The association of sexual orientation with prostate, breast, and cervical cancer screening and diagnosis.

PURPOSE: Data on heterogeneity in cancer screening and diagnosis rates among lesbians/gays and bisexuals (LGBs) is lacking. Recent studies showed that LGBs have decreased healthcare utilization compared to heterosexual counterparts. Few studies have examined how sexual orientation impacts cancer screening and prevalence. We, therefore, investigated the association between sexual orientation and prevalent sex-specific cancer including prostate (PCa), breast (BC), and cervical (CC) cancer. METHODS: This was a cross-sectional survey-based US study, including men and women aged 18 + from the Health Information National Trends Survey (HINTS) database between 2017 and 2019. The primary endpoint was individual-reported prostate, breast, and cervical cancer screening and prevalence rates among heterosexual and LGB men and women. Multivariable logistic regression analyses assessed association of various covariates with undergoing screening and diagnosis of these cancers. RESULTS: Overall, 4,441 and 6,333 heterosexual men and women, respectively, were compared to 225 and 213 LGB men and women, respectively. LGBs were younger and less likely to be screened for PCa, BC, and CC than heterosexuals. A higher proportion of heterosexual women than lesbian and bisexual women were screened for CC with pap smears (95.36% vs. 90.48% and 86.11%, p ≤ 0.001) and BC with mammograms (80.74% vs. 63.81% and 45.37%, p ≤ 0.001). Similarly, a higher proportion of heterosexual men than gay and bisexual men were screened for PCa with PSA blood tests (41.27% vs. 30.53% and 27.58%, p ≤ 0.001). CONCLUSION: There were more heterosexuals than LGBs screened for CC, BC, and PCa. However, no association between sexual orientation and cancer diagnosis was found. Healthcare professionals should be encouraged to improve cancer screening among LGBs.

The flavivirus polymerase NS5 regulates translation of viral genomic RNA.

Flaviviruses, including dengue virus and Zika virus, contain a single-stranded positive sense RNA genome that encodes viral proteins essential for replication and also serves as the template for new genome synthesis. As these processes move in opposite directions along the genome, translation must be inhibited at a defined point following infection to clear the template of ribosomes to allow efficient replication. Here, we demonstrate in vitro and in cell-based assays that the viral RNA polymerase, NS5, inhibits translation of the viral genome. By reconstituting translation in vitro using highly purified components, we show that this translation block occurs at the initiation stage and that translation inhibition depends on NS5-RNA interaction, primarily through association with the 5' replication promoter region. This work supports a model whereby expression of a viral protein signals successful translation of the infecting genome, prompting a switch to a ribosome depleted replication-competent form.

Prognostic Features of Biochemical Recurrence of Prostate Cancer Following Radical Prostatectomy Based on Multiparametric MRI and Immunohistochemistry Analysis of MRI-guided Biopsy Specimens.

Background Although prostate MRI is routinely used for the detection and staging of localized prostate cancer, imaging-based assessment and targeted molecular sampling for risk stratification are an active area of research. Purpose To evaluate features of preoperative MRI and MRI-guided biopsy immunohistochemistry (IHC) findings associated with biochemical recurrence (BCR) of prostate cancer after surgery. Materials and Methods In this retrospective case-control study, patients underwent multiparametric MRI before MRI-guided biopsy followed by radical prostatectomy between 2008 and 2016. Lesions were retrospectively scored with the Prostate Imaging Reporting and Data System (PI-RADS) (version 2) by radiologists who were blinded to the clinical-pathologic results. The IHC staining, including stains for the ETS-related gene, phosphatase and tensin homolog, androgen receptor, prostate specific antigen, and p53, was performed with targeted biopsy specimens of the index lesion (highest suspicion at MRI and pathologic grade) and scored by pathologists who were blinded to clinical-pathologic outcomes. Cox proportional hazards regression analysis was used to evaluate associations with recurrence-free survival (RFS). Results The median RFS was 31.7 months (range, 1-101 months) for 39 patients (median age, 62 years; age range, 47-76 years) without BCR and 14.6 months (range, 1-61 months) for 40 patients (median age, 59 years; age range, 47-73 years) with BCR. MRI features that showed a significant relationship with the RFS interval included an index lesion with a PI-RADS score of 5 (hazard ratio [HR], 2.10; 95% CI: 1.05, 4.21; P = .04); index lesion burden, defined as ratio of index lesion volume to prostate volume (HR, 1.55; 95% CI: 1.2, 2.1; P = .003); and suspicion of extraprostatic extension (EPE) (HR, 2.18; 95% CI: 1.1, 4.2; P = .02). Presurgical multivariable analysis indicated that suspicion of EPE at MRI (adjusted HR, 2.19; 95% CI: 1.1, 4.3; P = .02) and p53 stain intensity (adjusted HR, 2.22; 95% CI: 1.0, 4.7; P = .04) were significantly associated with RFS. Conclusion MRI features, including Prostate Imaging Reporting and Data System score, index lesion burden, extraprostatic extension, and preoperative guided biopsy p53 immunohistochemistry stain intensity are associated with biochemical relapse of prostate cancer after surgery. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Costa in this issue.

