scholarly journals Quality and cost assessment of Canadian Urological Association microscopic hematuria guidelines in clinical practice: Turning urine into gold

2019 ◽  
Vol 13 (10) ◽  
Author(s):  
Mark A. Assmus ◽  
D. Beyer ◽  
Joan Hanks ◽  
Mathew Estey ◽  
Keith F. Rourke ◽  
...  
Keyword(s):  
Guideline Adherence ◽  
Healthcare Costs ◽  
Patient Characteristics ◽  
Urine Samples ◽  
Microscopic Hematuria ◽  
Low Grade ◽  
Normal Cytology ◽  
Non Invasive ◽  
Database Evaluation ◽  
Alberta Health

Introduction: Asymptomatic microscopic hematuria (AMH) is defined in the Canadian Urological Association (CUA) guidelines as >2 red blood cells (RBCs) per high-powered field (hpf). Our objective is to evaluate guideline adherence for AMH at our centre. Secondarily, we aim to identify areas of the guideline that can be optimized. Methods: We retrospectively reviewed 875 consecutive adults referred to two urologists for hematuria from June 2010–2016. Patient characteristics, risk factors, and outcomes were added to an encrypted REDCap database. Evaluation of microscopic hematuria reporting was performed by analyzing 681 urine samples reported as 1–5 RBC/hpf. Healthcare costs were obtained from Alberta Health Services (AHS), Data Integration and Management Repository (DIMR), and Alberta Society of Radiologists (ASR). Results: Of the 875 patients referred with hematuria, 400 had AMH. Overall, 96.5% completed evaluation consistent with the CUA guideline. The incidence of pathology requiring surgical intervention was 21/400 (5%), with a 0.8% rate (3/400) of urothelial cell carcinoma (UCC) (non-invasive, low-grade). No malignancy was found in non-smokers with normal cytology, normal imaging and <50 RBC/hpf; 44% had AMH in the 1–5 RBCs/hpf range. Only 41% (279/681) of urine samples categorized as 1–5 RBCs/hpf had guideline-defined microscopic hematuria. By changing local microscopic hematuria reporting to differentiate 1–2 and 3–5 RBCs/hpf, we estimate $745 000 in annual savings. Conclusions: At our centre, CUA AMH guideline adherence is high. We did not find malignancy in non-smokers with normal cytology, imaging, and <50 RBC/hpf. We identified and changed regional microscopic hematuria reporting to fit the CUA definition, eliminating unnecessary investigations and healthcare costs.

scholarly journals Non-invasive detection of bladder cancer through the analysis of driver gene mutations and aneuploidy

2017 ◽  
Author(s):  
Simeon Springer ◽  
Maria Del Carmen Rodriguez Pena ◽  
Lu Li ◽  
Christopher Douville ◽  
Yuxuan Wang ◽  
...  
Keyword(s):  
At Risk ◽  
Bladder Cancer ◽  
Gene Mutations ◽  
Urine Samples ◽  
Driver Gene ◽  
Low Grade ◽  
Invasive Approach ◽  
Non Invasive ◽  
Patients At Risk ◽  
Copy Number Changes

AbstractCurrent non-invasive approaches for bladder cancer (BC) detection are suboptimal. We report the development of non-invasive molecular test for BC using DNA recovered from cells shed into urine. This “UroSEEK” test incorporates assays for mutations in 11 genes and copy number changes on 39 chromosome arms. We first evaluated 570 urine samples from patients at risk for BC (microscopic hematuria or dysuria). UroSEEK was positive in 83% of patients that developed BC, but in only 7% of patients who did not develop BC. Combined with cytology, 95% of patients that developed BC were positive. We then evaluated 322 urine samples from patients soon after their BCs had been surgically resected. UroSEEK detected abnormalities in 66% of the urine samples from these patients, sometimes up to 4 years prior to clinical evidence of residual neoplasia, while cytology was positive in only 25% of such urine samples. The advantages of UroSEEK over cytology were particularly evident in low-grade tumors, wherein cytology detected none while UroSEEK detected 67% of 49 cases. These results establish the foundation for a new, non-invasive approach to the detection of BC in patients at risk for initial or recurrent disease.

