Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial.

BACKGROUND: Etranacogene dezaparvovec, the first gene therapy approved for haemophilia B treatment, was shown to be superior to treatment with continuous prophylactic factor IX in terms of bleeding protection 18 months after gene therapy in a phase 3 trial. We report post-hoc 24-month efficacy and safety data from this trial to evaluate the longer-term effects of etranacogene dezaparvovec in individuals with haemophilia B. METHODS: The phase 3 HOPE-B trial enrolled males aged 18 years or older with inherited haemophilia B, classified as severe (plasma factor IX activity level <1%) or moderately severe (plasma factor IX activity level ≥1% and ≤2%), with a severe bleeding phenotype and who were on stable continuous factor IX prophylaxis. Participants were treated with a single infusion of etranacogene dezaparvovec (2 × 1013 genome copies per kg of bodyweight). The primary endpoint, reported previously, was non-inferiority of the annualised bleeding rate (ABR) during the 52 weeks following stable factor IX expression (defined as months 7-18 after treatment) versus an at least 6-month lead-in period in which participants received their usual continuous factor IX prophylaxis, and is updated here up to month 24. Additional, post-hoc efficacy analyses, including adjusted ABR, factor IX activity, participants within factor IX ranges, and factor IX use, and safety analyses were performed at 24 months after gene therapy. Data were analysed in the full analysis set, which comprised the 54 patients who received at least a partial dose of gene therapy. The trial is ongoing and is registered with ClinicalTrials.gov, number NCT03569891. FINDINGS: The study began on June 27, 2018, and participants were treated between January, 2019, and March, 2020; the date of data cutoff was April 21, 2022. 54 adult males (40 White, two Asian, one Black or African American, 11 other or missing) received a single intravenous infusion of etranacogene dezaparvovec and were followed for a median of 26·51 months (IQR 24·54-27·99), after a lead-in period of 7·13 months (6·51-7·82). In the updated analysis comparing months 7-24 after gene therapy to the lead-in period, mean adjusted ABR significantly reduced from 4·18 to 1·51 (p=0·0002) for all bleeds and from 3·65 to 0·99 (p=0·0001) for factor IX-treated bleeds. During each 6-month period after gene therapy, at least 67% of participants experienced no bleeding (36 of 54 during months 0-6 and stable thereafter), compared with 14 (26%) of 54 during the lead-in period. 24 months after gene therapy, 1 (2%) participant had one-stage factor IX activity less than 5%, whereas 18 (33%) had factor IX activity more than 40% (non-haemophilia range), with mean factor IX activity stable and sustained at 36·7% (SD 19·0%). 52 (96%) of 54 participants expressed endogenous factor IX, remaining free of factor IX prophylaxis at month 24. No new safety concerns were identified and no treatment-related serious adverse events or treatment-related deaths occurred. The most common treatment-related adverse events were an increase in alanine aminotransferase (nine [17%] of 54 patients), headache (eight [15%]), influenza-like illness (seven [13%]), and an increase in aspartate aminotransferase (five [9%]). INTERPRETATION: By providing durable disease correction throughout the 24 months after gene therapy, etranacogene dezaparvovec provides a safe and effective therapeutic option for patients with severe or moderately severe haemophilia B. FUNDING: uniQure and CSL Behring.

Effect of etranacogene dezaparvovec on quality of life for severe and moderately severe haemophilia B participants: Results from the phase III HOPE-B trial 2 years after gene therapy.

