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Using baseline (ages 9–10) and two-year follow-up (ages 11–12) data from monozygotic and dizygotic twins enrolled in the longitudinal Adolescent Brain Cognitive DevelopmentSM Study, we investigated the genetic and environmental contributions to microstructure and volume of nine subcortical gray matter regions. Microstructure was assessed using diffusion MRI data analyzed using restriction spectrum imaging (RSI) and diffusion tensor imaging (DTI) models. The highest heritability estimates (estimate [95% confidence interval]) for microstructure were found using the RSI model in the pallidum (baseline: 0.859 [0.818, 0.889], follow-up: 0.835 [0.787, 0.871]), putamen (baseline: 0.859 [0.819, 0.889], follow-up: 0.874 [0.838, 0.902]), and thalamus (baseline: 0.855 [0.814, 0.887], follow-up: 0.819 [0.769, 0.857]). For volumes the corresponding regions were the caudate (baseline: 0.831 [0.688, 0.992], follow-up: 0.848 [0.701, 1.011]) and putamen (baseline: 0.906 [0.875, 0.914], follow-up: 0.906 [0.885, 0.923]). The subcortical regions displayed high genetic stability (rA = 0.743–1.000) across time and exhibited unique environmental correlations (rE = 0.194–0.610). Individual differences in both gray matter microstructure and volumes can be largely explained by additive genetic effects in this sample.

To identify the incidence and factors impacting post-traumatic stress disorder (PTSD) at 6 months, 2 and 7 years following the 2005 Eyre Peninsula bushfires in South Australia.A questionnaire was used to assess symptoms.A longitudinal follow-up study with responses collected from a self-report booklet.179 respondents were present at 6 months post bushfires, with 103 and 87 participants at 2 and 7 years, respectively.PTSD rates and its precipitating factors.The proportion of PTSD cases at times 1, 2 and 3 were 13.4% (24/179), 10.7% (11/103), and 4.8% (4/87), respectively. At 6 months, terrifying experience of fire reduced odds of developing PTSD (Odds Ratio [OR]: 0.45; 95% CI 0.21-0.96) while relocation increased odds (OR: 2.93; 95% CI 1.06-8.08). At 2 years, relocation (OR: 6.81; 95% CI 1.07-43.41) was a positive predictor. At 7 years, personal loss from the fires (OR: 2.82; 95% CI 1.17-6.77) positively predicted PTSD.PTSD rates declined over time. Relocation may be a proxy measure of high levels of emotional trauma. Those most traumatised probably decided to relocate, and hence, relocation should be considered a trigger for PTSD in the aftermath of bushfire.

PURPOSE. Pediatric obesity is a growing public health concern. Previous work has observed diet to impact nucleus accumbens (NAcc) inflammation in rodents, measured by the reactive proliferation of glial cells. Recent work in humans has demonstrated a relationship between NAcc cell density—a proxy for neuroinflammation—and weight gain in youth; however, the directionality of this relationship in the developing brain and association with diet remain unknown. METHODS. Waist circumference (WC) and NAcc cell density were collected in a large cohort of children (n > 2,000) participating in the Adolescent Brain Cognitive Development(SM) (ABCD) Study (release 3.0) at baseline (9–10 y) and at a Year 2 follow-up (11–12 y). Latent change score modeling (LCSM) was used to disentangle contributions of baseline measures to two-year changes in WC percentile and NAcc cellularity. In addition, the role of NAcc cellularity in mediating the relationship between diet and WC percentile was assessed using dietary intake data collected at Year 2. RESULTS. LCSM indicates that baseline WC percentile influences change in NAcc cellularity and that baseline NAcc cell density influences change in WC percentile. NAcc cellularity was significantly associated with WC percentile at Year 2 and mediated the relationship between dietary fat consumption and WC percentile. CONCLUSIONS. These results implicate a vicious cycle whereby NAcc cell density biases longitudinal changes in WC percentile, and vice versa. Moreover, NAcc cell density may mediate the relationship between diet and weight gain in youth. These findings suggest that diet-induced inflammation of reward circuitry may lead to behavioral changes that further contribute to weight gain.

