Echocardiographic phenotype in severe aortic valve stenosis with and without cardiac amyloidosis: The AMY-TAVI trial

Background: Longitudinal Strain (LS) pattern in cardiac amyloidosis (CA) typically spares the apex of the heart, which is a sensitive and specific finding that can be used to distinguish CA from other causes of left ventricular (LV) hypertrophy. RELAPS >1 suggests with high specificity CA, and shows a bright red in the apical segments of the polar map. Purpose(s): To identify differential echocardiographic characteristics of aortic stenosis (AS) with concomitant TTR-CA (AS-CA) compared to AS alone. Method(s): Patients with severe symptomatic AS undergoing TAVI were prospectively and consecutively included between Jan-19 and Dec-20. Pre-procedure, a complete echocardiogram was performed that included deformation parameters using Speckle-Tracking. Strain derived Indices accepted for CA screening were calculated: RELAPS: Relative apical LS (average apical LS/average basal+mid LS);SAB: (apical-septal/basal-septal LS);EFSR: (LVEF/GLS). After TAVI, a 99Tc-DPD scintigraphy and a proteinogram were performed to screen for CA. Result(s): 324 patients were included. The mean age was 81 yo, 52% women. 39 (12%) patients presented cardiac uptake on scintigraphy: 14 (4.3%) grade 1;13 (4%) grade 2, and 11 (3.4%) grade 3. Strain analysis could be performed in 243 patients due to acoustic window and covid19 pandemic restrictions. Echocardiographic characteristics between AS alone and those with grade 1 (AS-DTD1) and grade 2/3 (AS-CA) are shown in Table 1. Compared with AS alone, patients with AS-CA had significantly lower transvalvular gradients, although similar AVA, and low flow-low gradient (LF-LG) AS was more prevalent. AS-CA exhibited slightly worse cardiac remodeling (LV mass ind: 202 g/m2 vs 176 g/m2, p=0.032), and worse diastolic dysfunction, but without significant differences in thickness, diameters or volumes, with similar relative wall thickness (RWT: 0.53 vs. 0.51 mm, p=0.52). LVEF was similar, however myocardial contraction fraction (MCF= stroke volume/myocardial volume) and MAPSE were worse in AS-CA. GLS, RELAPS, SAB and EFSR were not different, but RELAPS >1 pattern was more prevalent in AS-CA (74% vs 44%, p=0,006) (Figure 1). Mass/strain ratio (RMS) was similar. There were no differences in size and fractional emptying of left atrium, or atrial septum thickness. Right ventricle (RV) size was similar, as well as conventional function parameters (TAPSE and S'). However, RV LS was worse in AS-CA. Pericardial effusion was more prevalent in AS-CA (25% vs 7.4%, p=0.013). In the multivariate analysis, predictors of AS-CA were: Age (OR: 1,2, p=0,02), BG (OR: 0,2, p=0,01), E/A (OR: 4,7, p=0,02), LV Mass index (OR: 1,02, p=0,04) and RELAPS >1 (OR: 0,12, p=0,01). Conclusion(s): Dual pathology of AS-AC is common in older patients referred for TAVI. Although it is more prevalent in patients with AS-CA, RELAPS>1 pattern can be present in almost 50% of patients with severe AS alone, which reduces its value as screening tool for CA in this clinical setting respect to others. (Table Presented).

Echocardiographic phenotype and prognostic value of relative apical sparing of longitudinal strain pattern in severe aortic stenosis with and without cardiac amyloidosis. The AMYTAVI study

