bluuebunny/crossref_metadata_2025 huggingface dataset:
Risks of trastuzumab-related cardiotoxicity in breast cancer patients in Taiwan
Authors: Chang W T C , Chen P W C , Lin H W L , Lin H S L , Li Y H L
Published: October 2021

Aims

Despite being an essential therapy for breast cancer, trastuzumab has potential risks of cardiotoxicity. The incidence of trastuzumab-related major adverse cardiac and cerebrovascular event (MACCE) and its predictors remain unknown in Taiwan.

Methods and results

Through a three-hospital retrospective cohort study, we analyzed the incidence of MACCE in 386 breast cancer patients exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab nonusers, the incidence of MACCE was measured with a median follow-up of 36 months. In the hospital-based study, among 386 patients receiving trastuzumab, the 5-year incidences of MACCE and heart failure (HF) were 5.4% and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67% and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246–1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than nonusers.

Conclusions

From clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use.

Funding Acknowledgement

Type of funding sources: Private hospital(s). Main funding source(s): Chi-Mei Medical Center, National Cheng Kung University Hospital
Direct oral anti-coagulants in patients with atrial fibrillation and bioprosthetic valve: a meta-analysis of randomized controlled trials
Authors: Abella F , Castro R , Tiongco R H , Rosano A L , Bailon D
Published: October 2021

Background

Patients with atrial fibrillation (AF) and bioprosthetic valve (BPV) are at increased risk for thromboembolic events and require anticoagulation. However, management strategies for these patients have not yet been well addressed by randomized controlled trials (RCTs). For years, warfarin was the only available oral anticoagulant, but this changed with the introduction of the direct oral anticoagulants (DOACs). However, there is no clear consensus about indications for DOACs in these patients due to the lack of prospective trials.

Purpose

The objective of this meta-analysis is to show the efficacy of DOACs in AF patients with BPV in terms of composite cardiovascular outcomes. In addition, the study aims to show the safety of DOACs in terms of major bleeding.

Methods

A comprehensive literature search for randomized controlled trials (RCTs) was performed in MEDLINE, PubMed and Clinicaltrials.gov in human subjects done within 2010 to 2020. Results were pooled using fixed effects. The primary outcome was a composite cardiovascular outcome from all included studies, which include death, major bleeding and major adverse cardiac events (stroke, transient ischemic attack, valve thrombosis, myocardial infarction, systemic embolism, and hospitalization for heart failure). Secondary outcomes include all-cause stroke or systemic embolism, major bleeding, death from cardiovascular cause and all-cause death.

Results

Four RCTs were included in the meta-analysis. DOACs used were Apixaban, Dabigatran, Edoxaban and Rivaroxaban. In patients with AF and BPV, DOACs performed similarly with warfarin in terms of composite cardiovascular outcome (RR 1.01, 95% CI 0.86–1.19, P=0.88, I2=0%). On the other hand, DOACs performed better than warfarin in reduction of all cause stroke and systemic embolism (RR 0.48, 95% CI 0.27–0.87, P=0.01). There is non-statistically significant risk reduction for major bleeding (RR 0.81, 95% CI 0.56–1.17, P=0.26, I2=0%) and other secondary outcomes such as death from cardiovascular causes (RR 0.79, 95% CI 0.39–1.60, P=0.51, I2=0%) and all cause death (RR 0.94, 95% CI 0.55–1.62, P=0.71, I2=0%) showing similar outcomes with NOACs and warfarin.

Conclusion

DOACs compared with warfarin are similar in terms of composite cardiovascular outcome, major bleeding and death. However, DOACs performed better than warfarin in reducing all-cause stroke/systemic embolism and can be an alternative for oral anticoagulation in patients with AF and BPV.

Funding Acknowledgement

Type of funding sources: None. Forest plot for all-cause stroke or systemic embolism
The greek version of the professional quality of life (ProQoL) scale version 5
Authors: Lakatamitou I , Middleton N , Paikousis L , Kouta C , Lambrinou E
Published: October 2021

Background

The Professional Quality of Life (ProQoL) scale is one of the most widely measures of compassion satisfaction and fatigue used, despite there is not much of published evidence to support its validity. The ProQoL scale assesses multiple domains of work experiences; compassion satisfaction, burnout and secondary traumatic stress. Our aim was to examine the psychometric properties of the Greek version of the ProQoL scale version 5 (Gr-ProQoL-5).

Method

A methodological study was contacted in order to assess the construct validity and reliability of the Gr-ProQoL-5. For that reason, 264 questionnaires were administrated by Greek-Cypriot healthcare professionals (HPs). Confirmatory factor analysis (CFA) and Exploratory factor analysis (EFA) were conducted to examine the relationship between the three Gr-ProQoL-5 dimensions (compassion satisfaction, burnout and secondary traumatic stress). Cronbach's a was calculated as well.

Results

CFA for Gr-ProQOL-5, did not confirm the initial scale's dimensions. In EFA five models were emerged. The models were then tested with CFA and after a panel discussion, the research team decided to keep one final model for the Gr-ProQoL-5. Items 1, 2, 4, 10, 15, 17 and 29 were eliminated from the analysis due to low communalities and multiple components loading. Three components were found representing compassion satisfaction, burnout and secondary traumatic stress.

