Diagnostic tests for human Schistosoma mansoni and Schistosoma haematobium infection: a systematic review and meta-analysis.

BACKGROUND: Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity areas, microscopy-based urine filtration and the Kato-Katz technique are considered as reference diagnostic tests for Schistosoma haematobium and Schistosoma mansoni infections, respectively. We aimed to collate all available evidence on the accuracy of other proposed diagnostic techniques. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane Library, and LILACS for studies published from database inception to Dec 31, 2022, investigating the sensitivity and specificity of diagnostic tests for S haematobium and S mansoni infections against Kato-Katz thick smears or urine microscopy (reference tests) involving adults (aged ≥18 years), school-aged children (aged 7 to 18 years), or preschool-aged children (aged 1 month to 7 years). We extracted raw data on true positives, true negatives, false positives, and false negatives for the diagnostic tests and data on the number of participants, study authors, publication year, journal, study design, participants' age and sex, prevalence of Schistosoma infection, and treatment status. To account for imperfect reference tests, we used a hierarchical Bayesian latent class meta-analysis to model test accuracy. FINDINGS: Overall, we included 121 studies, assessing 28 different diagnostic techniques. Most studies (103 [85%] of 121) were done in Africa, 14 (12%) in South America, one (1%) in Asia, and one (1%) in an unknown country. Compared with the reference test, Kato-Katz thick smears, circulating cathodic antigen urine cassette assay version 1 (CCA1, 36 test comparisons) had excellent sensitivity (95% [95% credible interval 88-99]) and reasonable specificity (74% [63-83]) for S mansoni. ELISA-based tests had a performance comparable to circulating cathodic antigen, but there were few available test comparisons. For S haematobium, proteinuria (42 test comparisons, sensitivity 73% [62-82]; specificity 94% [89-98]) and haematuria (75 test comparisons, sensitivity 85% [80-90]; specificity 96% [92-99]) reagent strips showed high specificity, with haematuria reagent strips having better sensitivity. Despite limited data, nucleic acid amplification tests (NAATs; eg, PCR or loop-mediated isothermal amplification [LAMP]) showed promising results with sensitivity estimates above 90%. We found an unclear risk of bias of about 70% in the use of the reference or index tests and of 50% in patient selection. All analyses showed substantial heterogeneity (I2>80%). INTERPRETATION: Although NAATs and immunological diagnostics show promise, the limited information available precludes drawing definitive conclusions. Additional research on diagnostic accuracy and cost-effectiveness is needed before the replacement of conventional tests can be considered. FUNDING: WHO and Luxembourg Institute of Health.

Prevalence and associated factors for asymptomatic microscopic hematuria in adults in the PERSIAN Guilan cohort study (PGCS).

Although hematuria is not life-threatening, some could be the result of a more severe condition. Our objectives are to report on the prevalence and risk factors of asymptomatic microscopic hematuria (AMH) in the prospective epidemiological research studies of the Iranian adults (PERSIAN) Guilan cohort study (PGCS) population. This cross-sectional study was conducted from 2014 to 2017 and consisted of 10,520 individuals aged 35-70. Data collection was conducted using a questionnaire during a face-to-face interview. The urine analyses (UA) were done up to 2 h after sample collection. Based on a urine microscopy evaluation, AMH is defined as 3 or more red blood cells per high power field (HPF). Simple and multiple logistic regression analysis was conducted to explore factors associated with AMH. The prevalence of AMH in this study was 34.1% and was more prevalent in participants of older ages and female gender as well as those with low educational level, underweight-body mass index (BMI), high physical activity, smoking, alcohol consumption, and kidney stone disease. On the other hand, obesity, opium, and diabetes decreased the likelihood of AMH. The results of the present study shed light on the prevalence and risk factors of AMH and suggested that a significant portion of the study population is affected by AMH. Considering the lack of consensus on a definite clinical guideline for AMH in our country, the results of the present study could be used to design a unit algorithm for screening and therapy of AMH.