ObjectiveTo develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA).MethodsPatients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.ResultsThe development set for GPA consisted of 578 cases of GPA and 652 comparators. The validation set consisted of an additional 146 cases of GPA and 161 comparators. From 91 candidate items, regression analysis identified 26 items for GPA, 10 of which were retained. The final criteria and their weights were as follows: bloody nasal discharge, nasal crusting or sino-nasal congestion (+3); cartilaginous involvement (+2); conductive or sensorineural hearing loss (+1); cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3 ANCA positivity (+5); pulmonary nodules, mass or cavitation on chest imaging (+2); granuloma or giant cells on biopsy (+2); inflammation or consolidation of the nasal/paranasal sinuses on imaging (+1); pauci-immune glomerulonephritis (+1); perinuclear ANCA or antimyeloperoxidase ANCA positivity (−1); and eosinophil count ≥1×109 /L (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having GPA if the cumulative score was ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 93% (95% CI 87% to 96%) and the specificity was 94% (95% CI 89% to 97%).ConclusionThe 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for GPA demonstrate strong performance characteristics and are validated for use in research.

Race is a social construct that contributes to group membership and heightens emotional arousal in intergroup contexts. Little is known about how emotional arousal, specifically uncertain threat, influences behavior and brain processes in response to race information. We investigated the effects of experimentally manipulated uncertain threat on impulsive actions to Black versus White faces in a community sample (n = 106) of Black and White adults. While undergoing fMRI, participants performed an emotional go/no-go task under three conditions of uncertainty: 1) anticipation of an uncertain threat (i.e., unpredictable loud aversive sound); 2) anticipation of an uncertain reward (i.e., unpredictable receipt of money); and 3) no anticipation of an uncertain event. Representational similarity analysis was used to examine the neural representations of race information across functional brain networks between conditions of uncertainty. Participants—regardless of their own race—showed greater impulsivity and neural dissimilarity in response to Black versus White faces across all functional brain networks in conditions of uncertain threat relative to other conditions. This pattern of greater neural dissimilarity under threat was enhanced in individuals with high implicit racial bias. Our results illustrate the distinct and important influence of uncertain threat on global differentiation in how race information is represented in the brain, which may contribute to racially biased behavior.

Using baseline (ages 9-10) and two-year follow-up (ages 11-12) data from monozygotic and dizygotic twins enrolled in the longitudinal Adolescent Brain and Cognitive DevelopmentSM Study, we investigated the genetic and environmental contributions to microstructure and volume of nine subcortical gray matter regions. Microstructure was assessed using diffusion MRI data analyzed using restriction spectrum imaging (RSI) and diffusion tensor imaging (DTI) models. The highest heritability estimates for microstructure were found using the RSI model in the pallidum (0.862±0.037), putamen (0.845±0.041), and thalamus (0.849±0.040). For volumes the corresponding regions were the brainstem (0.880±0.026), caudate (0.881±0.027) and putamen (0.870±0.030). No significant evidence of contributions of the common environment or changes in the contributions with development were observed. Individual differences in both gray matter microstructure and volumes can be largely explained by additive genetic effects in this sample.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development. This paper reports activation patterns for fMRI tasks assessing response inhibition, working memory and reward processing obtained at baseline in the longitudinal ABCD Study, providing a reference for research into adolescent brain development.

The Adolescent Brain and Cognitive Development (ABCD) study aims to measure the trajectories of brain, cognitive, and emotional development. Cognitive and behavioural development during late childhood and adolescence have been associated with a myriad of microstructural and morphological alterations across the brain, as measured by magnetic resonance imaging (MRI). These associations may be strongly localised or spatially diffuse, therefore, it would be advantageous to analyse multimodal MRI data in concert, and across the whole brain. The ABCD study presents the unique challenge of integrating multimodal data from tens of thousands of scans at multiple timepoints, within a reasonable computation time. To address the need for a multimodal registration and atlas for the ABCD dataset, we present the synthesis of an ABCD atlas using the Multimodal Image Normalisation Tool (MINT). The MINT ABCD atlas was generated from baseline and two-year follow up imaging data using an iterative approach to synthesise a cohort-specific atlas from linear and nonlinear deformations of eleven channels of diffusion and structural MRI data. We evaluated the performance of MINT against two widely used methods and show that MINT achieves comparable alignment to current state-of-the-art multimodal registration, at a fraction of the computation time. To validate the use of the ABCD MINT atlas in whole brain, voxelwise analysis, we replicate and expand on previously published region-of-interest analysis between diffusion MRI-derived measures and body mass index (BMI). We also report novel association between BMI and brain morphology derived from the registration deformations. We present the ABCD MINT atlas as a publicly available resource to facilitate whole brain voxelwise analyses for the ABCD study.