Conclusions

The Gr-ProQoL-5 is an adequate instrument to assess ProQoL in Greek-Cypriot HPs and may be valuable for designing effective interventions to reduce burnout and compassion fatigue, and promote compassion satisfaction of HPs. More than ever and in the era of the pandemic the ProQoL seems to be a necessary quality indicator for health care systems.

Funding Acknowledgement

Type of funding sources: None.
Validity and reliability of a clinical non-exercise method for assessment of cardiorespiratory fitness using seismocardiography
Authors: Thunestvedt Hansen M , Roemer T , Hoejgaard A , Husted K , Soerensen K , Schmidt S , Dela F , Wulff Helge J
Published: October 2021

Introduction

Low cardiorespiratory fitness expressed as a low maximal oxygen consumption (V̇O2max) is associated with cardiovascular disease and all-cause mortality (1). Thus, V̇O2max is recognised as an important clinical tool in the assessment of patients (1,2). However, assessment of V̇O2max by exercise testing is both physically demanding and methodologically challenging and hence the clinical applicability is limited.

Purpose

Therefore, the aim of this study was to investigate the accuracy and precision of a clinical non-exercise method for assessment of V̇O2max.

Methods

On three separate days 20 healthy men (n=10) and women (n=10) with varying age (22–72 years) and fitness levels performed two tests for determination of V̇O2max; (a) a non-exercise test using seismocardiography (SCG V̇O2max) and (b) a graded exercise test to voluntary exhaustion on a cycle ergometer based on indirect calorimetry (IC V̇O2max). These tests were performed in order to examine the day-to-day reliability and the validity of SCG V̇O2max, respectively. Furthermore, SCG V̇O2max was assessed twice on each test day to investigate test-retest reliability. The SCG V̇O2max was performed in prone position following a short resting period by placing the SCG recording device on the xiphisternal joint with double adhesive tape. V̇O2max was assessed during a 5-minute recording of the sternal movement using SCG in combination with demographic data of the participants (3).

In addition, body composition was measured and a resting blood sample collected each test day.

Results

On average SCG V̇O2max was 3.3±2.4 ml/min/kg (mean ± 95% CI) lower than IC V̇O2max (p=0.013, SCG V̇O2max: 36.6±3.3 ml/min/kg, IC V̇O2max: 39.9±3.0 ml/min/kg). A significant positive correlation was found between SCG V̇O2max and IC V̇O2max (Pearson, r=0.72, p<0.001). Both SCG V̇O2max and IC V̇O2max was similar between test days (p=0.972) and the intra-individual coefficient of variation was 4.5±2.9% and 4.0±2.5%, respectively.

Within each test day SCG V̇O2max was highly correlated (r=0.99, p<0.0001) and no difference was observed between tests (p=0.993).

Conclusions

The accuracy of the current non-exercise assessment of cardiorespiratory fitness based on seismocardiography is not optimal as SCG V̇O2max was systematically lower than the gold standard assessment applying indirect calorimetry during a graded exercise test. Despite the abovementioned difference, SCG V̇O2max and IC V̇O2max were highly correlated. Furthermore, the precision of SCG V̇O2max is very high as both day-to-day and test-retest reliability were high.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): VentriJect ApS, Copenhagen, Denmark
Autophagy-related gene 5 (Atg5) is required for maintaining subcellular calcium homeostasis during acute cardiac stress
Authors: Djalinac N , Voglhuber J , Ljubojevic-Holzer S , Sedej S
Published: October 2021

Background

Autophagy exerts protective effects during cardiac stress inflicted by β-adrenergic stimulation and pressure overload. Contrarily, deletion of the cardiac-specific Atg5 gene contributes to left ventricular hypertrophy and contractile dysfunction, resulting in dilated cardiomyopathy. Heart failure is characterized by perturbations of excitation-contraction coupling (ECC) underlying alterations in intracellular calcium signaling.

Purpose

In this study, we aimed to understand whether loss of basal autophagy due to Atg5 deletion specifically in cardiomyocytes contributes directly to disturbances in subcellular calcium cycling.

Methods

Cardiac-specific Atg5−/− and Atg5+/+ mice were used to isolate ventricular cardiomyocytes, which were loaded with 8 μM Ca2+ indicator Fluo4/AM. Isolated cells were electrically stimulated and subjected to elevated workload by increasing pacing frequencies from 1 to 4 Hz. Cytosolic and nuclear calcium transients (CaTs) were recorded in line-scan mode using a laser scanning confocal microscope. Pharmacological inhibition of autophagic flux was performed by an intraperitoneal injection of 40 mg/kg leupeptin to Atg5+/+ mice.

Results

At baseline (1 Hz) stimulation the amplitude and kinetics of calcium transients were comparable between Atg5−/− and Atg5+/+ cells. However, after progressive increase of the pacing rate from 1 Hz to 4 Hz, Atg5−/− cardiomyocytes displayed reduced cytoplasmic and nuclear CaT amplitude, but increased nuclear time-averaged CaTs compared to controls. Such increase in nuclear calcium load stimulates Ca2+-dependent transcriptional activity, and likely involves CaMKII-mediated pro-hypertrophic gene program thus contributing to cardiac remodelling. In addition, we observed increased occurrence of arrhythmic events in Atg5−/− hearts at high pacing frequency, indicative of intracellular calcium overload and disturbed ECC. Acute pharmacological autophagy inhibition failed to elicit direct changes in time-averaged CaTs in the cytoplasm and nucleoplasm, suggesting that loss of Atg5-dependent autophagy seems to induce adverse cardiac remodelling that involves increased CaMKII activity due to the imbalances in nuclear Ca2+ levels.

