Anti-topoisomerase, but not anti-centromere B cell responses in systemic sclerosis display active, Ig-secreting cells associated with lung fibrosis.

OBJECTIVES: Almost all patients with systemic sclerosis (SSc) harbour autoantibodies. Anti-topoisomerase antibodies (ATA) and anti-centromere antibodies (ACA) are most prevalent and associate with distinct clinical phenotypes. B cell responses underlying these phenotypes are ill-defined. To understand how B cell autoreactivity and disease pathology connect, we determined phenotypic and functional characteristics of autoreactive B cells in ATA-positive and ACA-positive patients. METHODS: Levels and isotypes of autoantibodies secreted by ex vivo cultured peripheral blood mononuclear cells from patients with ATA-positive (n=22) and ACA-positive (n=20) SSc were determined. Antibody secreting cells (ASCs) were isolated by cell sorting and cultured separately. Correlations were studied between the degree of spontaneous autoantibody production and the presence and degree of interstitial lung disease (ILD). RESULTS: Circulating B cells secreting either ATA-immunoglobulin G (IgG) or ACA-IgG on stimulation was readily detectable in patients. The ATA response, but not the ACA response, showed additional secretion of autoreactive IgA. ATA-IgG and ATA-IgA were also secreted spontaneously. Additional cell sorting confirmed the presence of ATA-secreting plasmablasts. The degree of spontaneous ATA-secretion was higher in patients with ILD than in those without (p<0.001) and correlated with the degree of pulmonary fibrosis (p<0.001). CONCLUSION: In contrast to ACA-positive patients, ATA-positive patients show signs of recent activation of the B cell response that hallmarks this disease. The degree of activation correlates with the presence and severity of ILD, the most deleterious disease manifestation. This could explain differential responsiveness to B cell depleting therapy. The abundant and spontaneous secretion of ATA-IgG and ATA-IgA may point toward a continuously activating trigger.

Outcomes of the modified Yacoub aortocoronary flap technique for 'non-separable' single sinus coronary arteries with intramural course in the neonatal arterial switch operation.

OBJECTIVES: Coronary transfer remains the most crucial part of the arterial switch operation (ASO); yet, certain coronary anatomies prohibit the use of button or trap-door transfer techniques. In the rare setting of 'non-separable' single sinus coronary arteries with intramural course, the modified Yacoub aortocoronary flap technique is a viable option. The aim of this study is to describe this operative technique and review its early- and mid-term outcomes. METHODS: This retrospective analysis included all cases with 'non-separable' single sinus coronary arteries with intramural course where the modified Yacoub aortocoronary flap technique served as a bail-out option. RESULTS: Of 516 patients who underwent ASO at our institution between January 1977 and April 2022, 14 underwent the modified Yacoub aortocoronary flap technique. The median age at ASO was 10 (interquartile range 7-19) days. Hospital mortality occurred in 3 patients (21.4%), all being related to coronary complications. All hospital survivors were still alive at a median of 9.1 (interquartile range 4.2-18.3) years after the ASO. None of them developed complaints of ischaemia, ventricular arrhythmias, ventricular dysfunction or exercise intolerance. Surveillance computed tomography angiography showed stable aortocoronary relationships free from stenosis, compression and kinking. No reoperations for coronary artery problems and/or neoaortic valve or root problems were needed. CONCLUSIONS: Although close monitoring of early coronary events seems crucial to prevent perioperative mortality, the modified Yacoub aortocoronary flap technique may serve as a viable bail-out option in patients with 'non-separable' single sinus coronary anatomy with intramural course, with excellent results among hospital survivors.

CO-RADS: A Categorical CT Assessment Scheme for Patients Suspected of Having COVID-19-Definition and Evaluation.

