened patients. Methods: Enrollment was based on detection of prespecified FGFRalt from either tumor tissue obtained from previous biopsies (Qiagen Therascreen FGFR assay) or urine samples obtained prior to enrollment (PredicineCARE next-generation sequencing assay). Results: As of Jun 20, 2023, urine assay performance was compared to the tissue test from all screened patients with NMIBC (N=178). The proportions of samples that yielded results were 60% and 58% from tissue and urine, respectively, while the FGFRalt detection rates in the subsets that yielded results were 62% and 42%, respectively. FGFR3 S249C was the most frequent alteration detected in both tissue (48%) and urine (61%). For 36% of urine samples in which FGFRalt were detected, there was no corresponding tissue result. Of the disease-evaluable patients with high-risk (HR) NMIBC (N=11) or intermediate-risk (IR) NMIBC (N=15),18.2% and 33%, respectively, were enrolled based on urine assay alone due to insufficient tissue samples. A recurrence-free (RF) rate of 82% and a complete response (CR) rate of 87% were achieved at the first disease evaluation amongst patients with HR NMIBC and IR NMIBC, respectively. All patients (HR NMIBC, N=2, and IR NMIBC, N=5) enrolled by “urine only” were RF or achieved a CR. Based on the PredicineCARE panel, comprehensive genomic assessment of urine samples from all screened patients with NMIBC was performed. The prevalence of alterations detected was similar to that described in prior studies using tissue-based testing. Conclusions: Implementing a urine-based assay expands the molecular testing methods to identify additional patients that may respond to erdafitinib. Results justify further study. Clinical trial information: NCT05316155 .

Noninvasive Tests for Bladder Cancer Detection and Surveillance: A Systematic Review of Commercially Available Assays.

An important reason for the high health care costs associated with bladder cancer is the need for frequent cystoscopy for detection and surveillance of this disease. Cytologic analysis of voided urine specimens can assist, but is too inaccurate to replace cystoscopy. In an effort to create reliable, objective, noninvasive mechanisms for detecting bladder cancer, a number of urine-based molecular tests have been developed with the ultimate goal of reducing the frequency of cystoscopy. To summarize the performance of urine-based biomarker tests, currently commercially available in the US, as part of the initial workup for hematuria and for bladder cancer surveillance. In accordance with PRISMA guidelines we performed a systematic review of the literature on the performance of NMP22, BTA, UroVysion, ImmunoCyt/uCyt, CxBladder, and Bladder EpiCheck. Median sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were calculated for each test based on the included studies. Twenty-eight studies met inclusion criteria for the performance of five urine-based biomarker tests in the setting hematuria workup. Median sensitivity ranged from 65.7% -100% and specificity ranged from 62.5% -93.8%. Median NPV ranged from 94.2% -98.3% and PPV ranged from 29% -58.7%. Fourteen studies met inclusion criteria for the performance of six tests in the setting of bladder cancer surveillance. Median sensitivity ranged from 22.6% -92.0% and specificity from 20.5% -97.9%. Median NPV ranged from 52.9% -96.5% and PPV ranged from 48.1% -75.7%. Our analysis finds that while these tests may provide some clinical utility, none of the assays have thus far demonstrated objective evidence to supplant the gold diagnostic standard.

Individualized lipid profile in urine-derived extracellular vesicles from clinical patients with Mycobacterium tuberculosis infections.

Lipids are a key nutrient source for the growth and reproduction of Mycobacterium tuberculosis (Mtb). Urine-derived extracellular vesicles (EVs), because of its non-invasive sampling, lipid enrichment, and specific sorting character, have been recognized as a promising research target for biomarker discovery and pathogenesis elucidation in tuberculosis (TB). We aim to profile lipidome of Mtb-infected individuals, offer novel lipid signatures for the development of urine-based TB testing, and provide new insights into the lipid metabolism after Mtb infection. Urine-derived extracellular vesicles from 41 participants (including healthy, pulmonary tuberculosis, latent tuberculosis patients, and other lung disease groups) were isolated and individually detected using targeted lipidomics and proteomics technology platforms. Biomarkers were screened by multivariate and univariate statistical analysis and evaluated by SPSS software. Correlation analyses were performed on lipids and proteins using the R Hmisc package. Overall, we identified 226 lipids belonging to 14 classes. Of these, 7 potential lipid biomarkers for TB and 6 for latent TB infection (LTBI) were identified, all of which were classified into diacylglycerol (DAG), monoacylglycerol (MAG), free fatty acid (FFA), and cholesteryl ester (CE). Among them, FFA (20:1) was the most promising biomarker target in diagnosing TB/LTBI from other compared groups and also have great diagnostic performance in distinguishing TB from LTBI with AUC of 0.952. In addition, enhanced lipolysis happened as early as individuals got latent Mtb infection, and ratio of raft lipids was gradually elevated along TB progression. This study demonstrated individualized lipid profile of urinary EVs in patients with Mtb infection, revealed novel potential lipid biomarkers for TB/LTBI diagnosis, and explored mechanisms by which EV lipid raft-dependent bio-processes might affect pathogenesis. It lays a solid foundation for the subsequent diagnosis and therapeutic intervention of TB.

