Hindfoot motion according to subtalar compensation and ankle osteoarthritis stage analyzed by a multi-segment foot model.

BACKGROUND: The biomechanics of the hindfoot in ankle osteoarthritis (OA) are not yet fully understood. Here, we aimed to identify hindfoot motion in a gait analysis using a multi-segment foot model (MFM) according to ankle OA stage and the presence of subtalar compensation defined by hindfoot alignment. METHODS: We retrospectively reviewed the medical records, plain radiographs, and gait MFM data of 54 ankles admitted to our hospital for the treatment of advanced ankle OA. Spatiotemporal gait parameters and three-dimensional motions of the hindfoot segment were analyzed according to sex, age, body mass index, Takakura classification, and the presence of subtalar compensation. Twenty ankles were categorized as compensated group, and 34 ankles as decompensated group. RESULTS: No spatiotemporal gait parameters differed significantly according to the presence of subtalar compensation or ankle OA stage. Only normalized step width differed significantly (P = 0.028). Average hindfoot motion (decompensation vs. compensation) did not differ significantly between the sagittal and transverse planes. Graphing of the coronal movement of the hindfoot revealed collapsed curves in both groups that differed significantly. Compared with Takakura stages 3a, 3b, and 4, cases of more advanced stage 3b had a smaller sagittal range of motion than those of stage 3a (P = 0.028). Coronal movement of the hindfoot in cases of Takakura stage 3a/3b/4 showed a relatively flat pattern. CONCLUSIONS: The spatiotemporal parameters were not affected by the hindfoot alignment resulting from subtalar compensation. The sagittal range of hindfoot motion decreased in patients with advanced ankle OA. Once disrupted, the coronal movement of the subtalar joint in ankle OA did not change regardless of ankle OA stage or hindfoot compensation state.

COL6A1 expression as a potential prognostic biomarker for risk stratification of T1 high grade bladder cancer: Unveiling the aggressive nature of a distinct non-muscle invasive subtype.

PURPOSE: T1 high grade (T1HG) bladder cancer (BC) is a type of non-muscle invasive BC (NMIBC) that is recognized as an aggressive subtype with a heightened propensity for progression. Current risk stratification methods for NMIBC rely on clinicopathological indicators; however, these approaches do not adequately capture the aggressive nature of T1HG BC. Thus, new, more accurate biomarkers for T1HG risk stratification are needed. Here, we enrolled three different patient cohorts and investigated expression of collagen type VI alpha 1 (COL6A1), a key component of the extracellular matrix, at different stages and grades of BC, with a specific focus on T1HG BC. MATERIALS AND METHODS: Samples from 298 BC patients were subjected to RNA sequencing and real-time polymerase chain reaction. RESULTS: We found that T1HG BC and muscle invasive BC (MIBC) exhibited comparable expression of COL6A1, which was significantly higher than that by other NMIBC subtypes. In particular, T1HG patients who later progressed to MIBC had considerably higher expression of COL6A1 than Ta, T1 low grade patients, and patients that did not progress, highlighting the aggressive nature and higher risk of progression associated with T1HG BC. Moreover, Cox and Kaplan-Meier survival analyses revealed a significant association between elevated expression of COL6A1 and poor progression-free survival of T1HG BC patients (multivariate Cox hazard ratio, 16.812; 95% confidence interval, 3.283-86.095; p=0.001 and p=0.0002 [log-rank test]). CONCLUSIONS: These findings suggest that COL6A1 may be a promising biomarker for risk stratification of T1HG BC, offering valuable insight into disease prognosis and guidance of personalized treatment decisions.

Use of lateral-exit crossed-pin fixation for pediatric supracondylar humeral fractures: a retrospective case series.

