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Purpose To evaluate the performance of an artificial intelligence (AI) model in detecting overall and clinically significant prostate cancer (csPCa)-positive lesions on paired external and in-house biparametric MRI (bpMRI) scans and assess performance differences between each dataset. Materials and Methods This single-center retrospective study included patients who underwent prostate MRI at an external institution and were rescanned at the authors' institution between May 2015 and May 2022. A genitourinary radiologist performed prospective readouts on in-house MRI scans following the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 or 2.1 and retrospective image quality assessments for all scans. A subgroup of patients underwent an MRI/US fusion-guided biopsy. A bpMRI-based lesion detection AI model previously developed using a completely separate dataset was tested on both MRI datasets. Detection rates were compared between external and in-house datasets with use of the paired comparison permutation tests. Factors associated with AI detection performance were assessed using multivariable generalized mixed-effects models, incorporating features selected through forward stepwise regression based on the Akaike information criterion. Results The study included 201 male patients (median age, 66 years [IQR, 62-70 years]; prostate-specific antigen density, 0.14 ng/mL 2 [IQR, 0.10-0.22 ng/mL 2 ]) with a median interval between external and in-house MRI scans of 182 days (IQR, 97-383 days). For intraprostatic lesions, AI detected 39.7% (149 of 375) on external and 56.0% (210 of 375) on in-house MRI scans ( P < .001). For csPCa-positive lesions, AI detected 61% (54 of 89) on external and 79% (70 of 89) on in-house MRI scans ( P < .001). On external MRI scans, better overall lesion detection was associated with a higher PI-RADS score (odds ratio [OR] = 1.57; P = .005), larger lesion diameter (OR = 3.96; P < .001), better diffusion-weighted MRI quality (OR = 1.53; P = .02), and fewer lesions at MRI (OR = 0.78; P = .045). Better csPCa detection was associated with a shorter MRI interval between external and in-house scans (OR = 0.58; P = .03) and larger lesion size (OR = 10.19; P < .001). Conclusion The AI model exhibited modest performance in identifying both overall and csPCa-positive lesions on external bpMRI scans. Keywords: MR Imaging, Urinary, Prostate Supplemental material is available for this article. © RSNA, 2024.

Rationale and Objectives: The increasing use of focal therapy (FT) in localized prostate cancer (PCa) management requires a standardized MRI interpretation system to detect recurrent clinically significant PCa (csPCa). This pilot study evaluates the novel Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) and compares its performance to that of the Prostate Imaging after Focal Ablation (PI-FAB) system., Materials and Methods: This retrospective study included 38 patients who underwent primary FT for localized PCa, with follow-up multiparametric MRI (mpMRI) and biopsy. Two radiologists assessed the mpMRIs using both PI-FAB and TARGET independently. Diagnostic performance metrics and area under the receiver operating characteristic curve (AUC) were calculated. Inter-reader and intrareader agreement were assessed using Cohen's κ and Kendall's τ., Results: 14 patients had recurrent csPCa. PI-FAB showed high sensitivity (92.9% for both readers) and NPV (reader 1: 93.8%, reader 2: 92.9%) but moderate specificity (reader 1: 62.5%, reader 2: 54.2%). TARGET demonstrated lower sensitivity for one reader (reader 1: 78.6%, reader 2: 92.9%) but higher specificity (reader 1: 79.2%, reader 2: 62.5%) for both readers. Both systems displayed moderate inter-reader agreement (κ = 0.56 for PI-FAB, 0.57 for TARGET)., Conclusion: PI-FAB and TARGET exhibit similar performances in post-FT MRI. While PI-FAB had consistently high sensitivity, TARGET offered higher specificity for one reader. Moderate agreement levels demonstrate the viability of these systems in clinical settings and a promise for improvement., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B. J. Wood receives support as part of a cooperative research and development agreement (CRADA) between NIH and Philips Healthcare, receives royalties from NIH related to a licensing agreement with Philips Healthcare, and is party to patents or potential patents related to this work. P. L. Choyke receives royalties for MRI/ultrasound fusion biopsy patents licensed to Philips Medical. P. A. Pinto receives royalties from NIH related to a Philips licensing agreement and support as part of a CRADA between NIH and Philips Healthcare. B. Turkbey receives support as part of a CRADA between NIH and NVDIA and between NIH and Philips Healthcare, receives royalties from NIH, and is party to patents or potential patents related to this work. The remaining authors declare that there are no other disclosures relevant to the subject matter of this article. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government., (Published by Elsevier Inc.)

Rationale and Objectives: Extraprostatic extension (EPE) is well established as a significant predictor of prostate cancer aggression and recurrence. Accurate EPE assessment prior to radical prostatectomy can impact surgical approach. We aimed to utilize a deep learning-based AI workflow for automated EPE grading from prostate T2W MRI, ADC map, and High B DWI., Material and Methods: An expert genitourinary radiologist conducted prospective clinical assessments of MRI scans for 634 patients and assigned risk for EPE using a grading technique. The training set and held-out independent test set consisted of 507 patients and 127 patients, respectively. Existing deep-learning AI models for prostate organ and lesion segmentation were leveraged to extract area and distance features for random forest classification models. Model performance was evaluated using balanced accuracy, ROC AUCs for each EPE grade, as well as sensitivity, specificity, and accuracy compared to EPE on histopathology., Results: A balanced accuracy score of .390 ± 0.078 was achieved using a lesion detection probability threshold of 0.45 and distance features. Using the test set, ROC AUCs for AI-assigned EPE grades 0-3 were 0.70, 0.65, 0.68, and 0.55 respectively. When using EPE≥ 1 as the threshold for positive EPE, the model achieved a sensitivity of 0.67, specificity of 0.73, and accuracy of 0.72 compared to radiologist sensitivity of 0.81, specificity of 0.62, and accuracy of 0.66 using histopathology as the ground truth., Conclusion: Our AI workflow for assigning imaging-based EPE grades achieves an accuracy for predicting histologic EPE approaching that of physicians. This automated workflow has the potential to enhance physician decision-making for assessing the risk of EPE in patients undergoing treatment for prostate cancer due to its consistency and automation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B. J. Wood receives support as part of a cooperative research and development agreement (CRADA) between NIH and Philips Healthcare, receives royalties from NIH related to a licensing agreement with Philips Healthcare, and is party to patents or potential patents related to this work. P. L. Choyke receives royalties for MRI/ultrasound fusion biopsy patents licensed to Philips Medical. P. A. Pinto receives royalties from NIH related to a Philips licensing agreement and support as part of a CRADA between NIH and Philips Healthcare. B. Turkbey receives support as part of a CRADA between NIH and NVDIA and between NIH and Philips Healthcare, receives royalties from NIH, and is party to patents or potential patents related to this work. Jesse Tetreault: employee of NVIDIA Corporation. The remaining authors declare that there are no other disclosures relevant to the subject matter of this article. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government., (Published by Elsevier Inc.)