Hurricane Irma was the most powerful Atlantic hurricane in recorded history, displacing 6 million and killing over 120 people in the state of Florida alone. Unpredictable disasters like Irma are associated with poor cognitive and health outcomes that can disproportionately impact children. This study examined the effects of Hurricane Irma on the hippocampus and memory processes previously related to unpredictable stress. We used an innovative application of an advanced diffusion-weighted imaging technique, restriction spectrum imaging (RSI), to characterize hippocampal microstructure (i.e., cell density) in 9- to 10-year-old children who were exposed to Hurricane Irma relative to a non-exposed control group (i.e., assessed the year before Hurricane Irma). We tested the hypotheses that the experience of Hurricane Irma would be associated with decreases in: (a) hippocampal cellularity (e.g., neurogenesis), based on known associations between unpredictable stress and hippocampal alterations; and (b) hippocampal-related memory function as indexed by delayed recall. We show an association between decreased hippocampal cellularity and delayed recall memory in children who experienced Hurricane Irma relative to those who did not. These findings suggest an important role of RSI for assessing subtle microstructural changes related to functionally significant changes in the developing brain in response to environmental events.

The functional connectome supports information transmission through the brain at various spatial scales, from exchange between broad cortical regions to finer-scale connections that underlie specific information processing mechanisms. In adults, while both the coarse- and fine-scale functional connectomes predict cognition, the fine-scale can predict twice the variance. Yet, past brain-wide association studies, particularly using large developmental samples, limit their focus to the coarse connectome to understand the neural underpinnings of individual differences in cognition. We examine resting-state fMRI (n=1,115 children, 389 twin pairs) and use hyperalignment to access reliable information in the fine-scale connectome. Though individual differences in the fine-scale connectome are more reliable than those in the coarse-scale, they are less heritable. Further, the alignment and scale of connectomes influence their ability to predict behavior: both scales equally predict more heritable cognitive traits, but the fine-scale connectome predicts less heritable traits significantly better than the coarse-scale.

Significance As the prevalence of pediatric obesity continues to rise, determining neurobiological mechanisms underlying longitudinal childhood weight gain is critically important for informing early intervention and prevention strategies. We use an MRI technique to probe nucleus accumbens (NAcc) tissue microstructure and predict waist circumference after 1 y. We find that increased cell density in the NAcc is strongly associated with obesity in a large cohort of children and predicts future weight gain independent of waist circumference at baseline. These results extend animal studies showing a vicious cycle in which diet-induced neuroinflammation leads to disruption of the brain’s reward circuitry and subsequently promotes further unhealthy eating and weight gain., The prevalence of obesity in children and adolescents worldwide has quadrupled since 1975 and is a key predictor of obesity later in life. Previous work has consistently observed relationships between macroscale measures of reward-related brain regions (e.g., the nucleus accumbens [NAcc]) and unhealthy eating behaviors and outcomes; however, the mechanisms underlying these associations remain unclear. Recent work has highlighted a potential role of neuroinflammation in the NAcc in animal models of diet-induced obesity. Here, we leverage a diffusion MRI technique, restriction spectrum imaging, to probe the microstructure (cellular density) of subcortical brain regions. More specifically, we test the hypothesis that the cell density of reward-related regions is associated with obesity-related metrics and early weight gain. In a large cohort of nine- and ten-year-olds enrolled in the Adolescent Brain Cognitive Development (ABCD) study, we demonstrate that cellular density in the NAcc is related to individual differences in waist circumference at baseline and is predictive of increases in waist circumference after 1 y. These findings suggest a neurobiological mechanism for pediatric obesity consistent with rodent work showing that high saturated fat diets increase gliosis and neuroinflammation in reward-related brain regions, which in turn lead to further unhealthy eating and obesity.

The purpose of this study was to measure how body shame, sexual satisfaction, and relationship satisfaction predicted life satisfaction for female participants who have been in committed relationsh...