Conclusion

Specific loss of ATG5 protein impairs calcium cycling during acute stress exposure by reducing CaT amplitudes, promoting arrhythmia, and increasing nuclear calcium load, which may induce hypertrophic gene expression. Further work is needed to identify key components mediating autophagy-related cardioprotection to develop strategies against cardiac remodeling and its progression to heart failure.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund (FWF)
Genesis of epicardial adipocytes and its association with progenitor markers, muscarinic receptor type 3 and b-blockers intake in patients with cardiovascular disease
Authors: Fu X , Almenglo C , Couselo-Seijas M , Fernandez A L , Martinez-Cereijo J M , Duran D , Gonzalez-Juanatey J R , Rodriguez-Manero M , Eiras S
Published: October 2021

Introduction

Epicardial fat thickness or volume was found to be associated with cardiovascular disease (CVD). Our aim was to study the epicardial adipocyte-progenitors' markers and its association with cholinergic or adrenergic activity in patients with cardiovascular disease.

Materials and methods

We have included epicardial adipose tissue (EAT) biopsies from 29 patients underwent open-heart surgery. From 10 patients (69±5 years old, 31±8 kg/ m2, 40% CAD, 40% HF, 60% AF, 0% T2DM) stromal cells from epicardial and subcutaneous fat were isolated after collagenase activity and cultured for 14 days and then submitted to adipogenesis for next 14 days. Samples from 19 patients (60±9 years old, 29±4 kg/m2, 42% CAD, 37% HF, 32% AF, 32% T2DM, 53% β-blockers) were used for “ex vivo assays”. Explants were split into equal pieces (100 mg), treated with or without acetylcholine (ACh) for 30 min. Afterwards RNA was isolated and cDNA was amplified by real time PCR. We selected adipocytes progenitors (CD36, PREF1, COL1A1), adipocytes markers (ADIPO, FABP4), muscarinic (muscarinic receptor type 2 (CHRM2) and 3 (CHRM2)) and β-adrenergic receptors (ABRD1, ABRD2 and ABRD3). Gene expression was represented regarding ACTB as 2HK/GEN.

Results

The stromal vascular cells (SVC) from subcutaneous fat (SAT) had higher expression levels of CD36, PREF1 and COL1A1 than SVC from epicardial fat (EAT). It explains the higher adipocytes markers after adipogenesis induction in SAT than EAT cells. However, an upregulation of fibroblasts markers was detected on EAT. The levels of CD36 and PREF1 in SVC were associated with higher adipogenesis. Although CHRM2 was higher in EAT than SAT SVC, the adipogenesis induction upregulated only CHRM3 (1.48±0.065 vs 1.42±0.036 a.u.) in EAT cells. Thus, this receptor was associated with adipocytes markers in epicardial fat (r=0.777 for CD36 and r=0.746 for FABP4) and incremented in epicardial fat biopsies from patients who were taken β-blockers (1.61±0.011 n=10 vs 1.54±0.097 a.u. n=9; p=0.05) and modulated by ACh treatment (p=0.05).

Conclusions

Our results showed that CD36 and PREF1 in epicardial SVC are adipocytes progenitors. The higher presence of adipocytes markers is associated with higher levels of muscarinic receptor (CHRM3), which are upregulated in epicardial fat from patients who were taken β-blockers and modulated by cholinergic activity. Because a metabolic and lipolytic dysfunction was associated with CHRM3, the sympathetic modulation might play a role in the epicardial adipocytes genesis. Further studies are needed to understand if this mechanism might improve or not future cardiovascular events.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ISCIII (PFIS2020)
Human pericardial fluid exosomes regulate macrophage immunophenotype: new prospective for cardiovascular myocardium-epicardium crosstalk in coronary artery disease
Authors: Ben-Aicha S , Anwar M , Behmoaras J , Punjabi P , Emanueli C
Published: October 2021

Background

The incidence and severity of ischemic heart disease (IHD) is exacerbated by coronary artery disease (CAD). Monocytes and macrophages are central to atherosclerosis. Endogenous small extracellular vesicles (sEVs) can shuttle microRNAs and other molecular cargos from cell to cell, mediating expressional and functional response in the recipient cells. Recent evidence supports a role for sEVs in modulating macrophage phenotype. The pericardial fluid (PF) is in direct contact with the epicardium and contain sEVs of myocardial origin (C. Beltrami et.al 2017). We recently showed that human PF-sEVs are capable to modulate cardiovascular cells via microRNA shuttling (C.Beltrami et.al. 2017). Moreover, epicardial cells reportedly cross-talk with the myocardium to regulate immune response to IHD (V.Ramjee et.al 2017).

Purpose

This study sought to investigate whether PF-sEVs regulate macrophages, contributing to a specific immunophenotypes in CAD patients.

