Patterns of Progression and Treatment Discontinuation in a Real Life Latin American Prospective Cohort Study of Intermediate-Advanced Hepatocellular Carcinoma: Second Interim Analysis

Introduction and Objectives: Previously published regional real-world results of overall survival (OS) in Barcelona Clinic Liver Cancer (BCLC) B and C patients demanded a prospective cohort study nested in a systematic and continuous medical educational networking group. This study aimed to describe and evaluate the treatment decisions in patients with hepatocellular carcinoma (HCC) within BCLC B and C stages. Material(s) and Method(s): A multicenter prospective cohort study, conducted in different Latin American centers from Argentina, Brazil and Colombia, started on 15th May 2018 (delayed recruitment during COVID locked-down period). Patients within BCLC B or C stages were included. Survival, tumor progression and patterns of treatment suspension were evaluated. Result(s): At this second interim analysis (projected final analysis March 2023), 390 HCC BCLC-B or C patients were included (n=15 excluded);mean age 65 years, 75.6% males and 89.5% cirrhotic. Median OS since HCC diagnosis was 27.2 months. Among BCLC-B patients, the most frequent therapy was transarterial chemoembolization (TACE, 42.3%);51.8% using drug-eluting beads and 47.4% conventional TACE;with a median OS since 1st TACE of 41.9 months. Similar radiological responses after 1st TACE were observed between both modalities. Overall, 48.2% of the cohort received systemic therapy for HCC (n=188), 23.7% still on BCLC-B stage. The most frequent systemic treatments were Sorafenib (74.5%), atezolizumab bevacizumab (17.5%), and lenvatinib (12.2%), with a median OS since systemic therapy of 15.7 months. Lenvatinib or atezolizumab bevacizumab was used as the second line following sorafenib in 5 and 3 patients, respectively. The most common causes of systemic treatment discontinuation were tumor progression and liver function deterioration (15% to 36.4%). Patterns of tumor progression were not specifically associated with prognosis or treatment discontinuation. Conclusion(s): Liver function deterioration occurs in a third of patients following systemic therapies. The complexity of treatment decisions underly the need for a multidisciplinary team and the role of hepatologists.Copyright © 2023

Influence of diabetes mellitus on the prognosis of patients hospitalised for COVID-19

Background: Various studies have established a relationship between coronavirus infection (COVID-19) and diabetes mellitus (DM) as a factor of poor prognosis. Purpose(s): To determine the influence of DM on the evolution of patients hospitalised by COVID-19. Method(s): Retrospective observational study. All hospitalised patients with COVID-19 infection treated with Lopinavir/Ritonavir and Hydroxychloroquine during March and April 2020 were included. Two cohorts were performed: patients with DM and patients without DM. Patients who were not discharged or exited until April 30th 2020, were excluded. The treatment guidelines used were: Lopinavir/Ritonavir 200/50 every 12 hours mg for 14 days and Hydroxychloroquine 400 mg every 12 hours on the first day, followed by 200 mg every 12 hours during four days. Data were obtained through the Athos-Prisma inpatient prescription programme and review of medical records at Diraya. The chi-square test of comparison between data series of the two patient subgroups was performed. Result(s): Fifty-six (56) patients, 40 men and 16 women were included. The cohort of patients with DM (n=15) presented a mean of 66.7 years (53.8-79.6) vs 65.8 years (52.4-75.7) in the cohort of patients without DM (n=41). Mortality in the group with DM was 46.6% vs. 29.2% in the group without DM. After performing the chi-square test, a p>0.05 was obtained, so the differences between the two subgroups were not statistically significant. Conclusion(s): Our results do not associate DM with a poor prognostic factor in COVID-19 infection, although they are conditioned to the small sample size available. New studies with a larger number of patients will be necessary.

Unusual thyroid carcinoma metastasis in paranasal sinuses and parapharyngeal space

The prevalence of follicular cell-derived thyroid carcinoma with an unusual pattern in its metastatic spread is relatively unknown, and therefore its clinicopathological characteristics are not well defined and represent uncertainty in diagnosis and treatment. In this report, two cases of metastasis in the paranasal sinuses and one of metastasis in the parapharyngeal space are described. In the first case, given the extension of the lesion to the cavernous sinus, surgical resection was not possible and external radiotherapy management was determined. However, the patient died of COVID-19. In the second case, the patient underwent endoscopic release of the left maxillary nerve and partial resection of the tumor as a palliative measure, clinical improvement was observed, and he subsequently received 30Gy external radiotherapy. The third case was managed surgically using a minimally invasive approach using robotic transoral surgery, which was successful. Metastasis in the paranasal sinuses and parapharyngeal space due to differentiated thyroid carcinoma represents an unusual scenario. Its characterization and management will always be a challenge, but new minimally invasive techniques play an increasingly promising role. © 2022 EDIZIONI MINERVA MEDICA.