Objective: To assess impact of image quality on prostate cancer extraprostatic extension (EPE) detection on MRI using a deep learning-based AI algorithm., Materials and Methods: This retrospective, single institution study included patients who were imaged with mpMRI and subsequently underwent radical prostatectomy from June 2007 to August 2022. One genitourinary radiologist prospectively evaluated each patient using the NCI EPE grading system. Each T2WI was classified as low- or high-quality by a previously developed AI algorithm. Fisher's exact tests were performed to compare EPE detection metrics between low- and high-quality images. Univariable and multivariable analyses were conducted to assess the predictive value of image quality for pathological EPE., Results: A total of 773 consecutive patients (median age 61 [IQR 56-67] years) were evaluated. At radical prostatectomy, 23% (180/773) of patients had EPE at pathology, and 41% (131/318) of positive EPE calls on mpMRI were confirmed to have EPE. The AI algorithm classified 36% (280/773) of T2WIs as low-quality and 64% (493/773) as high-quality. For EPE grade ≥ 1, high-quality T2WI significantly improved specificity for EPE detection (72% [95% CI 67-76%] vs. 63% [95% CI 56-69%], P = 0.03), but did not significantly affect sensitivity (72% [95% CI 62-80%] vs. 75% [95% CI 63-85%]), positive predictive value (44% [95% CI 39-49%] vs. 38% [95% CI 32-43%]), or negative predictive value (89% [95% CI 86-92%] vs. 89% [95% CI 85-93%]). Sensitivity, specificity, PPV, and NPV for EPE grades ≥ 2 and ≥ 3 did not show significant differences attributable to imaging quality. For NCI EPE grade 1, high-quality images (OR 3.05, 95% CI 1.54-5.86; P < 0.001) demonstrated a stronger association with pathologic EPE than low-quality images (OR 1.76, 95% CI 0.63-4.24; P = 0.24)., Conclusion: Our study successfully employed a deep learning-based AI algorithm to classify image quality of prostate MRI and demonstrated that better quality T2WI was associated with more accurate prediction of EPE at final pathology., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Dapagliflozin has been associated with euglycemic ketoacidosis in adults with diabetes contributing to poor outcomes when continued prior to surgery. It is unknown if preoperative use of dapagliflozin may lead to adverse events (AE) in nondiabetic children with advanced heart failure (HF) undergoing heart transplantation (HTx). We performed a single-center, matched case-control analysis of nondiabetic primary pediatric HTx recipients < 21 years-old who underwent HTx and followed through postoperative day (POD) 3. Cases who received dapagliflozin leading up to HTx (n = 22) were matched by age and cardiac diagnosis to two historical controls who did not receive dapagliflozin (n = 44). Median age at HTx was 13.8 years (range 0.36-20.7) and 48% were female. Cardiac diagnoses included cardiomyopathy (45%), Fontan failure (41%), and single ventricle status post stage I palliation (14%). Cases received median dapagliflozin dose of 0.17 mg/kg once daily; therapy was stopped one day prior to HTx. There were no significant differences in blood glucose nadirs, arterial blood gas indices including nadirs of pH, bicarbonate, or peaks of arterial blood lactic acid POD0-3. Vasopressor, inotrope, and insulin infusion usage were not different. No patients were treated for severe hypoglycemia, euglycemic ketoacidosis, or urinary tract infections. There were no deaths. Length of stay in ICU and time from HTx to hospital discharge did not differ between cohorts. Use of dapagliflozin in children with advanced HF until HTx is not associated with AE in the immediate postoperative period nor increased length of hospitalization post-HTx. Potential cardiovascular benefits of dapagliflozin in patients awaiting HTx should be prioritized., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Inpatient delirium is common and associated with poor outcomes. Although most organisations have evidence-based guidelines to improve delirium prevention and management, delirium rates and outcomes have remained relatively unchanged over time. A lack of understanding of healthcare providers' experience of caring for people with delirium and its integration into existing guidance may explain some of the slow progress in improving delirium care., Objective: To review and synthesise existing qualitative evidence on healthcare providers' experience of caring for inpatients with delirium within and across disciplines., Methods: We systematically searched OVID Medline, CINAHL, Embase, Emcare, PsychINFO, AMED and Web of Science databases for articles published between January 1990 and November 2022. Article inclusion and study quality were assessed by two independent reviewers. Both thematic synthesis and content analysis were then conducted to synthesise findings from included studies., Results: Within the 25 included studies, the experience of nurses was the most commonly studied perspective, followed by medical and allied health. Nursing, medical and allied health staff all reported that their experience of caring for people with delirium was challenging, highlighting difficulties in delirium recognition and that they felt unsupported at organisational and local levels. Attitudes towards older people and the importance of delirium influenced identification and prioritisation., Conclusions: Healthcare providers often find caring for hospitalised patients with delirium challenging and complex. Although good communication within multidisciplinary teams was deemed helpful, more work is required to understand how to achieve this, recognising the unique perspectives of individual disciplines., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The prevalence of iron deficiency and anemia in the setting of modern-day maintenance immunosuppression in pediatric heart transplant (HTx) recipients is unclear. The primary aim was to determine the prevalence of iron deficiency (serum ferritin < 30 ng/mL ± transferrin saturation < 20%) and anemia per World Health Organization diagnostic criteria and associated risk factors., Methods: Single-center, cross-sectional analysis of 200 consecutive pediatric HTx recipients (<21 years old) from 2005 to 2021. Data were collected at 1-year post-HTx at the time of annual protocol biopsy., Results: Median age at transplant was 3 years (IQR .5-12.2). The median ferritin level was 32 ng/mL with 46% having ferritin < 30 ng/mL. Median transferrin saturation (TSAT) was 22% with 47% having TSAT < 20%. Median hemoglobin was 11 g/dL with 54% having anemia. Multivariable analysis revealed lower absolute lymphocyte count, TSAT < 20%, and estimated glomerular filtration rate <75 mL/min/1.73 m 2 were independently associated with anemia. Ferritin < 30 ng/mL in isolation was not associated with anemia. Ferritin < 30 ng/mL may aid in detecting absolute iron deficiency while TSAT < 20% may be useful in identifying patients with functional iron deficiency ± anemia in pediatric HTx recipients., Conclusion: Iron deficiency and anemia are highly prevalent in pediatric HTx recipients. Future studies are needed to assess the impact of iron deficiency, whether with or without anemia, on clinical outcomes in pediatric HTx recipients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: Patients with clinically lymph node-positive (cN1) prostate cancer (PCa) are traditionally regarded to have metastatic disease, and the role of local therapy (LT) in their treatment remains unclear., Objective: To evaluate the outcomes of cN1 PCa patients treated with LT, and secondarily to compare between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP)., Evidence Acquisition: A bibliographic search was performed using Medline, Embase, and the Cochrane Library to identify studies comparing the survival outcomes of cN1 PCa patients treated with LT (RT or RP) with those who did not receive any form of LT (observation or androgen deprivation therapy alone). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations were followed. Survival outcomes of the addition of LT were assessed using a random-effect model., Evidence Synthesis: A total of 8522 patients across eight studies were included. LT significantly improved overall survival (OS) across all time points from 2 to 10 yr compared with patients without LT, most notably providing a durable benefit in 10-yr OS (odds ratio [OR]: 1.49, 95% confidence interval [CI] 1.06-2.10). Both RT and RP were associated with benefits to both OS and recurrence-free survival, with no significant difference in OS between both modalities in medium-term follow-up (4-yr OR: 0.76, 95% CI 0.41-1.40, p = 0.19)., Conclusions: Regardless of modality, the use of LT in cN1 patients improved OS. Future studies should aim to identify patients who could benefit from LT and include more comprehensive survival data including biochemical recurrence., Patient Summary: In this study, we evaluated the outcomes of clinically lymph node-positive (cN1) prostate cancer (PCa) patients treated with local therapy (LT) and compared between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP). We found that the addition of LT for cN1 PCa patients leads to a significant improvement in survival outcomes, most notably for overall survival, with no significant difference between RT and RP., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Rationale and Objectives: Efficiently detecting and characterizing metastatic bone lesions on staging CT is crucial for prostate cancer (PCa) care. However, it demands significant expert time and additional imaging such as PET/CT. We aimed to develop an ensemble of two automated deep learning AI models for 1) bone lesion detection and segmentation and 2) benign vs. metastatic lesion classification on staging CTs and to compare its performance with radiologists., Materials and Methods: This retrospective study developed two AI models using 297 staging CT scans (81 metastatic) with 4601 benign and 1911 metastatic lesions in PCa patients. Metastases were validated by follow-up scans, bone biopsy, or PET/CT. Segmentation AI (3DAISeg) was developed using the lesion contours delineated by a radiologist. 3DAISeg performance was evaluated with the Dice similarity coefficient, and classification AI (3DAIClass) performance on AI and radiologist contours was assessed with F1-score and accuracy. Training/validation/testing data partitions of 70:15:15 were used. A multi-reader study was performed with two junior and two senior radiologists within a subset of the testing dataset (n = 36)., Results: In 45 unseen staging CT scans (12 metastatic PCa) with 669 benign and 364 metastatic lesions, 3DAISeg detected 73.1% of metastatic (266/364) and 72.4% of benign lesions (484/669). Each scan averaged 12 extra segmentations (range: 1-31). All metastatic scans had at least one detected metastatic lesion, achieving a 100% patient-level detection. The mean Dice score for 3DAISeg was 0.53 (median: 0.59, range: 0-0.87). The F1 for 3DAIClass was 94.8% (radiologist contours) and 92.4% (3DAISeg contours), with a median false positive of 0 (range: 0-3). Using radiologist contours, 3DAIClass had PPV and NPV rates comparable to junior and senior radiologists: PPV (semi-automated approach AI 40.0% vs. Juniors 32.0% vs. Seniors 50.0%) and NPV (AI 96.2% vs. Juniors 95.7% vs. Seniors 91.9%). When using 3DAISeg, 3DAIClass mimicked junior radiologists in PPV (pure-AI 20.0% vs. Juniors 32.0% vs. Seniors 50.0%) but surpassed seniors in NPV (pure-AI 93.8% vs. Juniors 95.7% vs. Seniors 91.9%)., Conclusion: Our lesion detection and classification AI model performs on par with junior and senior radiologists in discerning benign and metastatic lesions on staging CTs obtained for PCa., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bradford J. Wood: Principal investigator on cooperative research and development agreement (CRADA) between National Institutes of Health (NIH) and Philips and CRADAs with industry partners unrelated to this work; travel support related to CRADAs; royalties from NIH related to Philips licensing agreement; patents planned, issued, or pending. Peter L. Choyke: Receives payment from royalties paid to the U.S. government for patents on MRI US fusion biopsy licensed to Philips Medical. Peter A. Pinto: Institutional CRADA with Philips; royalties from NIH related to Philips licensing agreement; NIH-related patents planned, issued, or pending (U.S. patent nos. 8 447 384 and 10 215 830). Baris Turkbey: CRADAs with NVIDIA and Philips; royalties from NIH; patents planned, issued, or pending in the field of artificial intelligence. Dong Yang, Ziyue Xu, Jesse Tetreault, Daguang Xu: employee of NVIDIA Corporation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Image quality evaluation of prostate MRI is important for successful implementation of MRI into localized prostate cancer diagnosis., Purpose: To examine the impact of image quality on prostate cancer detection using an in-house previously developed artificial intelligence (AI) algorithm., Study Type: Retrospective., Subjects: 615 consecutive patients (median age 67 [interquartile range [IQR]: 61-71] years) with elevated serum PSA (median PSA 6.6 [IQR: 4.6-9.8] ng/mL) prior to prostate biopsy., Field Strength/sequence: 3.0T/T2-weighted turbo-spin-echo MRI, high b-value echo-planar diffusion-weighted imaging, and gradient recalled echo dynamic contrast-enhanced., Assessments: Scans were prospectively evaluated during clinical readout using PI-RADSv2.1 by one genitourinary radiologist with 17 years of experience. For each patient, T2-weighted images (T2WIs) were classified as high-quality or low-quality based on evaluation of both general distortions (eg, motion, distortion, noise, and aliasing) and perceptual distortions (eg, obscured delineation of prostatic capsule, prostatic zones, and excess rectal gas) by a previously developed in-house AI algorithm. Patients with PI-RADS category 1 underwent 12-core ultrasound-guided systematic biopsy while those with PI-RADS category 2-5 underwent combined systematic and targeted biopsies. Patient-level cancer detection rates (CDRs) were calculated for clinically significant prostate cancer (csPCa, International Society of Urological Pathology Grade Group ≥2) by each biopsy method and compared between high- and low-quality images in each PI-RADS category., Statistical Tests: Fisher's exact test. Bootstrap 95% confidence intervals (CI). A P value <0.05 was considered statistically significant., Results: 385 (63%) T2WIs were classified as high-quality and 230 (37%) as low-quality by AI. Targeted biopsy with high-quality T2WIs resulted in significantly higher clinically significant CDR than low-quality images for PI-RADS category 4 lesions (52% [95% CI: 43-61] vs. 32% [95% CI: 22-42]). For combined biopsy, there was no significant difference in patient-level CDRs for PI-RADS 4 between high- and low-quality T2WIs (56% [95% CI: 47-64] vs. 44% [95% CI: 34-55]; P = 0.09)., Data Conclusion: Higher quality T2WIs were associated with better targeted biopsy clinically significant cancer detection performance for PI-RADS 4 lesions. Combined biopsy might be needed when T2WI is lower quality., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Competing Interests: The authors declare no conflict of interest.