Surgeons have been reluctant to perform crossed-pin fixation for displaced pediatric supracondylar humeral (SCH) fractures because it carries a risk of iatrogenic ulnar nerve injury. This study aimed to introduce lateral-exit crossed-pin fixation for displaced pediatric SCH fractures and to evaluate its clinical and radiological outcomes, with a particular focus on iatrogenic ulnar nerve injuries. Children who underwent lateral-exit crossed-pin fixation for displaced SCH fractures between 2010 and 2015 were retrospectively reviewed. Lateral-exit crossed-pin fixation involved the introduction of a medial pin from the medial epicondyle, as in the conventional method, followed by pulling the pin through the lateral skin until the distal and medial aspects of the pin were just under the cortex of the medial epicondyle. The time to union and loss of fixation were assessed. Flynn's clinical criteria (cosmetic and functional factors) and complications including iatrogenic ulnar nerve injury were investigated. A total of 81 children with displaced SCH fractures were treated with lateral-exit crossed-pin fixation. All but one patient achieved union with good alignment, with an average time to union of 7.9 weeks (3.9-10.3 weeks). Only one patient exhibited cubitus varus deformity associated with loss of reduction. All patients recovered to almost their full range of motion. No case of iatrogenic ulnar nerve injury developed; however, iatrogenic radial nerve injury developed in one patient. Lateral-exit crossed-pin fixation provides sufficient stability with a lower risk of iatrogenic ulnar nerve injury in children with displaced SCH fractures. This method is an acceptable technique for crossed-pin fixation.

Black Bone Disease: Ochronotic Arthritis Detected during Knee Arthroplasty.

Alkaptonuria is an extremely rare autosomal recessive metabolic disorder characterized by dark urine, ochronosis, and arthritis of the spine and major joints. We report a case of ochronotic arthritis observed during total knee replacement surgery in a 65-year-old male patient with no relevant medical history. Based on a literature review, this is the first case of ochronotic arthritis reported in Korea.

Clinical and radiological outcomes of surgically treated osteochondral lesions of the talus in children and adolescents.

Background: Osteochondral lesions of the talus are uncommon in children and adolescents. Surgical procedures differ from those used for adults to avoid iatrogenic physeal injuries. This study aimed to evaluate the clinical and radiological outcomes of surgical treatment in pediatric patients with osteochondral lesions, specifically investigating the patient age and the status of distal tibial physis as factors associated with surgical success. Methods: We retrospectively reviewed 28 patients who had symptomatic osteochondral lesions of the talus that were treated surgically between 2003 and 2016. If the lesion was stable and articular cartilage was intact, retrograde drilling was performed under fluoroscopic guidance. Lesions with detached overlying cartilages were treated by debridement of the cartilage combined with microfracture and drilling. Radiographic outcomes, American Orthopaedic Foot & Ankle Society ankle-hindfoot score, and skeletal maturity were evaluated. Results: Radiological improvement was observed in 24 (24/28, 86%) patients and complete and incomplete healing in 8 and 16 patients, respectively. Changes in pain grades, American Orthopaedic Foot & Ankle Society scores, and radiological healing after surgery were significant (pain grade, p < 0.001; American Orthopaedic Foot & Ankle Society, p = 0.018; radiological healing, p < 0.001). In addition, patients in the younger age group (≤13 years) showed greater improvements in pain grades than older patients (p = 0.02). Improvement in pain grade after surgery was better in the skeletally immature group than in the skeletally mature group (p = 0.048). Conclusion: Clinical and radiological improvements were observed after surgical treatment. The younger age group and open physis group showed more pain improvement. Level of evidence: Therapeutic level IV.

Computed tomography arthrography versus magnetic resonance imaging for diagnosis of osteochondral lesions of the talus.