Introduction: It is estimated that 15% of patients with AS have concomitant cardiac amyloidosis (CA). Left ventricular (LV) longitudinal strain (LS) pattern with relative apical sparing (RELAPS>1), shown as bright red in the apical segments on the polar map, has been strongly associated with CA. Its presence and its significance in AS is yet to be determined. Purpose(s): To determine the prevalence of the RELAPS>1 pattern in patients with severe AS with and without concomitant CA, and to analyze the echocardiographic phenotype associated with this strain pattern and its prognostic value. Method(s): Patients with severe symptomatic AS undergoing TAVI were prospectively and consecutively included between Jan-19 and Dec-20. Pre-procedure, a complete echocardiogram was performed that included deformation parameters using Speckle-Tracking. Strain derived Indices accepted for CA screening were calculated: RELAPS: Relative apical LS (average apical LS/average basal+mid LS);SAB: (apical-septal/basal-septal LS);EFSR: (LVEF/GLS). After TAVI, a 99Tc-PYP scintigraphy and a proteinogram were performed to screen for CA. Result(s): 324 patients were included. The mean age was 81 yo, 52% women. Strain analysis could be performed in 243 patients due to acoustic window and covid19 pandemic restrictions. Among those, 111 (46%) presented relative apical sparing (RELAPS>1). There were no differences in clinical characteristics between patients with RELAPS <1 and >1: Similar age, sex, cardiovascular risk factors and funcional class, renal function or NT-proBNP. Among patients with RELAPS>1 there was more frecuently CA with uptake grade 2 and 3 on scintigraphy (15% vs. 4.5%, P=0.006) (Figure 1). RELAPS>1 group showed greater LV hypertrophic remodeling: Thicker myocardial wall with smaller ventricular cavity, especially concentric hypertrophy;LVEF and GLS was similar, however, MAPSE and myocardial contraction fraction (MCF) were worse in RELAPS >1 group, and EFSR was significantly higher (4.2 vs 3.9, p=0.002). RELAPS >1 group had smaller aortic valve area (AVA: 0.6 vs 0.7 cm2, p=0.045), but similar transvalvular gradients due to lower stroke volume. It had larger atria and less left atrial (LA) fractional emptying, as well as higher prevalence of atrial fibrillation (AF: 41% vs 27%, p=0.03). Right ventricle (RV) size were similar, however, RV function was worse in RELAPS >1 group (TAPSE: 19 vs 21 mm, p=0.003;free Wall LS: -24 vs -27%, p=0.008). There was no difference in all-cause mortality at 1 year of follow-up between groups (6.4% vs. 6.3%, p=1). Figure 2 represents the morphological characteristics according to the LS phenotype. Conclusion(s): In severe AS, RELAPS >1 is present in almost half of the patients. It is associated with worse cardiac remodeling, as well as higher prevalence of AF. However, it wasn't associated with higher mortality at 1 year. 1 in 7 patients with AS and RELAPS >1 have concomitant ATTR CA grade 2/3.

Effects of the COVID-19 pandemic on offering and acceptance in a cardiac rehabilitation programme: introduction of a remote CR programme

Background: The impact of the COVID-19 pandemic on multimodal cardiac rehabilitation (CR) programmes has forced a continuous readjustment of clinical practice. Our regional healthcare system was faced with providing quality remote CR to ischaemic heart disease (IHD) patients in a scattered, mostly rural population, for which three new CR modalities replaced the previous in-person CR program: 1) telephone follow-up programme, 2) TELEA online platform for patient follow-up and 3) TELEA online follow-up & online training sessions. Purpose: To study the impact of the COVID-19 pandemic on CR offering and acceptance and the reasons for patient refusal, and to assess the outcome of new remote CR modalities in this setting. Methods: Single center, observational retrospective study from all consecutive patients with IHD eligible for CR from 2015 to 2021. A descriptive analysis of patient baseline characteristics, CR modality, offering and acceptance rates, and reasons for refusal per year was performed. Additionally, a comparative analysis of “pre-COVID period” (Jan 2015–Feb 2020) vs. “COVID period” (Mar 2020–Dec 2021) was performed to assess the impact of the pandemic on patient recruitment and the usefulness of remote CR modalities to enhance participation. Results: N=2626 patients (20% women, 69.7±45.8 years) were offered CR from 2015 to 2021. CR offering decreased from the pre-COVID (78.6%) to the COVID period (52.6%), while participation increased (67.9% and 79.7%, respectively) Figure 1. Reasons for CR refusal significantly changed with an odds ratio (OR) of 5.63 and confidence interval (CI) 95% (3.2–9.9). In the pre-COVID period main reasons for CR refusal was “transportation difficulties” (47%);while during the COVID-19 period, the main reason shifted to “lack of interest” (78.2%) (Table 1). Conclusions: Offering CR decreased during the COVID pandemic possibly due to stricter inclusion criteria. However, the implementation of new remote CR modalities allowed not only to maintain similar levels of acceptance but also to improve it despite the unfavourable setting, and helped to amend transportation difficulties as the leading reason for refusal. Remote CR may be a useful tool, combined with in-person programs, to enhance participation in CR. Funding Acknowledgement: Type of funding sources: None.Figure 1

