High immunoglobulin-M levels to oxidation-specific epitopes are associated with lower risk of acute myocardial infarction.

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.

[Mediastinum-new compartment classification]. / Mediastinum ­ neue Kompartimenteinteilung.

BACKGROUND: Mediastinal masses are common and comprise a heterogeneous spectrum of disorders. Correct diagnosis has prognostic and therapeutic consequences, which is why precise localization of lesions and interdisciplinary management are essential in clinical practice. This article describes traditional divisions of mediastinum lesions and presents the new classification based on cross-sectional imaging, which was developed by the International Thymic Malignancy Interest Group (ITMIG). OBJECTIVES: Which divisions of the mediastinum have been used so far and how does the division developed by the ITMIG differ? What are the advantages of the new mediastinal classification? MATERIALS AND METHODS: Comparison of the previously used mediastinal classification with the new mediastinal classification developed by ITMIG and visualization of the respective methods. In addition, pathologies typical for the respective compartments are explained. RESULTS AND CONCLUSION: The traditional compartmentalization of the mediastinum into an anterior, middle, and posterior mediastinum is not clearly defined and may lead to confusing interdisciplinary communication. Since these classifications are mostly based on projection radiographs, the proposed three-dimensional classification of the ITMIG is a development that suits the modern clinical workflow and promotes standardization. The three mediastinal compartments should thus be termed prevascular, visceral, and paravertebral.

Fetal MRI radiomics: non-invasive and reproducible quantification of human lung maturity.

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.

Detection of Post-COVID-19 Lung Abnormalities: Photon-counting CT versus Same-Day Energy-integrating Detector CT.

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.

Combined Vaccination with B Cell Peptides Targeting Her-2/neu and Immune Checkpoints as Emerging Treatment Option in Cancer.

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.

[Smoking-related interstitial lung diseases]. / Raucherassoziierte interstitielle Lungenerkrankungen.

CLINICAL ISSUE: Smoking-related interstitial lung diseases are a heterogeneous group of pulmonary abnormalities. The correct diagnosis has prognostic and therapeutic implications. This article introduces the most common smoking-related interstitial lung diseases and describes a structured approach to support the diagnostic workflow. PRACTICAL RECOMMENDATIONS: Computed tomography is pivotal in the diagnostic workflow of smoking-related interstitial lung diseases and may reduce the number of unnecessary lung biopsies. To achieve high diagnostic accuracy, a standardized scanning protocol, and a structured assessment approach should be utilized. During inflammatory stages of respiratory bronchiolitis (RB), respiratory bronchiolitis interstitial lung diseases (RB-ILD), and desquamative interstitial pneumonia (DIP), cessation of smoking as well as the use of steroids are the treatment of choice. In case of fibrotic changes (e.g., in idiopathic pulmonary fibrosis [IPF]), antifibrotic therapy with nintedanib and pirfenidone may be used. Patients with suspected smoking-related interstitial lung disease should be discussed in interdisciplinary board meetings.

Comparison of donor scores in bilateral lung transplantation-A large single-center analysis.

Objectifying donor lung quality is difficult and currently there is no consensus. Several donor scoring systems have been proposed in recent years. They all lack large-scale external validation and widespread acceptance. A retrospective evaluation of 2201 donor lungs offered to the lung transplant program at the Medical University of Vienna between January 2010 and June 2018 was performed. Five different lung donor scores were calculated for each offer (Oto, ET, MALT, UMN-DLQI, and ODSS). Prediction of organ utilization, 1-year graft survival, and long-term outcome were analyzed for each score. 1049 organs were rejected at the initial offer (group I), 209 lungs declined after procurement (group II), and 841 lungs accepted and transplanted (group III). The Oto score was superior in predicting acceptance of the initial offer (AUC: 0.795; CI: 0.776-0.815) and actual donor utilization (AUC: 0.660; CI: 0.618-0.701). Prediction of 1-year graft survival was best using the MALT score, Oto score, and UMN-DLQI. Stratification of early outcome by MALT was significant for length of mechanical ventilation (LMV), PGD3 rates, ICU stay and hospital stay, and in-hospital-mortality, respectively. To the best of our knowledge, this study is the largest validation analysis comparing currently available donor scores. The Oto score was superior in predicting organ utilization, and MALT score and UMN-DLQI for predicting outcome after lung transplantation.

Low levels of IgM antibodies recognizing oxidation-specific epitopes are associated with human non-alcoholic fatty liver disease.

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.