Objectives: This study aimed to demonstrate how to estimate the value of health gain after patients with a multisystem disease achieve a condition-specific composite response endpoint. Methods: Data from patients treated in routine practice with an exemplar multisystem disease (systemic lupus erythematosus) were extracted from a national register (British Isles Lupus Assessment Group Biologics Register). Two bespoke composite response endpoints (Major Clinical Response and Improvement) were developed in advance of this study. Difference-in-differences regression compared health utility values (3-level version of EQ-5D; UK tariff) over 6 months for responders and nonresponders. Bootstrapped regression estimated the incremental quality-adjusted life-years (QALYs), probability of QALY gain after achieving the response criteria, and population monetary benefit of response. Results: Within the sample (n = 171), 18.2% achieved Major Clinical Response and 49.1% achieved Improvement at 6 months. Incremental health utility values were 0.0923 for Major Clinical Response and 0.0454 for Improvement. Expected incremental QALY gain at 6 months was 0.020 for Major Clinical Response and 0.012 for Improvement. Probability of QALY gain after achieving the response criteria was 77.6% for Major Clinical Response and 72.7% for Improvement. Population monetary benefit of response was £1 106 458 for Major Clinical Response and £649 134 for Improvement. Conclusions: Bespoke composite response endpoints are becoming more common to measure treatment response for multisystem diseases in trials and observational studies. Health technology assessment agencies face a growing challenge to establish whether these endpoints correspond with improved health gain. Health utility values can generate this evidence to enhance the usefulness of composite response endpoints for health technology assessment, decision making, and economic evaluation.

As public access to longitudinal developmental datasets like the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development Study (ABCD), a 10 year longitudinal neuroimaging study of the largest population based and demographically distributed cohort of 9-10 year olds (N=11,877), was designed to overcome reproducibility limitations of prior child mental health studies. Besides the fantastic wealth of research opportunities, the extremely large size of the ABCD data set also creates enormous data storage, processing, and analysis challenges for researchers. To ensure data privacy and safety, researchers are not currently able to share neuroimaging data derivatives through the central repository at the National Data Archive (NDA). However, sharing derived data amongst researchers laterally can powerfully accelerate scientific progress, to ensure the maximum public benefit is derived from the ABCD study. To simultaneously promote collaboration and data safety, we developed the ABCD-BIDS Community Collection (ABCC), which includes both curated processed data and software utilities for further analyses. The ABCC also enables researchers to upload their own custom-processed versions of ABCD data and derivatives for sharing with the research community. This NeuroResource is meant to serve as the companion guide for the ABCC. In section we describe the ABCC. Section II highlights ABCC utilities that help researchers access, share, and analyze ABCD data, while section III provides two exemplar reproducibility analyses using ABCC utilities. We hope that adoption of the ABCC’s data-safe, open-science framework will boost access and reproducibility, thus facilitating progress in child and adolescent mental health research.

Background Opioids have long been the mainstay of drugs used for intra-operative analgesia. Due to their well-known short and long term side effects, the use of non-opioid analgesics has often been encouraged to decrease the dose of opioid required and minimise these side effects. The trends in using non-opioid adjuvants among Australian Anaesthetists have not been examined before. This study has attempted to determine the use of non-opioid analgesics as part of an opioid sparing practice among anaesthetists across Australia and New Zealand. Methods A survey was distributed to 985 anaesthetists in Australia and New Zealand. The questions focused on frequency of use of different adjuvants and any reasons for not using individual agents. The agents surveyed were paracetamol, dexamethasone, non-steroidal anti-inflammatory agents (NSAIDs), tramadol, ketamine, anticonvulsants, intravenous lidocaine, systemic alpha 2 agonists, magnesium sulphate, and beta blockers. Descriptive statistics were used and data are expressed as a percentage of response for each drug. Results The response rate was 33.4%. Paracetamol was the most frequently used; with 72% of the respondents describing frequent usage (defined as usage above 70% of the time); followed by parecoxib (42% reported frequent usage) and dexamethasone (35% reported frequent usage). Other adjuvants were used much less commonly, with anaesthetists reporting their frequent usage at less than 10%. The majority of respondents suggested that they would never consider dexmedetomidine, magnesium, esmolol, pregabalin or gabapentin. Perceived disincentives for the use of analgesic adjuvants varied. The main concerns were side effects, lack of evidence for benefit, and anaesthetists’ experience. The latter two were the major factors for magnesium, dexmedetomidine and esmolol. Conclusion The uptake of tramadol, lidocaine and magnesium amongst respondents from anaesthetists in Australia and New Zealand was poor. Gabapentin, pregabalin, dexmedetomidine and esmolol use was relatively rare. Most anaesthetists need substantial evidence before introducing a non-opioid adjuvant into their routine practice. Future trials should focus on assessing the opioid sparing benefits and relative risk of using individual non-opioid adjuvants in the perioperative period for specific procedures and patient populations.