Methods

PF was collected from either CAD patients undergoing coronary bypass surgery (CABG) or non-atherosclerotic patients operated for mitral valve repair (non-CAD control group). sEVs were isolated using size exclusion chromatography and characterised for size (Nanosight tracking analysis; NTA) and microRNA content (Exiqon miR-array). Monocytes from healthy donors were isolated from buffy coats and differentiated into macrophages following established protocols. Macrophages were incubated with either CAD-sEVs or non-CAD sEVs for 24h at 37oC. PBS and sEV-free serum were used as negative controls and LPS as a proinflammatory control. The cells were collected and processed for mRNA analyses (qRT-PCR) and Flow cytometry (FACS).

Results

Twenty-four-hour exposure to CAD-sEVs induces a proinflammatory profile of human macrophages. While non-CAD-sEVs did not statistically differ from PBS nor Exo-free groups, CAD-sEVs increased the mRNA level of IL1a, NOS3, TNFa, CCL2 and IL6 (comparison to both non-CAD and negative controls). These data were not associated with changes in apoptosis. Bioinformatics analysis showed that 11 miRNAs where consistently increased, and 67 miRNAs decreased in the PF-sEVs from all CAD patients compared to non-CAD. miRNA targets prediction and pathway analyses (R-Project) revealed that the deregulated miRNAs could regulate macrophage motility and cytokine signalling.

Conclusions

We demonstrate, for the first time, that sEVs isolated from the PF of CAD patients induce a proinflammatory profile of human macrophages. These clinically relevant results could drive to decipher improved therapeutics able to modulate the epicardial/myocardial immune response in CAD patients.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Biritish Heart Fundation grant to Prof. Costanza Emanueli
Direct 3D printing of hiPSC-cardiomyocytes in collagen-based bioinks
Authors: Esser T U , Engel F B
Published: October 2021

Background

Cardiac tissue engineering is an effective strategy to generate tissues for drug testing and disease modelling as well as for cardiac repair. Tissues produced by casting show good functionality and advanced maturation, but do not replicate the native tissue architecture and hierarchy. Additive manufacturing technologies, such as 3D bioprinting, enable the generation of hierarchically structured tissues with complex geometries. This technology has been used previously to generate models of the heart. However, these approaches either showed limited tissue functionality or required a two-step procedure using a structural and a cell-laden bioink.

Purpose

Here, we aimed to develop a collagen-based bioink, which enables direct 3D-bioprinting of hiPSC-derived cardiomyocytes and supports the formation of functional cardiac tissue.

Methods

To generate cardiac tissues, a commercial pneumatic extrusion bioprinter with custom modifications to enable passive cooling of the bioink was used. Gelatin/gum arabic microparticles were obtained through complex coacervation, compacted by centrifugation and utilized as support bath. Cardiomyocytes were differentiated in 2D monolayer and expanded by CHIR99021-treatment and regular passaging. Cells were encapsulated in a rat collagen-I based bioink and printed into support bath prior to gelation. After bioink gelation at 37°C, support bath was removed, and constructs cultivated free-floating for up to 30 days.

Results

We printed ring-shaped cardiac tissues measuring 5 x 5 x 1 mm, which remained stable over the course of cultivation. First contractions were observed after three days, which increased in magnitude and synchronized across the tissue with prolonged culture. HiPSC-cardiomyocytes displayed striated sarcomeres and were responsive to pharmacological stimulation. In addition, using two distinct bioinks, multi-layered constructs were generated.

Conclusion

3D-bioprinting is a promising tool to generate engineered cardiac tissues with complex geometries and improved functionality through designed hierarchy. Our collagen-based bioink and associated printing strategy enables the fabrication of Collagen-based contractile cardiac tissues in a direct manner.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG) Contractions of printed cardiac tissue
MicroRNA let-7a, -7e and -133a attenuate hypoxia-induced atrial fibrosis via targeting collagen expression and the JNK pathway in HL1 cardiomyocytes
Authors: Lo C H , Yang S F , Li L C , Ueng K C
Published: October 2021

Background

Atrial fibrillation (AF) is becoming an enormous public health challenge, and it is associated with major cardiovascular morbidity and mortality. There is a need for a better understanding of the causes and consequences of the hypoxia-related development of AF and atrial remodeling. Fibrosis is a hallmark of atrial structural remodeling. Micro-ribonucleic acids (miRNAs) have been reported to have an impact on the pathogenesis of cardiac diseases. Evidence that specific miRNAs can influence AF related to atrial structural remodeling and fibrosis via the modulation of collagens under myocardial hypoxic conditions is lacking. The aim of this study was to investigate the role of miRNAs in the modulation of fibrotic molecular mechanisms in response to hypoxic conditions, which may mediate atrial fibrosis.

Methods

Hypoxia was induced by cobalt chloride and hypoxia chamber respectively. MiRNA arrays were used to identify the specific miRNAs associated with the modulation of fibrotic genes. Luciferase assay, real-time polymerase chain reaction, immunofluorescence and Western blotting were used to investigate the effects of miRNAs on the expressions of the fibrotic markers collagen I and III (COL1A, COL3A) and phosphorylation levels of the stress kinase c-Jun N-terminal kinase (JNK) pathway in cultured HL-1 atrial cardiomyocytes cell line.

