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Background: Ultrasound examination is an important application in obstetrics. Fetal motor assessment can help to discriminate severe diseases, such as those underlying abnormal fetal joint position. However, standardized training is lacking. It was investigated whether virtual traditional teaching (TT) initiated by the coronavirus 2019 (COVID-19) pandemic gave equal outcome, compared to the prior blended teaching (BT) course on fetal motility. Methods: : In total 96 medical students were included, 51 underwent BT versus 45 TT. BT underwent live supervised interactive e-learning and TT plenary virtual lecture. Both groups made the same individual assignments. The first assignment evaluated course knowledge in four video fragments on single specific movement patterns (SMPs), the second assignment consisted of three fragments with various SMPs, students were asked to score differentiation and qualitative performance. Results: : BT and TT showed equally high correct answers on four individual SMPs. The second assignment revealed that BT and TT scored similarly in differentiation of SMPs. Two fetuses with normal motility were equally well scored in half of the items, BT scored speed and amplitude better, TT scored better in speed (other fetus) and overall conclusion. The one fetus with abnormal movements was scored by BT and TT similarly, 75% of both groups scored the fetus as moving suspect or abnormal. Conclusions: : Evaluation of medical students' motor assessment skills after BT and TT revealed a nearly equally high yield of the courses in distinguishing SMPs and similar judgement of aspects and overall qualitative performance.
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Aim/Introduction: Immune checkpoint inhibitors (ICI), like targeting programmed death receptor ligand 1 (PD-L1), have revolutionized anti-cancer treatments, including non-small cell lung cancer (NSCLC) [1, 2]. Assessment of PD-L1 expression on tumor biopsies is current practice, but there is a need for additional biomarkers correlating to the complex mechanism of action of ICI. The presence of tumorinfiltrating CD8+ T-cells (TILs) is a robust biomarker associated with immune therapy success [3]. Tools to track TILs in patients during ICI treatment allow further development of immune-oncology drugs. Material(s) and Method(s): This ongoing single-center prospective study (NCT03853187) includes patients with histologically proven T1b-3N0-1M0 NSCLC eligible for resection. Exclusion criteria are previous anti-cancer therapy and known immune disorders or suppression. Patients receive two courses neo-adjuvant durvalumab (750mg Q2W), after which TIL imaging is performed. Cohort 1 underwent apheresis and magnetic-activated cells sorting to isolate 100 x10e6 autologous CD8+ T-cells for cell labeling with 111In-oxine. Re-injection was followed by 4h post-injection (p.i.) planar imaging, 70h p.i. SPECT imaging, standard-of-care surgery and 78h p.i. uSPECT of the resected lobe. Patients in cohort 2 (ongoing) receive 1.5mg 89Zr-Df-crefmirlimab followed by PET/CT 24h p.i. Result(s): In cohort 1, 8/10 patients underwent apheresis and TIL imaging;one procedure was withdrawn due to COVID-19 restrictions and one due to unsuccessful T-cell isolation. Yield ranged 240-714 x10e6 CD8+ T-cells, purity 84%-97% and cell viability 92%-100%. Labeling efficacy of 100 x10e6 cells for re-injection ranged 42%-64% and injected activity 22,4-36,7 MBq In-111.TIL imaging was completed by 4/5 patients in cohort 2, one subject discontinued neo-adjuvant treatment due to post-obstruction pneumonia.Tumor-to-bloodpool were determined to quantify specific TIL accumulation in the tumor. Our results favor quantification of T-cells on PET over SPECT given its higher sensitivity and spatial resolution. Correlation of imaging findings with density of CD8+ T-cells in the resected tumor is currently ongoing. Conclusion(s): We implemented two methods for tracking CD8+ T-cells in earlystage NSCLC patients after neo-adjuvant durvalumab treatment. Although ex vivo cell labeling perhaps more specifically targets migrating TILs into the tumor, 89Zr-Df-crefmirlimab has the potential to also target residing cells. Quantitative correlation with presence of TILs in the resected tumor will help to determine the role of these imaging tools in the development of immune-oncology drugs.