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. 68 Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, 68 Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model ( n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of 68 Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. 68 Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4-5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, 68 Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4-5 lesions, 68 Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of 68 Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and 68 Ga-PSMA-11 PET/CT.

Background Multiparametric MRI (mpMRI) improves prostate cancer (PCa) detection compared with systematic biopsy, but its interpretation is prone to interreader variation, which results in performance inconsistency. Artificial intelligence (AI) models can assist in mpMRI interpretation, but large training data sets and extensive model testing are required. Purpose To evaluate a biparametric MRI AI algorithm for intraprostatic lesion detection and segmentation and to compare its performance with radiologist readings and biopsy results. Materials and Methods This secondary analysis of a prospective registry included consecutive patients with suspected or known PCa who underwent mpMRI, US-guided systematic biopsy, or combined systematic and MRI/US fusion-guided biopsy between April 2019 and September 2022. All lesions were prospectively evaluated using Prostate Imaging Reporting and Data System version 2.1. The lesion- and participant-level performance of a previously developed cascaded deep learning algorithm was compared with histopathologic outcomes and radiologist readings using sensitivity, positive predictive value (PPV), and Dice similarity coefficient (DSC). Results A total of 658 male participants (median age, 67 years [IQR, 61-71 years]) with 1029 MRI-visible lesions were included. At histopathologic analysis, 45% (294 of 658) of participants had lesions of International Society of Urological Pathology (ISUP) grade group (GG) 2 or higher. The algorithm identified 96% (282 of 294; 95% CI: 94%, 98%) of all participants with clinically significant PCa, whereas the radiologist identified 98% (287 of 294; 95% CI: 96%, 99%; P = .23). The algorithm identified 84% (103 of 122), 96% (152 of 159), 96% (47 of 49), 95% (38 of 40), and 98% (45 of 46) of participants with ISUP GG 1, 2, 3, 4, and 5 lesions, respectively. In the lesion-level analysis using radiologist ground truth, the detection sensitivity was 55% (569 of 1029; 95% CI: 52%, 58%), and the PPV was 57% (535 of 934; 95% CI: 54%, 61%). The mean number of false-positive lesions per participant was 0.61 (range, 0-3). The lesion segmentation DSC was 0.29. Conclusion The AI algorithm detected cancer-suspicious lesions on biparametric MRI scans with a performance comparable to that of an experienced radiologist. Moreover, the algorithm reliably predicted clinically significant lesions at histopathologic examination. ClinicalTrials.gov Identifier: NCT03354416 © RSNA, 2024 Supplemental material is available for this article.

