Inhibition of tetraspanin functions impairs human papillomavirus and cytomegalovirus infections

Tetraspanins are suggested to regulate the composition of cell membrane components and control intracellular transport, which leaves them vulnerable to utilization by pathogens such as human papillomaviruses (HPV) and cytomegaloviruses (HCMV) to facilitate host cell entry and subsequent infection. In this study, by means of cellular depletion, the cluster of differentiation (CD) tetraspanins CD9, CD63, and CD151 were found to reduce HPV16 infection in HeLa cells by 50 to 80%. Moreover, we tested recombinant proteins or peptides of specific tetraspanin domains on their effect on the most oncogenic HPV type, HPV16, and HCMV. We found that the C-terminal tails of CD63 and CD151 significantly inhibited infections of both HPV16 and HCMV. Although CD9 was newly identified as a key cellular factor for HPV16 infection, the recombinant CD9 C-terminal peptide had no effect on infection. Based on the determined half-maximal inhibitory concentration (IC50), we classified CD63 and CD151 C-terminal peptides as moderate to potent inhibitors of HPV16 infection in HeLa and HaCaT cells, and in EA.hy926, HFF (human foreskin fibroblast) cells, and HEC-LTT (human endothelial cell-large T antigen and telomerase) cells for HCMV, respectively. These results indicate that HPV16 and HCMV share similar cellular requirements for their entry into host cells and reveal the necessity of the cytoplasmic CD151 and CD63 C-termini in virus infections. Furthermore, this highlights the suitability of these peptides for functional investigation of tetraspanin domains and as inhibitors of pathogen infections

Heart failure in COVID-19: the multicentre, multinational PCHF-COVICAV registry.

AIMS: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. METHODS AND RESULTS: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62-81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44-2.59], P < 0.001). After adjusting, HF remained associated with in-hospital mortality (OR 1.45 [95% confidence interval: 1.01-2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in-hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24-4.29], P < 0.001). CONCLUSIONS: Hospitalized COVID-19 patients with HF are at increased risk for in-hospital death. In-hospital worsening of HF or acute HF de novo are common and associated with a further increase in in-hospital mortality

Können Schaumverödung und Thermoablation das chirurgische Venenstripping ersetzen?

Zunehmend etablieren sich minimal-invasive Verfahren in der Varizenbehandlung. Die kurz- bis mittelfristigen Ergebnisse der endovenösen Verfahren sind gut: Die Erfolgsraten sind vergleichbar mit dem chirurgischen Stripping, die Rehabilitationszeiten und Komplikationsraten sind jedoch besser. Die höchste Erfolgsrate verzeichnet bislang die endovenöse Lasertherapie (EVLT). Die endovenöse Radiofrequenzobilateration (RFO) hat jedoch grosse Fortschritte gemacht und erzielt mittlerweile ähnlich gute Kurzzeitergebnisse bei einem besseren Nebenwirkungsprofil. Die ultraschallgesteuerte Schaumsklerosierung hat die Sklerosierungsverfahren mit flüssigem Agenz verdrängt. Prinzipiell kann dieses Verfahren mit allen anderen kombiniert werden. Als Monotherapie verliert die Schaumsklerosierung gegenüber den thermoablativen Verfahren EVLT und RFO jedoch klar an Stellenwert, da die mittelfristigen Ergebnisse schlechter sind. Um eine evidenzbasierte Rangfolge festzulegen, sind prospektive randomisierte Vergleichsstudien notwendig. Die minimale Invasivität ermöglicht eine ambulante Behandlung. Ob sie damit auch kostengünstiger ist, bleibt abzuwarten. = Minimally invasive treatments of varicosis are increasingly establishing. Short and intermediate-term outcomes of endovenous treatments are satisfying: success rates are comparable with conventional surgery, whereas recovery is faster and complication rates are lower. Success rates are highest for endovenous laser ablation (EVLA). However, endovenous radiofrequency ablation (RFA) has advanced. Its short term outcomes are now comparable to EVLA, but with less side-effects. Ultrasound guided foam sclerotherapy (UGFS) replaced other forms of liquid sclerotherapy. In principle, this treatment can be combined with every other treatment for varicosis, but it loses its position as a monotherapy, due to poorer intermediate-term outcomes compared with EVLA and RFA. More prospective randomized controlled trials are needed in order to state an evidence based hierarchy of treatments for varicosis. With the minimally invasive treatments it is possible to treat patients on an outpatient basis. It will have to be assessed whether this will lead to higher cost-effectiveness

Adaptive Statistical Iterative Reconstruction-V: Impact on Image Quality in Ultralow-Dose Coronary Computed Tomography Angiography