Coinfection Characteristics among Children with COVID-19

Background. Coinfection in patients with SARS-CoV-2 has been associated with greater complications. We describe the clinical characteristics and outcomes of 126 pediatric patients with COVID-19 and viral, bacterial, or fungal coinfection. Methods. We retrospectively reviewed and analyzed electronic data of all pediatric patients who tested positive for SARS-CoV-2 from April 16, 2020, to April 15, 2022, in our center. Confirmation of COVID-19 was based on positive RT-PCR. Viral coinfections (VC) were identified using a multiplex RT-PCR respiratory viral panel, bacterial coinfection (BC) was determined by positive bacterial culture (blood, bronchoalveolar lavage, sputum, urine) or clinical/radiological manifestations and antimicrobial assessment by a pediatric Infectious Diseases expert and fungal coinfection (FC) diagnosis based on Consensus definitions of invasive fungal disease. Results. During the study period, among 400 pediatric patients with COVID-19, 126 children had coinfection. Children >10 years were the most affected age group. Underlying disease was present in 69%, hematological malignancies were the most common (17.5%). BC was detected in 76.9% (n=97), bacterial pneumonia (54.6%) was the main diagnosis, followed by oncologic patients with initial febrile neutropenia and posterior SARS-CoV-2 detection (14,4%). Unusual BC as congenital syphilis w detected;acute appendicitis was the initial presentation of COVID-19 in 8 patients. VC was identified in 15.87% (n=20), prevailing rhinovirus (9.5%) and adenovirus (3.96%), One FC presented as proven pulmonary aspergillosis (0.8%). B-V and B-F coinfection were detected in 2 patients. Fever and cough were the most common symptoms, higher fever >40degreeC was mostly observed in the BC group (3%). Twenty-seven patients with BC (27.8%) were admitted to intensive care, with the OR 0.7 IR 95% (0.611-1.008), 4.1% died. One ICU admission was observed in the VC group (5%) and all VC cases resolved without complications. Conclusion. Pediatric patients with COVID-19 coinfection, especially BC were common in our center representing nearly one-third of the infected children, including unusual coinfections. BC was identified as a risk factor for ICU admission OR 0.7 IR 95% (0.611-1.008). Favorable outcomes were observed in most cases.

Learning strategies in e-learning formative processes in mathematical contents during the Covid-19 era

The aim of this study was to find out the learning strategies of university students in the on-line training of mathematical content so that the training content is assimilated, and active meaningful and motivating learning is promoted. A descriptive, correlational and predictive research method was used to study these strategies. The sample included 1,017 university students in Peru. Data collection was carried out using the LimSt instrument. The results show that the evaluation of the LimSt dimensions is medium-high. When determining the relationship between the analysis of the particularities of mathematics as a subject and the e-learning method, it is observed that there is a significant relationship with respect to gender and the branch of education. In addition, gender, age and branch of education provide a predictive model that mainly focuses on the learner's effort in relation to the e-learning pedagogical method. It is concluded that the e-learning pedagogical method applied for the training of Peruvian students for subjects related to the field of mathematics is positively evaluated. © 2022 WIETE

Classic and genetic cardiovascular risk burden and case-fatality from SARS-CoV-2 virus infection. The CARGENCORS study