High throughput assessment of biomarkers in tissue microarrays using artificial intelligence: PTEN loss as a proof-of-principle in multi-center prostate cancer cohorts.

Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and has clinical potential as a prognostic biomarker. The objective of this work was to develop an artificial intelligence (AI) system for automated detection and localization of PTEN loss on immunohistochemically (IHC) stained sections. PTEN loss was assessed using IHC in two prostate tissue microarrays (TMA) (internal cohort, n = 272 and external cohort, n = 129 patients). TMA cores were visually scored for PTEN loss by pathologists and, if present, spatially annotated. Cores from each patient within the internal TMA cohort were split into 90% cross-validation (N = 2048) and 10% hold-out testing (N = 224) sets. ResNet-101 architecture was used to train core-based classification using a multi-resolution ensemble approach (×5, ×10, and ×20). For spatial annotations, single resolution pixel-based classification was trained from patches extracted at ×20 resolution, interpolated to ×40 resolution, and applied in a sliding-window fashion. A final AI-based prediction model was created from combining multi-resolution and pixel-based models. Performance was evaluated in 428 cores of external cohort. From both cohorts, a total of 2700 cores were studied, with a frequency of PTEN loss of 14.5% in internal (180/1239) and external 13.5% (43/319) cancer cores. The final AI-based prediction of PTEN status demonstrated 98.1% accuracy (95.0% sensitivity, 98.4% specificity; median dice score = 0.811) in internal cohort cross-validation set and 99.1% accuracy (100% sensitivity, 99.0% specificity; median dice score = 0.804) in internal cohort test set. Overall core-based classification in the external cohort was significantly improved in the external cohort (area under the curve = 0.964, 90.6% sensitivity, 95.7% specificity) when further trained (fine-tuned) using 15% of cohort data (19/124 patients). These results demonstrate a robust and fully automated method for detection and localization of PTEN loss in prostate cancer tissue samples. AI-based algorithms have potential to streamline sample assessment in research and clinical laboratories.

CT and clinical assessment in asymptomatic and pre-symptomatic patients with early SARS-CoV-2 in outbreak settings.

