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Objectives: Bone marrow edema-like signal (BMELS) after cartilage repair is common, but its clinical significance remains uncertain. This study aimed to investigate the clinical and structural significance of BMELS following microfracturing (MFX) and matrix-induced autologous chondrocyte implantation (MACI)., Methods: In this multicenter study, MRI examinations were performed over a period of 5 years after cartilage repair surgery (MFX n = 17; MACI n = 28) in 45 patients. Morphological assessments, including the MOCART 2.0 (magnetic resonance observation of cartilage repair tissue), quantitative imaging biomarkers (QIB) with T2 mapping of the repair tissue, and, specifically, assessment of the presence and size of BMELS, were conducted along with patient-reported outcome measures, such as the Knee injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC). BMELS structural and clinical assessments were obtained after 3 months, 12 months, and 60 months. Statistical analysis included the Mann-Whitney U-test, Wilcoxon rank test, Shapiro-Wilk test, and simulation-based power analysis., Results: BMELS were a common finding 60 months after cartilage repair. The size of BMELS differed significantly only between MACI and MFX patients after 3 months, with larger BMELS occurring in the MFX group. There were no significant differences in patients with or without BMELS regarding the T2 ratio of the treated area, the MOCART 2.0, or clinical scores., Conclusion: BMELS frequently appeared after cartilage repair procedures. We could show that the postoperative size and change in the size of BMELS after MACI and MFX did not affect clinical scores, morphological MRI results, or biochemical properties of the treated area after 60 months., Key Points: Question What is the clinical significance of bone marrow edema-like signal (BMELS) appearance after matrix-induced autologous chondrocyte implantation (MACI) or microfracture (MFX)? Finding There were no significant differences in patients with or without BMELS regarding the T2 ratio of the treated area, the MOCART 2.0, or clinical scores. Clinical relevance BMELS frequently appeared after cartilage repair, the appearance or the size dynamic after MACI and MFX did not affect clinical scores, morphological MRI results, or biochemical properties after 60 months., (© 2024. The Author(s).)

Background Data on the diagnostic accuracy of ultralow-dose (ULD) CT protocols for periodic surveillance in recipients of lung transplant are lacking. Purpose To assess the potential for radiation dose reduction using ULD photon-counting CT (PCT) to detect lung abnormalities in recipients of lung transplant during repeat CT follow-up. Materials and Methods Consecutive adult recipients of lung transplant undergoing same-day standard-of-care low-dose (LD) and ULD PCT from March 2023 to May 2023 were prospectively included. The ULD protocols were performed with two target effective doses comprising 20% (hereafter, ULD1) and 10% (hereafter, ULD2) of the standard LD protocol. The 1-mm reconstructions were reviewed by three readers. Subjective image quality, the visibility of certain anatomic structures (using a five-point Likert scale), and the presence of lung abnormalities were independently assessed. The χ 2 or t tests were used to evaluate differences between the ULD1 and ULD2 protocols. Results A total of 82 participants (median age, 64 years [IQR, 54-69 years]; 47 male) were included (41 participants for each ULD protocol). The mean effective doses per protocol were 1.41 mSv ± 0.44 (SD) for LD, 0.26 mSv ± 0.08 for ULD1, and 0.17 mSv ± 0.04 for ULD2. According to three readers, the subjective image quality of the ULD images was deemed diagnostic (Likert score ≥3) in 39-40 (ULD1) and 40-41 (ULD2) participants, and anatomic structures could be adequately visualized (Likert score ≥3) in 33-41 (ULD1) and 34-41 (ULD2) participants. The detection accuracy for individual lung anomalies exceeded 70% for both ULD protocols, except for readers 1 and 3 detecting proximal bronchiectasis and reader 3 detecting bronchial wall thickening and air trapping. No evidence of a statistically significant difference in noise ( P = .96), signal-to-noise ratio ( P = .77), or reader accuracy (all P ≥ .05) was noted between the ULD protocols. Conclusion ULD PCT was feasible for detecting lung abnormalities following lung transplant, with a tenfold radiation dose reduction. © RSNA, 2024 Supplemental material is available for this article . See also the editorial by Ciet in this issue.