Background: The disease presentation of the severe acute respiratory syndrome coronavirus 2 infection (COVID-19) ranges from asymptomatic to fatal. COVID-19 patients with pre-existing coronary artery disease (CAD) risk factors or overt cardiovascular disease more often develop severe COVID-19, which are also related to thrombotic, inflammatory, and to viral infectivity response. We hypothesised that despite some genetic predisposition, especially in COVID-19 severity, the main determinants of fatal complications in COVID-19 patients are related to comorbidity. Purpose: To determine the role of genetics and cardiovascular comorbidity in mortality from COVID-19. Methods: We conducted a retrospective cohort study including 3,120 patients with positive COVID-19 test from several hospitals and primary care between February 2020 and June 2021. Among them 1,096 required hospitalization, and 121 died within 3 months after symptom onset. Standard parametric and non-parametric methods, as required, were used to compare patient characteristics by vital status. Individual genotypes for 32 CAD, 14 thrombosis, 19 inflammation, and 11 viral infectivity single nucleotide variants (SNV), as well as, 2 COVID-19 SNVs already published were tested for association with mortality with Cochran-Armitage statistics and p-values corrected for multiple comparisons. The mutually-adjusted odds ratio (OR) and 95% confidence interval (95% CI) of fatal COVID-19 was analysed for SNVs significantly associated to case-fatality, with their adverse alleles count (0, 1 or 2), and for comorbidity factors with logistic regression adjusted for age and sex. The discrimination of the models was also estimated by the area under the curve (AUC). Results: Fatal and non-fatal cases' characteristics are compared in Table 1. Fatal cases had a more adverse cardiovascular and anthropometric risk profile. After correcting for multiple testing by Benjamini-Hochberg method, we observed the inflammation-related rs6993770 SNV to be significantly associated with COVID-19 fatality (p-value = 0.04). The CAD-related rs9982601 and rs2505083 SNVs, and the thrombosis-related rs7853989 SNV were moderately associated with COVID-19 fatality (p-value ≤0.1). On Figure 1 we show the adjusted OR for rs6993770 (OR: 1.02;95% CI 1.01–1.03 per risk allele) and that for clinical factors related to COVID-19 case-fatality. The AUC of the model was 0.85 (95% CI 0.81–0.88), which not improved that of a model with clinical risk factors alone (AUC: 0.84;95% CI 0.81–0.87). Conclusion: The rs6993770 inflammation (interleukin measurement trait)-related SNV was independently associated to case fatality;however the outcome was mainly driven by age, male sex, diabetes, and glomerular filtration rate. Funding Acknowledgement: Type of funding sources: Other. Main funding source(s): Carlos III Health Institute and the European Regional Development FundAgency for Management of University and Research GrantsCrue-CSIC-Santander FONDO SUPERA COVID-19

Genetic risk score for risk stratification of patients positive for SARS-CoV-2 virus. The CARGENCORS study

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Carlos III Health Institute and the European Regional Development Fund Government of Catalonia through the Agency for Management of University and Research Grants Crue-CSIC-Santander FONDO SUPERA COVID-19 Background The disease presentation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from asymptomatic to fatal. COVID-19 patients with pre-existing coronary artery disease (CAD) risk factors or overt cardiovascular disease are at particular risk of severe disease. We hypothesised that a specific genetic risk score (GRS) based on single nucleotide polymorphisms (SNPs) allele count to score COVID-19 severity might include SNPs counts related to CAD incidence and to thrombosis, inflammation, and viral infectivity determinants involved in the severity of SARS-CoV-2. Such GRS could improve the early risk stratification of COVID-19 patients and optimize treatment strategies. Purpose To evaluate the capacity of a genetic risk score (GRS) with candidate genes to predict COVID-19 severity. Methods We conducted an age- and sex-matched case-control study with 1:2 ratio recruitment involving 2454 patients from Catalan hospitals and primary care. Cases were hospitalized severe (requiring at least oxygen treatment) or fatal COVID-19 patients;and controls were moderate-symptom and asymptomatic patients treated at home. Standard parametric and non-parametric methods, as required, were used to compare patient characteristics by severity. Individual genotypes for 33 CAD, 14 thrombosis, 22 inflammation, 15 viral infectivity SNPs and 2 COVID-19 SNPs already published were tested for association with severity with Cochran-Armitage statistics and p-values corrected for multiple comparisons. GRS was computed as the unweighted count of adverse alleles (0, 1 or 2). The odds ratio of severe COVID-19 was analysed for GRS (and its component SNPs) with logistic regression models adjusted for potential confounding factors. Area under the curve (AUC) improvement and net reclassification index (NRI) for GRS was estimated from a basic model including CAD and COVID-19 severity risk factors. Models’ performance was measured with the Akaike information criterion. Results SNPs identifications are not shown to prevent patent conflict. Cases and control characteristics are compared in Table 1. Cases had a more adverse cardiovascular and anthropometric risk profile. After correcting for multiple testing by Benjamini-Hochberg criteria, we observed 13 SNPs to be significantly associated with severity. After excluding the close SNPs in linkage disequilibrium, 7 were retained in the GRS model, which yielded the discrimination and reclassification characteristics described in Table 2. Conclusion A GRS with 7 SNPs related to CAD, thrombosis and inflammation significantly improves the severe COVID-19 risk assessment done with age, sex, comorbidity, and anthropometry alone. CV and anthropometric risk profile OR of COVID-19 severity for a 7-SNP GRS

Genetic risk score for risk stratification of patients positive for SARS-CoV-2 virus. The CARGENCORS study