The role of URO17® in diagnosis and follow up of bladder cancer patients.

OBJECTIVE: to evaluate the role of urinary URO17® biomarker in the detection of urothelial tumors in haematuria patients and the detection of recurrence in non-muscle invasive bladder urothelial tumors. MATERIALS AND METHODS: Our study was formed of two cohorts of patients, group I represents patients presenting with haematuria (n = 98), while group II represents patients with known non-muscle invasive bladder cancers on their scheduled follow up cystoscopic investigation (n = 51). For both groups, patients were asked to provide urine samples before cystoscopy, either primary as part of the haematuria investigation or as a scheduled follow-up. Urine samples were sent anonymously for standard urine cytology and URO17® biomarker immunostaining. Results were compared to cystoscopic findings using Chi-square analysis and Fisher's exact test (P < 0.05). RESULTS: Group I was formed of 98 patients, with an average age of 60 years. URO17® showed 100% sensitivity and 96.15% specificity with a negative predictive value (NPV) of 100 and a positive predictive value (PPV) of 95.83. The results showed statistical significance with P value < 0.001. Group II was formed of 51 patients, with an average age of 75 years. URO17® was shown to have a sensitivity of 85.71% and NPV of 95.45. Eleven patients of group II were on scheduled BacillusCalmette-Guerin (BCG) and another 5 received Mitomycin C (MMC). The overall results of both groups combined (n = 149) showed statistical significance between flexible cystoscopy results and the results of urinary URO17® and urine cytology. CONCLUSION: URO17® has a potential to be a reliable test for diagnosis and follow up of urothelial cancer patients and a screening tool adjunct to flexible cystoscopy. TRIAL REGISTRATION: Not applicable as the current study is not a clinical trial, as per according to the National Institutes of Health, "studies that involve a comparison of methods and that do not evaluate the effect of the interventions on the participant do not meet the NIH clinical trial definition."

Whole exome sequencing approach for identification of the molecular etiology in pediatric patients with hematuria.

BACKGROUND: Hematuria is a common condition in clinical practice of pediatric patients. It is related to a wide spectrum of disorders and has high heterogeneity both clinically and genetically, which contributes to challenges of diagnosis and lead many pediatric patients with hematuria not to receive accurate diagnosis and early management. METHODS: In this single center study, 42 children with hematuria were included in Tianjin Children's Hospital between 2019 and 2020. We analyzed the clinical information and performed WES (Whole exome sequencing) for all cases. Then the classification of identified variants was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines for interpreting sequence variants. For the fragment deletion, qPCR was performed to validate and confirm the inherited pattern. RESULTS: For the 42 patients, 16 cases had gross hematuria and 26 had microscopic hematuria. Molecular genetic causes were uncovered in 9 (21.4%) children, including 7 with Alport syndrome (AS), one with polycystic nephropathy and one with lipoprotein glomerulopathy. The genetic causes for other patients were not related with hematuria. CONCLUSIONS: WES is a rapid and effective way to evaluate patients with hematuria. The analysis of genotype-phenotype correlations of patients with AS indicated that severe variants were associated with early kidney failure. Secondary findings were not rare in Chinese children, thus the clinician should pay more attention to the clinical interpretation of sequencing results and properly interaction with patients and their family.

IgA nephropathy in a boy with frequently relapsing nephrotic syndrome.