Rationale and Objectives: Prostate MRI quality is essential in guiding prostate biopsies. However, assessment of MRI quality is subjective with variation. Quality degradation sources exert varying impacts based on the sequence under consideration, such as T2W versus DWI. As a result, employing sequence-specific techniques for quality assessment could yield more advantageous outcomes. This study aims to develop an AI tool that offers a more consistent evaluation of T2W prostate MRI quality, efficiently identifying suboptimal scans while minimizing user bias., Materials and Methods: This retrospective study included 1046 patients from three cohorts (ProstateX [n = 347], All-comer in-house [n = 602], enriched bad-quality MRI in-house [n = 97]) scanned between January 2011 and May 2022. An expert reader assigned T2W MRIs a quality score. A train-validation-test split of 70:15:15 was applied, ensuring equal distribution of MRI scanners and protocols across all partitions. T2W quality AI classification model was based on 3D DenseNet121 architecture using MONAI framework. In addition to multiclassification, binary classification was utilized (Classes 0/1 vs. 2). A score of 0 was given to scans considered non-diagnostic or unusable, a score of 1 was given to those with acceptable diagnostic quality with some usability but with some quality distortions present, and a score of 2 was given to those considered optimal diagnostic quality and usability. Partial occlusion sensitivity maps were generated for anatomical correlation. Three body radiologists assessed reproducibility within a subgroup of 60 test cases using weighted Cohen Kappa., Results: The best validation multiclass accuracy of 77.1% (121/157) was achieved during training. In the test dataset, multiclassification accuracy was 73.9% (116/157), whereas binary accuracy was 84.7% (133/157). Sub-class sensitivity for binary quality distortion classification for class 0 was 100% (18/18), and sub-class specificity for T2W classification of absence/minimal quality distortions for class 2 was 90.5% (95/105). All three readers showed moderate to substantial agreement with ground truth (R1-R3 κ = 0.588, κ = 0.649, κ = 0.487, respectively), moderate to substantial agreement with each other (R1-R2 κ = 0.599, R1-R3 κ = 0.612, R2-R3 κ = 0.685), fair to moderate agreement with AI (R1-R3 κ = 0.445, κ = 0.410, κ = 0.292, respectively). AI showed substantial agreement with ground truth (κ = 0.704). 3D quality heatmap evaluation revealed that the most critical non-diagnostic quality imaging features from an AI perspective related to obscuration of the rectoprostatic space (94.4%, 17/18)., Conclusion: The 3D AI model can assess T2W prostate MRI quality with moderate accuracy and translate whole sequence-level classification labels into 3D voxel-level quality heatmaps for interpretation. Image quality has a significant downstream impact on ruling out clinically significant cancers. AI may be able to help with reproducible identification of MRI sequences requiring re-acquisition with explainability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Rationale and Objectives: To evaluate the effect of compressed SENSE (CS) in clinical settings on scan time reduction and image quality., Materials and Methods: Ninety-five magnetic resonance imaging (MRI) scans from different anatomical regions were acquired, consisting of a standard protocol sequence (SS) and sequence accelerated with CS. Anonymized paired sequences were randomly displayed and rated by six blinded subspecialty radiologists. Side-by-side evaluation on perceived sharpness, perceived signal-to-noise-ratio (SNR), lesion conspicuity, and artifacts were compared and scored on a five-point Likert scale, and individual image quality was evaluated on a four-point Likert scale., Results: CS reduced overall scan time by 32% while maintaining acceptable MRI quality for all regions. The largest time savings were seen in the spine (mean = 68 seconds, 44% reduction) followed by the brain (mean = 86 seconds, 37% reduction). The sequence with maximum time savings was intracranial 3D-time-of-flight magnetic resonance angiography (202 seconds, 56% reduction). CS was mildly inferior to SS on perceived sharpness, perceived SNR, and lesion conspicuity (mean scores = 2.32-2.96, P < .001 [1: SS superior; 3: equivalent; 5: CS superior]). CS was equivalent to SS for joint and body scans on overall image quality (CS = 3.02-3.37, SS = 3.04-3.68, P > .05, [1: lowest quality and 4: highest quality]). The overall image quality of CS was slightly less for brain and spine scans (mean CS = 2.79-3.05, mean SS = 3.13-3.43, P = .021) but still diagnostic. Good overall clinical acceptance for CS (88%) was noted with full clinical acceptance for body scans (100%) and high acceptance for other regions (68%-95%)., Conclusion: CS significantly reduced MR acquisition time while maintaining acceptable image quality. The implementation of CS may improve departmental workflows and enhance patient care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18 years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6 months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8 years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6 mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Kidney disease is common after pediatric heart transplantation. Serum creatinine-based glomerular filtration rate is the most frequently reported measure of kidney function. Albuminuria is an additional marker of kidney dysfunction and is not well described in this population. In this study, we evaluate the prevalence and degree of albuminuria and describe clinical factors associated with albuminuria in a cohort of pediatric heart transplant recipients., Methods: This was a cross-sectional study of pediatric heart transplant recipients. Albuminuria was assessed using spot urine albumin-to-creatinine ratio collected at the most recent annual screening cardiac catheterization through August 2019., Results: In 115 patients at a median duration of 10.2 years post-transplant, 39% had albuminuria. Stage 3 or greater chronic kidney disease was present in 6%. The immunosuppressive regimen at the time of measurement contained a calcineurin inhibitor (CNI) in 88% and a proliferation signal inhibitor (PSI) in 62%. In multivariable modeling, lower eGFR, PSI use, and younger age at transplant were associated with higher levels of albuminuria, whereas CNI use was associated with lower levels of albuminuria., Conclusion: Albuminuria is a prevalent finding in medium-term follow up of pediatric heart transplant recipients, reflecting kidney injury, and is associated with other markers of kidney dysfunction, such as low eGFR. Younger age at transplant, lower eGFR, and PSI use were among the associations with albuminuria., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Children undergoing cardiac surgery are at risk for acute kidney injury (AKI) and cardiac dysfunction. Opportunity exists in protecting end organ function with remote ischemic preconditioning. We hypothesize this intervention lessens kidney and myocardial injury., Methods: We conducted a randomized, double blind, placebo controlled trial of remote ischemic preconditioning in children undergoing cardiac surgery. Pre-specified end points are change in creatinine, estimated glomerular filtration rate, development of AKI, B-type natriuretic peptide and troponin I at 6, 12, 24, 48, 72 h post separation from bypass., Results: There were 45 in the treatment and 39 patients in the control group, median age of 3.5 and 3.8 years, respectively. There were no differences between groups in creatinine, cystatin C, eGFR at each time point. There was a trend for a larger rate of decrease, especially for cystatin C (p = 0.042) in the treatment group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of treatment group (p = 0.094). Adjusting for baseline creatinine, the odds ratio for AKI in treatment versus control was 0.31 (p = 0.037); adjusting for clinical characteristics, the odds ratio was 0.34 (p = 0.056). There were no differences in natriuretic peptide or troponin levels between groups. All secondary end points of clinical outcomes were not different., Conclusions: There is suggestion of RIPC delivering some kidney protection in an at-risk pediatric population. Larger, higher risk population studies will be required to determine its efficacy. Trial registration and date: Clinicaltrials.gov NCT01260259; 2021., (© 2023. The Author(s).)

BACKGROUND. Precise risk stratification through MRI/ultrasound (US) fusion-guided targeted biopsy (TBx) can guide optimal prostate cancer (PCa) management. OBJECTIVE. The purpose of this study was to compare PI-RADS version 2.0 (v2.0) and PI-RADS version 2.1 (v2.1) in terms of the rates of International Society of Urological Pathology (ISUP) grade group (GG) upgrade and downgrade from TBx to radical prostatectomy (RP). METHODS. This study entailed a retrospective post hoc analysis of patients who underwent 3-T prostate MRI at a single institution from May 2015 to March 2023 as part of three prospective clinical trials. Trial participants who underwent MRI followed by MRI/US fusion-guided TBx and RP within a 1-year interval were identified. A single genitourinary radiologist performed clinical interpretations of the MRI examinations using PI-RADS v2.0 from May 2015 to March 2019 and PI-RADS v2.1 from April 2019 to March 2023. Upgrade and downgrade rates from TBx to RP were compared using chi-square tests. Clinically significant cancer was defined as ISUP GG2 or greater. RESULTS. The final analysis included 308 patients (median age, 65 years; median PSA density, 0.16 ng/mL 2 ). The v2.0 group ( n = 177) and v2.1 group ( n = 131) showed no significant difference in terms of upgrade rate (29% vs 22%, respectively; p = .15), downgrade rate (19% vs 21%, p = .76), clinically significant upgrade rate (14% vs 10%, p = .27), or clinically significant downgrade rate (1% vs 1%, p > .99). The upgrade rate and downgrade rate were also not significantly different between the v2.0 and v2.1 groups when stratifying by index lesion PI-RADS category or index lesion zone, as well as when assessed only in patients without a prior PCa diagnosis (all p > .01). Among patients with GG2 or GG3 at RP ( n = 121 for v2.0; n = 103 for v2.1), the concordance rate between TBx and RP was not significantly different between the v2.0 and v2.1 groups (53% vs 57%, p = .51). CONCLUSION. Upgrade and downgrade rates from TBx to RP were not significantly different between patients whose MRI examinations were clinically interpreted using v2.0 or v2.1. CLINICAL IMPACT. Implementation of the most recent PI-RADS update did not improve the incongruence in PCa grade assessment between TBx and surgery.