Background and purpose Quantitative susceptibility mapping (QSM) of the brain has become highly reproducible and has applications in an expanding array of diseases. To translate QSM from bench to bedside, it is important to automate its reconstruction immediately after data acquisition. In this work, a server system that automatically reconstructs QSM and exchange images with the scanner using the DICOM standard is demonstrated using a multi-site, multi-vendor reproducibility study and a large, single-site, multi-scanner image quality review study in a clinical environment. Methods A single healthy subject was scanned with a 3D multi-echo gradient echo sequence at nine sites around the world using scanners from three manufacturers. A high-resolution (HiRes, .5 × .5 × 1 mm3 reconstructed) and standard-resolution (StdRes, .5 × .5 × 3 mm3 ) protocol was performed. ROI analysis of various white matter and gray matter regions was performed to investigate reproducibility across sites. At one institution, a retrospective multi-scanner image quality review was carried out of all clinical QSM images acquired consecutively in 1 month. Results Reconstruction times using a GPU were 29 ± 22 seconds (StdRes) and 55 ± 39 seconds (HiRes). ROI standard deviation across sites was below 24 ppb (StdRes) and 17 ppb (HiRes). Correlations between ROI averages across sites were on average .92 (StdRes) and .96 (HiRes). Image quality review of 873 consecutive patients revealed diagnostic or excellent image quality in 96% of patients. Conclusion Online QSM reconstruction for a variety of sites and scanner platforms with low cross-site ROI standard deviation is demonstrated. Image quality review revealed diagnostic or excellent image quality in 96% of 873 patients.

Notas: Documento pegado a una hoja en blanco. Datos manuscritos encima del artículo., Tipo de publicación: Periódico, Título de la publicación: New York Post, Periodicidad: Diario

This paper responds to a recent critique by Bissett and colleagues (Bissett et al., eLife, In Press) of the fMRI Stop task being used in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). The critique focuses primarily on a design feature of the task that the authors contend lead to a violation of race model assumptions (i.e., that the Go and Stop processes are fully independent) which are relevant to the calculation of the Stop Signal Reaction Time, a measure of the inhibition process. Bissett and colleagues also raise a number of secondary concerns. In this response we note that satisfying race model assumptions is a pernicious challenge for Stop task designs but also that the race model is quite robust against violations of its assumptions. Most importantly, while Bissett et al. raise conceptual concerns with the task we focus here on analyses of both the performance and the neuroimaging data and we conclude that the concerns appear to have minimal impact on the neuroimaging data (the validity of which do not rely on race model assumptions) and have far less of an impact on the performance data than the critique suggests. We note that Bissett et al. did not apply any performance-based exclusions to the data they analyzed, that a number of the trial coding errors that they flagged were already identified and corrected in the ABCD annual data releases, that a number of the secondary concerns reflect sensible design decisions and, indeed, that their own computational modeling of the ABCD Stop task suggests the problems they identify have just a modest impact on the rank ordering of individual differences in subject performance. In this paper, we list some adjustments that have been made to the task and some new flags that are now added to the annual, curated data releases. We stress that the ABCD data are fully available to the scientific community who are empowered to apply whatever inclusion and exclusion criteria they deem appropriate for their analyses and we conclude that the ABCD Stop task yields valuable data that researchers can use to track adolescent neurodevelopment.