SORT IT OUT AS BEST YOU CAN! MORAL DILEMMAS IN FAMILY CARE FOR ELDERLY AND DEPENDENT PEOPLE DURING THE PANDEMIC

Households are essential places of observation for understanding the extent to which measures to contain COVID-19 have limited the availability of social care resources and have thus made families, in particular women, responsible once again for providing care. An analysis of interviews conducted during the CUMADE project allows us to reflect on how the pandemic has impacted what providing care means for those women who care for elderly and dependent persons. In particular, we are interested in how it has affected the arrangements inherent in the new care mosaics, and has accentuated the moral dilemmas that emerge when taking the decision to provide most care either inside or outside the home. © 2022 CSIC.

Predicted COVID-19 molecular effects on endometrium reveal key dysregulated genes and functions.

COVID-19 exerts systemic effects that can compromise various organs and systems. Although retrospective and in silico studies and prospective preliminary analysis have assessed the possibility of direct infection of the endometrium, there is a lack of in-depth and prospective studies on the impact of systemic disease on key endometrial genes and functions across the menstrual cycle and window of implantation. Gene expression data have been obtained from (i) healthy secretory endometrium collected from 42 women without endometrial pathologies and (ii) nasopharyngeal swabs from 231 women with COVID-19 and 30 negative controls. To predict how COVID-19-related gene expression changes impact key endometrial genes and functions, an in silico model was developed by integrating the endometrial and COVID-19 datasets in an affected mid-secretory endometrium gene co-expression network. An endometrial validation set comprising 16 women (8 confirmed to have COVID-19 and 8 negative test controls) was prospectively collected to validate the expression of key genes. We predicted that five genes important for embryo implantation were affected by COVID-19 (downregulation of COBL, GPX3 and SOCS3, and upregulation of DOCK2 and SLC2A3). We experimentally validated these genes in COVID-19 patients using endometrial biopsies during the secretory phase of the menstrual cycle. The results generally support the in silico model predictions, suggesting that the transcriptomic landscape changes mediated by COVID-19 affect endometrial receptivity genes and key processes necessary for fertility, such as immune system function, protection against oxidative damage and development vital for embryo implantation and early development.

Digital media in indigenous language education

Education has started a transformation by including digital media technologies to enhance the learning process. This transformation was accelerated by the COVID-19 pandemic, which paralyzed face-toface classes and switched to distance education modalities through various platforms. Animation and storytelling have been the most influential digital tools to transmit knowledge also, augmented reality has gained popularity in education. Indigenous languages are a cultural wealth and provide great philosophical and cultural value associated with linguistic diversity. This chapter describes different digital tools developed to teach Cuicateco, Mazateco, and Nahuatl, three indigenous languages spoken in Mexico;then, a usability study is described to evaluate the effectiveness of digital tools;finally, a case study is presented to evaluate the proposed methodology. © 2022, IGI Global. All rights reserved.

Treatment of severe COVID-19 patients with either low- or high-volume of convalescent plasma versus standard of care: A multicenter Bayesian randomized open-label clinical trial (COOP-COVID-19-MCTI).