INTRODUCTION: Osteochondral lesions of the talus (OLT) usually have non-specific clinical symptoms, and radiographs have a low sensitivity for detecting OLT. The purpose of this study is to compare the diagnostic value of CT arthrography (CTa) with that of MRI using arthroscopy as the reference standard for grading OLT. MATERIALS AND METHODS: We retrospectively reviewed patients who had OLT between 2015 and 2020. Patients with symptomatic OLT as a surgical indication, who were treated arthroscopically, and underwent both CTa and MRI before surgery were included. OLT was evaluated by both CTa and MRI using arthroscopy as the standard. We graded CTa, MRI, arthroscopic findings using Mintz classification. RESULTS: Thirty-five patients were included. Accuracy rates of MRI and CTa for grading OLT, compared to those of arthroscopy, were 57.1% and 88.6%, respectively. Among 15 mismatched cases in MRI, 12 lesions (80%) were matched in CTa and arthroscopy. CTa had significantly higher diagnostic performance than MRI for the detection of grade III lesions (p = 0.041). Using the receiver operating characteristics curves, the area under the curve values for lesion grading were 0.893 for CTa and 0.762 for MRI. CONCLUSION: CTa was statistically significantly better in detecting chondral flapping or subchondral exposure lesions for OLT than MRI on using arthroscopy as the reference standard. Because the stability of the OLT is essential in determining the treatment method, if an OLT is observed on MRI and is suspected to cause ankle pain, we recommend additional CTa examination to determine the more correct treatment strategies for OLT. LEVEL OF EVIDENCE: Diagnostic Level III.

Current treatment patterns within 1 year after prostate cancer diagnosis in Korean patients over 75 years old: a retrospective multicenter study.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

A New Treatment Landscape for RCC: Association of the Human Microbiome with Improved Outcomes in RCC.

Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes.

Efficacy of Far Cortical Locking Screws in Treating Distal Tibia Fractures in Comparison With That of Standard Locking Screws.

There are no clinical studies about treatment of distal tibia fractures using far cortical locking (FCL) screws, even though it has been shown to be superior to standard locking screws in biomechanical studies. We compared the efficacy of FCL screws to that of traditional locking screws. Twenty-five distal tibia fractures were treated with minimally invasive plate osteosynthesis using traditional locking screws, whereas 20 were treated using FCL screws. We retrospectively compared time taken for callus formation and radiographic bone union between 2 groups. The effect of age, sex, diabetes, and smoking history on bone healing was analyzed. Complications were also noted. As a result, there was no significant difference in age (p = .292), sex (p = 1.0), diabetes (p = 1.0), or smoking history (p = .704) between 2 groups. Time to callus formation was 77.5 days in the FCL group, and 96 days in the traditional group (p = .023). Average time to bone union was 134.8 days, and 163.1 days in the FCL group and the traditional group, respectively (p = .017). There was one case of screw loosening in the FCL group, and one case of screw breakage in the traditional group. This study suggests that FCL screws promote quicker healing of distal tibia fractures than traditional locking screws.

Foot and Ankle Motion after Tibiotalocalcaneal Arthrodesis: Comparison with Tibiotalar Arthrodesis Using a Multi-Segment Foot Model.

Background: Tibiotalocalcaneal arthrodesis is an established surgical procedure for treating patients with end-stage ankle joint arthritis and subtalar joint arthritis. Although it greatly relives pain, a major drawback is loss of range of motion. Although it is known to restrict an additional subtalar joint compared to tibiotalar arthrodesis, there is a lack of gait analysis studies comparing the two methods. This study aimed to evaluate the differences in kinematics of the foot and ankle joints between tibiotalar and tibiotalocalcaneal arthrodesis. We also compared preoperative and postoperative statuses for each surgical method. Methods: The study included 12 and 9 patients who underwent tibiotalar and tibiotalocalcaneal arthrodesis, respectively, and 40 healthy participants were included in the control group. The DuPont foot model was used to analyze intersegmental foot and ankle kinematics during gait. Results: Compared to controls, both tibiotalar and tibiotalocalcaneal arthrodesis resulted in slow gait speed with reduced stride length, increased step width, and decreased range of sagittal plane motion. Both fusion methods showed similar range of motion in all segments and planes following surgery. Coronal positions showed more supination of the forefoot and pronation of the hindfoot segment after each operation, particularly tibiotalocalcaneal arthrodesis. Gait after tibiotalocalcaneal arthrodesis did not significantly differ from that after tibiotalar arthrodesis, but there was a tendency of more pronation in the hindfoot segment. Conclusions: Both fusion methods limited foot and ankle motion in similar ways. Comparing tibiotalar and tibiotalocalcaneal arthrodesis suggests that additionally fusing the subtalar joint does not cause greater movement restriction in patients. Objectively comparing tibiotalar and tibiotalocalcaneal arthrodesis will facilitate further understanding of the effect of tibiotalocalcaneal arthrodesis on movement and the value of subtalar joint motion for improved preoperative counselling.