OBJECTIVES: The early infection dynamics of patients with SARS-CoV-2 are not well understood. We aimed to investigate and characterize associations between clinical, laboratory, and imaging features of asymptomatic and pre-symptomatic patients with SARS-CoV-2. METHODS: Seventy-four patients with RT-PCR-proven SARS-CoV-2 infection were asymptomatic at presentation. All were retrospectively identified from 825 patients with chest CT scans and positive RT-PCR following exposure or travel risks in outbreak settings in Japan and China. CTs were obtained for every patient within a day of admission and were reviewed for infiltrate subtypes and percent with assistance from a deep learning tool. Correlations of clinical, laboratory, and imaging features were analyzed and comparisons were performed using univariate and multivariate logistic regression. RESULTS: Forty-eight of 74 (65%) initially asymptomatic patients had CT infiltrates that pre-dated symptom onset by 3.8 days. The most common CT infiltrates were ground glass opacities (45/48; 94%) and consolidation (22/48; 46%). Patient body temperature (p < 0.01), CRP (p < 0.01), and KL-6 (p = 0.02) were associated with the presence of CT infiltrates. Infiltrate volume (p = 0.01), percent lung involvement (p = 0.01), and consolidation (p = 0.043) were associated with subsequent development of symptoms. CONCLUSIONS: COVID-19 CT infiltrates pre-dated symptoms in two-thirds of patients. Body temperature elevation and laboratory evaluations may identify asymptomatic patients with SARS-CoV-2 CT infiltrates at presentation, and the characteristics of CT infiltrates could help identify asymptomatic SARS-CoV-2 patients who subsequently develop symptoms. The role of chest CT in COVID-19 may be illuminated by a better understanding of CT infiltrates in patients with early disease or SARS-CoV-2 exposure. KEY POINTS: • Forty-eight of 74 (65%) pre-selected asymptomatic patients with SARS-CoV-2 had abnormal chest CT findings. • CT infiltrates pre-dated symptom onset by 3.8 days (range 1-5). • KL-6, CRP, and elevated body temperature identified patients with CT infiltrates. Higher infiltrate volume, percent lung involvement, and pulmonary consolidation identified patients who developed symptoms.

Circularization of flavivirus genomic RNA inhibits de novo translation initiation.

Members of the Flaviviridae family, including dengue virus (DENV) and yellow fever virus, cause serious disease in humans, whilst maternal infection with Zika virus (ZIKV) can induce microcephaly in newborns. Following infection, flaviviral RNA genomes are translated to produce the viral replication machinery but must then serve as a template for the transcription of new genomes. However, the ribosome and viral polymerase proceed in opposite directions along the RNA, risking collisions and abortive replication. Whilst generally linear, flavivirus genomes can adopt a circular conformation facilitated by long-range RNA-RNA interactions, shown to be essential for replication. Using an in vitro reconstitution approach, we demonstrate that circularization inhibits de novo translation initiation on ZIKV and DENV RNA, whilst the linear conformation is translation-competent. Our results provide a mechanism to clear the viral RNA of ribosomes in order to promote efficient replication and, therefore, define opposing roles for linear and circular conformations of the flavivirus genome.

Deep-Learning-Based Artificial Intelligence for PI-RADS Classification to Assist Multiparametric Prostate MRI Interpretation: A Development Study.

BACKGROUND: The Prostate Imaging Reporting and Data System (PI-RADS) provides guidelines for risk stratification of lesions detected on multiparametric MRI (mpMRI) of the prostate but suffers from high intra/interreader variability. PURPOSE: To develop an artificial intelligence (AI) solution for PI-RADS classification and compare its performance with an expert radiologist using targeted biopsy results. STUDY TYPE: Retrospective study including data from our institution and the publicly available ProstateX dataset. POPULATION: In all, 687 patients who underwent mpMRI of the prostate and had one or more detectable lesions (PI-RADS score >1) according to PI-RADSv2. FIELD STRENGTH/SEQUENCE: T2 -weighted, diffusion-weighted imaging (DWI; five evenly spaced b values between b = 0-750 s/mm2 ) for apparent diffusion coefficient (ADC) mapping, high b-value DWI (b = 1500 or 2000 s/mm2 ), and dynamic contrast-enhanced T1 -weighted series were obtained at 3.0T. ASSESSMENT: PI-RADS lesions were segmented by a radiologist. Bounding boxes around the T2 /ADC/high-b value segmentations were stacked and saved as JPEGs. These images were used to train a convolutional neural network (CNN). The PI-RADS scores obtained by the CNN were compared with radiologist scores. The cancer detection rate was measured from a subset of patients who underwent biopsy. STATISTICAL TESTS: Agreement between the AI and the radiologist-driven PI-RADS scores was assessed using a kappa score, and differences between categorical variables were assessed with a Wald test. RESULTS: For the 1034 detection lesions, the kappa score for the AI system vs. the expert radiologist was moderate, at 0.40. However, there was no significant difference in the rates of detection of clinically significant cancer for any PI-RADS score in 86 patients undergoing targeted biopsy (P = 0.4-0.6). DATA CONCLUSION: We developed an AI system for assignment of a PI-RADS score on segmented lesions on mpMRI with moderate agreement with an expert radiologist and a similar ability to detect clinically significant cancer. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Prospective Evaluation of PI-RADS Version 2.1 for Prostate Cancer Detection.