A Japanese boy developed nephrotic syndrome (NS) and had microscopic hematuria at 8 years old. Renal biopsy was performed. Light microscopy study revealed mesangial proliferation and all immunofluorescent stains (including IgA) were negative, so he was diagnosed with non-IgA diffuse mesangial proliferation (DMP). Complete remission was achieved at 13 days after the initiation of oral prednisolone, and hematuria also disappeared 3 days later, but the patient developed frequently relapsing nephrotic syndrome. Cyclosporine A (CyA) was introduced at 10 years old, and there were no relapses between then and when it was discontinued at 12 years old. A second renal biopsy revealed minimal change without CyA nephrotoxicity. However, there was repeated relapse of NS after discontinuation, so CyA was reintroduced 8 months later, and NS remained in remission thereafter. Microscopic hematuria appeared at 13 years old, however, with gross hematuria appearing at the time of infection. A third renal biopsy revealed mesangial proliferation with IgA-dominant deposition, so the patient was diagnosed with IgA nephropathy. Currently (14 years old), CyA treatment has been discontinued and the patient is undergoing lisinopril therapy for IgA nephropathy, but there are still relapses of NS. To the best of our knowledge, there have been no previous reports of a patient with non-IgA DMP at the onset of NS who had later development of IgA nephropathy. The patient showed non-IgA DMP at the onset, suggesting that NS with non-IgA DMP and IgA nephropathy has some common pathophysiology. Treatment for NS, such as PSL and/or CyA treatment, may suppress the clinical manifestation of late IgA nephropathy.

Budgetary Impact of Including the Urinary Genomic Marker Cxbladder Detect in the Evaluation of Microhematuria Patients.

INTRODUCTION: Current AUA guidelines mandate a risk-stratified approach for the evaluation of microhematuria. Urine genomic tests with high negative predictive value could further reduce unnecessary diagnostic testing and morbidity, but the economic impact is unknown. This study modeled the financial impact of Cxbladder Detect on microhematuria evaluations. METHODS: A decision tree analysis was constructed by Coreva Scientific comparing 1-year costs of the standard microhematuria evaluation using the AUA guidelines vs an algorithm incorporating Cxbladder Detect. Cxbladder Detect-positive patients had cystoscopy and imaging, whereas patients with negative tests were reevaluated in 6 months. Patients with positive diagnostic testing underwent cystoscopy, and positive cystoscopies led to transurethral resection of bladder tumor. Test performance was based on published literature, and costs were based on Medicare allowable fees. RESULTS: Using the decision tree model, the average savings of using Cxbladder Detect was $559 compared with the standard of care, with an average reduction of 0.38 procedures per patient. Probabilistic analysis showed statistical significance with a median reduction in the total cost of $498 per patient (95% CrI [-1356, -2]) and a significant median reduction in diagnostic procedures per patient of 0.36 (95% CrI [-0.52, -0.16]) without impact on the number of cancers diagnosed. CONCLUSIONS: This model-based study demonstrates the potential economic value of using a Cxbladder-driven protocol for microhematuria evaluations.

Association between gingival bleeding and hematuria as biomarkers of periodontitis and renal disease: a review.

Gingival bleeding is a common complaint and symptom in patients with periodontitis. In clinics, gingival bleeding is regarded as an important sign of gingival inflammation, which is also of great significance in predicting the activity of periodontitis. Existing research has indicated that periodontitis has an impact on distant sites, such as the kidney. Hematuria is the principal feature of glomerular disease, which can reflect the degree and condition of glomerular inflammation. Previous studies have revealed an association between periodontal diseases with renal diseases, so a study is necessary to discuss their representative signs of them. For the moment, there are no reports that are concerned about the correlation between gingival bleeding with hematuria. The main point of this text is to review the potential association between gingival bleeding with hematuria, reveal their underlying mechanisms, and provide instructions for the therapy of periodontitis and glomerular diseases.

Nutcracker syndrome in pediatrics: initial findings and long-term follow-up results.