INTRODUCTION: For people with haemophilia B (PwHB), bleeding may occur despite prophylaxis, negatively affecting health-related quality of life (HRQoL). The pivotal phase 3 HOPE-B trial investigating the adeno-associated virus gene transfer product, etranacogene dezaparvovec (EDZ), demonstrated sustained factor IX (FIX) activity and bleed protection in PwHB with baseline FIX levels ≤2%. AIM: Assess how EDZ affects HRQoL in HOPE-B trial participants. METHODS: HRQoL was evaluated using generic and disease-specific patient reported outcomes (PROs) including the EQ-5D-5L and the Hem-A-QoL questionnaires. Mean domain and total scores were compared 6 months pre- and the first 2 years post-EDZ administration using repeated measures linear mixed models. The percentage of participants with minimal clinically important improvements in HRQoL was also evaluated. RESULTS: Two years post-EDZ, there were nominally significant increases in the least squares (LS) mean score for the EQ-5D-5L Index Value (.04; p = .0129), reflecting better HRQoL. Nominally significant decreases in the LS mean scores, reflecting better HRQoL, were also found for the Hem-A-QoL total score (-6.0; p < .0001) and the Treatment (-13.94; p < .0001), Feelings (-9.01; p < .0001), Future (-6.45; p = .0004) and Work/School (-5.21; p = .0098) domains. The percentage of participants with ≥15-point improvement ranged from 45.83% (95% CI: 31.37%, 60.83%) for Treatment to 13.89% (95% CI: 4.67%, 29.50%) for Family Planning. Results were similar for Year 1. CONCLUSION: In conclusion, gene therapy with EDZ improved HRQoL in the first and second years in several Hem-A-QoL domains, including Treatment, Feelings, Work/School and Future domains, whereas improvement in other aspects of HRQoL were not demonstrated.

Patterns of Access to Radiology Reports and Images Through a Patient Portal.

Access to radiology reports and images through a patient portal offers several advantages. The purpose of this study was to characterize patient's interactions with their radiology results. This was a retrospective study that evaluated radiography, ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography, exams performed between July 2020 and June 2021 for patients aged 12 and older. Exam information, access logs of radiology reports and images, and patient demographics were obtained from the electronic health record and image viewing software. Descriptive statistics were computed. The study included 1,685,239 exams. A total of 54.1% of reports were viewed. MRI and PET reports were viewed with the greatest frequency (70.2% and 67.6%, respectively); 25.5% of exam images were viewed, with the greatest frequency for MRI (40.1%). Exams were shared a total of 17,095 times and downloaded 8409 times; 64% of reports were viewed for patients aged 18-39 and 34% for patients aged 80 and greater. The rate of reports viewed was greater for patients with English as their preferred language (57.1%) compared to other languages (33.3%). Among those viewed, 56.5% of reports and 48.2% of images were viewed multiple times; 72.8% of images were viewed on smartphones, 25.8% on desktop computers, and 1.4% on tablets. Patients utilize a portal to view reports and view and share images. Continued efforts are warranted to promote the use of portals and create patient-friendly imaging results to help empower patients.

Observational cohort study of long-term outcomes of liver transplantation in haemophilia.

INTRODUCTION: Gene therapy is now a reality for individuals with haemophilia, yet little is known regarding the quality-of-life impact of factor correction. As few data exist, and recognizing the analogy to liver transplantation (OLTX), we identified OLTX+ and OLTX- men in the ATHNdataset to compare post-OLTX factor VIII and IX on quality of life (QoL) by Haem-A-QoL and PROMIS-29. METHODS: OLTX- were matched to OLTX+ by age, race, and haemophilia type and severity. Deidentified demographic data, including post-transplant factor levels, genotype and target joint disease were analysed by descriptive statistics. Haem-A-Qol and PROMIS-29 were compared in OLTX+ and OLTX- by student's t-test and univariate regression models. RESULTS: Of 86 people with haemophilia A (HA) or haemophilia B (HB) cared for at 10 haemophilia treatment centers (HTCs), 21 (24.4%) OLTX+ and 65 (75.6%) OLTX- were identified. OLTX+ and OLTX- had a similar frequency of target joint disease (p = .806), HA genotypes, null versus non-null (p = .696), and HIV infection (p = .316). At a median 9.2 years post-OLTX, median FVIII, .63 IU/mL [IQR 0.52-0.97] and FIX, .91 IU/mL [IQR .63-1.32], Haem-A-QoL, PROMIS-29, and HOT scores were comparable. Severe HA/HB had lower post-OLTX 'dealing with haemophilia' scores (p = .022) and higher 'sports and leisure' (p = .010) and 'view of yourself' scores (p = .024) than OLTX+ non-severe participants. Non-caucasian OLTX+ had significantly lower scores in sports and leisure (p = .042), future expectations (p = .021) and total score (p = .010). CONCLUSION: Nine years after OLTX, QoL is comparable to OLTX-, but significantly better in OLTX+ with severe than non-severe disease and in caucasians than non-caucasians.