OBJECTIVE. The purpose of this study was to prospectively evaluate Prostate Imaging Reporting and Data and System version 2.1 (PI-RADSv2.1), which was released in March 2019 to update version 2.0, for prostate cancer detection with transrectal ultrasound-MRI fusion biopsy and 12-core systematic biopsy. SUBJECTS AND METHODS. This prospective study included 110 consecutively registered patients who underwent multiparametric MRI evaluated with PI-RADSv2.1 criteria followed by fusion biopsy and systematic biopsy between April and September 2019. Lesion-based cancer detection rates (CDRs) were calculated for prostate cancer (Gleason grade group, > 0) and clinically significant prostate cancer (Gleason grade group, > 1). RESULTS. A total of 171 lesions (median size, 1.1 cm) in 110 patients were detected and evaluated with PI-RADSv2.1. In 16 patients no lesion was detected, and only systematic biopsy was performed. Lesions were categorized as follows: PI-RADS category 1, 1 lesion; PI-RADS category 2, 34 lesions; PI-RADS category 3, 54 lesions; PI-RADS category 4, 52 lesions; and PI-RADS category 5, 30 lesions. Histopathologic analysis revealed prostate cancer in 74 of 171 (43.3%) lesions and clinically significant prostate cancer in 57 of 171 (33.3%) lesions. The CDRs of prostate cancer for PI-RADS 2, 3, 4, and 5 lesions were 20.0%, 24.1%, 51.9%, and 90.0%. The CDRs of clinically significant prostate cancer for PI-RADS 1, 2, 3, 4, and 5 lesions were 0%, 5.7%, 14.8%, 44.2%, and 80.0%. In 16 patients with normal multiparametric MRI findings (PI-RADS 1), the CDRs were 50.0% for PCa and 18.8% for clinically significant prostate cancer. CONCLUSION. This investigation yielded CDRs assessed with prospectively assigned PI-RADSv2.1 scores. CDRs increased with higher PI-RADSv2.1 scores. These results can be compared with previously published outcomes derived with PI-RADS version 2.0.

Data Augmentation and Transfer Learning to Improve Generalizability of an Automated Prostate Segmentation Model.

OBJECTIVE. Deep learning applications in radiology often suffer from overfitting, limiting generalization to external centers. The objective of this study was to develop a high-quality prostate segmentation model capable of maintaining a high degree of performance across multiple independent datasets using transfer learning and data augmentation. MATERIALS AND METHODS. A retrospective cohort of 648 patients who underwent prostate MRI between February 2015 and November 2018 at a single center was used for training and validation. A deep learning approach combining 2D and 3D architecture was used for training, which incorporated transfer learning. A data augmentation strategy was used that was specific to the deformations, intensity, and alterations in image quality seen on radiology images. Five independent datasets, four of which were from outside centers, were used for testing, which was conducted with and without fine-tuning of the original model. The Dice similarity coefficient was used to evaluate model performance. RESULTS. When prostate segmentation models utilizing transfer learning were applied to the internal validation cohort, the mean Dice similarity coefficient was 93.1 for whole prostate and 89.0 for transition zone segmentations. When the models were applied to multiple test set cohorts, the improvement in performance achieved using data augmentation alone was 2.2% for the whole prostate models and 3.0% for the transition zone segmentation models. However, the best test-set results were obtained with models fine-tuned on test center data with mean Dice similarity coefficients of 91.5 for whole prostate segmentation and 89.7 for transition zone segmentation. CONCLUSION. Transfer learning allowed for the development of a high-performing prostate segmentation model, and data augmentation and fine-tuning approaches improved performance of a prostate segmentation model when applied to datasets from external centers.

IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA.

Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed during the cell-intrinsic immune response to viral infection. IFIT1 inhibits translation by binding directly to the 5' end of foreign RNAs, particularly those with non-self cap structures, precluding the recruitment of the cap-binding eukaryotic translation initiation factor 4F and ribosome recruitment. The presence of IFIT1 imposes a requirement on viruses that replicate in the cytoplasm to maintain mechanisms to avoid its restrictive effects. Interaction of different IFIT family members is well described, but little is known of the molecular basis of IFIT association or its impact on function. Here, we reconstituted different complexes of IFIT1, IFIT2 and IFIT3 in vitro, which enabled us to reveal critical aspects of IFIT complex assembly. IFIT1 and IFIT3 interact via a YxxxL motif present in the C-terminus of each protein. IFIT2 and IFIT3 homodimers dissociate to form a more stable heterodimer that also associates with IFIT1. We show for the first time that IFIT3 stabilizes IFIT1 protein expression, promotes IFIT1 binding to a cap0 Zika virus reporter mRNA and enhances IFIT1 translation inhibition. This work reveals molecular aspects of IFIT interaction and provides an important missing link between IFIT assembly and function.

Use of multiparametric magnetic resonance imaging and fusion-guided biopsies to properly select and follow African-American men on active surveillance.

OBJECTIVES: To determine the rate of Gleason Grade Group (GGG) upgrading in African-American (AA) men with a prior diagnosis of low-grade prostate cancer (GGG 1 or GGG 2) on 12-core systematic biopsy (SB) after multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB); and whether AA men who continued active surveillance (AS) after mpMRI and FB fared differently than a predominantly Caucasian (non-AA) population. PATIENTS AND METHODS: A database of men who had undergone mpMRI and FB was queried to determine rates of upgrading by FB amongst men deemed to be AS candidates based on SB prior to referral. After FB, Kaplan-Meier curves were generated for AA men and non-AA men who then elected AS. The time to GGG upgrading and time continuing AS were compared using the log-rank test. RESULTS: AA men referred with GGG 1 disease on previous SB were upgraded to GGG ≥3 by FB more often than non-AA men, 22.2% vs 12.7% (P = 0.01). A total of 32 AA men and 258 non-AA men then continued AS, with a median (interquartile range) follow-up of 39.19 (24.24-56.41) months. The median time to progression was 59.7 and 60.5 months, respectively (P = 0.26). The median time continuing AS was 61.9 months and not reached, respectively (P = 0.80). CONCLUSIONS: AA men were more likely to be upgraded from GGG 1 on SB to GGG ≥3 on initial FB; however, AA and non-AA men on AS subsequently progressed at similar rates following mpMRI and FB. A greater tendency for SB to underestimate tumour grade in AA men may explain prior studies that have shown AA men to be at higher risk of progression during AS.

Protein kinase D inhibitor CRT0066101 suppresses bladder cancer growth in vitro and xenografts via blockade of the cell cycle at G2/M.

The protein kinase D (PKD) family of proteins are important regulators of tumor growth, development, and progression. CRT0066101, an inhibitor of PKD, has antitumor activity in multiple types of carcinomas. However, the effect and mechanism of CRT0066101 in bladder cancer are not understood. In the present study, we show that CRT0066101 suppressed the proliferation and migration of four bladder cancer cell lines in vitro. We also demonstrate that CRT0066101 blocked tumor growth in a mouse flank xenograft model of bladder cancer. To further assess the role of PKD in bladder carcinoma, we examined the three PKD isoforms and found that PKD2 was highly expressed in eight bladder cancer cell lines and in urothelial carcinoma tissues from the TCGA database, and that short hairpin RNA (shRNA)-mediated knockdown of PKD2 dramatically reduced bladder cancer growth and invasion in vitro and in vivo, suggesting that the effect of the compound in bladder cancer is mediated through inhibition of PKD2. This notion was corroborated by demonstrating that the levels of phospho-PKD2 were markedly decreased in CRT0066101-treated bladder tumor explants. Furthermore, our cell cycle analysis by flow cytometry revealed that CRT0066101 treatment or PKD2 silencing arrested bladder cancer cells at the G2/M phase, the arrest being accompanied by decreases in the levels of cyclin B1, CDK1 and phospho-CDK1 (Thr161) and increases in the levels of p27Kip1 and phospho-CDK1 (Thr14/Tyr15). Moreover, CRT0066101 downregulated the expression of Cdc25C, which dephosphorylates/activates CDK1, but enhanced the activity of the checkpoint kinase Chk1, which inhibits CDK1 by phosphorylating/inactivating Cdc25C. Finally, CRT0066101 was found to elevate the levels of Myt1, Wee1, phospho-Cdc25C (Ser216), Gadd45α, and 14-3-3 proteins, all of which reduce the CDK1-cyclin B1 complex activity. These novel findings suggest that CRT0066101 suppresses bladder cancer growth by inhibiting PKD2 through induction of G2/M cell cycle arrest, leading to the blockade of cell cycle progression.