BACKGROUND: Nutcracker syndrome (NCS) describes a set of symptoms and signs resulting from compression of the left renal vein (LRV). There is a lack of knowledge about its natural course, diagnosis, and management, especially in children. Herein, we present our single-center experience with a large number of patients who have long-term follow-up results. METHODS: All patients with NCS diagnosed between January 2011 and March 2021 were included and their data were obtained retrospectively. RESULTS: A total of 123 NCS patients (85 females) were included. The median age at the time of diagnosis was 12 (IQR 10-14) years, and BMI percentiles were below 5% in 38% of the cases. At the time of diagnosis, two-thirds of the patients were asymptomatic. The most common laboratory finding was nephritic proteinuria (98%), followed by microscopic hematuria (16%). Signs of LRV compression were significantly more evident in upright position Doppler ultrasonography (DUS) examination. All patients have been followed conservatively; hematuria and/or proteinuria resolved in 43 of the 108 patients (40%) within 35.8 ± 25.8 months of follow-up. Control DUS was performed in 52 patients after a mean period of 39.1 ± 21.3 months. The median peak velocity and diameter ratios of the LRV in the upright position were found to be decreased significantly when compared to the initial assessment (p < 0.05). Normal DUS findings were noted in 13 patients at the final evaluation. CONCLUSIONS: In unexplained proteinuria and/or hematuria, NCS should be considered, especially in asthenic adolescents. Our results support conservative management in children as the first-line treatment approach.

[Macrohematuria in children and adolescents]. / Makrohämaturie im Kindes- und Jugendalter.

Hematuria is usually only noticed early in the case of macrohematuria. In around half of affected children, macrohematuria is caused by a urinary tract infection. In all other cases, a careful diagnosis is required. In addition to a detailed medical history, this builds upon a precise examination of the urine (microscopy, quantitative determination of proteinuria [mg albumin/g creatinine in spontaneously voided urine]) and measurement of blood pressure. The work-up usually includes sonography as the primary imaging modality. Invasive diagnostic tests using cystoscopy are only necessary in exceptional cases. If there is evidence of glomerulonephritis, a kidney biopsy may be indicated. Careful attention should be given to persisting microhematuria (> 6 months) and Alport syndrome should be confirmed or ruled out. Heterozygotic Alport syndrome can also be a possible cause of chronic renal failure.

Abandoning testing for asymptomatic microscopic haematuria in Sweden - a long-term follow-up.

OBJECTIVES: To test the hypothesis that the Swedish national policy of abandoning testing for asymptomatic microscopic haematuria (AMH) introduced in 1999 did not adversely affect the prognosis of patients with urinary bladder cancer. Specific aims were to investigate possible effects on (1) Diagnostic delay as represented by stage distribution at diagnosis, (2) Survival and mortality trends, also in comparison to other countries and (3) National health care costs. MATERIAL AND METHODS: The design was an observational study using open sources on patients included in the Swedish National Bladder Cancer Registry 1997-2016. Outcome measures were: Changes in initial tumour presentation during 5 years after the change and long-term relative survival and mortality in comparison to the other Nordic countries. Costs related to investigations were estimated based on the national price lists. RESULTS: The proportion of patients diagnosed with muscle-invasive bladder cancer decreased following the policy change. The long-term relative 5-year survival increased during the study period. Mortality has remained constant during the period. In comparison to the other Nordic countries, Sweden remains among those with the best outcome despite a more restrictive approach. Cost savings because of the policy change were estimated to be substantial. CONCLUSIONS: Based on open-source registry data, the new restrictive policy was not found to adversely affect the survival of patients with urinary bladder cancer in Sweden. These observations argue against a major negative impact of abandoning further work-up for patients with AMH and may be of use for other countries when revising guidelines. The reduced number of patients undergoing investigation may allow for increased focus and be a relief both for caregivers and the health budget.

Risk of genitourinary malignancy in patients that receive anticoagulant or antiplatelet therapy.