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Background: Variation in fibrinogen caused by degradation or extension of the Aalpha chain affects the fibrin network structure and interaction of fibrin(ogen) with cells. The plasma level of these fibrinogen variants might be altered during COVID-19, potentially affecting disease severity or the risk of thrombosis. Aim(s): To investigate the level of fibrinogen Aalpha chain variants in plasma of COVID-19 patients. Method(s): Using the Clauss assay, we measured plasma levels of functional fibrinogen. ELISAs were used to measure antigen levels of total, intact (non-degraded Aalpha chain), and extended Aalpha chain fibrinogen (alphaE) in intensive care unit (ICU) patients with COVID-19 (with and without thrombosis, at two time points), COVID-19 ward patients without thrombosis, ICU patients with pneumococcal infection, and healthy controls. Ethical approval was obtained and written informed consent was obtained or an opt-out procedure was in place. Result(s): Higher levels of functional and intact fibrinogen were observed in COVID-19 ICU patients (before diagnosis of thrombosis) with (n = 18) and without thrombosis (n = 19) and ICU patients with pneumococcal infection (n = 6) than in COVID-19 ward patients (n = 10) and healthy controls (n = 7) (Figure 1). Total fibrinogen levels were higher in all ICU patients compared to healthy controls. Interestingly, the percentage of alphaE fibrinogen was significantly higher in COVID-19 ICU patients who do and do not develop thrombosis than in healthy controls. COVID-19 ICU patients who develop thrombosis also showed significantly higher percentages of alphaE fibrinogen than COVID-19 ward patients. After diagnosis of thrombosis, functional fibrinogen levels were significantly higher in COVID-19 ICU patients with thrombosis than in those without, while no differences were observed in intact, total, or alphaE fibrinogen (Figure 2). Conclusion(s): Our results show that severe COVID-19 is associated with increased percentages of alphaE fibrinogen, which may be the cause or consequence of severe disease, but does not explain the development of thrombosis. (Figure Presented).
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Background: SARS-CoV- 2 infection is associated with an increased incidence of thrombosis. Aim(s): By studying the fibrin network structure of COVID-19 patients, we aimed to unravel pathophysiological mechanisms that contribute to this increased risk of thrombosis. This may contribute to optimal prevention and treatment of COVID-19 related thrombosis. Method(s): In this case-control study, we collected plasma samples from intensive care unit (ICU) patients with COVID-19, with and without confirmed thrombosis, between April and December 2020. Additionally, we collected plasma from COVID-19 patients admitted to general wards without thrombosis, from ICU patients with pneumococcal infection, and from healthy controls. Fibrin fiber diameters and fibrin network density were quantified in plasma clots imaged with stimulated emission depletion (STED) microscopy and confocal microscopy. Finally, we determined the sensitivity to fibrinolysis. Ethical approval was obtained and written informed consent was obtained or an opt-out procedure was in place. Result(s): COVID-19 ICU patients (n = 37) and ICU patients with pneumococcal disease (n = 7) showed significantly higher fibrin network densities and longer plasma clot lysis times than healthy controls (n = 7) (Figure 1). No differences were observed between COVID-19 ICU patients with and without thrombosis, or ICU patients with pneumococcal infection. At a second time point, after thrombosis or at a similar time point in patients without thrombosis, we observed thicker fibers and longer lysis times in COVID-19 ICU patients with thrombosis (n = 19) than in COVID-19 ICU patients without thrombosis (n = 18). Conclusion(s): Our results suggest that severe COVID-19 is associated with a changed fibrin network structure and decreased susceptibility to fibrinolysis. Since these changes were not exclusive to COVID-19 patients, they may not explain the increased thrombosis risk. (Figure Presented).
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Introduction: SARS-CoV-2 is responsible for a global pandemic, with almost 200 million confirmed cases. SARS-CoV-2 infection can lead to various disease states, from only mild symptoms in the majority of cases to severe disease, which is associated with an increased incidence of venous thromboembolism (VTE). We hypothesized that an altered fibrin network structure contributes to VTE in COVID-19 patients by affecting thrombus stability and fibrinolysis sensitivity. By studying the fibrin network of COVID-19 patients, we aimed to unravel the mechanisms that contribute to the increased risk of VTE in COVID-19 patients. Methods: Between April 2020 and December 2020, we collected plasma samples from patients with COVID-19 admitted to the intensive care unit (ICU) of the Erasmus Medical Center. We included patients with confirmed VTE diagnosed on CT-angiography, and COVID-19 patients without confirmed VTE during ICU admission. Samples were collected on admission to the ICU and after confirmed VTE or at similar time points in ICU patients without confirmed VTE. In addition, we collected plasma from COVID-19 patients at admission to general wards without confirmed VTE and from healthy controls. Clots were formed by mixing citrated plasma with thrombin (final concentration 1 U/ml) and calcium (17 mM). We imaged the clots using stimulated emission depletion (STED) microscopy, a super-resolution technique in which a depletion laser is used to selectively switch off fluorophores surrounding the focal point, thereby increasing the resolution. In these images, fibrin fiber diameters were measured using the Local Thickness plugin of ImageJ. Fiber density was quantified as percentage of area in Z-stacks of confocal microscopy images. Finally, a clot lysis assay based on turbidity was used to determine