Cycling, and Male Sexual and Urinary Function: Results from a Large, Multinational, Cross-Sectional Study.

PURPOSE: We explored the relation of cycling to urinary and sexual function in a large multinational sample of men. MATERIALS AND METHODS: Cyclists were recruited to complete a survey through Facebook® advertisements and outreach to sporting clubs. Swimmers and runners were recruited as a comparison group. Cyclists were categorized into low and high intensity cyclists. Participants were queried using validated questionnaires, including SHIM (Sexual Health Inventory for Men), I-PSS (International Prostate Symptom Score) and NIH-CPSI (National Institutes of Health Chronic Prostatitis Symptom Index), in addition to questions about urinary tract infections, urethral stricture, genital numbness and saddle sores. RESULTS: Of 5,488 complete survey responses 3,932 (72%) were included in our analysis. On multivariate analysis swimmers/runners had a lower mean SHIM score than low and high intensity cyclists (19.5 vs 19.9 and 20.7, p = 0.02 and <0.001, respectively). No significant differences were found in I-PSS or NIH-CPSI scores, or urinary tract infection history. Cyclists had statistically higher odds of urethral stricture compared to swimmers/runners (OR 2.5, p = 0.042). Standing more than 20% of the time while cycling significantly reduced the odds of genital numbness (OR 0.4, p = 0.006). Adjusting the handlebar higher or even with the saddle had lower odds of genital numbness and saddle sores (OR 0.8, p = 0.005 and 0.6, p <0.001, respectively). CONCLUSIONS: Cyclists had no worse sexual or urinary functions than swimmers or runners but cyclists were more prone to urethral stricture. Increased time standing while cycling and a higher handlebar height were associated with lower odds of genital sores and numbness.

Cycling and Female Sexual and Urinary Function: Results From a Large, Multinational, Cross-Sectional Study.

BACKGROUND: Bicycle riding has become an increasingly popular mode of transportation and exercise, especially among women, and previous studies have demonstrated a relationship between cycling and sexual dysfunction, albeit using non-validated questionnaires. AIM: We aimed to explore the relationship between cycling and sexual and urinary dysfunction. METHODS: Cyclists were recruited to complete a survey through Facebook advertisements and outreach to sporting clubs across 5 English-speaking countries. Swimmers and runners were recruited as a comparison group. OUTCOMES: Participants were queried using validated questionnaires, including the Female Sexual Function Index, the American Urological Association Symptom Index, and non-validated questions about history of urinary tract infections (UTIs), genital numbness, and genital saddle sores (all self-reported). RESULTS: 3,118 (53.3%) Women completed the survey, comprising 1,053 (34%) non-cyclists, 1,656 (53%) low-intensity cyclists, and 409 (13%) high-intensity cyclists. After adjusting for age, body mass index, hypertension, diabetes, ischemic heart disease, tobacco use, race, marital status, urinary symptoms, and sexual activity, high-intensity cyclists had lower odds of self-reported sexual dysfunction compared to non-cyclists (adjusted odds ratio [aOR] 0.7, P = .02). There were no statistically significant differences in urinary symptoms across groups. Compared to non-cyclists, both low- and high-intensity cyclists had higher odds of reporting a previous UTI (aOR 1.4, P < .001, and aOR 1.4, P = .009, respectively), genital numbness (odds ratio [OR] 6.5, P < .001, and OR 9.1, P < .001, respectively), and saddle sores (OR 6.3, P < .001, and OR 22.7, P < .001, respectively). CLINICAL TRANSLATION: Women cyclists were more likely to report other genitourinary conditions, including UTIs, genital numbness, and saddle sores. CONCLUSIONS: This is the largest study comparing cyclists to other athletes with respect to sexual and urinary function. The study is limited by its cross-sectional design and sampling methods. We found that women cyclists were no more likely to report sexual dysfunction or urinary symptoms than swimmers or runners. Gaither TW, Awad MA, Murphy GP, et al. Cycling and Female Sexual and Urinary Function: Results From a Large, Multinational, Cross-Sectional Study. J Sex Med 2018;15:510-518.