OBJECTIVES: Haematuria is a common indication for a urology evaluation. In many cases, its cause is not determined unequivocally, but it does not pose any threat to the patient. However, it can represent the first symptom of urinary tract cancer. BACKGROUND: The present study aimed to compare the risk of urological malignancies in patients with haematuria who received antiplatelet or anticoagulant therapy versus those who did not. METHODS: This prospective study included 562 patients with haematuria during the period of 2018‒2021. Among these, 129 patients had macroscopic haematuria. All patients underwent a urinary tract ultrasound, CT with urography, and cystoscopy. Patients with suspected malignancy underwent an appropriate surgical procedure with a pathology examination. Data were analysed with univariate and multiple logistic regression. RESULTS: The incidence rates of malignancies were 21.5 % overall, and 44.2 % and 14.8 % among patients with macroscopic and microscopic haematuria, respectively. Univariate regression showed that the odds of malignancy was significantly higher among patients with antiplatelet therapy compared to patients without antiplatelet therapy (OR: 1.88, 95% CI: 1.14‒3.05). In contrast, anticoagulation therapy did not significantly increase the odds of malignancy compared to no anticoagulation therapy (OR: 1.45, 95% CI: 0.74‒2.69). However, a multiple logistic regression model that included other known risk factors (e.g., sex or age) showed similar odds of malignancy among these patient groups. CONCLUSIONS: Malignancy risk for patients who received anticoagulant or antiplatelet therapy was similar to the risk observed in the general population. Antiplatelet and anticoagulant therapy were not significant risk factors of urological malignancy in patients with haematuria. The results from the present study will be used in a power analysis for an upcoming multicentre study (Tab. 4, Ref. 17). Text in PDF www.elis.sk Keywords: anticoagulation therapy, antiplatelet therapy, cancer, haematuria, risk factor.

Performance Characteristics of a Rule-Based Electronic Health Record Algorithm to Identify Patients with Gross and Microscopic Hematuria.

BACKGROUND: Two million patients per year are referred to urologists for hematuria, or blood in the urine. The American Urological Association recently adopted a risk-stratified hematuria evaluation guideline to limit multi-phase computed tomography to individuals at highest risk of occult malignancy. OBJECTIVES: To understand population-level hematuria evaluations, we developed an algorithm to accurately identify hematuria cases from electronic health records (EHRs). METHODS: We used International Classification of Diseases (ICD)-9/ICD-10 diagnosis codes, urine color, and urine microscopy values to identify hematuria cases and to differentiate between gross and microscopic hematuria. Using an iterative process, we refined the ICD-9 algorithm on a gold standard, chart-reviewed cohort of 3,094 hematuria cases, and the ICD-10 algorithm on a 300 patient cohort. We applied the algorithm to Geisinger patients ≥35 years (n = 539,516) and determined performance by conducting chart review (n = 500). RESULTS: After applying the hematuria algorithm, we identified 51,500 hematuria cases and 488,016 clean controls. Of the hematuria cases, 11,435 were categorized as gross, 26,658 as microscopic, 12,562 as indeterminate, and 845 were uncategorized. The positive predictive value (PPV) of identifying hematuria cases using the algorithm was 100% and the negative predictive value (NPV) was 99%. The gross hematuria algorithm had a PPV of 100% and NPV of 99%. The microscopic hematuria algorithm had lower PPV of 78% and NPV of 100%. CONCLUSION: We developed an algorithm utilizing diagnosis codes and urine laboratory values to accurately identify hematuria and categorize as gross or microscopic in EHRs. Applying the algorithm will help researchers to understand patterns of care for this common condition.

The relationship between abnormal urinalysis findings and appendicitis location.