Background: Administration of convalescent plasma may serve as an adjunct to supportive treatment to prevent COVID-19 progression and death. We aimed to evaluate the efficacy and safety of 2 volumes of intravenous convalescent plasma (CP) with high antibody titers for the treatment of severe cases of COVID-19. Methods: We conducted a Bayesian, randomized, open-label, multicenter, controlled clinical trial in 7 Brazilian hospitals. Adults admitted to hospital with positive RT-PCR for SARS-CoV2, within 10 days of the symptom onset, were eligible. Patients were randomly assigned (1:1:1) to receive standard of care (SoC) alone, or in combination with 200 mL (150-300 mL) of CP (Low-volume), or 400 mL (300-600 mL) of CP (High-volume); infusion had to be performed within 24 h of randomization. Randomization was centralized, stratified by center. The primary outcome was the time until clinical improvement up to day 28, measured by the WHO ten-point scale, assessed in the intention-to-treat population. Interim and terminal analyses were performed in a Bayesian framework. Trial registered at ClinicalTrials.gov: NCT04415086. Findings: Between June 2, 2020, and November 18, 2020, 129 patients were enrolled and randomly assigned to SoC (n = 42), Low-volume (n = 43) or High-volume (n = 44) CP. Donors presented a median titer of neutralizing antibodies of 1:320 (interquartile range, 1:160 to 1:1088). No evidence of any benefit of convalescent plasma was observed, with Bayesian estimate of 28-day clinical improvement of 72.7% (95%CI, 58.8 to 84.7) in the SoC versus 64.1% (95%ci, 53.8 to 73.7) in the pooled experimental groups (mean difference of -8.7%, 95%CI, -24.6 to 8.2). There was one case of cutaneous mild allergic reaction related to plasma transfusion and one case of suspected transfusion-related acute lung injury but deemed not to be related to convalescent plasma infusion. Interpretation: In this prospective, randomized trial of adult hospitalized patients with severe COVID-19, convalescent plasma was not associated with clinical benefits. Funding: Brazilian Ministry of Science, Technology and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo.

'YOU HAVE NOWHERE TO GO (AND I DO)'. HOW FEAR OF CONTAGION AFFECTS MIGRANT DOMESTIC WORKERS

In the current COVID-19 context, we analyze how fear of contagion impacts on the working conditions of female migrant domestic workers in Spain. The article opens up the liminality in which the conditions of domestic work reproduction, and its regulatory framework, place these workers. It focuses on three related dimensions. First, how the power relations between workers, the person who is cared for and the family are reworked, and the new forms of coexistence within the households that it entails. Second, the emotional overload that home lockdown and social isolation means for these female workers. Third, how the gender, class and race boundaries between "us" and "others" are reshaped within the framework of domestic work servile relationships. Fear as a social category stems from a labour and immigration regulatory framework that deprives these female workers of their rights, and from a care economy that neglects and makes invisible the abuses and suffering that characterize this sector.

Among asynchronous monologues and synchronous dialogues: Some scenes of remote teaching internship in history teaching in 2020

From the observation of school scenes via online, and the dialogues with interns and trainees in the area of History and heritage education, working in remote mode, we report challenges posed by the pandemic of Covid-19 in 2020 We present alternatives implemented to allow the continuity of the educational bond. We place school culture in times of pandemic at the center of numerous tensions, and we examine these tensions from the university and school connection. This connection occurs when the teaching internships are mandatory for the training of male and female students in the undergraduate program. We take the Covid-19 pandemic into the category of experience and, therefore, not exactly as something that happens to us, but as what we do with what happens to us, and what we learn from it. In the face of a health problem with such an impact on the educational field, actions are needed. Careful reflection around the daily life of online alternatives provides clues to these actions. © 2021 UNIVERSIDADE FEEVALE . All Rights Reserved.

Characteristics and outcome of adults with acute lymphoblastic leukemia and COVID 19 infection in the first vs. Second epidemic wave in Spain: A study from the Pethema and Geth groups