Objectives: To assess the reproducibility of radiomics features extracted from the developing lung in repeated in-vivo fetal MRI acquisitions., Methods: In-vivo MRI (1.5 Tesla) scans of 30 fetuses, each including two axial and one coronal T2-weighted sequences of the whole lung with all other acquisition parameters kept constant, were retrospectively identified. Manual segmentation of the lungs was performed using ITK-Snap. One hundred radiomics features were extracted from fetal lung MRI data using Pyradiomics, resulting in 90 datasets. Intra-class correlation coefficients (ICC) of radiomics features were calculated between baseline and repeat axial acquisitions and between baseline axial and coronal acquisitions., Results: MRI data of 30 fetuses (12 [40%] females, 18 [60%] males) at a median gestational age of 24 + 5 gestational weeks plus days (GW) (interquartile range [IQR] 3 + 3 GW, range 21 + 1 to 32 + 6 GW) were included. Median ICC of radiomics features between baseline and repeat axial MR acquisitions was 0.92 (IQR 0.13, range 0.33 to 1), with 60 features exhibiting excellent (ICC > 0.9), 27 good (> 0.75-0.9), twelve moderate (0.5-0.75), and one poor (ICC < 0.5) reproducibility. Median ICC of radiomics features between baseline axial and coronal MR acquisitions was 0.79 (IQR 0.15, range 0.2 to 1), with 20 features exhibiting excellent, 47 good, 29 moderate, and four poor reproducibility., Conclusion: Standardized in-vivo fetal MRI allows reproducible extraction of lung radiomics features. In the future, radiomics analysis may improve diagnostic and prognostic yield of fetal MRI in normal and pathologic lung development., Key Points: • Non-invasive fetal MRI acquired using a standardized protocol allows reproducible extraction of radiomics features from the developing lung for objective tissue characterization. • Alteration of imaging plane between fetal MRI acquisitions has a negative impact on lung radiomics feature reproducibility. • Fetal MRI radiomics features reflecting the microstructure and shape of the fetal lung could complement observed-to-expected lung volume in the prediction of postnatal outcome and optimal treatment of fetuses with abnormal lung development in the future., (© 2023. The Author(s).)

Immunoglobulin M (IgM) autoantibodies to oxidation-specific epitopes (OSEs) can be present at birth and protect against atherosclerosis in experimental models. This study sought to determine whether high titers of IgM titers to OSE (IgM OSE) are associated with a lower risk of acute myocardial infarction (AMI) in humans. IgM to malondialdehyde (MDA)-LDL, phosphocholine-modified BSA, IgM apolipoprotein B100-immune complexes, and a peptide mimotope of MDA were measured within 24 h of first AMI in 4,559 patients and 4,617 age- and sex-matched controls in the Pakistan Risk of Myocardial Infarction Study. Multivariate-adjusted logistic regression was used to estimate odds ratio (OR) and 95% confidence interval for AMI. All four IgM OSEs were lower in AMI versus controls (P < 0.001 for all). Males, smokers and individuals with hypertension and diabetes had lower levels of all four IgM OSE than unaffected individuals (P < 0.001 for all). Compared to the lowest quintile, the highest quintiles of IgM MDA-LDL, phosphocholine-modified BSA, IgM apolipoprotein B100-immune complexes, and MDA mimotope P1 had a lower OR of AMI: OR (95% confidence interval) of 0.67 (0.58-0.77), 0.64 (0.56-0.73), 0.70 (0.61-0.80) and 0.72 (0.62-0.82) (P < 0.001 for all), respectively. Upon the addition of IgM OSE to conventional risk factors, the C-statistic improved by 0.0062 (0.0028-0.0095) and net reclassification by 15.5% (11.4-19.6). These findings demonstrate that IgM OSE provides clinically meaningful information and supports the hypothesis that higher levels of IgM OSE may be protective against AMI., Competing Interests: Conflict of interest S. T and J. L. W. are co-inventors and receive royalties from patents owned by University of California San Diego (UCSD) and are co-founders and have an equity interest in Oxitope, Pharmaceuticals and Kleanthi Diagnostics. Although these relationships have been identified for conflict-of-interest management based on the overall scope of the project, the research findings included in this publication may not necessarily relate to the interests of the above companies. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. S. T. has a dual appointment at UCSD and Ionis Pharmaceuticals. J. L. W. is a consultant to Ionis Pharmaceuticals. The other co-authors have nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Photon-counting detector (PCD) CT enables ultra-high-resolution lung imaging and may shed light on morphologic correlates of persistent symptoms after COVID-19. Purpose To compare PCD CT with energy-integrating detector (EID) CT for noninvasive assessment of post-COVID-19 lung abnormalities. Materials and Methods For this prospective study, adult participants with one or more COVID-19-related persisting symptoms (resting or exertional dyspnea, cough, fatigue) underwent same-day EID and PCD CT between April 2022 and June 2022. The 1.0-mm EID CT images and, subsequently, 1.0-, 0.4-, and 0.2-mm PCD CT images were reviewed for the presence of lung abnormalities. Subjective and objective EID and PCD CT image quality were evaluated using a five-point Likert scale (-2 to 2) and lung signal-to-noise ratios (SNRs). Results Twenty participants (mean age, 54 years ± 16 [SD]; 10 men) were included. EID CT showed post-COVID-19 lung abnormalities in 15 of 20 (75%) participants, with a median involvement of 10% of lung volume [IQR, 0%-45%] and 3.5 lobes [IQR, 0-5]. Ground-glass opacities and linear bands (10 of 20 participants [50%] for both) were the most frequent findings at EID CT. PCD CT revealed additional lung abnormalities in 10 of 20 (50%) participants, with the most common being bronchiectasis (10 of 20 [50%]). Subjective image quality was improved for 1.0-mm PCD versus 1.0-mm EID CT images (median, 1; IQR, 1-2; P < .001) and 0.4-mm versus 1.0-mm PCD CT images (median, 1; IQR, 1-1; P < .001) but not for 0.4-mm versus 0.2-mm PCD CT images (median, 0; IQR, 0-0.5; P = .26). PCD CT delivered higher lung SNR versus EID CT for 1.0-mm images (mean difference, 0.53 ± 0.96; P = .03) but lower SNR for 0.4-mm versus 1.0-mm images and 0.2-mm vs 0.4-mm images (-1.52 ± 0.68 [ P < .001] and -1.15 ± 0.43 [ P < .001], respectively). Conclusion Photon-counting detector CT outperformed energy-integrating detector CT in the visualization of subtle post-COVID-19 lung abnormalities and image quality. © RSNA, 2023 Supplemental material is available for this article.