Clinical Biofluid Assays for Prostate Cancer.

This mini review summarizes the currently available clinical biofluid assays for PCa. The second most prevalent cancer worldwide is PCa. PCa is a heterogeneous disease, with a large percentage of prostate tumors being indolent, and with a relatively slow metastatic potential. However, due to the high case numbers, the absolute number of PCa-related deaths is still high. In fact, it causes the second highest number of cancer deaths in American men. As a first step for the diagnosis of PCa, the PSA test has been widely used. However, it has low specificity, which results in a high number of false positives leading to overdiagnosis and overtreatment. Newer derivatives of the original PSA test, including the Food and Drug Administration (FDA)-approved 4K (four kallikreins) and the PHI (Prostate Health Index) blood tests, have higher specificities. Tissue-based PCa tests are problematic as biopsies are invasive and have limited accuracy due to prostate tumor heterogeneity. Liquid biopsies offer a minimally or non-invasive choice for the patients, while providing a more representative reflection of the spatial heterogeneity in the prostate. In addition to the abovementioned blood-based tests, urine is a promising source of PCa biomarkers, offering a supplementary avenue for early detection and improved tumor classification. Four urine-based PCa tests are either FDA- or CLIA-approved: PCA3 (PROGENSA), ExoDX Prostate Intelliscore, MiPS, and SelectMDx. We will discuss these urine-based, as well as the blood-based, clinical PCa tests in more detail. We also briefly discuss a few promising biofluid marker candidates (DNA methylation, micro-RNAs) which are not in clinical application. As no single assay is perfect, we envision that a combination of biomarkers, together with imaging, will become the preferred practice.

Urine-based point-of-care testing for factor-Xa-inhibitors in acute ischemic stroke patients: a feasibility study.

Direct oral anticoagulants (DOACs) have become widely used in clinical practice for preventing thromboembolic events. Point-of-care testing methods, particularly those based on urine samples, offer a promising approach for rapid and accurate assessment of DOAC presence. This pilot study aims to evaluate the utility of a urine-based DOAC dipstick test as a point-of-care tool for identifying DOAB presence in acute ischemic stroke (AIS) or transient ischemic attack (TIA) patients. This prospective pilot study included patients with AIS/TIA eligible for DOAC-measurement. After exclusion of 3 patients, 23 patients with DOAC-intake (DOAC group; factor-Xa-inhibitors; n = 23) and 21 patients without DOAC-intake (control-group) remained for analyses. The urine-based DOAC dipstick test and parallel blood-based specific DOAC-level assessment were performed in all patients. Time-intervals of sampling urine/blood sampling and result of DOAC-test were recorded to analyze a potential time benefit based on dipstick evaluation. The urine-based DOAC dipstick test demonstrated high sensitivity (100%) and specificity (100%), correctly identifying all patients with anticoagulatory activity due to DOAC intake (i.e., anti-Xalevel ≥30 ng/mL). Moreover, the visual readout of the test provided semiquantitative information on drug-specific anti-Xa levels, showing a sensitivity of 83% and specificity of 93% to detect anti-Xa levels ≥120 ng/mL. The dipstick test exhibited a median time-benefit of 2:25 h compared to standard blood-based DOAC-level testing. The results of this pilot study underline the efficacy of urine-based point-of-care testing as a rapid and reliable method for assessing DOAC presence in patients with acute ischemic stroke. The value of this tool for clinical decision-making in stroke management needs to be established in future trials.Clinical Trial Registration: Clinicaltrails.org identifier [NCT06037200].