Purpose: To evaluate CycleGAN's ability to enhance T2-weighted image (T2WI) quality., Method: A CycleGAN algorithm was used to enhance T2WI quality. 96 patients (192 scans) were identified from patients who underwent multiple axial T2WI due to poor quality on the first attempt (RAD1) and improved quality on re-acquisition (RAD2). CycleGAN algorithm gave DL classifier scores (0-1) for quality quantification and produced enhanced versions of QI1 and QI2 from RAD1 and RAD2, respectively. A subset (n = 20 patients) was selected for a blinded, multi-reader study, where four radiologists rated T2WI on a scale of 1-4 for quality. The multi-reader study presented readers with 60 image pairs (RAD1 vs RAD2, RAD1 vs QI1, and RAD2 vs QI2), allowing for selecting sequence preferences and quantifying the quality changes., Results: The DL classifier correctly discerned 71.9 % of quality classes, with 90.6 % (96/106) as poor quality and 48.8 % (42/86) as diagnostic in original sequences (RAD1, RAD2). CycleGAN images (QI1, QI2) demonstrated quantitative improvements, with consistently higher DL classifier scores than original scans (p < 0.001). In the multi-reader analysis, CycleGAN demonstrated no qualitative improvements, with diminished overall quality and motion in QI2 in most patients compared to RAD2, with noise levels remaining similar (8/20). No readers preferred QI2 to RAD2 for diagnosis., Conclusion: Despite quantitative enhancements with CycleGAN, there was no qualitative boost in T2WI diagnostic quality, noise, or motion. Expert radiologists didn't favor CycleGAN images over standard scans, highlighting the divide between quantitative and qualitative metrics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

BACKGROUND. Currently most clinical models for predicting biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) incorporate staging information from RP specimens, creating a gap in preoperative risk assessment. OBJECTIVE. The purpose of our study was to compare the utility of presurgical staging information from MRI and postsurgical staging information from RP pathology in predicting BCR in patients with PCa. METHODS. This retrospective study included 604 patients (median age, 60 years) with PCa who underwent prostate MRI before RP from June 2007 to December 2018. A single genitourinary radiologist assessed MRI examinations for extraprostatic extension (EPE) and seminal vesicle invasion (SVI) during clinical interpretations. The utility of EPE and SVI on MRI and RP pathology for BCR prediction was assessed through Kaplan-Meier and Cox proportional hazards analyses. Established clinical BCR prediction models, including the University of California San Francisco Cancer of the Prostate Risk Assessment (UCSF-CAPRA) model and the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) model, were evaluated in a subset of 374 patients with available Gleason grade groups from biopsy and RP pathology; two CAPRA-MRI models (CAPRA-S model with modifications to replace RP pathologic staging features with MRI staging features) were also assessed. RESULTS. Univariable predictors of BCR included EPE on MRI (HR = 3.6), SVI on MRI (HR = 4.4), EPE on RP pathology (HR = 5.0), and SVI on RP pathology (HR = 4.6) (all p < .001). Three-year BCR-free survival (RFS) rates for patients without versus with EPE were 84% versus 59% for MRI and 89% versus 58% for RP pathology, and 3-year RFS rates for patients without versus with SVI were 82% versus 50% for MRI and 83% versus 54% for RP histology (all p < .001). For patients with T3 disease on RP pathology, 3-year RFS rates were 67% and 41% for patients without and with T3 disease on MRI. AUCs of CAPRA models, including CAPRA-MRI models, ranged from 0.743 to 0.778. AUCs were not significantly different between CAPRA-S and CAPRA-MRI models ( p > .05). RFS rates were significantly different between low- and intermediate-risk groups for only CAPRA-MRI models (80% vs 51% and 74% vs 44%; both p < .001). CONCLUSION. Presurgical MRI-based staging features perform comparably to postsurgical pathologic staging features for predicting BCR. CLINICAL IMPACT. MRI staging can preoperatively identify patients at high BCR risk, helping to inform early clinical decision-making. TRIAL REGISTRATION. ClinicalTrials.gov NCT00026884 and NCT02594202.

Introduction: Pharmacokinetics of mycophenolic acid (MPA) display substantial interpatient variability, with up to 10-fold difference of exposure in individual patients under a fixed-dose regimen. MPA trough level (C0) monitoring is common in clinical practice but has not proven sufficiently informative in predicting MPA exposure or patient outcomes, especially in children. No limited sampling strategies (LSSs) have been generated from pediatric heart transplant (HTx) recipients to estimate MPA AUC., Methods: Single-center, observational analysis of 135 de novo pediatric HTx recipients ≤21 years old who underwent MPA AUC between 2011 and 2021., Results: Median age was 4 years (IQR .6-12.1). Median time from transplant to MPA AUC sampling was 15 days (IQR 11-19). MMF doses (mg or mg/day) had low, negative Pearson correlation coefficients (r) while doses adjusted for weight or body surface area had low correlation with Trapezoidal MPA AUC 0-24 h (r = .3 and .383, respectively). MPA C0 had weak association (r = .451) with Trapezoidal MPA AUC 0-24 h . LSS with two pharmacokinetic sampling time points at 90 (C 3 ) and 360 (C 5 ) min after MMF administration (estimated AUC 0-24 h  = 32.82 + 4.12 × C 3  + 11.53 × C 5 ) showed strong correlation with Trapezoidal MPA AUC 0-24 h (r = .87)., Conclusion: MMF at fixed or weight-adjusted doses, as well as MPA trough levels, correlate poorly with MPA AUC 0-24 h . We developed novel LSSs to estimate Trapezoidal MPA AUC from a large cohort of pediatric HTx recipients. Validation of our LSSs should be completed in a separate cohort of pediatric HTx recipients., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Multiparametric magnetic resonance imaging (mpMRI) surveillance post focal cryotherapy (FT) of prostate cancer is challenging as post treatment artefacts alter mpMRI findings. In this initial experience, we assessed diagnostic performance of mpMRI in detecting clinically significant prostate cancer (csPCa) after FT., Materials and Methods: This single-centre phase II prospective clinical trial recruited 28 men with localized csPCa for FT between October 2019 and April 2021. 12-months post FT mpMRI were performed prior to biopsy and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of all mpMRI positive subjects were analysed. Chi square goodness of fit test correlated biopsy positive PIRADS3 (P3) and PIRADS4/5 lesions with histology grade group. One way ANOVA test assessed performance of ADC values in differentiating csPCa, non csPCa and benign lesions., Results: Sensitivity, specificity, PPV and NPV of mpMRI were 100%, 14.28%, 53.84% and 100% for subjects with histologically proven cancer. Correlation of PIRADS v2.1 scores with histologically proven prostate cancer was statistically significant (p < 0.5). Correlation of P3 lesions with non-csPCa was statistically significant (p < 0.02535). Higher ADC value was associated with benign histology (adjusted odds ratio OR 0.97, 95% confidence interval: 0.94, 0.99) (p = 0.008). Among the malignant lesions, higher ADC value was associated with non-csPCa (adjusted OR: 0.97; 95% CI: 0.95, 0.99) (p = 0.032)., Conclusion: mpMRI is highly sensitive in detecting residual cancer. ADC values and PIRADS scores may be of value in differentiating csPCa from non-csPCa with a potential for risk stratification of men requiring re-biopsy versus non-invasive surveillance of remnant prostate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

We conducted a scientific survey of paediatric practitioners who manage heart failure with dilated cardiomyopathy in children. The survey covered management from diagnosis to treatment to monitoring, totalling 63 questions. There were 54 respondents from 40 institutions and 3 countries. There were diverse selections of management options by the respondents in general, but also unanimity in some management options. Variation in practice is likely due to the relative paucity of scientific data in this field and lack of strong evidence-based recommendations from guidelines, which presents an opportunity for future research and quality improvement efforts as the evidence base continues to grow.