Pressure Properties of Three Different Types of Prefabricated Insoles Related to Plantar Pressure in Asymptomatic Men.

Background: In clinical fields, many types of insoles are used to not only realign movement patterns, but also treat pressure-related foot diseases. However, the characteristics of and plantar pressure in each type of insole are still unclear. Therefore, the aim of this study was to validate the plantar pressure-relieving effect of three representative types of insoles (metatarsal padding insole [MPI], lateral heel wedge insole [LHI], and arch support insole [ASI]) in asymptomatic men. Methods: A total of 35 feet of 35 asymptomatic men with a mean age of 23.4 ± 2.0 years were included. Pedobarographic data were evaluated by dividing the foot into eight designated regions to compare the three types of insoles. Peak plantar pressure (PPP) and pressure time integral (PTI) were assessed using the Pedar-X system. A repeated measures analysis of variance was used for statistical analyses. Results: In the hallux region, there was no statistically significant difference. MPI showed highest pressure in the 2nd-5th toe and midfoot region, but lowest in the central and lateral forefoot regions. Meanwhile, ASI showed highest pressure in the medial forefoot region but lowest in the lateral heel region. Lastly, pressure in the lateral heel region was highest in LHI. Overall, results of PTI were similar to those of PPP. Conclusions: This study demonstrated that the three types of insole each could reduce and redistribute pressure of specific part of the foot to help select an appropriate insole for each purpose.

Utility of a Molecular Signature for Predicting Recurrence and Progression in Non-Muscle-Invasive Bladder Cancer Patients: Comparison with the EORTC, CUETO and 2021 EAU Risk Groups.

To evaluate the utility of different risk assessments in non-muscle-invasive bladder cancer (NMIBC) patients, a total of 178 NMIBC patients from Chungbuk National University Hospital (CBNUH) were enrolled, and the predictive value of the molecular signature-based subtype predictor (MSP888) and risk calculators based on clinicopathological factors (EORTC, CUETO and 2021 EAU risk scores) was compared. Of the 178 patients, 49 were newly analyzed by the RNA-sequencing, and their MSP888 subtype was evaluated. The ability of the EORTC, MSP888 and two molecular subtyping systems of bladder cancer (Lund and UROMOL subtypes) to predict progression of 460 NMIBC patients from the UROMOL project was assessed. Cox regression analyses showed that the MSP888 was an independent predictor of NMIBC progression in the CBNUH cohort (p = 0.043). Particularly in patients without an intravesical BCG immunotherapy, MSP888 significantly linked with risk of disease recurrence and progression (both p < 0.05). However, the EORTC, CUETO and 2021 EAU risk scores showed disappointing results with respect to estimating the NMIBC prognosis. In the UROMOL cohort, the MSP888, Lund and UROMOL subtypes demonstrated a similar capacity to predict NMIBC progression (all p < 0.05). Conclusively, the MSP888 is favorable for stratifying patients to facilitate optimal treatment.

Study on the use of Nanostring nCounter to analyze RNA extracted from formalin-fixed-paraffin-embedded and fresh frozen bladder cancer tissues.