Patient-centered radiology: a roadmap for outpatient imaging.

Creating a patient-centered experience is becoming increasingly important for radiology departments around the world. The goal of patient-centered radiology is to ensure that radiology services are sensitive to patients' needs and desires. This article provides a framework for addressing the patient's experience by dividing their imaging journey into three distinct time periods: pre-exam, day of exam, and post-exam. Each time period has aspects that can contribute to patient anxiety. Although there are components of the patient journey that are common in all regions of the world, there are also unique features that vary by location. This paper highlights innovative solutions from different parts of the world that have been introduced in each of these time periods to create a more patient-centered experience. CLINICAL RELEVANCE STATEMENT: Adopting innovative solutions that help patients understand their imaging journey and decrease their anxiety about undergoing an imaging examination are important steps in creating a patient centered imaging experience. KEY POINTS: • Patients often experience anxiety during their imaging journey and decreasing this anxiety is an important component of patient centered imaging. • The patient imaging journey can be divided into three distinct time periods: pre-exam, day of exam, and post-exam. • Although components of the imaging journey are common, there are local differences in different regions of the world that need to be considered when constructing a patient centered experience.

Designing Clinical MRI for Enhanced Workflow and Value.

MRI is an expensive and traditionally time-intensive modality in imaging. With the paradigm shift toward value-based healthcare, radiology departments must examine the entire MRI process cycle to identify opportunities to optimize efficiency and enhance value for patients. Digital tools such as "frictionless scheduling" prioritize patient preference and convenience, thereby delivering patient-centered care. Recent advances in conventional and deep learning-based accelerated image reconstruction methods have reduced image acquisition time to such a degree that so-called nongradient time now constitutes a major percentage of total room time. For this reason, architectural design strategies that reconfigure patient preparation processes and decrease the turnaround time between scans can substantially impact overall throughput while also improving patient comfort and privacy. Real-time informatics tools that provide an enterprise-wide overview of MRI workflow and Picture Archiving and Communication System (PACS)-integrated instant messaging can complement these efforts by offering transparent, situational data and facilitating communication between radiology team members. Finally, long-term investment in training, recruiting, and retaining a highly skilled technologist workforce is essential for building a pipeline and team of technologists committed to excellence. Here, we highlight various opportunities for optimizing MRI workflow and enhancing value by offering many of our own on-the-ground experiences and conclude by anticipating some of the future directions for process improvement and innovation in clinical MR imaging. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 1.

Fast and Frictionless: A Novel Approach to Radiology Appointment Scheduling Using a Mobile App and Recommendation Engine.

Many outpatient radiology orders are never scheduled, which can result in adverse outcomes. Digital appointment self-scheduling provides convenience, but utilization has been low. The purpose of this study was to develop a "frictionless" scheduling tool and evaluate the impact on utilization. The existing institutional radiology scheduling app was configured to accommodate a frictionless workflow. A recommendation engine used patient residence, past and future appointment data to generate three optimal appointment suggestions. For eligible frictionless orders, recommendations were sent in a text message. Other orders received either a text message for the non-frictionless app scheduling approach or a call-to-schedule text. Scheduling rates by type of text message and scheduling workflow were analyzed. Baseline data for a 3-month period prior to the launch of frictionless scheduling showed that 17% of orders that received an order notification text were scheduled using the app. In an 11-month period after the launch of frictionless scheduling, the rate of app scheduling was greater for orders that received a text message with recommendations (frictionless approach) versus app schedulable orders that received a text without recommendations (29% vs. 14%, p < 0.01). Thirty-nine percent of the orders that received a frictionless text and scheduled using the app used a recommendation. The most common recommendation rules chosen for scheduling included location preference of prior appointments (52%). Among appointments that were scheduled using a day or time preference, 64% were based on a rule using the time of the day. This study showed that frictionless scheduling was associated with an increased rate of app scheduling.

