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Glycyrrhizin, an active component of liquorice root extract, exhibits antiviral and immunomodulatory properties by direct inhibition of the pro-inflammatory alarmin HMGB1 (High-mobility group box 1). The aim of this study was to explore the role of liquorice intake on the viral entry receptor ACE2 (angiotensin-converting enzyme 2) and the immunoregulatory HMGB1 in healthy individuals and to explore HMGB1 expression in coronavirus disease 2019 (COVID-19) or non-COVID-19 in ARDS (acute respiratory distress syndrome patients). This study enrolled 43 individuals, including hospitalised patients with i) acute respiratory distress syndrome (ARDS) due to COVID-19 (n = 7) or other underlying causes (n = 12), ii) mild COVID-19 (n = 4) and iii) healthy volunteers (n = 20). Healthy individuals took 50 g of liquorice (containing 3% liquorice root extract) daily for 7 days, while blood samples were collected at baseline and on day 3 and 7. Changes in ACE2 and HMGB1 levels were determined by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Additionally, HMGB1 levels were measured in hospitalised COVID-19 patients with mild disease or COVID-19 associated acute respiratory distress syndrome (ARDS) and compared with a non-COVID-19-ARDS group. Liquorice intake significantly reduced after 7 days both cellular membranous ACE2 expression (-51% compared to baseline levels, p = 0.008) and plasma HMGB1 levels (-17% compared to baseline levels, p<0.001) in healthy individuals. Half of the individuals had a reduction in ACE2 levels of at least 30%. HMGB1 levels in patients with mild COVID-19 and ARDS patients with and without COVID-19 were significantly higher compared with those of healthy individuals (+317%, p = 0.002), but they were not different between COVID-19 and non-COVID-19 ARDS. Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.

The requirements for ensuring functional safety have always been very high. Modern safety-related systems are becoming increasingly complex, making also the safety integrity assessment more complex and time-consuming. This trend is further intensified by the fact that AI-based algorithms are finding their way into safety-related systems or will do so in the future. However, existing and expected standards and regulations for the use of AI methods pose significant challenges for the development of embedded AI software in functional safety-related systems. The consideration of essential requirements from various perspectives necessitates an intensive examination of the subject matter, especially as different standards have to be taken into account depending on the final application. There are also different targets for the “safe behavior” of a system depending on the target application. While stopping all movements of a machine in industrial production plants is likely to be considered a “safe state”, the same condition might not be considered as safe in flying aircraft, driving cars or medicine equipment like heart pacemaker. This overall complexity is operationalized in our approach in such a way that it is straightforward to monitor conformity with the requirements. To support safety integrity assessments and reduce the required effort, a Self-Enforcing Network (SEN) model is presented in which developers or safety experts can indicate the degree of fulfillment of certain requirements with possible impact on the safety integrity of a safety-related system. The result evaluated by the SEN model indicates the achievable safety integrity level of the assessed system, which is additionally provided by an explanatory component.

IntroductionHughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by widespread venous/arterial thrombosis and pulmonary artery aneurysms (PAAs), which is associated with serious morbidity and mortality. All fatalities reported in HSS resulted from unpredictable fatal suffocating hemoptysis. Therefore, it is necessary to recognize pulmonary complications at an early stage of the disease.ObjectivesThe aims of this study are to develop a reference atlas of images depicting the characteristic features of HSS by computed tomography pulmonary angiography (CTPA). To make a guide for physicians by developing a classification of PAAs according to the severity and risk of complications associated with each distinct lesion type.MethodsThe Members of the HSS International Study Group (HSSISG) collected 42 cases, with high-quality CTPA images in one radiology station and made reconstructions from the source images. These detailed CTPA studies were reviewed for final image selection and approved by HSSISG board members. We classified these findings according to the clinical course of the patients.ResultsThis atlas describes the CTPA images that best define the wide spectrum of pulmonary vasculitis observed in HSS. Pulmonary aneurysms were classified into six radiographic patterns: from true stable PAA with adherent in-situ thrombosis to unstable leaking PAA, BAA and/or PAP with loss of aneurysmal wall definition (most prone to rupture), also CTPA images demonstrating right ventricular strain and intracardiac thrombosis.ConclusionThe HSSISG reference atlas is a guide for physicians regarding the CTPA radiological findings, essential for early diagnosis and management of HSS-related pulmonary vasculitis. Key Points• The Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by extensive vascular thrombosis and pulmonary artery aneurysms (PAAs) that can lead to significant morbidity and mortality.• All fatalities reported in HSS were related to unpredictable massive hemoptysis; therefore, it is critical to recognize pulmonary complications at an early stage of the disease.• The HSS International Study Group reference atlas classifies pulmonary vasculitis in HSS at 6 different stages of the disease process and defines the different radiological patterns of pulmonary vasculitis notably pulmonary artery aneurysms, as detected by computed tomography pulmonary angiography (CTPA).• The main aim of the classification is to make a guide for physicians about this rare syndrome. Such a scheme has never been reached before since the first description of the syndrome by Hughes and Stovin since 1959. This classification will form the basis for future recommendations regarding diagnosis and treatment of this syndrome.

COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.

PURPOSE:Debulking strategies prior to drug-coated balloon (DCB) angioplasty were suggested to improve clinical results in femoro-popliteal lesions. Currently, there are no data regarding plaque modification with a scoring balloon with subsequent DCB-angioplasty. Recently published 6-month results of the DCB-Trak registry in patients treated with scoring-balloon angioplasty and DCB-angioplasty were promising without any safety concerns. Herein, we report the 12-month follow-up data. METHODS:In a single center registry, 29 consecutive patients with 32 femoro-popliteal lesions were treated with a scoring-balloon (VascuTrak®) and a DCB subsequently. The primary endpoint was the clinically driven target lesion revascularization (TLR). Secondary endpoints were clinically driven target vessel revascularization (TVR), binary restenosis (peak systolic velocity ratio >2.4), change in Rutherford classification and ankle-brachial-index (ABI). Safety endpoints were major cardiovascular events (cardiovascular death, myocardial infarction, stroke, death) and need for amputation. RESULTS:The procedure was successful in 29 lesions. There were no clinically driven TLRs after 12 months. Two patients required clinically driven TVR and one patient had a binary restenosis. ABI significantly increased after the procedure (0.87±0.24 to 1.04±0.18, P < 0.01) without a relevant change after 6 months (1.01±0.15, P < 0.05) or 12 months (1.01±0.20, P < 0.05). Rutherford classification improved in more than 90% of patients after 6 and 12 months. There was one major cardiovascular event at 6-month follow-up, but no amputations at 6- or 12-month follow-up. CONCLUSION:Vessel preparation with a scoring-balloon and subsequent DCB-angioplasty was safe and effective in patients with femoro-popliteal lesions. Further multicenter trials have to validate these results. You may cite this article as: Baumhäkel M, Chkhetia S, Kindermann M. Treatment of femoro-popliteal lesions with scoring- and drug-coated balloon angioplasty: 12-month results of the DCB-Trak registry. Diagn Interv Radiol 2018; 24:153–157.

IL-1RA and Myocarditis after SARS-CoV-2 VaccinationNeutralizing autoantibodies to interleukin-1 receptor antagonist were present in the circulation of the majority of patients with biopsy-confirmed myocarditis after SARS-CoV-2 vaccination.

