Citations

Abstract Posterior Fossa Group A (PFA) ependymomas are pediatric brain tumors with extremely poor survival outcomes. As protein-coding mutations in PFA are exceedingly rare, the underlying etiology of these tumors remains elusive. Elevated CpG island methylation and depletion of H3K27me3 have been described in PFA, leading to the hypothesis that PFA may be driven by a dysregulated epigenetic state. In this study, we sought to determine how three-dimensional (3D) genome features (such as DNA loops, domains, and compartments) differ between pediatric brain tumors. We performed Hi-C sequencing on a collection of 64 patient specimens and patient-derived primary cultures that collectively span multiple subgroups of ependymoma, medulloblastoma, high-grade glioma, and non-neoplastic brain. For certain samples, we further performed RNA-seq, histone modification ChIP-seq, or whole-genome bisulfite sequencing to allow multiomic data integration. Overall, the 3D genome organization of PFA samples appeared distinct from other tumor types. We identified and defined TULIPs: a subset of type B compartments, separated by genomic distances greater than 10 Mbp, that exhibit a striking fivefold increase in reciprocal interaction strength. These TULIPs recurred at the same genomic positions across the vast majority of PFA samples with minimal representation among other tumor or non-tumor samples. TULIPs displayed enrichment for heterochromatic features such as H3K9me3 and late replication timing and were depleted of euchromatic features such as H3K27ac and protein-coding genes. By using immuno-fluorescence for H3K9me3 and oligo-FISH to label TULIP regions, we demonstrated that TULIP regions are more compact in PFA than other tumors. Finally, by applying inhibitors of H3K9 lysine methylation to PFA cultures we showed that TULIPs become more diffuse and cell viability is reduced. Altogether, this work defines TULIPs as highly recurrent epigenetic features of PFA tumors.

Abstract BACKGROUND Radiation Therapy Oncology Group 9802 was a phase III trial for patients with centrally confirmed LGG (WHO grade II). Participants ³ 40 years or those with neurosurgeon defined less than gross total resection (GTR) were randomized to radiotherapy (RT) +/- PCV. In a separate cohort, adults age < 40 years with neurosurgeon defined GTR were observed by MRI every 6 months without adjuvant therapy. At last report, outcome for the observation cohort was immature with median follow-up of only 4.4 years. Here, we present mature outcomes for the observation arm. METHODS Eligible adults (as above) were observed by MRI every 6 months. OS and PFS were estimated by Kaplan-Meier method and estimated hazard ratios to characterize the prognostic variables. RESULTS There were 111 eligible patients (median age 30; median KPS = 100). Median follow-up was 16.1 years with 71 (64%) alive at the last follow-up. 79 patients (71%) had progressed with median PFS of 6.9 years. 5, 10, and 15 year-PFS and OS rates were 54%, 39%, 28% and 94%, 77%, and 65%. 1p19q status was codeleted in 32%, IDH1/2 mutant in 78% and MGMT promoter methylated in 39% of tested cases. Multivariate Cox analyses showed that preoperative tumor size ³ 4 cm (HR = 2.43 for PFS, p = 0.001; HR = 2.58 for death, p = 0.016) and residual disease on imaging ³ 1 cm (HR = 2.97 for PFS, P < 0.001; HR = 2.02 for death, p = 0.05) were associated with worse outcomes. Analyses based on molecular results will be presented. CONCLUSION A subset of low-grade gliomas can be observed after the initial resection based on younger age, smaller tumor size, and no residual disease on neuroimaging. This can likely be further refined by prognostic molecular markers. Patients with the most favorable prognostic factors can avoid or delay the acute and long-term side effects of RT and chemotherapy for several years.

Abstract Background and study aims Gastric outlet obstruction (GOO) is traditionally managed with surgical gastroenterostomy (surgical-GE) and enteral stenting (ES). Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is now a third option. Large studies assessing their relative risks and benefits with adequate follow-up are lacking. We conducted a comparative analysis of patients who underwent EUS-GE, ES, or surgical-GE for GOO. Patients and methods In this retrospective comparative cohort study, consecutive patients presenting with GOO who underwent EUS-GE, ES, or surgical-GE at two academic institutions were reviewed and independently cross-edited to ensure accurate reporting. The primary outcome was need for reintervention. Secondary outcomes were technical and clinical success, length of hospital stay (LOS), and adverse events (AEs). Results A total of 436 patients (232 EUS-GE, 131 ES, 73 surgical-GE) were included. The median duration of follow-up of the entire cohort was 185.5 days (interquartile range 55.25–454.25 days). The rate of reintervention in the EUS-GE group was lower than in the ES and surgical-GE groups (0.9 %, 12.2 %, and 13.7 %, P < 0.0001). Technical success was achieved in 98.3 %, 99.2 %, and 100 % (P = 0.58), and clinical success was achieved in 98.3 %, 91.6 %, and 90.4 % (P < 0.0001) in the EUS-GE, ES, and surgical-GE groups, respectively. The EUS-GE group had a shorter LOS (2 days vs. 3 days vs. 5 days, P < 0.0001) and a lower AE rate than the ES and surgical-GE groups (8.6 % vs. 38.9 % vs. 27.4 %, P < 0.0001). Conclusion This large cohort study demonstrates the safety and palliation durability of EUS-GE as an alternative strategy for GOO palliation in select patients.