Background: SARS-CoV-2 infection has bimodal distribution in Europe with a 1st wave in March-June 2020 and a 2nd in September 2020-February 2021. In cancer patients (pts) the lethality of COVID- 19 infection was 25%>35% in the 1st wave. Comparison on impact of COVID-19 infection in the 1st vs. 2nd waves have not been performed in ALL. Aims: We compared the frequency, clinical characteristics and outcome of adults with ALL and COVID-19 infection in the 1st vs. 2nd waves in Spain. Methods: Between March 1, 2020-May 31, 2020, and between September 12, 2020- January 12, 2021 (date of vaccination onset in Spain), a registry from the PETHEMA (Programa Espa.ol de Tratamientos en Hematologia) and GETH (Grupo Espa.ol de Trasplante Hematopoyético y Terapia Celular) groups prospectively recruited adult ALL pts with COVID-19 infection confirmed by PCR. Demographic and clinical characteristics of ALL and COVID-19 infection, comorbidities, treatment and outcome were collected and compared in the two periods. In addition, prognostic factors for survival were analyzed. Results: Fifty-six patients were collected in 82 centers contacted, 4 of them being excluded (COVID infection >3 yr. after end of ALL therapy [n=3] and Burkitt lymphoma [n=1]). Twenty-eight pts were collected in the 1st wave and 24 in the 2nd. Median age was 46 (range 20-83), (34 pts [65%] >40 yr). Comorbidities were present in 18 pts (35%). ALL was of B-cell precursors in 38 pts (74%) (Ph+ in 8, 15%). Thirtyone pts (60%) were under frontline treatment, 16 (31%) in rescue, 1 (2%) palliative and 4 (7%) had recently finished the therapy. Eight pts had received allogeneic HSCT (5 of them at COVID-19 infection diagnosis), CAR T (n=1, 2 yr prior to COVID-19 infection) or received immunotherapy (inotuzumab, n=6, 2 at COVID-19 infection, and blinatumomab, n=1, prior to COVID-19 infection). Eleven pts were receiving immunosuppressive drugs at COVID infection (fludarabine in 6, among others). No significant differences were observed in ALL characteristics in the two COVID-19 waves, except for a significantly higher number of patients on first line therapy in the second wave, and a higher frequency of severe neutropenia and lymphocytopenia in the first wave. COVID19 therapy was different in the two periods, with significantly higher use of hydroxychloroquine, remdesivir and lopinavir-ritonavir in the first wave and corticosteroids in the second wave. No significant differences were observed in need of oxygen support (12 vs. 8 pts), ICU requirement (7 vs. 4 pts), days in ICU (medians 16 vs. 21) and time to COVID infection recovery (medians 17 vs. 13 days). Seventeen patients (33%) died (11 vs. 6), being death attributed to COVID infection in 15 (29%), without significant differences in the 100-day survival probabilities (Figure 1). By multivariable analysis only comorbidities at COVID-19 infection had a negative impact on survival (HR: 5.358 [95% CI: 1.875;15.313]). Summary/Conclusion: COVID-19 infection was frequent in ALL pts, especially in those with advanced age and under ALL frontline or rescue therapy. The frequency of severe COVID-19 infection and mortality were high, with negative impact of comorbidities on survival. No significant differences were observed in ALL characteristics, response to therapy and outcome in the two waves of COVID infection. The poor outcome of COVID infection makes vaccination a priority for ALL patients in this pandemic period. Supported in part by 2017 SGR288 (GRC) Generalitat de Catalunya and "la Caixa" Foundation.

FIND integrated biobanks (FIB) and Virtual Biobank Directory (VBD): A framework for sample access and sharing to facilitate diagnostic development and evaluation and pandemic preparedness

Problem: Diagnostic development and validation require consistent availability of well-characterized, high-quality biospecimens. There is a great disconnect between biobanks and industry or developers' needs, leading to slow reaction to outbreaks and missed opportunities for sample access and sharing. Long-term sustainability and fit-for-purpose collections are still unresolved biobank issues, even more relevant when activities are performed in LMICs (low- and middle-income countries) who are often reticent to distribute samples due to legal/ethical barriers and mistrust of research and use of samples. Proposed Solution: Building on its biobank experience focused on infectious diseases in LMICs, FIND has established a strategy for a disease-agnostic, network-based biobank model, adapted to industry needs. The model focuses on: 1) increasing sample visibility and access and 2) empowering research and capacity building in LMICs The two main components of the model are the FIND Integrated Biobanks (FIB) and the Virtual Biobank Directory (VBD). The FIB is a network of biobanks for pandemic preparedness that work under FIND's coordination to conduct collection activities to support diagnostic research, development, and evaluation. Due to the FIB structure, network sites based in LMICs will be able to rapidly scale-up activities to support both outbreaks and local clinical and research needs. FIND serves as the central coordinator, managing sample requests from external users, and ensures standardization among FIB sites in terms of documentation, operating procedures, infrastructure building, training, and study conduct. Local storage of banked samples and data will be managed within the FIB sites, which will also participate in decision making regarding the use of samples collected at their site. To enhance the visibility of existing biological resources, FIND created the VBD, a searchable directory of information on collections either hosted by FIND or by other organizations or networks. The VBD is an open-access, free-of-charge tool allowing users and sample custodians to interact on sample transfers without FIND's intervention. Conclusion: Both the FIB and VBD are currently being piloted to support FIND's COVID-19 work. FIND plans to expand the model to respond to needs within its disease programmes, such as neglected tropical diseases, tuberculosis, malaria, fever, HIV/HCV, and pandemic preparedness.