Results

COL1A and COL3A were found to be the direct regulatory targets of miR-let-7a, miR-let-7e and miR-133a in hypoxic atrial cardiac cells in vitro. The expressions of COL1A and COL3A were influenced by treatment with miRNA mimic and antagomir. The delivery of miR-133a, miR-let-7a or miR-let-7e inhibited hypoxia-induced collagen expression. The JNK pathway was critical in the pathogenesis of atrial fibrosis. Inhibition of JNK phosphorylation (JNK inhibitor SP600125) could be able to increase expression of miRNAs and repressed the fibrotic markers COL1A and COL3A which in turn might reduce the arrhythmogenic atrial remodeling. This study highlights the important role of miRNA in hypoxia-related atrial remodeling as well as atrial fibrosis.

Conclusion

MiRNA let-7a, miR-let-7e and miR-133a play important roles in hypoxia-related atrial fibrosis by inhibiting collagen expression and post-transcriptional repression by the JNK pathway. These novel findings may lead to the development of new therapeutic strategies.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the grants from the Ministry of Science and Technology (MOST), Taiwan, ROC Regulation of cardiac fibrosisRegulation of collagen types by miRNAs
Two types of humoral response in acute myocardial infraction
Authors: Konstantinova E , Bogdanova A , Gilyarov M , Sergeev A , Svet A , Konovalova M , Sapozhnikov A , Svirshchevskaya E
Published: October 2021

Background

Atherothrombosis and myocardial infarction are accompanied by the development of an inflammatory reaction. The severity of the immune reaction and its role in the acute myocardial infarction (AMI) remain contradictory to date.

Purpose

The objective of this study was to analyze 39 cytokines and chemokines in the serum of patients hospitalized with AMI compared to the healthy volunteers.

Methods

All patients included in the study were COVID-19 negative. Patients' blood was collected within 1–2 days after hospitalization in the cardiology department. Cytokine and chemokine detection in the serum of patients (n=20) and donors (n=20) was performed using a 39-plex set of cytometric beads.

Results

Among all factors analyzed TGFa, IL-17A, IL-1b, 3, 5, 9 were not detected both in patient and donor sera. Three groups of factors were identified in the normal serum: housekeeping chemokines and vascular factors (F1) ranged from 1000 to 22000 pg/mL (Fig. a); sentinel innate immunity factors F2 (Fig. b), 30–200 pg/mL; and acute phase factors F3 (Fig. c, d), 0–30 pg/mL, detected only in 0–30% of donors but in all AMI patients. Severe imbalance was found in AMI sera at all three levels including chemokine, growth factors, and cytokines. Among AMI patients 65% (Gr1) demonstrated 2–4 times increased level (Fig. a, grey brackets) while 35% (Gr2) had a decreased level of F1 factors in a comparison with donor sera. There was not significant difference between clinical features of the patients in Gr1 and Gr2. GRO, PDGF-AA, and sCD40L levels decreased 35, 15, and 10 times accordingly. Gr1 and Gr2 also differed in F2 and some F3 concentrations: Gr1 had 3–5 times increased level of multiple factors (Fig, b), among them – IL-6, IL-8, and IL-10 were increased 5, 6, and 14 times. At the same time Gr2 had a normal level of these factors (Fig, b, blue brackets). Finally, multiple cytokines and growth factors F3 were significantly increased in both AMI groups (Fig, b, d, red brackets). Of note, IL-12, IFN-g, IL-15, GM-CSF, FLT-3T were increased 8, 6, 5, 5, 5 times accordingly in pooled Gr1+Gr2. There were no correlations found between cytokine profiles in Gr1 and Gr2 and their clinical parameters.

Conclusions

Two types of humoral response in AMI patients were identified which differed in the levels of GRO, PDGF-AA, and sCD40L. IL-6 as well as TNF-a can not serve as master cytokines because their levels were increased only in Gr1 patients. These data show that Th1 cytokine increase is specific for AMI. Further studies are needed to identify groups of patients who may be exposed to new therapeutic targets.

Funding Acknowledgement

Type of funding sources: None.
Asylum seekers’ and refugees’ understanding of government restrictions during the COVID-19 pandemic
Authors: Morisod K , Durand M , Selby K , Le Pogam M , Grazioli V , Sanchis Zozaya J , Bodenmann P , Van Plessen C
Published: October 2021

Background

Asylum seekers and refugees risk poorer public health information and difficulties to follow measures during the COVID-19 pandemic because of language, cultural, administrative barriers and social insecurity. We investigate their attitudes and knowledge about COVID-19 measures.

Methods

A cross-sectional survey conducted between August and October 2020 in the canton of Vaud, Switzerland. The 24 questions covered health literacy, perception of the pandemic, understanding of health measures and adherence to conspiracy theories. The questionnaire was translated into the ten most common languages. It was distributed online through social networks of charitable and public organisations and in paper in asylum centres. Associations between participants responses and their characteristics were studied using multivariable logistic regressions.

Results

The 242 respondents had a mean age of 33 years, 63% were men and 42% had low health literacy. They were 16% asylum seekers, 45% temporarily admitted persons, 12% refugees and 26% rejected asylum seekers. All languages were used.