AIMS: Acute appendicitis is a common cause of acute abdomen in general surgery and early diagnosis is crucial for prognosis. Abnormal urinalysis results have been associated with appendicitis in some studies, with reports of microscopic hematuria or pyuria in laboratory tests. The aim of this article is to evaluate the relationship between laboratory findings of hematuria, pyuria, and the location of acute appendicitis. METHODS: This retrospective study included 577 patients who underwent appendectomy for suspected acute appendicitis between January 1, 2018, and December 31, 2022, at the general surgery clinic of Samsun Training and Research Hospital. RESULTS: Among the 577 patients, 247 were female and 330 were male, with a median age of 34 years. A statistically significant difference was observed between appendicitis location and erythrocyte values (p = 0.009), specifically in paraileal and retrocecal locations. There was a statistically significant difference between appendicitis location and leukocyte values (p < 0.001), with significant differences found in paraileal, promontoric, and retrocecal locations. A statistically significant difference was observed between appendicitis location and leukocyte esterase values (p = 0.002), specifically in paraileal and retrocecal locations. DISCUSSION/CONCLUSION: Abnormal urinalysis findings are not uncommon in patients with acute appendicitis. Our study demonstrated a significant correlation between tit erythrocyte, tit leukocyte, and tit leukocyte esterase positivity with appendicitis locations. Therefore, we believe that pathological findings in urine tests of patients undergoing surgery with a preliminary diagnosis of appendicitis can provide valuable information to surgeons regarding the location of the appendix, ultimately aiding in optimizing the timing and cost of the operation.

Synergistic effect of proteinuria on dipstick hematuria-related decline in kidney function: The Japan Specific Health Checkups (J-SHC) Study.

BACKGROUND: The effect of isolated hematuria without proteinuria on kidney function decline, and the modification by the severity of proteinuria in general population are not fully elucidated. METHODS: Participants were included in the Japan Specific Health Checkups Study between 2008 and 2014. The exposure of interest was the frequency of dipstick hematuria during the observation. In each proteinuria frequency category (non-, occasional, persistent), hematuria-related decline in the eGFR rate was examined by analysis of covariance (ANCOVA). eGFR decline trajectories were also assessed using mixed-effects models. RESULTS: Among the 552,951 participants, 146,753 (26.5%) had hematuria, and 56,021 (10.1%) and 8,061 (1.5%) had occasional and persistent proteinuria, respectively. During the median follow-up of 3.0 years, annual change in eGFR decline in participants with hematuria was significantly faster than in those without hematuria (mean [95% confidence interval]: - 0.95 [- 0.98 to - 0.92] vs - 0.86 [- 0.87 to - 0.84] mL/min/1.73 m2/year; P < 0.001). In ANCOVA, the hematuria-related annual eGFR decline rate increased as proteinuria frequency categories increased (differences in annual eGFR decline rate between participants with and without hematuria: 0.08 [0.06 to 0.09] in participants with non-proteinuria category, 0.17 [0.15 to 0.18] in occasional proteinuria category, and 0.68 [0.65 to 0.71] mL/min/1.73 m2/year in persistent proteinuria category; P for interaction < 0.001). Similar results were obtained by the linear mixed-effect model. CONCLUSIONS: Proteinuria has a synergistic effect on dipstick hematuria-related decline in kidney function. Among the general population without proteinuria throughout the observational period, the "isolated hematuria"-related eGFR decline was statistically significant but the difference was small.

Secondary immunoglobulin A nephropathy with gross hematuria leading to rapidly progressive glomerulonephritis following severe acute respiratory syndrome coronavirus 2 vaccination: a case report.

BACKGROUND: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been followed by many reports of the development and relapse of autoimmune diseases associated with SARS-CoV-2 vaccination. Some of these reports have involved relapse or onset of immunoglobulin A (IgA) nephropathy following SARS-CoV-2 vaccination. Here, we report on a patient with IgA nephropathy who presented with gross hematuria and rapidly progressive glomerulonephritis following SARS-CoV-2 vaccination. CASE PRESENTATION: A 63-year-old male patient with a history of habitual tonsillitis underwent bilateral tonsillectomy. He had a history of alcoholic cirrhosis of the liver and microscopic hematuria and proteinuria were indicated during a health checkup 2 years before hospital admission. He developed hematuria after the SARS-CoV-2 vaccination, which led to rapidly progressive glomerulonephritis, for which he was hospitalized. A renal biopsy led to the diagnosis of IgA nephropathy. Although pulse steroid therapy during his condition resulted in hepatic encephalopathy, three courses combined with mizoribine improved his renal function. CONCLUSION: SARS-CoV-2 mRNA vaccines activate T cells, which are involved in the pathophysiology of IgA nephropathy. Therefore, this case suggests that the exacerbation of IgA nephropathy by the vaccine favors the vasculitis aspect of the disease.