BackgroundPrevious research has shown an association between thalamus and cognition in Parkinson’s disease (PD).ObjectivesTo investigate the microstructural integrity of the nuclei of the thalamus and relationship with cognition.MethodsLevel II Movement Disorder Society Task Force Criteria characterised patients with Parkinson’s disease as cognitively normal (PDN, n=51); with mild cognitive impairment (PD-MCI, n=16) or with dementia (PDD, n=15). Twenty-three healthy control subjects were included for comparison. A k-means clustering approach segmented the thalamus into regions representing nine major nuclei. Volume, fractional anisotropy and mean diffusivity of nuclei were compared between cognitive groups and the relationship with cognitive domain z-scores investigated using hierarchical Bayesian regression models.ResultsThere was an overall progressive increase in mean diffusivity as cognition deteriorated (PDN: 1.4 µm2/s (95% uncertainty interval [0.2, 2.7]), PDMCI: 2.4 µm2/s [0.8,4.0], PDD: 4.5 µm2/s [2.8, 6.3]). The largest increase was in the lateral dorsal nucleus (PDN: 0.3 µm2/s [-6.7, 7.2], PDMCI: 5.4 µm2/s [-4.7, 16.1], PDD: 14.8 µm2/s [5.0, 25.0]). Fractional anisotropy showed minimal change between cognitive groups (PDN: 0.001 [-0.005, 0,007], PDMCI: −0.005 [-0.013, 0.003], PDD: −0.005 [-0.014, 0.003]). Increase in mean diffusivity of the thalamus is associated with a global decline in cognition, the magnitude of the effect was greatest in lateral dorsal nucleus. Fractional anisotropy only showed evidence of a relationship with cognitive domain scores in the lateral dorsal nucleus.ConclusionsThe relationship between lateral dorsal nucleus integrity and cognitive changes is likely due to its primary connectivity with frontal and temporal regions.

469 Background: The objective of the present study was to assess FGFR mutattions and fusions from matched urine and tissue samples from patients suspicious of bladder cancer and undergoing first TURB within BRIDGister RealWorld Experience trial. Methods: FFPE samples from the first TURB of 39 pts participating in the BRIDGister trial and matched urine samples were prospectively collected and analyzed. RNA from FFPE tissues were extracted by commercial kits and analyzed by Therascreen FGFR IVD kit (Qiagen GmbH, Hilden). In addition extracellular vesicles were centrally isolated for subsequent RNA extraction (exoRNA.Exosome Diagnostics GmbH, Martinsried) and centrall analysis by QIAcuity digital PCR (Qiagen, Hilden). In addition mRNA based profiling of urine was done by dPCR. Concordance, Spearman, Kruskal-Wallis and MannWhitney were analyzed by JMP 9.0.0 (SAS software). Results: The pilot cohort of the BRIDGister trial consisted of 39 patients (median age: 75, male 69% vs female 31%) of diverse clinical stages (Benign lesions/no tumor 23%, pTa 31%, pT1 26%, pT2 21%) and WHO 1973 grade (G1 8%, G2 39%, G3 34%). Based on FFPE tissue testing using Therascreen FGFR IVD kit and exosomal RNA extraction follwoed by dPCR 12 out of 39 patients exhibited FGFR alterations (31%). Comparison with tissue testing as probable gold standard revealed 67% sensitivity, 85% specificity, 67% PPV and 85%NPV. There were 4 patients being FGFR positive for exoRNA from urine with no mutation found in the corresponding TUR biopsy. Determining ERBB2 mRNA by dPCR from urine revealed that high ERBB2 mRNA correlated with higher WHO1973grade, while high FGFR3 mRNA correlated with lower grade tumors (Spearman r=0.4386 p=0.0075 and r=-0.4663 p=0.0042). Similiarly, trends were seen for association of ERBB2 and FGFR3 mRNA with clinical stage tumors in this pilote cohort (Spearman r=0.2359 p=0.0923 and r=-0.2249 p=0.1089). Conclusions: Extraction of exosomal RNA from urine followed by highly sensitive dPCR mutation testing is feasible with good concordance to matched tissue testing. Urine testing might evolve as alternative approach for FGFR3 screening in a non invasive fashion without the need of transurethral biopsy. Interestingly, mRNA assessment of exosomal RNA from urine before TURB correlated with clinical parameters such as WHO Grade 1973 with ERBB2 mRNA being associated with high grade tumors and FGFR3 mRNA being associated with low grade tumors, which is in line with previous tissue tsting results. This indicates the potential to clinically characterize tumor grade and stage before TUR biopsy or surgery which might be helpful for future risk stratification and planning of surgical intervention. Further exploration is warranted and includes the potential of monitoring patients with regard to urine based mutation detection and risk stratification.