Purpose: Our objective is to evaluate the clinically significant prostate cancer detection rate of overlapping and perilesional systematic biopsy cores and its impact on grade group (GG) concordance at prostatectomy., Materials and Methods: Biopsy maps of those undergoing MRI-targeted (TB) and systematic biopsy (SB) were reviewed to reclassify systematic cores. Perilesional (PL) cores were defined as adjacent cores within 10 mm of the target lesion ("penumbra") whilst overlap (OL) cores were defined as cores within the ROI itself ("umbra"). All other cores were designated as distant cores (DC). The incremental csPCa detection rate (GG ≥ 2) and the rate of GG upgrading on prostatectomy as OL, PL and DC sequentially added to TB were determined., Results: Out of the 398 patients included, the median number of OL and PL cores was 5 (IQR 4-7) and 5 (IQR 3-6) respectively. OL cores detected more csPCa than PL cores (31 vs 16%, p < 0.001). OL and PL cores improved the csPCa detection rate of TB from 34 to 39% (p < 0.001) and 37% (p = 0.001) respectively. TB+OL+PL had greater csPCa detection compared to just TB+OL (41 vs 39%, p = 0.016) and TB+PL (41 vs 37%, p < 0.001). Of the 104 patients who underwent prostatectomy, GG upgrading rate for TB+OL+PL was lower compared to TB (21 vs 36%, p < 0.001) and was not significantly different compared to TB+OL+PL+DC (21 vs 19%, p = 0.500)., Conclusion: A biopsy strategy incorporating both intensive sampling of the umbra and penumbra improved csPCa detection and reduced risk of GG upgrading at prostatectomy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: We report herein the impact of focal therapy (FT) on multi-domain functional outcomes in a Phase II prospective clinical trial (NCT04138914) in focal cryotherapy for clinically significant prostate cancer (csPCa)., Methods: The primary outcome was the detection of a ≥5 point deterioration in any of the four main expanded prostate index composite (EPIC) functional domains. Pretreatment multiparametric magnetic resonance imaging (mpMRI) and transperineal targeted and systematic saturation biopsy were used to select patients with prostate-specific antigen (PSA)≤20 ng/mL, Gleason grade group (GG) ≤4, mpMRI lesion volume ≤ 3 mL (for a single lesion) or ≤1.5 mL (where two lesions were present). Focal cryotherapy was performed with a minimum 5 mm margin around each target lesion. EPIC scores were obtained at baseline and posttreatment at 1, 3, 6, and 12 months. Mandatory repeat mpMRI and prostate biopsy were performed at 12 months to determine the infield and outfield recurrence., Results: Twenty-eight patients were recruited. The mean age was 68 years, with PSA of 7.3 ng/mL and PSA density of 0.19 ng/mL 2 . No Clavien-Dindo ≥3 complications occurred. Transient worsening of EPIC urinary (mean diff 16.0, p < 0.001, 95% confidence interval [CI]: 8.8-23.6) and sexual function scores (mean diff 11.0, p:0.005, 95% CI: 4.0-17.7) were observed at 1-month posttreatment, with recovery by Month 3. A subgroup who had ablation extending to the neurovascular bundle had a trend to delayed recovery of sexual function to Month 6. At 12-month repeat mpMRI and biopsy, 22 patients (78.6%) had no detectable csPCa. Of the six patients (21.4%) who had csPCa recurrences, four were GG2, one GG3, and one GG4. Four patients underwent repeat FT, one underwent radical prostatectomy, while the remaining one patient with low-volume GG2 cancer opted for active surveillance., Conclusion: FT using cryotherapy was associated with a transient deterioration of urinary and sexual function with resolution at 3 months posttreatment and with reasonable early efficacy in well-selected csPCa patients., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: Literature is limited comparing adverse effects (AEs) of the proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (EVL) in pediatric heart transplant (HTx) recipients., Methods: Single-center, observational cohort analysis assessing first use of SRL or EVL in pediatric HTx recipients <21 years of age with up to 2 years follow-up between 2009 and 2020., Results: Eighty-seven patients were included, with 52 (59.8%) receiving EVL and 35 (40.2%) receiving SRL. Tacrolimus with PSI was the most common regimen. Intergroup comparison revealed lower baseline estimated glomerular filtration rate (eGFR) and greater increase in eGFR from baseline to 6 months and latest follow-up in SRL cohort compared to EVL cohort. There was greater increase in HDL cholesterol in SRL cohort compared to EVL cohort. Intragroup analysis revealed eGFR and HDL cholesterol increased significantly within SRL cohort, triglycerides and glycosylated hemoglobin increased in EVL cohort, and LDL cholesterol and total cholesterol increased in both cohorts (all p < .05). There were no differences in hematological indices or rates of aphthous ulcers, effusions, or infections between cohorts. Incidence of proteinuria was not significantly different among those screened within cohorts. Of those included in our analysis, one patient in SRL cohort (2.9%) and two in EVL cohort (3.8%) had PSI withdrawn due to AE., Conclusion: Low-dose PSIs in calcineurin inhibitor minimization regimens appear well-tolerated with low withdrawal rate secondary to AE in pediatric HTx recipients. While incidence of most AE was similar between PSI, our results suggest EVL may be associated with less favorable metabolic impact than SRL in this population., (© 2023 Wiley Periodicals LLC.)

Type 1 glycogen storage disease (GSDI) is a rare autosomal recessive disorder caused by glucose-6-phosphatase (G6Pase) deficiency. We discuss a case of a 29-year-old gentleman who had GSDI with metabolic complications of hypoglycemia, hypertriglyceridemia, hyperuricemia, and short stature. He also suffered from advanced chronic kidney disease, nephrotic range proteinuria, and hepatic adenomas. He presented with acute pneumonia and refractory metabolic acidosis despite treatment with isotonic bicarbonate infusion, reversal of hypoglycemia, and lactic acidosis. He eventually required kidney replacement therapy. The case report highlights the multiple contributing mechanisms and challenges to managing refractory metabolic acidosis in a patient with GSDI. Important considerations for dialysis initiation, decision for long-term dialysis modality and kidney transplantation for patients with GSDI are also discussed in this case report.