The application of monoclonal antibodies (mAbs), targeting tumor-associated (TAAs) or tumor-specific antigens or immune checkpoints (ICs), has shown tremendous success in cancer therapy. However, the application of mAbs suffers from a series of limitations, including the necessity of frequent administration, the limited duration of clinical response and the emergence of frequently pronounced immune-related adverse events. However, the introduction of mAbs has also resulted in a multitude of novel developments for the treatment of cancers, including vaccinations against various tumor cell-associated epitopes. Here, we reviewed recent clinical trials involving combination therapies with mAbs targeting the PD-1/PD-L1 axis and Her-2/neu, which was chosen as a paradigm for a clinically highly relevant TAA. Our recent findings from murine immunizations against the PD-1 pathway and Her-2/neu with peptides representing the mimotopes/B cell peptides of therapeutic antibodies targeting these molecules are an important focus of the present review. Moreover, concerns regarding the safety of vaccination approaches targeting PD-1, in the context of the continuing immune response, as a result of induced immunological memory, are also addressed. Hence, we describe a new frontier of cancer treatment by active immunization using combined mimotopes/B cell peptides aimed at various targets relevant to cancer biology.

Background: Lipid oxidation of membrane phospholipids is accompanied by the formation of oxidation-specific epitopes (OSE). These epitopes are recognized by specific antibodies and represent danger-associated molecular patterns that are generated during chronic inflammatory processes. In a murine model for hepatic inflammation during non-alcoholic fatty liver disease (NAFLD), increased antibody levels targeting OSE were found to be protective. Here, our aim was to determine an association between OSE-specific antibody titers and NAFLD in humans., Methods: IgM and IgG levels with specificity for various OSE were assessed in the plasma of patients with NAFLD (n = 71) and healthy controls (n = 68). Antibody titers were comprehensively analyzed in patients with NAFLD after classification by histological evaluation of liver biopsies. Statistical analysis was performed to determine significant correlations and odds ratios. To study the specificity for NAFLD, plasma antibody titers were measured in patients with hepatitis C (n = 40) and inflammatory bowel disease (n = 62)., Results: IgM titers against OSE were lower in patients with NAFLD compared to controls. Further biopsy-based classification of patients with NAFLD did not show any difference in IgM levels. Plasma IgM titers towards the P1 mimotope demonstrated an inverse correlation with markers for obesity, systemic inflammation, and liver damage. In contrast, hepatitis C and increased disease activity during inflammatory bowel disease was not associated with reduced IgM titers., Conclusions: Our data highlight the importance of immune recognition of OSE by IgM antibodies in the pathophysiology of NAFLD.