Formalin-fixed paraffin-embedded (FFPE) tissue is the most common source of archived material for genomic medicine. However, FFPE tissue is suboptimal for high-throughput analyses, such as RNA sequencing, because the quality of nucleic acids in FFPE tissues is low. We compared RNA-seq with the nCounter system to evaluate use of FFPE tissue for genomic medicine. Twelve fresh frozen bladder cancer samples were analyzed by both RNA sequencing and nCounter, and matched FFPE samples, by nCounter. Gene-expression values obtained by these two platforms were compared by calculating Pearson correlation coefficients for each sample (across the set of matched genes) and for each matched gene (across the set of samples). For each sample, gene-expression levels measured by RNA sequencing highly correlated with those measured by nCounter (all Pearson's R > 0.8, P < 0.0001), as seen by hierarchical clustering. RNA sequencing results for fresh frozen tissues positively correlated with nCounter results for FFPE tissues (R ranged from 0.675 to 0.873, all P < 0.0001). Correlation and hierarchical-clustering analyses of nCounter data from the two specimens demonstrated a strong positive correlation between each group (R ranged from 0.779 to 0.977, all P < 0.0001). Our findings suggest that the nCounter system is useful for assaying archived-FFPE samples and that the gene-expression signatures obtained from FFPE samples represent those from fresh frozen tissues.

Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways.

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.

Expression of RPL9 predicts the recurrence of non-muscle invasive bladder cancer with BCG therapy.

Numerous biomarkers and risk tables can be used to predict recurrence or progression of patients with primary or recurrent non-muscle invasive bladder cancer (NMIBC) receiving Bacillus Calmette-Guerin (BCG). However, few are suitable for BCG-unresponsive disease (i.e., recurrence or progression after BCG treatment). Therefore, identification of a novel marker that allows accurate prediction of prognosis, particularly risk of recurrence, is critically important in clinical practice. In the current study, gene ontology and gene set enrichment analyses of microarray datasets (GSE13507, n = 47) revealed that differentially expressed genes in recurred NMIBC patients after BCG treatment were associated with virus and ribosomal pathways. Among the core-enrichment genes, the expression of RPL9, a putative tumor suppressor, was lower in recurred NMIBC patients after BCG therapy than in patients without recurrence (P = 0.033) from the E-MTAT-4321 European cohort (n = 84). Data from The Cancer Genome Atlas (n = 406) showed that bladder cancer patients with higher RPL9 expression had a longer overall survival probability than patients with lower RPL9 expression (P = 0.011). Moreover, we used the latest digital PCR platform to examine 59 NMIBC patients and identified downregulation of RPL9 in patients with recurrence after BCG therapy (P = 0.031). The Kaplan-Meier survival estimator showed that NMIBC patients with higher expression of RPL9 had longer recurrence-free survival (log-rank test, P = 0.015). Therefore, we conclude that RPL9 expression is a prospective predictor of recurrence after BCG therapy in NMIBC patients.

Coronal plane Calcaneal-Talar Orientation in Varus Ankle Osteoarthritis.

BACKGROUND: We do not yet fully understand how the subtalar joint position is related to the varus osteoarthritic ankle joint. The purposes of this study were (1) to investigate the coronal orientation of the calcaneus relative to the talus according to the ankle osteoarthritis stage, talar tilt (TT), and (2) to determine if there is TT threshold at which apparent subtalar compensation begins to fade. METHODS: We retrospectively reviewed 132 ankles that underwent weightbearing computed tomography (WBCT) for varus ankle osteoarthritis. The TT, subtalar inclination angle (SIA), and calcaneal inclination angle (CIA) were measured using WBCT. Ankles were divided into 5 groups according to Takakura stage and 2 groups according to the apparent compensation status of the subtalar joint and compared the index of the inclination of the subtalar joint relative to the ankle (SIA) or the index of the inclination of the calcaneus relative to the ankle (CIA). Additionally, we explored the relationship between SIA or CIA and the TT. RESULTS: Apparent subtalar compensation (SIA and CIA) was significantly lower in Takakura stages 3b and 4. The SIA and CIA significantly differed according to the apparent compensation status (P < .001 and P = .030, respectively). The CIA of the noncompensated group varied widely, whereas the SIA was relatively constant. Furthermore, TT was greater than 9.5, which indicated a high probability of a noncompensated heel (sensitivity, 92.6%; specificity, 89.7%). CONCLUSION: The position of the calcaneus appears compensatory with coronal plane orientation in varus ankle osteoarthritis when the TT is ≤9.5 degrees. LEVEL OF EVIDENCE: Level IV, case series.