Multiparametric magnetic resonance imaging (mpMRI) of the urinary bladder has shown high diagnostic performance in accurate staging of bladder cancer. Vesical Imaging Reporting and Data System (VI-RADS) scoring was developed in 2018 to standardize imaging and reporting of bladder cancer on mpMRI and is an excellent tool in preoperative T-staging of patients with high risk bladder cancer. However, there is no concise guide in the literature for practical use of VI-RADS in everyday clinical reporting. In this review, we describe our experience with mpMRI in pretreatment workup of bladder cancer, illustrate the imaging characteristics of VI-RADS categories 1 to 5 using case review, and discuss practical pearls and pitfalls in the use of mpMRI and VI-RADS in the hope of providing an accessible reference for radiologists in daily reporting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Pediatric heart failure (HF) is associated with significant morbidity and mortality. Medical treatment for pediatric HF is largely derived from adult studies. Previously, there has been no described use of dapagliflozin in pediatric HF patients. We describe our single-center experience using dapagliflozin in addition to standard HF medical therapy in 38 pediatric HF patients since January 2020. Median age was 12.2 years (interquartile range 6.2-17.5). Majority of patients had dilated cardiomyopathy (68.4%) and reduced left ventricular ejection fraction (LVEF) of 40% or less (65.8%). HF regimens commonly included sacubitril/valsartan, beta-blocker, mineralocorticoid receptor antagonist, and loop diuretic. Median follow-up from dapagliflozin initiation for the whole cohort was 130 days (IQR 76-332). Median B-type natriuretic peptide decreased significantly from 222 to 166 pg/mL at latest clinical follow-up (P = .04). Estimated glomerular filtration rate trended lower at latest follow-up but was not significant from baseline. There were no clinically significant changes in blood chemistries or vital signs after initiation of dapagliflozin. No patients experienced symptomatic hypoglycemia or hypovolemia. Six patients (15.8%) experienced a symptomatic urinary tract infection necessitating antibiotic treatment. In a separate analysis of 16 patients with dilated cardiomyopathy who received dapagliflozin for a median of 313 days (IQR 191-414), median LVEF increased significantly from 32 to 37.2% (P = .006). Dapagliflozin, when added to a background of guideline-directed medical therapy, appears well tolerated in children with HF. Larger studies are needed to evaluate safety and efficacy of dapagliflozin in this population., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Infants listed for heart transplant are at high risk for waitlist mortality. While waitlist mortality for children has decreased in the current era of increased ventricular assist device use, outcomes for small infants supported by ventricular assist device remain suboptimal. We evaluated morbidity and survival in critically ill infants listed for heart transplant and managed without ventricular assist device support., Methods: Critically ill infants (requiring ≥1 inotrope and mechanical ventilation or ≥2 inotropes without mechanical ventilation) listed between 2008 and 2019 were included. During the study period, infants were managed primarily medically. Mechanical circulatory support, specifically extracorporeal membrane oxygenation, was utilized as "rescue therapy" for decompensating patients., Results: Thirty-two infants were listed 1A, 66% with congenital heart disease. Median age and weight at listing were 2.2 months and 4.4 kg, with 69% weighing <5 kg. At listing, 97% were mechanically ventilated, 41% on ≥2 inotropes, and 25% under neuromuscular blockade. Five patients were supported by ECMO after listing. A favorable outcome (transplant or recovery) was observed in 84%. One-year posttransplant survival was 92%. Infection was the most common waitlist complication occurring in 75%. Stroke was rare, occurring in one patient who was supported on ECMO. Renal function improved from listing to transplant, death, or recovery (eGFR 70 vs 87 ml/min/1.73m 2 , p = .001)., Conclusion: A strategy incorporating a high threshold for mechanical circulatory support and acceptance of prolonged mechanical ventilation and neuromuscular blockade can achieve good survival and morbidity outcomes for critically ill infants listed for heart transplant., (© 2022 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: Longitudinal evaluation of allograft diastolic function in paediatric heart transplant recipients is important for early detection of acute rejection, cardiac allograft vasculopathy, and graft dysfunction. Mean diastolic right atrial and pulmonary capillary wedge pressures obtained at catheterisation are the reference standards for assessment. Echocardiography is non-invasive and more suitable for serial surveillance, but individual parameters have lacked accuracy. This study aimed to identify covariates of post-transplant mean right atrial and pulmonary capillary wedge pressures, including B-type natriuretic peptide and certain echocardiographic parameters., Methods: A retrospective review of 143 scheduled cardiac catheterisations and echocardiograms from 56 paediatric recipients transplanted from 2007 to 2011 was performed. Samples with rejection were excluded. Univariate and multivariate linear regression models using backward selection were applied to a database consisting of B-type natriuretic peptide, haemodynamic, and echocardiographic data., Results: Ln B-type natriuretic peptide, heart rate z-score, left ventricular end-diastolic dimension z-score, mitral E/e', and percent interventricular septal thickening in systole were independently associated with mean right atrial pressure. Ln B-type natriuretic peptide, heart rate z-score, left ventricular end-diastolic dimension z-score, left ventricular mass (observed/predicted), and mitral E/e' were independently associated with mean pulmonary capillary wedge pressure. Covariates of B-type natriuretic peptide included mean pulmonary artery and pulmonary capillary wedge pressures, height, haemoglobin, fractional shortening, percent interventricular septal thickening in systole, and pulmonary vascular resistance index., Conclusions: B-type natriuretic peptide and echocardiographic indices of diastolic function were independently related to post-transplant mean right atrial and pulmonary capillary wedge pressures in paediatric heart transplant recipients without rejection.

Background: The optimal number of systematic biopsy cores in the era of multi-parametric MRI targeted biopsy remains unclear, especially on its impact of focal therapy planning. Our objective is to investigate the impact of reducing the number of systematic cores on prostate cancer detection in the era of MRI-US fusion targeted biopsy and as well as its relevance in template planning for focal therapy., Materials and Methods: A retrospective analysis of 398 consecutive men who underwent both systematic saturation (~24 cores) and MRI-US fusion targeted biopsy was performed. Four reduced-core systematic biopsy strategies (two-thirds, half, one-third and one-quarter systematic cores) were modelled and the detection rates of clinically-significant prostate cancer (csPCa defined as grade group ≥2) were compared to that of a full systematic biopsy using McNemar's test. Focal therapy treatment plans were made based on positive cores on combined (targeted and systematic) biopsy and the various reduced-cores strategies to compare the proportion who had a change in treatment plan., Results: csPCa was detected in 42% (168/398) of this patient cohort. Non-targeted systematic saturation biopsy had a 21% (83/398) csPCa detection rate. Our four strategies reduced the mean number of non-targeted systematic cores from 21.8 to 14.5, 10.9, 7.3 and 5.4 cores and their csPCa detection rates were significantly decreased to 16%, 13%, 9% and 8% respectively (all p < 0.05). Compared to the reduced-core strategies, a full systematic saturation biopsy resulted in change to the focal therapy treatment plan in 12% (2/3 cores), 19% (1/2 cores), 24% (1/3 cores) and 29% (1/4 cores) of the time (p = 0.0434)., Conclusions: Reducing the number of systematic biopsies when performing an MRI-targeted biopsy leads to reduced detection of csPCa and alter the treatment plans for focal therapy, possibly limiting its oncological efficacy., (© 2022. The Author(s).)

Background: Cytomegalovirus (CMV) is an important complication of heart transplantation and has been associated with graft loss in adults. The data in pediatric transplantation, however, is limited and conflicting. We conducted a large-scale cohort study to better characterize the relationship between CMV serostatus, CMV antiviral use, and graft survival in pediatric heart transplantation. Methods: 4,968 pediatric recipients of solitary heart transplants from the Scientific Registry of Transplant Recipients were stratified into three groups based on donor or recipient seropositivity and antiviral use: CMV seronegative (CMV-) transplants, CMV seropositive (CMV+) transplants without antiviral therapy, and CMV+ transplants with antiviral therapy. The primary endpoint was retransplantation or death. Results: CMV+ transplants without antiviral therapy experienced worse graft survival than CMV+ transplants with antiviral therapy (10-year: 57 vs 65%). CMV+ transplants with antiviral therapy experienced similar survival as CMV- transplants. Compared to CMV seronegativity, CMV seropositivity without antiviral therapy had a hazard ratio of 1.21 (1.07-1.37 95% CI, p -value = .003). Amongst CMV+ transplants, antiviral therapy had a hazard ratio of .82 (0.74-.92 95% CI, p -value < .001). During the first year after transplantation, these hazard ratios were 1.32 (1.06-1.64 95% CI, p -value .014) and .59 (.48-.73 95% CI, p -value < .001), respectively. Conclusions: CMV seropositivity is associated with an increased risk of graft loss in pediatric heart transplant recipients, which occurs early after transplantation and may be mitigated by antiviral therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rabbani, Kronmal, Wagner, Kemna, Albers, Hong, Friedland-Little, Spencer and Law.)