Self-reported adherence to recommendations was 82%. Respectively, 39% and 31% of participants reported sleep disorders or fear of dying. Adjusted for age, gender, health literacy and French language skills, rejected asylum seekers were less worried about the pandemic (aOR 0.37, p = 0.007) and more sensitive to conspiracy theories (aOR 3.47, p = 0.006) than other respondents. They also reported lower adherence to recommendations (aOR 0.45, p = 0.034).

Conclusions

We contribute new knowledge about a varied group of vulnerable persons under precarious conditions during the COVID-19 pandemic. The network based multi-language survey combining online and center based distribution was useful but also tedious. Our results highlight the low health literacy of asylum seekers and refugees and their deep concerns about the pandemic. Public health messages should be adapted to rejected asylum seekers.

Key messages

Asylum seekers and refugees have deep concerns about the Covid-19 pandemic (including sleep disorders and fear of dying) but a low health literacy. Public health messages should be adapted to socially vulnerable groups, especially rejected asylum seekers.
COVID-19 vaccination readiness: use of digital technologies for data-driven decision making
Authors: Syundyukov E , Mednis M , Zaharenko L , Pildegovica E , Danovska I , Kistkins S , Seidmann A , Bennis A , Pirags V , Tzivian L
Published: October 2021

Background

Digital technology can help scientists and governments to inform large auditoriums about COVID-19 and vaccination. Existing technological solutions for assessment of risk of COVID-19 are foreseen for individual use but not for use in scientific research. We aimed to develop a digital platform for communication between scientists and the general population and to use this digital platform for a pilot study on factors associated with the vaccination readiness.

Methods

We developed a digital platform, ensuring researchers an ability to create and manage study projects and to stratify participant cohorts in real-time. Platform provides an interface for participants to be engaged in the studies and receive personalized reports. We assessed demographic (9 items), COVID-19-related behavioral factors that increase a risk of infection (15 items) and a risk of severe disease (10 items), and a readiness for vaccination (10 items). Multiple logistic regression models adjusted for personal covariates, factors affecting the motivation to vaccinate, and risk of infection/severe disease were built to investigate their association with a vaccination readiness.

Results

The newly developed digital platform was equipped with a dynamic consent management, allowing participants to opt-out or/and receive invitations for follow-up studies. Data collection was performed between 2021.02.01 and 2021.03.10, and 467 participants were enrolled during this period. In fully adjusted multiple logistic regression models, factors associated with the vaccination readiness were anxiety (odds ratio, OR = 3.09 [95% confidence interval 1.88; 5.09]), trust in pharmaceutical companies (OR = 1.53 [1.03; 2.27]), and social responsibility (OR = 1.61 [1.16; 2.22]).

Conclusions

The major factor that affects the vaccination readiness was anxiety. Lack of association with the risk of infection/severe disease indicates that people do not understand how the vaccine can help them to avoid the infection.

Key messages

Assessment of a large number of participants in a short time confirms the fact that people are motivated to collaborate using digital platforms. Applying a digital platform can help to create a data-driven dialogue on vaccination readiness, opening an evidence-based scientific discussion between state authorities and the population.
Meals adequacy during weekdays and weekends in an Italian primary school children sample
Authors: Soldà G , Salussolia A , Zanutto G , Sanmarchi F , Marini S , Dallolio L , Ferretti F , Arrichiello F , Lorenzini A , Masini A
Published: October 2021

Background

Between 15 and 50% of European children aged 6-9 are overweight or obese and this number is rising dramatically over time, making it one of the most important public health challenges. Selection of healthy food and a balanced diet are key when addressing this obesity epidemic. At the same time, it is essential to consider schools' role and parents' influence on children's dietary habits. This study aims to assess the adequacy of meals during the weekdays (WD) and weekends (WE), therefore highlighting the critical moments where schools' and parents' involvement needs to be of greater impact.

Methods

A cross-sectional study was conducted among 428 children aged 6-11 recruited in a primary school of Calderara di Reno (Italy) in 2017. A weekly diary was administered between May and June 2017 to explore the dietary habits of the participants. Every day for each meal (breakfast, morning snack, lunch, dinner) it was required to report what types of food and beverages were consumed, and where (home/school). The adequacy of each meal was determined by using national guidelines. A McNemar test was performed to evaluate the differences in meal adequacy between the WD and WE.

Results

Our analysis showed that meals consumed at school, i.e. morning snacks and lunches, were more adequate during WD than WE (69.6% vs 22.2%, 53.5% vs 32.5%; P-value <0.001), underlying the positive influence of school. On the other hand, breakfasts and dinners were more adequate during WE than WD (64.5% vs 51.4%, 23.8% vs 15.7%; P-value <0.001); this difference might be partially explained by the different amount of time parents have for food preparation during workdays versus weekends.

Conclusions

Further preventive interventions should address childrens' and parents' home dietary routine as a tool to improve meal adequacy at home and therefore reduce childhood obesity. Parental school-based interventions could have a key role in changing childrens' dietary habits.

Key messages

Our study showed a significant difference of healthy dietary habits between meals served at school during weekdays and at home during weekends, highlighting a higher dietary adequacy in the first ones. The results underline the importance of implementing educational programs addressing childrens’ and their parents' home meals routine and dietary habits.
No evidence for an effect of the first COVID-19 lockdown on work stress conditions in office workers
Authors: Aegerter AM , Deforth M , Johnston V , Sjøgaard G , Luomajoki H , Volken T , Distler O , Dressel H , Melloh M , Elfering A
Published: October 2021

Background

The COVID-19 pandemic has forced around 50 % of employees of Switzerland into a working from home setting during March and April 2020. Working from home appears to change the work experience of office workers considerably. The aim of this analysis was to investigate the effect of the first COVID-19 lockdown on work stress conditions.