Estimated total costs from non-fatal and fatal bicycle crashes in the USA: 1997-2013.

INTRODUCTION: Emergency department visits and hospital admissions resulting from adult bicycle trauma have increased dramatically. Annual medical costs and work losses of these incidents last were estimated for 2005 and quality-of-life losses for 2000. METHODS: We estimated costs associated with adult bicycle injuries in the USA using 1997-2013 non-fatal incidence data from the National Electronic Injury Surveillance System with cost estimates from the Consumer Product Safety Commission's Injury Cost Model, and 1999-2013 fatal incidence data from the National Vital Statistics System costed by similar methods. RESULTS: Approximately 3.8 million non-fatal adult bicycle injuries were reported during the study period and 9839 deaths. In 2010 dollars, estimated adult bicycle injury costs totalled $24.4 billion in 2013. Estimated injury costs per mile bicycled fell from $2.85 in 2001 to $2.35 in 2009. From 1999 to 2013, total estimated costs were $209 billion due to non-fatal bicycle injuries and $28 billion due to fatal injuries. Inflation-free annual costs in the study period increased by 137% for non-fatal injuries and 23% for fatal injuries. The share of non-fatal costs associated with injuries to riders age 45 and older increased by 1.6% (95% CI 1.4% to 1.9%) annually. The proportion of costs due to incidents that occurred on a street or highway steadily increased by 0.8% (95% CI 0.4% to 1.3%) annually. CONCLUSIONS: Inflation-free costs per case associated with non-fatal bicycle injuries are increasing. The growth in costs is especially associated with rising ridership, riders 45 and older, and street/highway crashes.

The Cancer of the Bladder Risk Assessment (COBRA) score: Estimating mortality after radical cystectomy.

BACKGROUND: Risk stratification of patients with urothelial carcinoma of the bladder (UCB) after cystectomy has important clinical and research implications. The authors assessed the relative effect of tumor stage and lymph node status on cancer-specific survival (CSS) after cystectomy and developed a simplified risk-assessment tool. METHODS: In total, 14,828 patients who underwent cystectomy with lymph node dissection for UCB were identified from the Surveillance, Epidemiology, and End Results database (1988-2011). The relative importance of tumor stage and lymph node status with regard to CSS was assessed using stratified Kaplan-Meier and Cox proportional-hazards analyses. The patients were split randomly into development and validation cohorts. Additional validation using overall survival was performed on 19,362 patients from the National Cancer Data Base. The Cancer of Bladder Risk Assessment (COBRA) tool was created using a Cox model incorporating age, tumor stage, and lymph node density. Performance was validated using observed versus expected survival plots and the Harrell concordance index. RESULTS: Patients with muscle invasive (T2), lymph node-positive disease had a survival curve similar to that in patients with extravesical (T3 and T4), lymph node-negative disease (2-year CSS, 67% and 70%, respectively). Each point increase in the COBRA score (range, 0-7) was associated with a 1.61-fold increase (95% confidence interval, 1.56-fold to 1.65-fold increase) in the risk of bladder cancer death in the development cohort. The model accurately stratified patients across risk levels in the development cohort and the 2 validation cohorts (C-index, 0.712, 0.705, and 0.68, respectively). CONCLUSIONS: The COBRA score offers a straightforward, validated risk-stratification tool that incorporates the relative contribution of tumor stage and lymph node involvement to patient prognosis after cystectomy for UCB. Cancer 2017;123:4574-4582. © 2017 American Cancer Society.