sensitivity to fibrinolysis (clot lysis time) and clot density (difference between maximum and baseline absorbance). Differences in fibrin network properties between groups were tested using One-Way ANOVA with Bonferroni post-hoc tests and linear regression with and without adjustment for fibrinogen levels. Results: We included 21 COVID-19 ICU patients with confirmed VTE, 20 COVID-19 ICU patients without confirmed VTE, 10 COVID-19 ward patients and 7 healthy controls. Mean age was comparable between the groups, while BMI was higher in COVID-19 patients than in healthy controls (Table 1). Levels of fibrinogen, D-dimer and anti-Xa were significantly higher in COVID-19 ICU patients than in COVID-19 ward patients and healthy controls. FVIII levels were significantly higher in COVID-19 ICU patients than in healthy controls, while FXIII levels were significantly lower. On admission to the ICU, clot density was significantly higher in COVID-19 ICU patients with and without confirmed VTE than in healthy controls (Figure 1 and Table 2). However, after adjustment for fibrinogen levels, this difference disappears. Clot lysis time was significantly longer in clots from COVID-19 ICU patients than in clots from healthy controls, regardless of fibrinogen levels (Table 2). COVID-19 ICU patients with confirmed VTE also showed a significant longer clot lysis time than COVID-19 ward patients. Interestingly, in the clot lysis assay, fibrinolysis did not occur in 25% of COVID-19 ICU patients with VTE versus 9.5% of COVID-19 ICU patients without VTE (Figure 2). This fibrinolysis shutdown was never observed in clots from healthy controls and COVID-19 ward patients. Fibrin fiber diameters were comparable between the groups. In the clots from plasma samples collected at admission to the ICU, there were no differences between COVID-19 ICU patients with and without VTE (Figure 2). However, when comparing clots prepared from plasma collected at the second time point (after VTE or at a similar time point for patients without VTE), we observed significant longer clot lysis times in patients with confirmed VTE (97.4 [88.5-158.8] min) than in patients without confirmed VTE (80.0 [76.0-97.8] min) (p=0.03). Finally, there were no significant changes between clots fro plasma before and after VTE or between the two time points in patients without VTE, except for a decreased clot lysis time over time for COVID-19 ICU patients without confirmed VTE. Conclusion: Our results suggest that SARS-CoV-2 infection increases clot density and decreases clot susceptibility to fibrinolysis, and that these changes relate to the severity of the disease. [Formula presented] Disclosures: Kruip: Daiichi Sankyo: Research Funding;Bayer: Honoraria, Research Funding.
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The effects of COVID-19 are unevenly distributed geographically, with regional areas likely to face different issues and therefore have different recovery needs in the wake of the pandemic. This research uses Tasmania as a case study to examine how COVID-19 has affected regional housing markets and communities. © 2021 Australian Housing and Urban Research Institute. All rights reserved.
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BACKGROUND: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients.In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped. METHODS: We evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status. FINDINGS: Eighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients. INTERPRETATION: Overall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role.
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Background: 'Paranoid attention to inspiratory effort - checking it and correcting it - is something where we can make the difference between death and life' (Gattinoni L., 2020). Current methods to track inspiratory effort (IE) in Covid-19 patients are not applicable for non-bedbound subjects. Aims: Monitoring and quantifying IE with and without CPAP. Methods: We used a wireless bioimpedance device (Onera Health, Eindhoven, NL) that monitors IE and airflow (Figure 1) through a chest patch. We conducted overnight studies in two individuals with and without CPAP of 10 cmH2O. To compare the effect of CPAP on IE, we calculated inspiratory duty cycle (IDC), a known marker for increased inspiratory drive and effort. Results: 8562 breaths for subject 1 and 5768 breaths for subject 2 were analyzed. Both individuals had elevated IDC at baseline (0.45±0.08 and 0.46±0.08). In subject 1, CPAP reduced (p<0.001) mean IDC to 0.41±0.06 and proportion of breaths with severe IE, as defined by IDC>0.5, from 25% to 7%. CPAP did not lower respiratory loads in subject 2 (IDC 0.46 ± 0.06, % IDC>0.5: 25% to 21%). Conclusions: A wearable and wireless bioimpedance monitor can detect patients with increased IE, and can quantify the relief of increased effort with CPAP. It would therefore ease the triaging of patients who are at higher risks for respiratory failure by early detection of increased IE and response to CPAP.
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Research is imperative in addressing the COVID-19 epidemic, both in the short and long term. Informed consent is a key pillar of research and should be central to the conduct of COVID-19 research. Yet a range of factors, including physical distancing requirements, risk of exposure and infection to research staff, and multiple pressures on the healthcare environment, have added layers of challenges to the consent process in COVID-19 patients. Internationally, the recognition that consent for COVID-19 research may be imperfect has led to a range of suggestions to ensure that research remains ethical. Drawing on these guidelines, we propose a consent process for COVID-19 research in the South African context that combines individual consent with delayed and proxy consent for individuals who may be temporarily incapacitated, combined with key principles that should be considered in the design of a consent process for COVID-19 research.