A low aldosterone/renin ratio and high soluble ACE2 associate with COVID-19 severity.

BACKGROUND: The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers have been suggested to upregulate ACE2, their use in COVID-19 patients is now considered well tolerated. The aim of our study was to investigate parameters that determine COVID-19 severity, focusing on RAAS-components and variation in the genes encoding for ACE2 and TMPRSS2. METHODS: Adult patients hospitalized due to SARS-CoV-2 infection between May 2020 and October 2020 in the Haga Teaching Hospital were included, and soluble ACE2 (sACE2), renin, aldosterone (in heparin plasma) and polymorphisms in the ACE2 and TMPRSS2 genes (in DNA obtained from EDTA blood) were determined. MEASUREMENTS AND MAIN RESULTS: Out of the 188 patients who were included, 60 were defined as severe COVID-19 (ICU and/or death). These patients more often used antidiabetic drugs, were older, had higher renin and sACE2 levels, lower aldosterone levels and a lower aldosterone/renin ratio. In addition, they displayed the TMPRSS2-rs2070788 AA genotype less frequently. No ACE2 polymorphism-related differences were observed. Multivariate regression analysis revealed independent significance for age, sACE2, the aldosterone/renin ratio, and the TMPRSS2 rs2070788 non-AA genotype as predictors of COVID-19 severity, together yielding a C-index of 0.79. Findings were independent of the use of RAAS blockers. CONCLUSION: High sACE2, a low aldosterone/renin ratio and having the TMPRSS2 rs2070788 non-AA genotype are novel independent determinants that may help to predict COVID-19 disease severity. TRIAL REGISTRATION: retrospectively registered.

Finding the origin of pulmonary emboli with a total-body magnetic resonance direct thrombus imaging technique.

Pulmonary embolism is considered to originate from embolization of a deep-vein thrombosis, resulting in two manifestations of one disease: venous thrombosis. However, in up to 50% of patients with pulmonary embolism no deep-vein thrombosis is found with ultrasonography. An explanation for this low proportion is currently lacking. Other imaging modalities may increase the yield of detection of deep-vein thrombosis in the calf or in the abdominal region. Alternatively, not all pulmonary emboli may originate from deep-vein thromboses in the extremities. We searched for the origin of pulmonary emboli, by performing total-body magnetic resonance imaging-scans to visualize thrombi. Ninety-nine patients with a first pulmonary embolism confirmed by computed tomography underwent a magnetic resonance direct thrombus imaging-scan, a validated technique using endogenous contrast. Additionally, acquired and genetic risk factors were assessed. No thrombus was found in 55 patients, whereas a thrombus was identified in 44 patients. The commonest thrombus location was the lower leg; 12 patients had isolated calf vein thrombosis and five had isolated superficial vein thrombosis. A peripheral thrombus was found by magnetic resonance imaging in less than half of patients with pulmonary embolism. We propose several hypotheses to explain the absence of thrombi, such as a cardiac thrombus origin or embolization of the whole deep-vein thrombus. The possibility that pulmonary embolism arises de novo in the lungs, due to local inflammation-driven coagulation, needs to be considered.

Measurement of right and left ventricular function by ECG-synchronized CT scanning in patients with acute pulmonary embolism: usefulness for predicting short-term outcome.

BACKGROUND: Right ventricular (RV) function is predictive of outcome in patients with acute pulmonary embolism (PE). We assessed the possible incremental value of ventricular function with ECG-synchronized cardiac CT scanning over pulmonary CT scan angiography (CTA) for predicting short-term outcome in patients with suspected acute PE. METHODS: The local ethics committee approved the study, and informed consent was obtained. In addition to standard CTA, 430 consecutive patients (193 men, 237 women; age, 55 ± 17 years) with suspected acute PE underwent ECG-synchronized CT scanning to assess ventricular function. RV/left ventricular (LV) function ratio and pulmonary obstruction index were obtained from non-ECG-synchronized CTA. Ventricular function was used to predict adverse events (< 6 weeks). Receiver operating characteristic analysis was performed to determine differences between ECG-synchronized CT scan and CTA in predicting outcome. RESULTS: In 113 patients with PE, RV and LV ejection fraction (EF) and RV/LV diameter and volume ratios were associated with adverse outcome (P < .05), whereas vascular obstruction index was not. RVEF had the largest area under the receiver operating characteristic curve (0.75; 95% CI, 0.62-0.88) for predicting adverse outcome but had no significant incremental value over the RV/LV function ratio (0.72; 95% CI, 0.57-0.86; P = .25). All parameters revealed high negative predictive values (94%-98%) but low positive predictive values (13%-18%). For disease-specific outcome, areas under the curve were 0.80 (95% CI, 0.69-0.91) for RVEF vs 0.68 (95% CI, 0.48-0.88) for axial RV/LV ratio; the difference was not significant (P = .07). RVEF and RV/LV ratio proved better predictors for outcome than pulmonary obstruction index (both P < .001). CONCLUSIONS: RVEF was the best predictor for clinical outcome in patients with acute PE. However, incremental value of RVEF over axial RV/LV ratio was not found.

[Desmoid tumours in the abdominal wall]. / Desmoïdtumoren in de buikwand.

Desmoid tumours are benign tumours originating from musculoaponeurotic structures and the fascia. They usually are slow-growing, without metastatic potential. However, their local behaviour can be infiltrative and aggressive, leading to damage of adjacent structures causing organ dysfunction. They carry a high risk of relapse. In this paper, three case studies of women aged 33, 35 and 42 years, respectively, illustrate the presentation, diagnostics and therapy of abdominal desmoid tumours. All three were surgically treated and recovered. Desmoid tumours occur most commonly in fertile women. Although the etiology is unknown, there is a correlation with scar tissue, pregnancy and radiotherapy. Abdominal desmoid tumours have the lowest relapse rate of all desmoid tumours. In toto resection is the treatment of choice. Radiotherapy in addition to surgery may be considered when risk of relapse is high.