Histo-blood group A is a risk factor for severe COVID-19.

OBJECTIVES: Evaluate the impact of ABO histo-blood group type on COVID-19 severity. BACKGROUND: ABO histo-blood type has been associated with different outcomes in infectious diseases. It has also shown a higher proportion of type A patients with SARS-CoV-2. In this observational study, extracted from an ongoing clinical trial on the efficacy of convalescent plasma transfused in COVID-19 patients, we describe the impact of ABO blood type on the risk of developing severe COVID-19. MATERIALS AND METHODS: Seventy-two consecutive patients (37 type A, 23 type O, 11 type B, 1 type AB) with severe (respiratory failure) COVID-19 were included. Control group was composed of 160 individuals randomly selected from the same populational basis. RESULTS: Blood group A was overrepresented (51.39%) in the patient group in relation to the control group (30%), whereas blood group O was less represented (31.94%) in patient than in control group (48%). Odds ratio (A vs. O) was 2.581 (1.381-4.817), CI 95%; p = 0.004. Also, blood group A patients appeared to have more severe disease, given by the scores of the Sequential Organ Failure Assessment and Simplified Acute Physiologic Score 3 (p = 0.036 and p = 0.058, respectively). CONCLUSION: Histo-blood type A is associated with a higher risk of developing severe COVID-19 in relation to blood type O.

Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods

The unprecedent situation generated by the COVID-19 global emergency has prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients. In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way. To this end a multi-target virtual screening approach focused on host-based targets related to viral entry, followed by the experimental evaluation of the antiviral activity of selected compounds, has been carried out. As a result, five different potentially repurposable drugs interfering with viral entry-cepharantine, clofazimine, metergoline, imatinib and efloxate-have been identified.

Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses.

The endocytic pathway is a common strategy that several highly pathogenic viruses use to enter into the cell. To demonstrate the usefulness of this pathway as a common target for the development of broad-spectrum antivirals, the inhibitory effect of drug compounds targeting endosomal membrane proteins were investigated. This study entailed direct comparison of drug effectiveness against animal and human pathogenic viruses, namely Ebola (EBOV), African swine fever virus (ASFV), and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A panel of experimental and FDA-approved compounds targeting calcium channels and PIKfyve at the endosomal membrane caused potent reductions of entry up to 90% in SARS-CoV-2 S-protein pseudotyped retrovirus. Similar inhibition was observed against transduced EBOV glycoprotein pseudovirus and ASFV. SARS-CoV-2 infection was potently inhibited by selective estrogen receptor modulators in cells transduced with pseudovirus, among them Raloxifen inhibited ASFV with very low 50% inhibitory concentration. Finally, the mechanism of the inhibition caused by the latter in ASFV infection was analyzed. Overall, this work shows that cellular proteins related to the endocytic pathway can constitute suitable cellular targets for broad range antiviral compounds.

Ontological implications in the learning of social distancing of covid-19 pandemic

The world pandemic situation affects all economics sector and specially education;the objective was to show new models of learning to mitigate the negative impacts of the pandemic. Qualitative and reflexive methodology is used from grounded theory, this paper proposes to the student, teacher and Higher Education Institution (HEI) from its ontology in teaching process with its features and B-learning method relation. It is concluded the relevance participation of HEI and government as fundamental actors to alleviate the negative impacts of COVID-19. © 2020, Universidad del Zulia. All rights reserved.