The National Hemophilia Foundation State of the Science Research Summit initiative: executive summary.

INTRODUCTION: The National Hemophilia Foundation State of the Science Research Summit initiative sought to unify research efforts in the US inherited bleeding disorders (BDs) community around key topics of importance to people living with inherited BDs, the lived experience experts. AREAS COVERED: This community-led and -informed project focused on six broad areas - hemophilia A or B; von Willebrand Disease (VWD), platelet dysfunctions and other mucocutaneous inherited BDs; ultra-rare inherited BDs; the unique challenges of people with the potential to menstruate with inherited BDs; diversity, equity and inclusion, health services research, and implementation science; and facilitating research in the inherited BD community through designing an optimizied research infrastructure, enabling resources and funding, and furthering workforce capabilities required to execute the research priorities. EXPERT OPINION: The work summarized here, and in the accompanying supplement manuscripts , has implications not only for the US population but for people globally who have inherited BDs. The information is equally relevant to people living with hemophilia, VWD, the spectrum of inherited platelet disorders, ultra-rare factor deficiencies, and all other inherited BDs as it is to the health care providers and researchers focused on the care and treatment of inherited BDs in the US and globally.

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities for ultra-rare inherited bleeding disorders.

BACKGROUND: Ultra-rare inherited bleeding disorders (BDs) present important challenges for generating a strong evidence foundation for optimal diagnosis and management. Without disorder-appropriate treatment, affected individuals potentially face life-threatening bleeding, delayed diagnosis, suboptimal management of invasive procedures, psychosocial distress, pain, and decreased quality-of-life. RESEARCH DESIGN AND METHODS: The National Hemophilia Foundation (NHF) and the American Thrombosis and Hemostasis Network identified the priorities of people with inherited BDs and their caregivers, through extensive inclusive community consultations, to inform a blueprint for future decades of research. Multidisciplinary expert Working Group (WG) 3 distilled highly feasible transformative ultra-rare inherited BD research opportunities from the community-identified priorities. RESULTS: WG3 identified three focus areas with the potential to advance the needs of all people with ultra-rare inherited BDs and scored the feasibility, impact, and risk of priority initiatives, including 13 in systems biology and mechanistic science; 2 in clinical research, data collection, and research infrastructure; and 5 in the regulatory process for novel therapeutics and required data collection. CONCLUSIONS: Centralization and expansion of expertise and resources, flexible innovative research and regulatory approaches, and inclusion of all people with ultra-rare inherited BDs and their health care professionals will be essential to capitalize on the opportunities outlined herein.

Living with an ultra-rare inherited bleeding disorder is challenging. Patients can feel alone and unsure of where to find support because their disorder is so rare. In this paper, a group of ultra-rare bleeding disorder experts, including doctors, researchers, regulators, patient advocates, and patients, identify the research that could best improve the lives of people with these disorders. They propose a national network of specialists who can help doctors, who may never have seen these disorders before, to find the right diagnosis faster. A centralized laboratory specialized in ultra-rare bleeding disorders could also improve diagnosis and do research studies. This would help us learn, for example, how symptoms change throughout a patient's life, how effective different treatments are, and what it is like for patients to live with these disorders. A second research priority is to better understand each individual disorder so that the best treatments can be chosen or developed. A pathway showing doctors which treatment options to try, in which order, would help them help their patients. The third research priority is to make it easier to study new treatments for ultra-rare bleeding disorders. This requires designing studies with very small numbers of participants, identifying meaningful outcomes to measure, and convincing pharmaceutical companies to invest in these studies. International agreement on these requirements would allow more patients to participate and benefit from the research. These top-priority research goals should greatly improve knowledge about, and diagnosis and treatment of, ultra-rare inherited bleeding disorders.