Experiences and perceptions of urine sampling for tuberculosis testing among HIV patients: a multisite qualitative descriptive study

ObjectivesEvidence on the acceptability of urine-based assays for tuberculosis (TB) diagnosis among patients remains limited. We sought to describe patients’ experiences and perceptions of urine sampling for TB testing at...

Bladder cancer.

Bladder cancer is a global health issue with sex differences in incidence and prognosis. Bladder cancer has distinct molecular subtypes with multiple pathogenic pathways depending on whether the disease is non-muscle invasive or muscle invasive. The mutational burden is higher in muscle-invasive than in non-muscle-invasive disease. Commonly mutated genes include TERT, FGFR3, TP53, PIK3CA, STAG2 and genes involved in chromatin modification. Subtyping of both forms of bladder cancer is likely to change considerably with the advent of single-cell analysis methods. Early detection signifies a better disease prognosis; thus, minimally invasive diagnostic options are needed to improve patient outcomes. Urine-based tests are available for disease diagnosis and surveillance, and analysis of blood-based cell-free DNA is a promising tool for the detection of minimal residual disease and metastatic relapse. Transurethral resection is the cornerstone treatment for non-muscle-invasive bladder cancer and intravesical therapy can further improve oncological outcomes. For muscle-invasive bladder cancer, radical cystectomy with neoadjuvant chemotherapy is the standard of care with evidence supporting trimodality therapy. Immune-checkpoint inhibitors have demonstrated benefit in non-muscle-invasive, muscle-invasive and metastatic bladder cancer. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics.

Clinical Characteristics, Support System, and Personality Differences of Cannabis and Stimulant Users in South Korea.

To compare the clinical characteristics, support system, and personality traits of cannabis and stimulant users in South Korea. This study was based on electronic medical records. Among a total of 152 subjects who suspected of drug use and who underwent six types of urine-based drug screening tests at the National Center for Mental Health, 104 people who underwent both an interview with a psychiatrist and a psychological test were selected and classified according to the type of substance used. Psychological and personality characteristics were examined through the National Center for Mental Health psychological test battery for addiction. The differences in characteristics between cannabis (n=60) and stimulant (n=18) users were analyzed by an independent t-test for parametric data and chi-square test or Fisher's exact test for nonparametric data, and analysis of covariance for psychological tests. The average age of cannabis users was lower than that of stimulant users and they were more often single. Substance cravings were higher in stimulant users, who more often had a psychiatric history than cannabis users. Moreover, stimulant users had higher clinical scale scores for depression and anxiety. Among the Minnesota Multiphasic Personality Inventory-II clinical scale scores, there was a significant difference in social introversion scores between groups. We found differences in demographic, psychological, and personality characteristics between cannabis and stimulant users in South Korea. Considering the recent increase in illegal drug use in South Korea, further follow-up and policy research on drug users are needed.

Can HPV Test on Random Urine Replace Self-HPV Test on Vaginal Self-Samples or Clinician-Collected Cervical Samples?

This study investigated whether random urine (RU) samples can be used to accurately identify human papillomavirus (HPV) and whether these samples can replace self-collected vaginal samples in HPV tests. A total of 167 patients with abnormal Pap smears were recruited. The patients provided self-collected vaginal and RU samples for HPV testing. Clinicians obtained cervical samples from the patients. Colposcopy examination and cervical biopsy were performed. Hybrid Capture II (HC II) and Cervista tests were used to detect HPV in the RU samples. The results of tests on clinician-collected cervical samples were used as the benchmark. The sensitivities of the Cervista tests on vaginal samples and the HC II and Cervista tests on RU samples were 75.00%, 49.07%, and 44.44%, respectively. After we adjusted the HPV detection cutoff value for urine samples based on values in the receiver operating characteristic curve, the sensitivities of the HC II and Cervista tests increased to 63.89% and 58.33%, respectively. In 167 patients, 59 had cervix biopsies showing CIN2 or worse (CIN2+). For CIN2+, the sensitivity was 47.5% and 50.8% in the HC II and Cervista tests on RU samples, respectively. HPV tests on RU samples had approximately 60% sensitivity to HPV tests on clinician-collected cervical samples after the cutoff values were adjusted. For CIN2+, the sensitivity was only approximately 50%. Further studies and improvements in urine-based HPV testing are needed to establish it as a more convenient and accessible method for detecting HPV and cervical dysplasia in patients.