scholarly journals TAMI-08. A TALE OF TWO TELOMERE MAINTENANCE MECHANISMS: TERT EXPRESSION AND THE ALT PATHWAY INDUCE UNIQUE MRS-DETECTABLE METABOLIC REPROGRAMMING IN LOW-GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii214-ii214
Author(s):  
Pavithra Viswanath ◽  
Georgios Batsios ◽  
Anne Marie Gillespie ◽  
Hema Artee Luchman ◽  
Joseph Costello ◽  
...  
Keyword(s):  
Treatment Response ◽  
Metabolic Reprogramming ◽  
Telomere Maintenance ◽  
Imaging Biomarker ◽  
Low Grade ◽  
Tumor Proliferation ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Non Invasive ◽  
Key Enzyme ◽  
Tert Expression

Abstract Telomeres are nucleoprotein structures at chromosomal ends that shorten with cell division and constitute a natural barrier to proliferation. In order to proliferate indefinitely, all tumors require a telomere maintenance mechanism (TMM). Telomerase reverse transcriptase (TERT) expression is the TMM in most tumors, including low-grade oligodendrogliomas (LGOGs). In contrast, low-grade astrocytomas (LGAs) use the alternative lengthening of telomeres (ALT) pathway as their TMM. As molecular hallmarks of tumor proliferation, TMMs are attractive tumor biomarkers and therapeutic targets. Non-invasive imaging of TMM status will, therefore, allow assessment of tumor proliferation and treatment response. However, translational methods of imaging TMM status are lacking. Here, we show that TERT expression and the ALT pathway are associated with unique magnetic resonance spectroscopy (MRS)-detectable metabolic reprogramming in LGOGs and LGAs respectively. In genetically-engineered and patient-derived LGOG models, TERT expression is linked to elevated 1H-MRS-detectable NAD(P)/H, glutathione, aspartate and AXP. In contrast, the ALT pathway in LGAs is associated with higher α-ketoglutarate, glutamate, alanine and AXP. Importantly, elevated flux of hyperpolarized [1-13C]-alanine to pyruvate, which depends on α-ketoglutarate, is a non-invasive in vivo imaging biomarker of the ALT pathway in LGAs while elevated flux of hyperpolarized [1-13C]-alanine to lactate, which depends on NADH, is an imaging biomarker of TERT expression in LGOGs. Mechanistically, the ALT pathway in LGAs is linked to higher glutaminase (GLS), a key enzyme for α-ketoglutarate biosynthesis while TERT expression in LGOGs is associated with elevated nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme for NADH biosynthesis. Notably, TERT expression and the ALT pathway are linked to MRS-detectable metabolic reprogramming in LGOG and LGA patient biopsies, emphasizing the clinical validity of our observations. Collectively, we have identified unique metabolic signatures of TMM status that integrate critical oncogenic information with noninvasive imaging modalities that can improve diagnosis and treatment response monitoring for LGOG and LGA patients.

scholarly journals Identification of miR-20a-5p as Robust Normalizer for Urine microRNA Studies in Renal Cell Carcinoma and A Profile of Dysregulated microRNAs

2021 ◽  
Vol 22 (15) ◽  
pp. 7913
Author(s):  
Julia Oto ◽  
Raquel Herranz ◽  
Emma Plana ◽  
José Vicente Sánchez-González ◽  
Javier Pérez-Ardavín ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Diagnostic Value ◽  
Diagnostic Model ◽  
Low Grade ◽  
Non Invasive ◽  
Good Expression ◽  
Independent Cohort

Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.

scholarly journals A non-invasive method to generate induced pluripotent stem cells from primate urine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Johanna Geuder ◽  
Lucas E. Wange ◽  
Aleksandar Janjic ◽  
Jessica Radmer ◽  
Philipp Janssen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Sendai Virus ◽  
Cell Types ◽  
Urine Samples ◽  
Comparative Approach ◽  
Non Invasive ◽  
Human Ipscs ◽  
Induced Pluripotent

AbstractComparing the molecular and cellular properties among primates is crucial to better understand human evolution and biology. However, it is difficult or ethically impossible to collect matched tissues from many primates, especially during development. An alternative is to model different cell types and their development using induced pluripotent stem cells (iPSCs). These can be generated from many tissue sources, but non-invasive sampling would decisively broaden the spectrum of non-human primates that can be investigated. Here, we report the generation of primate iPSCs from urine samples. We first validate and optimize the procedure using human urine samples and show that suspension- Sendai Virus transduction of reprogramming factors into urinary cells efficiently generates integration-free iPSCs, which maintain their pluripotency under feeder-free culture conditions. We demonstrate that this method is also applicable to gorilla and orangutan urinary cells isolated from a non-sterile zoo floor. We characterize the urinary cells, iPSCs and derived neural progenitor cells using karyotyping, immunohistochemistry, differentiation assays and RNA-sequencing. We show that the urine-derived human iPSCs are indistinguishable from well characterized PBMC-derived human iPSCs and that the gorilla and orangutan iPSCs are well comparable to the human iPSCs. In summary, this study introduces a novel and efficient approach to non-invasively generate iPSCs from primate urine. This will extend the zoo of species available for a comparative approach to molecular and cellular phenotypes.

