Citations

Abstract Photon counting detector (PCD) CT represents the newest advance in CT technology, with improved radiation dose efficiency, increased spatial resolution, inherent spectral imaging capabilities, and the ability to eliminate electronic noise. Its design fundamentally differs from conventional energy integrating detector CT because photons are directly converted to electrical signal in a single step. Rather than converting X-rays to visible light and having an output signal that is a summation of energies, PCD directly counts each photon and records its individual energy information. The current commercially available PCD-CT utilizes a dual-source CT geometry, which allows 66 ms cardiac temporal resolution and high-pitch (up to 3.2) scanning. This can greatly benefit pediatric patients by facilitating high quality fast scanning to allow sedation-free imaging. The energy-resolving nature of the utilized PCDs allows “always-on” dual-energy imaging capabilities, such as the creation of virtual monoenergetic, virtual non-contrast, virtual non-calcium, and other material-specific images. These features may be combined with high-resolution imaging, made possible by the decreased size of individual detector elements and the absence of interelement septa. This work reviews the foundational concepts associated with PCD-CT and presents examples to highlight the benefits of PCD-CT in the pediatric population.

Abstract AIMS High-grade glioma continues to have dismal survival with current standard-of-care treatment, owing in part to its intra- and inter-patient heterogeneity. Typical diagnostic biopsies are taken from the dense tumor core to determine the presence of abnormal cells and the status of a few key genes (e.g. IDH1, MGMT). However, the tumor core is typically resected, leaving behind possibly genetically, transcriptomically and/or phenotypically distinct invasive margins that repopulate the disease. As these remaining populations are the ones ultimately being treated, it is important to know their compositional differences from the tumor core. We aim to identify the phenotypic niches defined by the relative composition of key cellular populations and understand their variation amongst patients. METHOD We have established an image-localized research biopsy study, that samples from both the invasive margin and tumor core. From this protocol, we currently have 202 samples from 58 patients with available bulk RNA-Seq, collected between Mayo Clinic and Barrow Neurological Institute. Using a single-cell reference dataset from our collaborators at Columbia University, we used CIBERSORTx, a deconvolution method, to predict relative abundances of 7 normal, 6 glioma, and 5 immune cell states for each sample. RESULTS We find that these cell state abundances connect to patient survival and show regional differences. For example, proneural glioma states were higher in invasive regions, whereas proliferative and mesenchymal states were higher in the tumor core. CONCLUSIONS Our analysis demonstrates a need to characterize the residual tissue following glioma resection to better understand the recurrent disease.

Importance Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress. Objective To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing. Design, Setting, and Participants Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US residents, and had access to the internet and a health care professional. Previous cancer genetic testing or counseling was exclusionary. In the family history cohort, participants had a personal or family history of breast or ovarian cancer. In the familial pathogenic variant (PV) cohort, participants reported 1 biological relative with a PV in an actionable cancer susceptibility gene. Data analysis was performed between December 13, 2020, and May 31, 2023. Intervention Participants completed baseline questionnaires, watched an educational video, and were randomized to 1 of 4 arms: the control arm with pretest and/or posttest genetic counseling, or 1 of 3 study arms without pretest and posttest counseling. Genetic counseling was provided by phone appointments and testing was done using home-delivered saliva kits. Main Outcomes and Measures The primary outcome was participant distress measured by the Impact of Event Scale 3 months after receiving the results. Secondary outcomes included completion of testing, anxiety, depression, and decisional regret. Results A total of 3839 women (median age, 44 years [range 22-91 years]), most of whom were non-Hispanic White and college educated, were randomized, 3125 in the family history and 714 in the familial PV cohorts. In the primary analysis in the family history cohort, all experimental arms were noninferior for distress at 3 months. There were no statistically significant differences in anxiety, depression, or decisional regret at 3 months. The highest completion rates were seen in the 2 arms without pretest counseling. Conclusions and Relevance In the MAGENTA clinical trial, omitting individualized pretest counseling for all participants and posttest counseling for those without PV during remote genetic testing was not inferior with regard to posttest distress, providing an alternative care model for genetic risk assessment. Trial Registration ClinicalTrials.gov Identifier: NCT02993068

See the Reply by Semla and Steinman in this issue.

Abstract Objectives To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. Methods Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1γ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron’s papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). Results In total 1054 patients were included (DM, n = 405; ASyS, n = 649). In the ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic’s hands, Raynaud’s phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P < 0.001), whereas higher frequency of any of four DM-type rashes—heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V-sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%)—differentiated DM from ASyS-DMskin (all P < 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both P < 0.001). Conclusion DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

Background: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. Aim: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. Methods: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. Results: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). Conclusions: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

Objective Systemic juvenile idiopathic arthritis–associated lung disease (SJIA‐LD) is a life‐threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA‐LD detection, characterize overall disease courses, and measure long‐term outcomes. Methods This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. Results We enrolled 41 patients with SJIA‐LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow‐up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty‐four percent of patients carried the HLA‐DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA‐LD also showed markedly elevated serum interleukin‐18 (IL‐18), variable C‐X‐C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti–IL‐1/6 biologics and addition of other immunomodulatory treatments and lung‐directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. Conclusion Patients with SJIA‐LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.