Methods

We based this longitudinal analysis on control group data from an ongoing stepped-wedge cluster randomized controlled trial. Office workers from two Swiss organizations, aged 18-65 years, were included. Baseline data from January 2020 (before the COVID-19 pandemic) were compared with follow-up data collected during the fourth and fifth week of the first lockdown (April 2020). Work stress conditions were measured using the Job-Stress-Index (JSI). The JSI indicates the ratio of work-related resources (e.g., appreciation at work) and stressors (e.g., work organisation) on a scale from 0 (stressors < resources) to 100 (stressors > resources). Paired sample t-tests were performed for statistical analysis.

Results

Data from 75 participants were analysed. Fifty-three participants were female (70.7 %). The mean age was 42.8 years (range from 21.8 to 62.7) at baseline. At baseline, the mean JSI was 47.6 (SD = 5.0), with 77.7 (SD = 12.4) for resources and 22.3 (SD = 10.1) for stressors. At follow-up, the mean JSI was 47.4 SD = 4.5), with 77.5 (SD = 11.7) for resources and 21.4 (SD = 9.6) for stressors. We found no evidence for a difference in JSI (estimate = 0.67, 95 % CI: -0.33 to 0.66, p-value = 0.50), its index of resources (estimate = 0.23, 95 % CI: -1.32 to 1.69, p-value = 0.82) or the index of work stressors (estimate = 1.4, 95 % CI: -0.32 to 2.02, p-value = 0.15) between measurement time points.

Conclusions

The first COVID-19 lockdown did not result in a difference of work stress conditions among our sample of Swiss office workers. Improved working times and work-life balance may have contributed to this finding.

Key messages

Improved working times and work-life balance may have contributed to stable task-related stressors and resources in the early phase of the lockdown. Other, non-work-related environmental stressors should be investigated to explain COVID-19-related changes in mental and physical health.
Are antigen tests useful as screening for the identification of SARS-CoV-2 in emergency rooms?
Authors: Cigliano F , Boccuzzi A , Basile V , Ferraro A , Macciotta A , Catalano A , Costa G , Vineis P , Sacerdote C , Caramello V
Published: October 2021

Background

A quick and accurate case identification in the Emergency Department (ED) during the SARS-CoV-2 pandemic is crucial for clinical management and to prevent spread of infections. The gold standard for diagnosing SARS-CoV-2 infection is the real-time reverse transcription polymerase chain reaction (RT-PCR) test in upper airways swabs. However, the procedure is available in few specialized laboratories and requires an average sample processing time of about 6 hours from its inception. The development of reliable but cheaper and faster point-of-care tests was expected to be useful either for population-screening or as first aid tests in the ED. Rapid antigenic diagnostic tests (Ag-RDTs), directly detect SARS-CoV-2 proteins produced by the replicating virus in respiratory specimens, were proved to be candidates in both cases. However, data on their effectiveness are still few and controversial. The aim of the study is to establish the accuracy of antigen tests to identify SARS-CoV-2 in a high prevalence setting.

Methods

Results of 324 patients, consecutively admitted to the ED of San Luigi Gonzaga University Hospital in Orbassano (Turin, Italy) between 26 October and 10 November 2020 and subjected to both molecular and antigen tests, were compared.

Results

Using RT-PCR as gold standard, specificity and sensitivity of Ag-RDT were 0.94 (95%CI: 0.90-0.98) and 0.80 (95%CI: 0.75-0.85), respectively. The Ag-RDT positive predictive value was 0.96 (95%CI 0.93- 0.99), and the negative predictive value was 0.72 (95% CI: 0.65-0.79). Patients that tested negative to Ag-RDT but presented with fever and cough or had pneumonia at imaging were more likely to be false negatives. Ag-RDTs best performance occurs in the first days after symptom onset.

Conclusions

These results confirm the limits of antigenic tests as first line screening tests and suggest that the antigenic test should be integrated with clinical judgement, based on physical and instrumental examinations.

Key messages

Antigenic tests have a limited effectiveness as first line screening tests. In a high-prevalence setting these tests incorrectly judge as negative many COVID-19 symptomatic patients, making necessary to integrate their results with clinical judgement.
Factors associated with avoidance of emergency department visits in Portugal during the pandemic
Authors: Lopes S , Soares P , Gama A , Pedro AR , Moniz M , Laires P , Goes AR , Nunes C , Dias S
Published: October 2021

Background

Avoiding an emergency department (ED) visit risks irreversible negative consequences for patients' health. EDs are a frequent access point to the Portuguese health system. Previous studies have shown that patients may avoid visiting ED during the pandemic. This study aims to identify factors associated with avoidance of ED visits in Portugal during the COVID-19 pandemic.