scholarly journals Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice—Which to Use Regarding Disease Outcomes?

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 414
Author(s):  
Alain Menzel ◽  
Hanen Samouda ◽  
Francois Dohet ◽  
Suva Loap ◽  
Mohammed S. Ellulu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Practice ◽  
Acute Phase Proteins ◽  
Ex Vivo ◽  
Chronic Obstructive ◽  
Low Grade ◽  
Obstructive Pulmonary Disease ◽  
Amyloid A ◽  
Non Invasive ◽  
Markers Of Inflammation

Many chronic conditions such as cancer, chronic obstructive pulmonary disease, type-2 diabetes, obesity, peripheral/coronary artery disease and auto-immune diseases are associated with low-grade inflammation. Closely related to inflammation is oxidative stress (OS), which can be either causal or secondary to inflammation. While a low level of OS is physiological, chronically increased OS is deleterious. Therefore, valid biomarkers of these signalling pathways may enable detection and following progression of OS/inflammation as well as to evaluate treatment efficacy. Such biomarkers should be stable and obtainable through non-invasive methods and their determination should be affordable and easy. The most frequently used inflammatory markers include acute-phase proteins, essentially CRP, serum amyloid A, fibrinogen and procalcitonin, and cytokines, predominantly TNFα, interleukins 1β, 6, 8, 10 and 12 and their receptors and IFNγ. Some cytokines appear to be disease-specific. Conversely, OS—being ubiquitous—and its biomarkers appear less disease or tissue-specific. These include lipid peroxidation products, e.g., F2-isoprostanes and malondialdehyde, DNA breakdown products (e.g., 8-OH-dG), protein adducts (e.g., carbonylated proteins), or antioxidant status. More novel markers include also –omics related ones, as well as non-invasive, questionnaire-based measures, such as the dietary inflammatory-index (DII), but their link to biological responses may be variable. Nevertheless, many of these markers have been clearly related to a number of diseases. However, their use in clinical practice is often limited, due to lacking analytical or clinical validation, or technical challenges. In this review, we strive to highlight frequently employed and useful markers of inflammation-related OS, including novel promising markers.

scholarly journals A 25-year retrospective, single center analysis of 343 WHO grade II/III glioma patients: implications for grading and temozolomide therapy

2021 ◽  
Author(s):  
Eike Steidl ◽  
Katharina Filipski ◽  
Pia S. Zeiner ◽  
Marlies Wagner ◽  
Emmanouil Fokas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Molecular Markers ◽  
Treatment Time ◽  
Real Life ◽  
Patient Characteristics ◽  
Low Grade ◽  
Who Grade ◽  
Idh1 R132h ◽  
Treatment Data ◽  
Grade Ii

Abstract Purpose Classification and treatment of WHO grade II/III gliomas have dramatically changed. Implementing molecular markers into the WHO classification raised discussions about the significance of grading and clinical trials showed overall survival (OS) benefits for combined radiochemotherapy. As molecularly stratified treatment data outside clinical trials are scarce, we conducted this retrospective study. Methods We identified 343 patients (1995–2015) with newly diagnosed WHO grade II/III gliomas and analyzed molecular markers, patient characteristics, symptoms, histology, treatment, time to treatment failure (TTF) and OS. Results IDH-status was available for all patients (259 mutant, 84 IDH1-R132H-non-mutant). Molecular subclassification was possible in 173 tumors, resulting in diagnosis of 80 astrocytomas and 93 oligodendrogliomas. WHO grading remained significant for OS in astrocytomas/IDH1-R132H-non-mutant gliomas (p < 0.01) but not for oligodendroglioma (p = 0.27). Chemotherapy (and temozolomide in particular) showed inferior OS compared to radiotherapy in astrocytomas (median 6.1/12.1 years; p = 0.03) and oligodendrogliomas (median 13.2/not reached (n.r.) years; p = 0.03). While radiochemotherapy improved TTF in oligodendroglioma (median radiochemotherapy n.r./chemotherapy 3.8/radiotherapy 7.3 years; p < 0.001/ = 0.06; OS data immature) the effect, mainly in combination with temozolomide, was weaker in astrocytomas (median radiochemotherapy 6.7/chemotherapy 2.3/radiotherapy 2.0 years; p < 0.001/ = 0.11) and did not translate to improved OS (median 8.4 years). Conclusion This is one of the largest retrospective, real-life datasets reporting treatment and outcome in low-grade gliomas incorporating molecular markers. Current histologic grading features remain prognostic in astrocytomas while being insignificant in oligodendroglioma with interfering treatment effects. Chemotherapy (temozolomide) was less effective than radiotherapy in both astrocytomas and oligodendrogliomas while radiochemotherapy showed the highest TTF in oligodendrogliomas.