Toward the Deimplementation of Computed Tomography Urogram for Patients With Low- to Intermediate-risk Microscopic Hematuria: A Mixed-method Study of Factors Influencing Continued Use.

INTRODUCTION: Citing high costs, limited diagnostic benefit, and ionizing radiation-associated risk from CT urogram, in 2020 the AUA revised its guidelines from recommending CT urogram for all patients with microscopic hematuria to a deintensified risk-stratified approach, including the deimplementation of low-value CT urogram (ie, not recommending CT urogram for patients with low- to intermediate-risk microscopic hematuria). Adherence to revised guidelines and reasons for continued low-value CT urogram are unknown. METHODS: With the overarching objective of improving guideline implementation, we used a mixed-method convergent explanatory design with electronic health record data for a retrospective cohort at a single academic tertiary medical center in the southeastern United States and semistructured interviews with urology and nonurology providers to describe determinants of low-value CT urogram following guideline revision. RESULTS: Of 391 patients with microscopic hematuria, 198 (51%) had a low-value CT urogram (136 [69%] pre-guideline revision, 62 [31%] postrevision). The odds of ordering a low-value CT urogram were lower after guideline revisions, but the change was not statistically significant (OR: 0.44, P = .08); odds were 1.89 higher (P = .06) among nonurology providers than urology providers, but the difference was not statistically significant. Provider interviews suggested low-value CT urogram related to nonurology providers' limited awareness of revised guidelines, the role of clinical judgment in microscopic hematuria evaluation, and professional and patient influences. CONCLUSIONS: Our findings suggest low-value CT urogram deimplementation may be improved with guidelines and implementation support directed at both urology and nonurology providers and algorithms to support guideline-concordant microscopic hematuria evaluation approaches. Future studies should test these strategies.

Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.

PURPOSE: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. EXPERIMENTAL DESIGN: This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. RESULTS: uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. CONCLUSIONS: uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.

Outcomes of Hematuria Evaluation by Advanced Practice Providers and Urologists.

OBJECTIVE: To examine the quality and costs of care for patients evaluated for hematuria by urologic advanced practice providers (APPs) and urologists. The roles of APPs in urology are growing, but their clinical and financial outcomes compared to urologists are not well understood. METHODS: We conducted a retrospective cohort study of commercially insured patients using data from 2014 to 2020. We included adult beneficiaries with a diagnosis code for hematuria and an initial outpatient evaluation and management visit with a urologic APP or urologist. We assessed receipt of cystoscopy procedure, imaging study, bladder biopsy procedure, and bladder cancer diagnosis within 6 months of the initial visit. Secondary outcomes included the time until each of these outcomes occurred and the out-of-pocket spending and total payments. RESULTS: We identified 59,923 patients who were initially evaluated for hematuria. Visits with urologic nurse practitioners rather than urologists were associated with significantly lower odds of receiving cystoscopy procedures (odds ratio [OR] 0.93, 95% confidence interval [95% CI] 0.54-0.72, P < .001), imaging studies (OR 0.79, 95% CI 0.69-0.91, P < .001), and bladder biopsy procedures (OR 0.61, 95% CI 0.41-0.92, P = .02). Visits with urologic physician assistants were associated with 11% greater out-of-pocket payments (incident risk ratio 1.11, CI 1.01-1.22, P = .02) and 14% greater total payments (incident risk ratio 1.14, CI 1.04-1.25, P = .004). CONCLUSION: There are clinical and financial differences in hematuria care delivered by urologic APPs and urologists. The incorporation of APPs into urologic care warrants further study, and specialty-specific training for APPs should be considered.