Background A categorical CT assessment scheme for suspicion of pulmonary involvement of coronavirus disease 2019 (COVID-19 provides a basis for gathering scientific evidence and improved communication with referring physicians. Purpose To introduce the COVID-19 Reporting and Data System (CO-RADS) for use in the standardized assessment of pulmonary involvement of COVID-19 on unenhanced chest CT images and to report its initial interobserver agreement and performance. Materials and Methods The Dutch Radiological Society developed CO-RADS based on other efforts for standardization, such as the Lung Imaging Reporting and Data System or Breast Imaging Reporting and Data System. CO-RADS assesses the suspicion for pulmonary involvement of COVID-19 on a scale from 1 (very low) to 5 (very high). The system is meant to be used in patients with moderate to severe symptoms of COVID-19. The system was evaluated by using 105 chest CT scans of patients admitted to the hospital with clinical suspicion of COVID-19 and in whom reverse transcription-polymerase chain reaction (RT-PCR) was performed (mean, 62 years ± 16 [standard deviation]; 61 men, 53 with positive RT-PCR results). Eight observers used CO-RADS to assess the scans. Fleiss κ value was calculated, and scores of individual observers were compared with the median of the remaining seven observers. The resulting area under the receiver operating characteristics curve (AUC) was compared with results from RT-PCR and clinical diagnosis of COVID-19. Results There was absolute agreement among observers in 573 (68.2%) of 840 observations. Fleiss κ value was 0.47 (95% confidence interval [CI]: 0.45, 0.47), with the highest κ value for CO-RADS categories 1 (0.58, 95% CI: 0.54, 0.62) and 5 (0.68, 95% CI: 0.65, 0.72). The average AUC was 0.91 (95% CI: 0.85, 0.97) for predicting RT-PCR outcome and 0.95 (95% CI: 0.91, 0.99) for clinical diagnosis. The false-negative rate for CO-RADS 1 was nine of 161 cases (5.6%; 95% CI: 1.0%, 10%), and the false-positive rate for CO-RADS category 5 was one of 286 (0.3%; 95% CI: 0%, 1.0%). Conclusion The coronavirus disease 2019 (COVID-19) Reporting and Data System (CO-RADS) is a categorical assessment scheme for pulmonary involvement of COVID-19 at unenhanced chest CT that performs very well in predicting COVID-19 in patients with moderate to severe symptoms and has substantial interobserver agreement, especially for categories 1 and 5. © RSNA, 2020 Online supplemental material is available for this article.

Iodine Maps from Subtraction CT or Dual-Energy CT to Detect Pulmonary Emboli with CT Angiography: A Multiple-Observer Study.

Background Dual-energy CT iodine maps are used to detect pulmonary embolism (PE) with CT angiography but require dedicated hardware. Subtraction CT, a software-only solution, results in iodine maps with high contrast-to-noise ratios. Purpose To compare the use of subtraction CT versus dual-energy CT iodine maps to CT angiography for PE detection. Materials and Methods In this prospective study ( https://clinicaltrials.gov , NCT02890706), 274 participants suspected of having PE underwent precontrast CT followed by contrast material-enhanced dual-energy CT angiography between July 2016 and April 2017. Iodine maps from dual-energy CT were derived. Subtraction maps (contrast-enhanced CT minus precontrast CT) were calculated after motion correction. Truth was established by expert consensus. A total of 75 randomly selected participants with and without PE (1:1 ratio) were evaluated by three radiologists and six radiology residents (blinded to final diagnosis) for the presence of PE using three types of CT: CT angiography alone, dual-energy CT, and subtraction CT. The partial area under the receiver operating characteristic curve (AUC) for the clinically relevant specificity region (maximum partial AUC, 0.11) was compared by using multireader multicase variance. A P value less than or equal to .025 was considered indicative of a significant difference due to multiple comparisons. Results There were 35 men and 40 women in the reader study (mean age, 63 years ± 12 [standard deviation]). The pooled sensitivities were not different (P ≥ .31 among techniques) (95% confidence intervals [CIs]: 67%, 89% for CT angiography; 72%, 91% for dual-energy CT; 70%, 91% for subtraction CT). However, pooled specificity was higher for subtraction CT (95% CI: 100%, 100%) than for CT angiography (95% CI: 89%, 97%) or dual-energy CT (95% CI: 89%, 98%) (P < .001). Partial AUCs for the average observer improved equally when adding iodine maps (subtraction CT [0.093] vs CT angiography [0.088], P = .03; dual-energy CT [0.094] vs CT angiography, P = .01; dual-energy CT vs subtraction CT, P = .68). Average reading times were equivalent (range, 97-101 seconds; P ≥ .41) among techniques. Conclusion Subtraction CT iodine maps had greater specificity than CT angiography alone in pulmonary embolism detection. Subtraction CT had comparable diagnostic performance to that of dual-energy CT, without the need for dedicated hardware. © RSNA, 2019 Online supplemental material is available for this article.

Imaging of nontraumatic thoracic emergencies.