OBJECTIVE The clinical utility of a latest generation iterative reconstruction algorithm (adaptive statistical iterative reconstruction [ASiR-V]) has yet to be elucidated for coronary computed tomography angiography (CCTA). This study evaluates the impact of ASiR-V on signal, noise and image quality in CCTA. METHODS Sixty-five patients underwent clinically indicated CCTA on a 256-slice CT scanner using an ultralow-dose protocol. Data sets from each patient were reconstructed at 6 different levels of ASiR-V. Signal intensity was measured by placing a region of interest in the aortic root, LMA, and RCA. Similarly, noise was measured in the aortic root. Image quality was visually assessed by 2 readers. RESULTS Median radiation dose was 0.49 mSv. Image noise decreased with increasing levels of ASiR-V resulting in a significant increase in signal-to-noise ratio in the RCA and LMA (P < 0.001). Correspondingly, image quality significantly increased with higher levels of ASiR-V (P < 0.001). CONCLUSIONS ASiR-V yields substantial noise reduction and improved image quality enabling introduction of ultralow-dose CCTA

Prevalence and characteristics of coronary artery anomalies detected by coronary computed tomography angiography in 5 634 consecutive patients in a single centre in Switzerland

STUDY PRINCIPLES Coronary computed tomography angiography (CCTA) allows three-dimensional visualisation of the origin, course and ending of the coronary vessels with high spatial resolution, yielding an accurate depiction of coronary artery anomalies (CAAs). This study sought to determine the prevalence, incidence and characteristics of CAAs detected with CCTA in a single centre in Switzerland. METHODS CAAs were retrospectively identified in 5 634 consecutive patients referred for CCTA between March 2007 and July 2015. Single coronary arteries, Bland-White-Garland syndrome, anomalous coronary arteries originating from the opposite site of the sinus of Valsalva (ACAOS) with an interarterial course and coronary artery fistulas were classified as potentially malignant CAAs. RESULTS We identified 145 patients with CAAs, resulting in an overall prevalence of 2.6% and cumulative incidence of 2.1% in all patients referred for CCTA in the observation period. Forty-nine (33.8%) patients showed malignant CAAs including 1 (0.7%) patient with Bland-White-Garland syndrome, 7 (4.8%) with single coronary arteries, 36 (24.8%) with ACAOS and an interarterial course, and 5 (3.5%) with coronary artery fistulas. The remaining 96 (66.2%) patients were classified as having benign variants. CONCLUSIONS The prevalence of CAA detected by CCTA is not negligible. Because of its noninvasive nature, relatively low cost and low radiation exposure, a further increase in the utilisation of CCTA may be expected, which may consequently be paralleled by an increasing absolute number of incidentally detected CAAs. Hence, awareness of the main issues and possible management strategies regarding CAAs is of importance for every treating physician

MR-based attenuation correction for cardiac FDG PET on a hybrid PET/MRI scanner: comparison with standard CT attenuation correction

PURPOSE: The aim of this study was to evaluate the feasibility of attenuation correction (AC) for cardiac (18)F-labelled fluorodeoxyglucose (FDG) positron emission tomography (PET) using MR-based attenuation maps. METHODS: We included 23 patients with no known cardiac history undergoing whole-body FDG PET/CT imaging for oncological indications on a PET/CT scanner using time-of-flight (TOF) and subsequent whole-body PET/MR imaging on an investigational hybrid PET/MRI scanner. Data sets from PET/MRI (with and without TOF) were reconstructed using MR AC and semi-quantitative segmental (20-segment model) myocardial tracer uptake (per cent of maximum) and compared to PET/CT which was reconstructed using CT AC and served as standard of reference. RESULTS: Excellent correlations were found for regional uptake values between PET/CT and PET/MRI with TOF (n = 460 segments in 23 patients; r = 0.913; p < 0.0001) with narrow Bland-Altman limits of agreement (-8.5 to +12.6 %). Correlation coefficients were slightly lower between PET/CT and PET/MRI without TOF (n = 460 segments in 23 patients; r = 0.851; p < 0.0001) with broader Bland-Altman limits of agreement (-12.5 to +15.0 %). PET/MRI with and without TOF showed minimal underestimation of tracer uptake (-2.08 and -1.29 %, respectively), compared to PET/CT. CONCLUSION: Relative myocardial FDG uptake obtained from MR-based attenuation corrected FDG PET is highly comparable to standard CT-based attenuation corrected FDG PET, suggesting interchangeability of both AC techniques

Early and late mortality in patients undergoing transcatheter aortic valve implantation: Comparison of the Novel EuroScore II with established risk scores

Objectives: In the evaluation of patients considered for transcatheter aortic valve implantation (TAVI), the EuroScore II might be superior to established risk scores. Methods: We assessed the performance of the EuroScore II in predicting mortality in a cohort of 350 TAVI patients. Results: The EuroScore II and the logistic EuroScore were higher in nonsurvivors compared to survivors at 30 days (12.6 ± 1.8 vs. 7.5 ± 0.3%, p 9%, 30-day mortality, 17.1%; p = 0.03). Regarding cumulative mortality, the AUC was 0.67 for the EuroScore II, 0.62 for the logistic EuroScore and 0.55 for the STS-PROM score for predicting mortality at total follow-up. Conclusions: In this patient cohort, the EuroScore II performed best in predicting short- and long-term mortality