Direct oral anticoagulants in pediatric venous thromboembolism: Experience in specialized pediatric hemostasis centers in the United States.

Background: Before the official US Food and Drug Administration approval in 2021, pediatric hematologists across the United States have used direct oral anticoagulants (DOACs) "off-label" and based on extrapolation from labeling for adults with venous thromboembolism (VTE) and interim results of pediatric-specific DOAC clinical studies. Objectives: The American Thrombosis and Hemostasis Network 15 (ATHN 15) study aimed to characterize the use of DOACs from 2015 to 2021 at 15 specialized pediatric hemostasis centers in the United States, with emphasis on safety and effectiveness. Methods: Eligible participants were those aged 0 to 21 years who had a DOAC included as part of their anticoagulation regimen for the treatment of acute VTE or secondary prevention of VTE. Data were collected for up to 6 months after initiation of the DOAC. Results: A total of 233 participants were enrolled, with a mean age of 16.5 years. Rivaroxaban was the most commonly prescribed DOAC (59.1%) followed by apixaban (38.8%). Thirty-one (13.8%) participants reported bleeding complications while on a DOAC. Major or clinically relevant nonmajor bleeding events occurred in 1 (0.4%) and 5 (2.2%) participants, respectively. Worsening menstrual bleeding was reported in 35.7% of females aged >12 years and occurred more frequently in those using rivaroxaban (45.6%) compared with apixaban (18.9%). The recurrent thrombosis rate was 4%. Conclusion: Pediatric hematologists at specialized hemostasis centers in the United States have been using DOACs for the treatment and prevention of VTEs, primarily in adolescents and young adults. Reported DOAC use showed adequate safety and effectiveness rates.

Hopping as an Indicator of Chemotoxicity: Gait Analysis in Patients With Leukemia and Lymphoma.

BACKGROUND: Survivors of acute lymphoblastic leukemia (ALL) can experience chemotherapy-related changes in neuromuscular function, which can persist and impact the quality of life. Clinically, neuromuscular changes are assessed by observing gait. The primary aims of this study were to compare observational gait/functional movement analysis to matched electronic gait analysis in children with ALL and lymphoblastic lymphoma at specific time points during and after treatment. PATIENTS AND METHODS: Participants 2 to 27 years old diagnosed with ALL/lymphoblastic lymphoma who were on or off therapy within 10 years were eligible. Participants underwent electronic gait assessment using GAITRite, observational gait, and functional movement analysis and completed quality of life questionnaires. Parents also completed quality-of-life assessments. RESULTS: Electronic gait parameters were not different in this cohort compared with controls. Mean overall scores on observational gait and functional movement analysis improved over time. Hopping was the most frequent and walking was the least frequent noted deficit. Participants had a lower patient and parent-reported QoL scores compared with the general population. CONCLUSION: Observational gait and functional movement analysis identified more deficits than the electronic gait assessment. Future studies are warranted to determine whether hopping deficits are an early clinical indicator of toxicity and signal for intervention.

A Retrospective Analysis of the American Thrombosis and Hemostasis Network Dataset Describing Outcomes of Dental Extractions in Persons with Hemophilia.