Background Myocarditis might be associated with increased markers of myocardial injury. However, data on novel biomarkers, such as high-sensitive Troponin T (hs-TnT) or Copeptin, are lacking. This study aimed to determine the diagnostic and prognostic utility of biomarkers in patients with suspected myocarditis. Methods Seventy patients with clinically suspected myocarditis (age 43.4 ± 14 years, 76 % male, ejection fraction 36.9 ± 17.8) underwent endomyocardial biopsy (EMB) and were followed for 7.5 (2–21) months. At the time of EMB, blood samples to evaluate concentrations of hs-TnT, Copeptin, NT-proBNP and mid-regional pro-adrenomedullin (MR-proADM) were collected. Results According to EMB, 6 patients were diagnosed with acute myocarditis (AM) and 36 patients with chronic myocarditis (CM). In 28 patients, EMB revealed no myocardial inflammation (NM). Acute myocarditis was associated with the highest concentrations of hs-TnT compared to other groups (AM 262.9 pg/ml (61.4–884.2); CM 20.4 pg/ml (15.6–20.4); NM 19.5 pg/ml (13.8–50.7); p  < 0.0001). No significant differences existed in the Copeptin, NT-proBNP, and MR-proADM concentrations between the groups. The concentration of hs-TnT was significantly higher in myocarditis when myocardial viral genome was detected (37.4 pg/ml (21.9–163.6) vs. 20 pg/ml (14–44.4); p  = 0.042). During follow-up, only NT-proBNP in the highest quartile (>4,225 ng/ml) was predictive for cardiac death or heart transplantation (hazard ratio 9.2; 95 % confidence interval 1.7–50; p  = 0.011). Conclusions Biopsy-proven acute and viral myocarditis is associated with elevated concentrations of hs-TnT. Elevated hs-TnT is highly suggestive of acute myocarditis, if other causes of increased myocardial necrosis markers such as myocardial infarction have been systematically excluded.

Abstract Background  Creation of an iatrogenic aorto-right atrial fistula is a rare but clinically relevant complication of cardiac surgery. Transfemoral percutaneous closure is an attractive alternative to surgical repair, but there are no reports about transcatheter repair using a complete arm access. Case summary  We present the case of a 44-year-old woman with heart failure (NewYork Heart Association Class III) due to a longstanding iatrogenic fistula from the non-coronary aortic cusp to the right atrium (RA) with aorta to RA shunting and severe tricuspid regurgitation (TR) caused by mitral valve replacement 15 years ago. The patient was successfully treated by percutaneous closure with an Amplatzer Vascular Plug II using complete brachial access. Following the procedure right heart chambers and TR decreased and symptoms resolved. Discussion  To the best of our knowledge this is the first report of percutaneous repair of an aorto-right atrial fistula using total arm accesses (radial artery and basilic vein). In appropriately selected patients, this approach is an attractive alternative to femoral access.

Aortic valve preservation is a promisingalternative to conventional composite replacement of aortic valve andascending aorta. This approach may have a physiologic benefit comparedwith valve replacement similar to that seen in mitral valvereconstruction. We investigated aortic valve gradients at rest andduring exercise in patients who had undergone valve-preserving aorticreplacement and compared them with composite replacement of valve andaorta. Four groups were studied: ninepatients underwent composite valve replacement (group A: valvediameter, 23 to 27 mm), eight patients underwent remodeling of theaortic root (group B), and another nine patients had reimplantation ofthe aortic valve (group C). Healthy volunteers were studied as acontrol group (group D). Using continuous-wave Dopplerechocardiography, all patients were examined on a bicycle ergometer foraortic valve gradients (0 to 75 W). Therewere no differences among the groups with respect to age, body surface,left ventricular end-diastolic diameter, fractional shortening, or leftventricular mass. Maximum resting gradients were significantly elevatedin group A compared with groups B, C, and D (group A: 21.3 ± 7.1 mmHg; group B: 9.0 ± 4.5 mm Hg; group C: 8.6 ± 3.7 mm Hg; group D:4.9 ± 1.6 mm Hg; p < 0.05). At 75 W, group A exhibitedsignificantly higher gradients than all other groups (group A:31.3 ± 7.5 mm Hg; group B: 13.9 ± 6.6 mm Hg; group C:12.8 ± 3.5 mm Hg; group D: 9.2 ± 1.9 mm Hg; p < 0.05). Therewas no significant difference among the other groups. Bothvalve-preserving groups had only insignificantly higher gradients thanthe control group. Our data stronglysupport the suggestion that preserving the aortic valve restores nearlynormal hemodynamic function of the aortic valve. Long-term observationswill have to prove the clinical relevance of restoring physiologicaortic valve hemodynamics.