Prevalence and Risk Factors of T-Score Spine-Hip Discordance in Patients with Osteoporotic Vertebral Compression Fracture.

BACKGROUND: T-score discordance between the spine and hip is commonly observed when dual energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis. However, information is scarce regarding the prevalence and risk factors for this problem in Korea. This study evaluated the prevalence of major/minor discordance and associated risk factors in elderly Korean patients with osteoporotic vertebral compression fractures (OVCFs). METHODS: This study included 200 patients (37 men, 163 women) treated for thoracic or lumbar compression fractures between January 2015 and August 2021. DXA was performed to examine T-scores and determine the prevalence of discordance, defined as a difference between the T-score categories of the femur and spine in the same individual. The t-tests, χ2 tests, and regression analyses were used to assess the associated risk factors of T-score discordance among the subjects. RESULTS: T-score concordance, minor discordance, and major discordance were observed in 137 (68.5%), 59 (29.5%), and 4 (2%) patients with OVCFs, respectively. The spinal T-score was lower than the femoral T-score in all major discordance and 81.3% (48/59) of minor discordant cases. Overall, the only factor related to T-score discordance was the age at fracture (odds ratio, -0.01; P=0.014). CONCLUSIONS: The results of this study showed that a significant number of subjects (31.5%) showed spine-hip discordance, even with a mean age in their 80s. More attention should be paid to the appropriate evaluation and management of elderly patients with OVCFs. Moreover, a longitudinal study is necessary to verify the clinical importance of T-score discordance in this population.

Urinary hsv2-miR-H9 to hsa-miR-3659 ratio is an effective marker for discriminating prostate cancer from benign prostate hyperplasia in patients within the prostate-specific antigen grey zone.

PURPOSE: Tumor microRNAs (miRNAs) are released to biofluids directly or indirectly. Although urinary miRNAs are promising non-invasive biomarkers for the diagnosis of prostate cancer (PCa), their clinical application is challenging for technical reasons. We examined the efficacy of urinary hsv2-miR-H9 to hsa-miR-3659 ratio as a non-invasive diagnostic biomarker of PCa. MATERIALS AND METHODS: The expression of urinary miRNAs was quantified by real-time PCR in 116 samples from 53 patients with benign prostatic hyperplasia (BPH) and 63 patients with PCa. The miRNA expression ratio was calculated using an upregulated miRNA (hsv2-miR-H9) as the numerator and a downregulated miRNA (hsa-miR-3659) as the denominator. RESULTS: The urinary miR-H9 to miR-3659 ratio was significantly higher in PCa than in BPH controls (p<0.001). The diagnostic accuracy of the urinary miRNA expression ratio was comparable with that of prostate-specific antigen (PSA) (receiver operating characteristic [ROC] curve comparison, p=0.287). The area under the curve for urinary miRNA expression ratio was 0.862 and that for PSA was 0.642 in the "PSA gray zone" (3-10 ng/mL) (ROC curve comparison, p=0.034). The use of the urinary miRNA expression ratio would have prevented 70.6% of unnecessary prostate biopsies; however, 28.6% of PCa cases could be missed in patients within the PSA gray zone. CONCLUSIONS: The expression ratio of urinary miR-H9 to miR-3659 could be a relevant non-invasive biomarker for PCa diagnosis, particularly for patients within the PSA gray zone.