INTRODUCTION: dental extractions (DEs) in persons with hemophilia A or B (PWH-A or PWH-B) are often associated with bleeding and needing hemostatic therapies (HTs). AIM: to analyze the American Thrombosis and Hemostasis Network (ATHN) dataset (ATHNdataset) to assess trends, uses and impacts of HT on bleeding outcomes following DEs. METHODS: PWH seen at ATHN affiliates who underwent DEs and opted to share their data with the ATHNdataset between 2013-2019 were identified. The type of DEs, use of HT and bleeding outcomes were assessed. RESULTS: Among 19,048 PWH ≥2 years of age, 1157 underwent 1301 episodes of DE. Those on prophylaxis experienced a nonsignificant reduction in dental bleeding episodes. Standard half-life factor concentrates were used more often than extended half-life products. PWHA were more likely to undergo DE in the first 30 years of life. Those with severe hemophilia were less likely to undergo DE than those with a mild disease (OR: 0.83; 95% CI: 0.72-0.95). PWH with inhibitors had statistically significantly increased odds of dental bleeding (OR: 2.09, 95% CI; 1.21-3.63). CONCLUSION: our study showed that persons with mild hemophilia and younger age were more likely to undergo DE; the presence of inhibitors increased the likelihood of bleeding, while those with prophylaxis and receiving HT experienced a non-statistically significant reduction in bleeding.

Deep Learning Diagnosis and Classification of Rotator Cuff Tears on Shoulder MRI.

BACKGROUND: Detection of rotator cuff tears, a common cause of shoulder disability, can be time-consuming and subject to reader variability. Deep learning (DL) has the potential to increase radiologist accuracy and consistency. PURPOSE: The aim of this study was to develop a prototype DL model for detection and classification of rotator cuff tears on shoulder magnetic resonance imaging into no tear, partial-thickness tear, or full-thickness tear. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant, institutional review board-approved study included a total of 11,925 noncontrast shoulder magnetic resonance imaging scans from 2 institutions, with 11,405 for development and 520 dedicated for final testing. A DL ensemble algorithm was developed that used 4 series as input from each examination: fluid-sensitive sequences in 3 planes and a sagittal oblique T1-weighted sequence. Radiology reports served as ground truth for training with categories of no tear, partial tear, or full-thickness tear. A multireader study was conducted for the test set ground truth, which was determined by the majority vote of 3 readers per case. The ensemble comprised 4 parallel 3D ResNet50 convolutional neural network architectures trained via transfer learning and then adapted to the targeted domain. The final tear-type prediction was determined as the class with the highest probability, after averaging the class probabilities of the 4 individual models. RESULTS: The AUC overall for supraspinatus, infraspinatus, and subscapularis tendon tears was 0.93, 0.89, and 0.90, respectively. The model performed best for full-thickness supraspinatus, infraspinatus, and subscapularis tears with AUCs of 0.98, 0.99, and 0.95, respectively. Multisequence input demonstrated higher AUCs than single-sequence input for infraspinatus and subscapularis tendon tears, whereas coronal oblique fluid-sensitive and multisequence input showed similar AUCs for supraspinatus tendon tears. Model accuracy for tear types and overall accuracy were similar to that of the clinical readers. CONCLUSIONS: Deep learning diagnosis of rotator cuff tears is feasible with excellent diagnostic performance, particularly for full-thickness tears, with model accuracy similar to subspecialty-trained musculoskeletal radiologists.

Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B.

BACKGROUND: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. METHODS: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. RESULTS: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. CONCLUSIONS: Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile. (Funded by uniQure and CSL Behring; HOPE-B ClinicalTrials.gov number, NCT03569891.).

Deep Learning Reconstruction Enables Prospectively Accelerated Clinical Knee MRI.