Background: While mismatching between donor and recipient human leukocyte antigen (HLA) alleles has been associated with increased graft loss in pediatric heart recipients, it is actually the surface amino acid structures, termed eplets, which determine the antigenicity of each HLA molecule. We hypothesized that HLA eplet mismatch analysis is a better predictor of adverse outcomes after pediatric heart transplant than conventional allele mismatch comparison., Methods: A retrospective review of the Pediatric Heart Transplant Society database identified pediatric heart recipients (<18 years at listing) with complete donor and recipient HLA typing (A, B, and DR). Imputed high-resolution HLA genotypes were entered into HLAMatchmaker software which then calculated the number of eplet mismatches between each donor-recipient pair. Multivariable Cox regression analysis was used to examine associations between allele or eplet mismatching and adverse outcomes., Results: Compared to those with <20 HLA class I eplet mismatches, recipients with 20 or more HLA class I eplet mismatches had an increased risk of graft loss (HR 1.46 [1.01-2.12], p = .049). HLA class I eplet mismatching was also associated with rejection (>20 mismatches: HR 1.30 [1.03-1.65], p = .030), while HLA class II eplet mismatching was associated with specified antibody-mediated rejection (10-20 mismatches: HR 1.57 [1.06-2.34], p = .025; >20 mismatches: HR 3.14 [1.72-5.71], p < .001). Neither HLA class I nor class II allele mismatching was significantly associated with graft loss or rejection., Conclusion: Eplet mismatch analysis was more predictive of adverse post-transplant outcomes (including graft loss and rejection) than allele mismatch comparison. Further study, including prospective high-resolution HLA typing, is warranted., (© 2021 Wiley Periodicals LLC.)

Purpose: Several multiparametric magnetic resonance imaging (mpMRI)-based models have been developed with significant improvements in diagnostic accuracy for clinically significant prostate cancer (csCaP), but lack proper external validation. We therefore sought to externally validate and compare all published mpMRI-based csCaP risk prediction models in an independent Asian population., Patients and Methods: A total of 449 men undergoing combined transperineal fusion-targeted/systematic prostate biopsy at our specialist center between 2015 to 2019 were retrospectively analyzed. csCaP was defined as lesions with ISUP (International Society of Urological Pathology) grade group ≥2. The performance of 6 mpMRI-based risk models (MRI-ERSPC-3/4, Distler, Radtke, Mehralivand, van Leeuwen and He) were evaluated in terms of discrimination, calibration and clinical utility, using area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analyses., Results: A total of 202 (45%) subjects were diagnosed with csCaP. All models demonstrated excellent accuracy with AUCs ranging from 0.75 to 0.86, and most significantly outperformed mpMRI PIRADSv2.0 (Prostate Imaging Reporting and Data System version 2.0) alone. The models by Mehralivand and He showed good calibration to our validation population, with respective intercepts of -0.08 and -0.84. All models were nevertheless recalibrated to the csCaP prevalence in our population for analysis. Decision curve analysis showed that above a threshold probability of 10%, all mpMRI-based models demonstrated superior net benefit compared to mpMRI PIRADSv2.0 or a biopsy-all-men strategy. The van Leeuwen model had the greatest net benefit, avoiding 39% of unnecessary biopsies while missing only 4% of csCaP, at a threshold probability of 15%., Conclusions: The mpMRI-based risk models demonstrate excellent discrimination and clinical utility and are easy to apply in practice, suggesting that individualized risk-based approaches can be considered over mpMRI alone to avoid unnecessary biopsies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the clinically-significant prostate cancer (csCaP) detection rate of systematic (SBx) vs. targeted biopsy (TBx), after accounting for the overlapping systematic cores within the MRI regions of interest., Materials and Methods: We identified 398 consecutive men who underwent both transperineal systematic and targeted biopsy between January 2015 to January 2019. We reclassified overlapping systematic cores in the MRI regions of interest as target cores. The detection rates of SBx and TBx were compared using McNemar's test., Results: Detection rate of csCaP (grade group ≥2) was 42% (168/398). Median number of systematic and targeted cores were 23 (IQR 19-29) and 9 (IQR 6-12) respectively. A median of 3 (IQR 2-4) overlapping systematic cores were reclassified as targeted cores. After accounting for overlap, csPC detection rate on SBx decreased from 37% and 21% while the csCaP detection rate of TBx increased from 34% to 39% (both P < 0.001), with TBx having a better detection rate (39% vs. 21%, P < 0.001). A previous negative biopsy was associated with a lower risk of having csCaP on non-targeted SBx (OR 0.27, 95% CI: 0.12 - 0.58, P = 0.001). Only 5% (13/243) of those who had no cancer detected on TBx had csCaP on non-targeted SBx compared to 45% (70/155) of those who had csCaP on TBx (P< 0.001)., Conclusions: The utility of SBx in detecting csCaP decreases after accounting for overlap into the MRI region of interest, especially in men with a prior negative biopsy. Overlapping systematic cores improve the csCaP detection rate on TBx., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Reconstructing the hepatic artery in living donor liver transplantation presents the challenges of a short and small donor vessel stump, which is compounded by poor surgical access for microsurgical anastomosis. Arterial interpositional grafts (eg, the radial artery) have been used to overcome these problems. The purpose of this presentation is to describe the use of the descending branch of the lateral circumflex femoral artery (DLCFA) as an alternative when the patient has had an abnormal Allen's test precluding the use of the radial artery or if a Y-graft is needed., Methods: The DLCFA resides in the septum between the rectus femoris and vastus lateralis muscles. A linear incision made over the proximal third of this septum exposed the avascular plane in which the vessel resides. A graft exceeding 10 cm could be harvested with diameters ranging between ≤2 and 7 mm. There were several muscular branches emanating from the profunda femoris artery system that could be dissected to the required length for a Y-shaped graft. Three cases of living donor liver transplantation using the DLCFA (straight and Y grafts) are described., Results: After DLCFA interpositional grafting, all patients had normal resistive indices on duplex ultrasonography of the intrahepatic arterial system. Follow-up of the 3 patients was between 2 and 6 months. There was no donor site morbidity., Conclusions: The DLCFA graft was a useful arterial graft for hepatic artery reconstruction. It was easily harvested with minimal donor site morbidity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To demonstrate the key steps to perform robot-assisted magnetic resonance imaging-ultrasound fusion transperineal prostate biopsy., Materials and Methods: Men with suspicion of prostate cancer underwent 3-Tesla multi-parametric MRI and were assigned a Prostate Imaging Reporting and Data System v2 score (PI-RADS). The prostate outline and suspicious lesions were marked by our radiologist using our software to produce a 3-dimensional prostate MRI model. All biopsies were performed under general anaesthesia and the real-time transrectal ultrasound model is created and subsequently fused with the MRI model using non-rigid software fusion. Transperineal targeted and systematic biopsy were then performed under stereotactic guidance using our robot-assisted prostate biopsy platform. Our clinically significant prostate cancer (Grade group ≥2) detection rates were previously described. 1 RESULTS: Out of the 433 patients who underwent targeted and systematic biopsy, clinically-significant cancer detection rate was 46% (85% for PI- RADS 5 vs 38% for PI-RADS 4 vs 16% for PI-RADS 3; P < .001). Our overall complication rate was 13%, out of which the majority were Clavien-Dindo I (99%). The most common complications encountered were urinary retention (10%) and significant gross hematuria requiring bladder irrigation (2%). A higher prostate volume was associated with greater odds of urinary retention (OR 1.4, 95% CI: 1.21-1.65, P < .001 for every 10 mL increase in prostate volume). There was only 1 reported case of mild urinary tract infection., Conclusion: Robot-assisted transperineal prostate biopsy has established itself as a reliable and accurate method of prostate cancer detection with minimal morbidity., (Copyright © 2021 Elsevier Inc. All rights reserved.)