Abstract Background Scapholunate (SL) ligament injuries are rarely diagnosed in children. This study reports the outcomes of surgically treated SL ligament injuries in patients younger than 18 years. Methods A retrospective review was performed on 20 pediatric patients with SL ligament injuries. Records were reviewed for preoperative and postoperative radiographic data, intraoperative findings, classifications of interosseous ligament injury, and postoperative course. Results Thirteen girls and seven boys sustained SL injuries requiring operative intervention and were followed for an average of 26 months. Magnetic resonance imaging (MRI) was performed in 15 patients, which revealed an SL tear in 7 patients. Arthroscopically, SL injuries were classified as Geissler grade III in 12 patients and grade IV in 5 patients. Based on the Mayo Wrist Score, nine patients had excellent or good results, while six demonstrated fair results. The mean wrist flexion–extension arc was 109 degrees, while the mean grip strength was 82% of the unaffected side. Patients treated >1 year following injury had significantly decreased grip strength and Mayo Wrist Score. Conclusion In this study, worse results were seen in children with a protracted course prior to treatment of an SL injury. A high index of suspicion is necessary to detect an SL injury in the younger age group and should be in the differential for those with persistent dorsal wrist pain, tenderness over the dorsal SL joint, and/or positive Watson's test. MRI may assist in diagnosis but is not definitive to rule out injury. Arthroscopy is valuable to determine the extent of injury.

PurposeThe goal of this work is to present the implementation of 3D spiral high‐resolution MPRAGE and to demonstrate that SNR and scan efficiency increase with the increment of readout time.TheorySimplified signal equations for MPRAGE indicate that the T1 contrast can be kept approximately the same by a simple relationship between the flip angle and the TR. Furthermore, if T1 contrast remains the same, image SNR depends on the square root of the product of the total scan time and the readout time.MethodsMPRAGE spiral sequences were implemented with distributed spirals and spiral staircase on 3 Tesla scanners. Brain images of three volunteers were acquired with different readout times. Spiral images were processed with a joint water–fat separation and deblurring algorithm and compared to Cartesian images. Pure noise data sets were also acquired for SNR evaluation.ResultsConsistent T1 weighting can be achieved with various spiral readout lengths, and between spiral MPRAGE imaging and the traditional Cartesian MPRAGE imaging. Noise performance analysis demonstrates higher SNR efficiency of spiral MPRAGE imaging with matched T1 contrast compared to the Cartesian reference imaging.ConclusionFast, high SNR MPRAGE imaging is feasible with long readout spiral trajectories.

AbstractThere is a lack of understanding in the performance of flexible noise control (FNC) processing, which is used in digital radiography on a scanner vendor and has four parameters each involving multiple options. The aim of this study was to investigate the impact of FNC on portable chest imaging. An anthropomorphic chest phantom was imaged using a clinical chest program with 85 kV and five radiation dose levels at 40″ source‐to‐image distance with software‐based scatter reduction method. All images were processed without and with FNC. Noise analysis was performed in two regions of interest (ROI) on subtracted noise‐only images, and line profiles were generated through a lung‐rib interface. In addition, noise power spectra (NPS) analysis was performed in solid water phantoms of 10 and 20 cm thicknesses, using the same acquisition program and a range of dose levels. Last, feedback on retrospectively deidentified, reprocessed, and randomized clinical images from 20 portable chest exams was gathered from two thoracic radiologists. Noise reduction performances of FNC were demonstrated, with the level depending on specific FNC parameters, dose levels, ROI placement, and phantom sizes. Higher frequency textural patterns were revealed through the NPS analysis, which varied based on FNC parameters, dose levels, and phantom sizes. Overall, the vendor default parameter FGA0.5 yielded the highest noise reduction and textural artifacts. Radiologist feedback showed consistent preference of no FNC due to the presence of textural artifacts in the FNC‐processed images. An algorithm improvement to avoid introducing artifacts would be desired.

Background: Unrepaired truncus arteriosus (TA) carries poor prognosis due to complications of unrestricted pulmonary flow, truncal valve insufficiency, and pulmonary vascular disease. Currently, the hemodynamic profile of adults late after TA repair is unknown. We reviewed the hemodynamics, prevalence, and pathophysiology of pulmonary hypertension (PH) in this population. Methods: Eighteen adult patients with repaired TA who underwent cardiac catheterization at Mayo Clinic, MN, between 1997 and 2021 were identified. PH was defined as either precapillary (mean pulmonary artery pressure [mPAP] ≥25 mm Hg, pulmonary artery wedge pressure [PAWP] ≤15 mm Hg, and pulmonary vascular resistance [PVR] >3 Wood units), isolated postcapillary (mPAP ≥25, PAWP >15, PVR ≤3), or combined (mPAP ≥25, PAWP >15, and PVR >3). Diastolic pressure and transpulmonary gradients were used as ancillary data for classification. Results: Mean age at catheterization was 34 ± 10 years. Mean right ventricular (RV) systolic pressure was 82 ± 22.6 mm Hg, mean right and left mPAPs 28.1 ± 16.2 and 27.9 ± 11.9 mm Hg, respectively. Seven patients (41.2%) had PAWP >15 mm Hg and, among those undergoing arterial catheterization, 7 (53.8%) had a left ventricular (LV) end-diastolic pressure >15 mm Hg. PH was diagnosed in 13 patients (72.2%): 6 (33.3%) precapillary, 4 (22.2%) isolated postcapillary, and 3 (16.7%) combined. PAWP >15 mm Hg was associated with male sex ( P = .049), <moderate RV dysfunction ( P = .049), and lesser RV conduit mean systolic gradient ( P = .02). Patients with PH with precapillary component were older at catheterization ( P = .046). Conclusions: In adults with repaired TA, precapillary PH was only present in one-third of patients with mPAPs not significantly increased in most, whereas elevated PAWP and left-heart disease were common.