The Role of the 24-Hour Urine Collection in the Prevention of Kidney Stone Recurrence.

PURPOSE: Kidney stone prevention relies on the 24-hour urine collection to diagnose metabolic abnormalities and direct dietary and pharmacological therapy. While its use is guideline supported for high risk and interested patients, evidence that the test can accurately predict recurrence or treatment response is limited. We sought to critically reassess the role of the 24-hour urine collection in stone prevention. MATERIALS AND METHODS: In addition to a MEDLINE® search to identify controlled studies of dietary and pharmacological interventions, evidence supporting the AUA (American Urological Association) and EAU (European Association of Urology) guidelines for metabolic stone prevention were evaluated. Additionally, the placebo arms of these studies were examined to assess the stone clinic effect, that is the impact of regular office visits without specific treatment on stone recurrence. RESULTS: The 24-hour urine test has several limitations, including the complexity of interpretation, the need for repeat collections, the inability to predict stone recurrence with individual parameters and supersaturation values, the unclear rationale of laboratory cutoff values and the difficulty of determining collection adequacy. Only 1 prospective trial has compared selective dietary recommendations based on 24-hour urine collection results vs general dietary instructions. While the trial supported the intervention arm, significant limitations to the study were found. Placebo arms of intervention trials have noted a 0% to 61% decrease in stone recurrence rate and a remission rate during the study of 20% to 86%. CONCLUSIONS: Whether all recurrent stone formers benefit from 24-hour urine collection has not been established. Additional comparative effectiveness trials are needed to determine which stone former benefits from selective therapy, as guided by the 24-hour urine collection.

Urethral Stricture Score is Associated with Anterior Urethroplasty Complexity and Outcome.

PURPOSE: Several surgical techniques are available to treat anterior urethral stricture. The choice of surgical technique largely depends on the severity of stricture disease. The U-score (urethral stricture score) is based on urethral stricture characteristics, namely length (1 to 3 points), number (1 or 2 points), location (1 or 2 points) and etiology (1 or 2 points), which are tallied to provide a total score of 4 to 9 points. Our aim was to identify whether the U-score system is predictive of the surgical complexity and outcome of anterior urethroplasty. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent anterior urethroplasty from 2002 to 2012 by examining our prospectively collected urethroplasty database. We calculated the U-score and looked for an association with surgical complexity, recurrent stricture and time to recurrence. We defined recurrent stricture as the need for a secondary procedure. RESULTS: There were 341 patients who underwent low complexity urethroplasty (anastomotic, buccal mucosal graft and augmented anterior urethroplasty) with a mean U-score of 4.7 while 48 underwent high complexity urethroplasty (double buccal mucosal graft, flap and graft/flap combination) with a mean score of 6.9. Higher U-score was predictive of higher surgical complexity (p <0.001). U-score was also significantly associated with recurrence. There was a consistent increase in the risk of recurrence with each additional U-score point. However, there was no association of U-score with time to recurrence. CONCLUSIONS: We confirmed the validity of U-score to predict the complexity of surgery for anterior urethral strictures. For the first time to our knowledge we report an association between higher U-score and anterior urethroplasty outcome. The U-score could be used to risk stratify patients and help with perioperative counseling.

Host Microbiota Contributes to Health and Response to Disease.

Recent studies have revealed that normal microbiota interacts with the host through four mechanisms: the normal microbiome acts as a barrier against pathogens; second, as modulators of the permeability of host mucosa; third, as modulators of energy extraction from, and metabolic utilization of ingested food; and lastly, as modulators of the immune system. An alteration of the normal microbiota increases predisposition of the host to diseases through these four mechanisms.