Methods

We used data from a community-based survey, “COVID-19 Barometer: Social Opinion”, which includes healthcare utilisation, health status, and risk perception in Portugal from 11th April 2020 to 16th April 2021. We included respondents that reported having needed ED care. Data were collected on sociodemographics, health status (comorbidities, mental health), risk perception (COVID-19 and complications), level of trust in health services and self-assessment of the severity of the reason for ED visit. The outcome of interest was the decision to avoid ED care. We used logistic regression to identify factors associated with the decision to avoid ED.

Results

Preliminary data showed that 914 respondents reported needing ED care (74.8% female; mean age 43 years). From those, 224 (25%) decided to avoid ED care. ED visits avoidance was higher during lockdowns (28%). People reporting specific comorbidities (cardiac, autoimmune, respiratory) avoided ED more than those without them. Perception of no severe reason for ED visit, poor mental health, perception of higher risk of COVID-19 and complications, and low trust in health services response to the pandemic were associated with higher odds of ED visit avoidance.

Conclusions

People avoiding ED visits represented a considerable share. The decision to avoid ED visit was associated with clinical characteristics, but the perception of risk and assessment of the context and health system response also played a role in decision making.

Key messages

The effect of avoided ED visits on health should be a research and policy concern. People with certain comorbidities or perception of high risk of COVID-19 and complications may be closely monitored.
Social stigma among COVID-19 patients after quarantine in Sousse, Tunisia
Authors: Mlouki I , Zammit N , Ghammem R , Ben Fredj S , Bannour R , El Echi A , Bennasrallah C , Maatoug J , Ghannem H
Published: October 2021

Background

Assessing stigma related to COVID-19 is crucial to better understand the pandemic's impacts and establish effective stigma-reducing interventions. The aim of this study was to screen for stigma and evaluate its associated factors among adults with COVID-19 living in the governorate of Sousse (Tunisia).

Methods

A cross sectional study was conducted among a representative sample of patients with COVID-19 between the 6th of November and the 12th of December 2020 in the governorate of Sousse. The 12-item HIV stigma scale was translated in Arabic and then adapted to the Tunisian context.Three pre-trained medical doctors administrated the pre-tested Arabic questionnaire to each participant by phone calls. Higher scores reflect a higher level of perceived Covid-19-related stigma.

Results

Responses of 346 participants with COVID-19 infection were obtained. The majority of participants were females (60.4%) with a median age of 40 years (interquartile range, 30 to 54.5 years). Among them, 12.7% were health professionals and 12.5% had at least secondary educational level. Because of COVID-19 illness, 17.1% reported financial deterioration. We found mean scores of 14.6 ±4.07, 6.8±2.39 and 6.2±1.95 for social stigma, disclosure concerns and negative self-image dimensions respectively. Social stigma score was significantly higher among adults (14.9±3.9 versus 13.05±4.4 among elderly; p = 0.01) and people with low socioeconomic level (15.8±4.8 versus 14.3±3.8; p = 0.02). Lower scores of social stigma were found among health caregivers (13.3±2.6 versus 14.8±4.2; p = 0.002). Those factors remained as predictors of social stigma after linear regression analysis.

Conclusions

Screening for stigma is required in order to identify the most vulnerable patients and could prevent among them social repercussions. Psychological assistance of patients with social stigma would help them to overcome this crisis.

Key messages

Being adult with low socioeconomic level and not being health worker were determinants of social stigma. Psychological assistance for COVID-19 patients is crucial to prevent social stigma repercussion during this outbreak.
Discriminatory attitudes against people tested for corona virus in the region of Mahdia (Tunisia)
Authors: Omri N , Mlouki I , Sfar H , Ben Youssef F , Jandoubi M , El Mhamdi S
Published: October 2021

Background

Several incidents of stigmatization of healthcare workers, COVID-19 patients and their families have come up during the current pandemic across the world.

Aim

To evaluate discriminative behaviors against people tested for Covid-19 in the governorate of Mahdia in Tunisia.

Methods

We performed a cross sectional study among people tested for Covid-19 from November to December 2020 in the region of Mahdia. Discrimination was assessed using a pretested brief questionnaire inspired from the reliable French version of HIV stigma scale. Trained members of the study team explained the study's purpose and collected data from each participant via phone calls.

Results

A total of 277 participants were recruited with a mean age of 34.32 ±13.7 years. Among them, 60.8% were women and 62.2% were tested positive for Covid-19. Fourty three percent of participants were health professionals with 25.3% of them were directly involved in the care of COVID-19 patients. More than half of respondents (61%) have experienced discrimination. Thus, 40% were subjected to verbal and physical assaults. Concerning stigma among health care workers, 60% were doctors and 67.2% have worked in a covid-19 care service. Our survey shows a higher level of Covid-19 related stigma among married respondents and those living with elderly people (46.8% and 43.8% respectively). Discrimination was associated with being a health care professional (p = 0.05), mainly a doctor (p = 0.03) and having COVID-19 infection (p = 0.02).

Conclusions

The continued discriminatory and stigmatising attitudes towards people tested for Covid-19 negatively impacts their access to health care services. We recognise a pressing need to improve the knowledge of Covid-19 transmission, and implement universal precautions across all health facilities.

Key messages

The high prevalence of discriminatory attitudes against people tested for Covid-19 is alarming. It’s an unpleasant experience causing numerous psychological distresses among those who undergo it. Establishing a positive safety culture and providing appropriate education to reduce the stigma towards infected people offers an effective way to improve the quality of care.