scholarly journals BIMG-08. DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY USING 2H-PYRUVATE ALLOWS NON-INVASIVE IN VIVO IMAGING OF TERT EXPRESSION IN BRAIN TUMORS

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i2-i2
Author(s):  
Georgios Batsios ◽  
Celine Taglang ◽  
Meryssa Tran ◽  
Anne Marie Gillespie ◽  
Joseph Costello ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
In Vivo Imaging ◽  
Lactate Production ◽  
Telomere Maintenance ◽  
Resonance Spectroscopy ◽  
Low Grade ◽  
Non Invasive ◽  
Tert Expression

Abstract Telomere shortening constitutes a natural barrier to uncontrolled proliferation and all tumors must find a mechanism of maintaining telomere length. Most human tumors, including high-grade primary glioblastomas (GBMs) and low-grade oligodendrogliomas (LGOGs) achieve telomere maintenance via reactivation of the expression of telomerase reverse transcriptase (TERT), which is silenced in normal somatic cells. TERT expression is, therefore, a driver of tumor proliferation and, due to this essential role, TERT is also a therapeutic target. However, non-invasive methods of imaging TERT are lacking. The goal of this study was to identify magnetic resonance spectroscopy (MRS)-detectable metabolic biomarkers of TERT expression that will enable non-invasive visualization of tumor burden in LGOGs and GBMs. First, we silenced TERT expression by RNA interference in patient-derived LGOG (SF10417, BT88) and GBM (GS2) models. Our results linked TERT silencing to significant reductions in steady-state levels of NADH in all models. NADH is essential for the conversion of pyruvate to lactate, suggesting that measuring pyruvate flux to lactate could be useful for imaging TERT status. Recently, deuterium (2H)-MRS has emerged as a novel, clinically translatable method of monitoring metabolic fluxes in vivo. However, to date, studies have solely examined 2H-glucose and the use of [U-2H]pyruvate for non-invasive 2H-MRS has not been tested. Following intravenous injection of a bolus of [U-2H]pyruvate, lactate production was higher in mice bearing orthotopic LGOG (BT88 and SF10417) and GBM (GS2) tumor xenografts relative to tumor-free mice, suggesting that [U-2H]pyruvate has the potential to monitor TERT expression in vivo. In summary, our study, for the first time, shows the feasibility and utility of [U-2H]pyruvate for in vivo imaging. Importantly, since 2H-MRS can be implemented on clinical scanners, our results provide a novel, non-invasive method of integrating information regarding a fundamental cancer hallmark, i.e. TERT, into glioma patient management.

scholarly journals AST to Platelet Ratio Index (APRI) is an easy-to-use predictor score for cardiovascular risk in metabolic subjects

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carlo De Matteis ◽  
Marica Cariello ◽  
Giusi Graziano ◽  
Stefano Battaglia ◽  
Patrizia Suppressa ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Liver Fibrosis ◽  
Visceral Obesity ◽  
Premenopausal Women ◽  
Cross Sectional Study ◽  
Serum Markers ◽  
Low Grade ◽  
Cross Sectional ◽  
Alcoholic Fatty Liver ◽  
Non Invasive