Background MRI is a powerful diagnostic tool with a long acquisition time. Recently, deep learning (DL) methods have provided accelerated high-quality image reconstructions from undersampled data, but it is unclear if DL image reconstruction can be reliably translated to everyday clinical practice. Purpose To determine the diagnostic equivalence of prospectively accelerated DL-reconstructed knee MRI compared with conventional accelerated MRI for evaluating internal derangement of the knee in a clinical setting. Materials and Methods A DL reconstruction model was trained with images from 298 clinical 3-T knee examinations. In a prospective analysis, patients clinically referred for knee MRI underwent a conventional accelerated knee MRI protocol at 3 T followed by an accelerated DL protocol between January 2020 and February 2021. The equivalence of the DL reconstruction of the images relative to the conventional images for the detection of an abnormality was assessed in terms of interchangeability. Each examination was reviewed by six musculoskeletal radiologists. Analyses pertaining to the detection of meniscal or ligament tears and bone marrow or cartilage abnormalities were based on four-point ordinal scores for the likelihood of an abnormality. Additionally, the protocols were compared with use of four-point ordinal scores for each aspect of image quality: overall image quality, presence of artifacts, sharpness, and signal-to-noise ratio. Results A total of 170 participants (mean age ± SD, 45 years ± 16; 76 men) were evaluated. The DL-reconstructed images were determined to be of diagnostic equivalence with the conventional images for detection of abnormalities. The overall image quality score, averaged over six readers, was significantly better (P < .001) for the DL than for the conventional images. Conclusion In a clinical setting, deep learning reconstruction enabled a nearly twofold reduction in scan time for a knee MRI and was diagnostically equivalent with the conventional protocol. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Roemer in this issue.

AUR Radiology Resident Core Curriculum Lecture Series - A Model for Multi-Society Collaborative Virtual Education.

To fulfill ACGME requirements, radiology residency programs are required to provide an educational experience that includes a core didactic curriculum for each subspecialty. Although developing and delivering such a core curriculum may not present a problem for large academic programs, it can present a significant challenge for smaller programs with limited faculty in each subspecialty area. Success of the core curriculum lectures series developed for cardiothoracic radiology by the Society of Thoracic Radiology and for musculoskeletal radiology by the International Skeletal Society in collaboration with the Society for Skeletal Radiology prompted the idea of creating a comprehensive core curriculum lecture series encompassing all subspecialties. This paper aims to describe the multi-society collaborative effort entailed in building a curated, on line resident focused core curriculum lecture series detailing the barriers encountered, effects of the COVID-19 pandemic and impact of the finished project.

Stable and durable factor IX levels in patients with hemophilia B over 3 years after etranacogene dezaparvovec gene therapy.

Etranacogene dezaparvovec (AMT-061) is a recombinant adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with a liver-specific promoter. Here, we report 3-year outcomes from a phase 2b, open-label, single-dose, single-arm, multicenter trial conducted among adults with severe or moderately severe hemophilia B (FIX ≤2%). All participants (n = 3) received a single intravenous dose (2 × 1013 gene copies per kg) and will be followed up for 5 years. The primary end point of FIX activity ≥5% at 6 weeks was met. Secondary end points included bleed frequency, FIX concentrate use, joint health, and adverse events (AEs). All participants required routine FIX prophylaxis and had neutralizing antibodies to AAV5 before etranacogene dezaparvovec treatment. After administration, FIX activity rose to a mean of 40.8% in year 1 and was sustained in year 3 at 36.9%. All participants discontinued FIX prophylaxis. Bleeding was completely eliminated in 2 out of 3 participants. One participant required on-demand FIX replacement therapy per protocol because of elective surgical procedures, for 2 reported bleeding episodes, and twice for a single self-administered infusion because of an unreported reason. One participant experienced 2 mild, self-limiting AEs shortly after dosing. During the 3-year study period, there were no clinically significant elevations in liver enzymes, no requirement for steroids, no FIX inhibitor development, and no late-emergent safety events in any participant. Etranacogene dezaparvovec was safe and effective in adults with hemophilia B over 3 years after administration. This trial was registered at www.clinicaltrials.gov as #NCT03489291.

Work From Home in Academic Radiology Departments: Advantages, Disadvantages and Strategies for the Future.

To achieve necessary social distancing during the Covid-19 pandemic, working from home was introduced at most if not all academic radiology departments. Although initially thought to be a temporary adaptation, the popularity of working from home among faculty has made it likely that it will remain a component of radiology departments for the long term. This paper will review the potential advantages and disadvantages of working from home for an academic radiology department and suggest strategies to try to preserve the advantages and minimize the disadvantages.