PURPOSE OF REVIEW: Acute chest symptoms form an important incentive for imaging in the emergency setting. This review discusses the radiologic features of various vascular and pulmonary diseases leading to acute respiratory distress and recent developments on important emergency radiologic examinations. RECENT FINDINGS: Recently, triple-rule-out computed tomography protocol was introduced in diagnosis of chest pain, and advancing computed tomography technology and knowledge have led to discussion on treatment of pulmonary embolism. Diffuse pulmonary opacities remain a diagnostic dilemma in the emergency setting and although imaging findings can often be nonspecific, they help in guiding toward accurate diagnosis and timely management. SUMMARY: Though promising, triple-rule-out is not yet justified because of low incidence of additional findings compared with conventional computed tomography angiography in chest pain, but it might be suited for clinical practice in the near future. Relevance of isolated subsegmental pulmonary embolism is unknown and research on this topic is needed and on its way. We provided some key findings in differentiating diffuse pulmonary opacities and describe the additional value of chest ultrasound in this clinical dilemma. A brief sidestep to pneumothorax is made, as this is also a frequent finding in the acute dyspneic patient, as well as in patients with acute chest pain.

Macrophage microRNA-155 promotes cardiac hypertrophy and failure.

BACKGROUND: Cardiac hypertrophy and subsequent heart failure triggered by chronic hypertension represent major challenges for cardiovascular research. Beyond neurohormonal and myocyte signaling pathways, growing evidence suggests inflammatory signaling pathways as therapeutically targetable contributors to this process. We recently reported that microRNA-155 is a key mediator of cardiac inflammation and injury in infectious myocarditis. Here, we investigated the impact of microRNA-155 manipulation in hypertensive heart disease. METHODS AND RESULTS: Genetic loss or pharmacological inhibition of the leukocyte-expressed microRNA-155 in mice markedly reduced cardiac inflammation, hypertrophy, and dysfunction on pressure overload. These alterations were macrophage dependent because in vivo cardiomyocyte-specific microRNA-155 manipulation did not affect cardiac hypertrophy or dysfunction, whereas bone marrow transplantation from wild-type mice into microRNA-155 knockout animals rescued the hypertrophic response of the cardiomyocytes and vice versa. In vitro, media from microRNA-155 knockout macrophages blocked the hypertrophic growth of stimulated cardiomyocytes, confirming that macrophages influence myocyte growth in a microRNA-155-dependent paracrine manner. These effects were at least partly mediated by the direct microRNA-155 target suppressor of cytokine signaling 1 (Socs1) because Socs1 knockdown in microRNA-155 knockout macrophages largely restored their hypertrophy-stimulating potency. CONCLUSIONS: Our findings reveal that microRNA-155 expression in macrophages promotes cardiac inflammation, hypertrophy, and failure in response to pressure overload. These data support the causative significance of inflammatory signaling in hypertrophic heart disease and demonstrate the feasibility of therapeutic microRNA targeting of inflammation in heart failure.

Hematopoietic miR155 deficiency enhances atherosclerosis and decreases plaque stability in hyperlipidemic mice.

microRNA-155 (miR155) is a central regulator of immune responses that is induced by inflammatory mediators. Although miR155 is considered to be a pro-inflammatory microRNA, in vitro reports show anti-inflammatory effects in lipid-loaded cells. In this study we examined the role of miR155 in atherosclerosis in vivo using bone marrow transplantation from miR155 deficient or wildtype mice to hyperlipidemic mice. Hematopoietic deficiency of miR155 enhanced atherosclerotic plaque development and decreased plaque stability, as evidenced by increased myeloid inflammatory cell recruitment to the plaque. The increased inflammatory state was mirrored by a decrease in circulating CD4(+)CD25(+)FoxP3(+) regulatory T cells, and an increase in granulocytes (CD11b(+)Ly6G(+)) in blood of miR155(-/-) transplanted mice. Moreover, we show for the first time a crucial role of miR155 in monocyte subset differentiation, since hematopoietic deficiency of miR155 increases the 'inflammatory' monocyte subset (CD11b(+)Ly6G(-)Ly6C(hi)) and reduces 'resident' monocytes (CD11b(+)Ly6G(-)Ly6C(low)) in the circulation. Furthermore, cytokine production by resident peritoneal macrophages of miR155(-/-) transplanted hyperlipidemic mice was skewed towards a more pro-inflammatory state since anti-inflammatory IL-10 production was reduced. In conclusion, in this hyperlipidemic mouse model miR155 acts as an anti-inflammatory, atheroprotective microRNA. Additionally, besides a known role in lymphoid cell development, we show a crucial role of miR155 in myeloid lineage differentiation.