AbstractVisceral obesity is characterized by a low-grade inflammatory systemic state that contributes to the genesis of non-alcoholic fatty liver disease (NAFLD), frequently associated with liver fibrosis. Non-invasive serum markers have recently emerged as reliable, easy-to-use scores to predict liver fibrosis. NAFLD is often linked to metabolic and cardiovascular risk. Thus, in this cross-sectional study, we investigated in a population of 1225 subjects if AST to Platelet Ratio Index (APRI), one of the non-invasive liver fibrosis serum markers, can predict cardiovascular risk (CVR). APRI has been previously validated as an efficient score to predict liver fibrosis in viral hepatitis patients with a cut-off of 0.5 for fibrosis and 1.5 for cirrhosis. Our study showed that APRI significantly correlates with CVR and determines, when elevated, a significant increase in CVR for both genders, especially females. This spike in CVR, observed when APRI is elevated, is relatively high in patients in the age of 51–65 years, but it is significantly higher in younger and premenopausal women, approaching risk values usually typical of men at the same age. Taken together, our data highlighted the role of APRI as a reliable predictor easy-to-use score for CVR in metabolic patients.

Healthcare Resource Utilization and Healthcare Costs of COVID-19 Patients in A Tertiary Care Public Hospital: A Retrospective Cohort Study in Thailand

2021 ◽  
Vol 104 (12) ◽  
pp. 1953-1958
Keyword(s):  
Linear Regression ◽  
Resource Utilization ◽  
Healthcare Costs ◽  
Healthcare Resource ◽  
Tertiary Care ◽  
Patient Characteristics ◽  
Healthcare Resource Utilization ◽  
Linear Regression Models ◽  
Personal Protection Equipment ◽  
Objective Health

Objective: Health care costs (HCCs) are a significant concern in developing countries. The authors investigated the healthcare resource utilization (HCRU) and HCCs for patients with COVID-19 based on disease severity and infection site. Materials and Methods: The authors reviewed data from the electronic medical records of COVID-19 patients admitted to the present study hospital between January 2020 and April 2020. The authors used comorbidities and patient characteristics as covariates. Analyses were conducted using simple linear regression and generalized linear regression models with a log-link and gamma distribution. Results: Two hundred two patients had confirmed SARS-CoV-2 infection. Total costs per patient were 6,626 USD (756 to 45,586). Personal protection equipment costs were the most significant cost for COVID-19 patients with a mean of 3,778 USD. The mean treatment cost per patient was 326 USD. Patients with severe symptoms and lower respiratory tract infection (LRI) had a higher cost and resource utilization value before and after adjusting for covariates. Conclusion: COVID-19 patients with severe symptoms and LRI had higher HCRU. Length of stay, severity of symptoms, and LRI were associated with higher cost of treatment. Keywords: SARS-CoV-2; COVID-19; Healthcare resource utilization; Healthcare costs; Thailand

Prevalence of underlying malignancies in complex cysts of the breast

2021 ◽  
pp. 1-7
Author(s):  
J.C.W.L. Gerets ◽  
M. Kool ◽  
P.C.G. Simons ◽  
F. Aarts ◽  
F.J. Vogelaar
Keyword(s):  
Healthcare Costs ◽  
Disease Burden ◽  
Watchful Waiting ◽  
Absolute Risk ◽  
Absolute Risk Reduction ◽  
Patient Characteristics ◽  
Number Needed To Treat ◽  
Single Center ◽  
Underlying Malignancy

INTRODUCTION: The management of complex cysts of the breast is an ongoing topic of discussion. The aim of this study was to determine the prevalence of underlying malignancy in radiologically diagnosed complex cysts, and to assess whether watchful waiting could be the preferred method to safely manage complex cysts of the breast. SUBJECTS AND METHODS: A single-center retrospective study was performed between May 2003 and November 2019 in the VieCuri Medical Centre. Women with a radiologically diagnosed complex cyst of the breast were included. Prevalence of underlying malignancy was calculated, as were absolute risk reduction and number needed to treat in order to diagnose malignancy. In addition, patient characteristics were compared to determine characteristics associated with malignancy. RESULTS: Of 78 radiologically diagnosed complex cysts of the breast, five (6,4%) were found to be malignant. The number needed to treat was calculated at 12,8 (absolute riks reduction 0,078). Age (P = 0,003) was associated with malignancy. CONCLUSION: Complex cysts of the breast could be managed more conservatively. Patient characteristics can be used to assess the eligibility for radiological follow-up. This, in turn, would lead to a lower NNT and possibly a decrease in disease burden and healthcare costs.

Sign in / Sign up

Export Citation Format

Share Document