Background: The disease presentation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from asymptomatic to fatal. COVID-19 patients with pre-existing coronary artery disease (CAD) risk factors or overt cardiovascular disease are at particular risk of severe disease. We hypothesised that a specific genetic risk score (GRS) based on single nucleotide polymorphisms (SNPs) allele count to score COVID-19 severity might include SNPs counts related to CAD incidence and to thrombosis, inflammation, and viral infectivity determinants involved in the severity of SARS-CoV-2. Such GRS could improve the early risk stratification of COVID-19 patients and optimize treatment strategies. Purpose: To evaluate the capacity of a genetic risk score (GRS) with candidate genes to predict COVID-19 severity. Methods: We conducted an age- and sex-matched case-control study with 1:2 ratio recruitment involving 2454 patients from Catalan hospitals and primary care. Cases were hospitalized severe (requiring at least oxygen treatment) or fatal COVID-19 patients;and controls were moderate-symptom and asymptomatic patients treated at home. Standard parametric and non-parametric methods, as required, were used to compare patient characteristics by severity. Individual genotypes for 33 CAD, 14 thrombosis, 22 inflammation, 15 viral infectivity SNPs and 2 COVID-19 SNPs already published were tested for association with severity with Cochran-Armitage statistics and p-values corrected for multiple comparisons. GRS was computed as the unweighted count of adverse alleles (0, 1 or 2). The odds ratio of severe COVID-19 was analysed for GRS (and its component SNPs) with logistic regression models adjusted for potential confounding factors. Area under the curve (AUC) improvement and net reclassification index (NRI) for GRS was estimated from a basic model including CAD and COVID-19 severity risk factors. Models' performance was measured with the Akaike information criterion. Results: SNPs identifications are not shown to prevent patent conflict. Cases and control characteristics are compared in Table 1. Cases had a more adverse cardiovascular and anthropometric risk profile. After correcting for multiple testing by Benjamini-Hochberg criteria, we observed 13 SNPs to be significantly associated with severity. After excluding the close SNPs in linkage disequilibrium, 7 were retained in the GRS model, which yielded the discrimination and reclassification characteristics described in Table 2. Conclusion: A GRS with 7 SNPs related to CAD, thrombosis and inflammation significantly improves the severe COVID-19 risk assessment done with age, sex, comorbidity, and anthropometry alone. (Figure Presented).

Systematic Review on Digital Competence in the Spanish Context

The widespread use of information and communication technologies has accelerated profound changes in society. This has prompted education systems to adapt to these changes. These responses focus on digital competence. The general objective of the study is to analyse the evolution of digital competence in the Spanish context. This study has followed a bibliometric methodology. An analysis of 286 documents extracted from Web of Science has been performed. The results show that only two lines are observed that stand out from the rest. These are the cases of “digital competence-ICT-students” and “teacher-education_educational-technology_teacher-digital competence.” This indicates that over time the research focus has shifted to the use of technological resources in students and teachers. It can be concluded that the subject of study focused on digital competence in the Spanish field is being established from 2018 to the present, with its lines of research focusing on pedagogical teaching methods, technological resources and on the agents involved in training processes. This refers to the skills required by students and teachers for them to be able to successfully conduct training processes using technology. This study has been funded by the project Socio-economic impact of COVID-19 on Andalusian university students. Reference: CV20-01,248. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

ICT Motivation in Sixth-Grade Students in Pandemic Times—The Influence of Gender and Age

Information and communication technology (ICT) is being immersed in people’s daily lives at an increasingly younger age. It has been key for adolescents to pursue distance education, and their use and mastery of technological means and tools with Internet access has increased. In this study, the motivation, specifically in the interest, digital competence, autonomy, and social interaction, generated by ICTs in the daily lives of adolescents during the pandemic caused by COVID-19 was analyzed. In the study, the objective was to study the motivation, use and commitment generated by ICTs in these students in relation to their gender and age after their confinement to the classroom caused by the first wave of incoming students. An experimental method of descriptive and correlative design was used along with a quantitative method to analyze the data. The data were obtained in the year 2020 through a validated questionnaire committed to the ICT scale used by PISA (Programme for International Student Assessment). A total of 924 students from the sixth grade of primary education in the autonomous city of Ceuta (Spain), aged between 10 and 13, participated in the sample. The results reveal that the motivation and commitment to ICT in these age groups were medium in relation to the total mean of results on a Likert-5 scale. Boys scored higher in all the variables analyzed, and both age and gender show correlations, in addition to the factor of prediction. In conclusion, students in the sixth year of primary education, after the confinement period, were medium-high in their use and engagement of ICT. In addition, gender and age affected ICT use and engagement. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Vaginal birth after caesarean section before and during COVID-19 pandemic. Factors associated with successful vaginal birth.

BACKGROUND: The ratio of caesarean has been increasing considerably in many countries. Planning a vaginal birth after a previous caesarean is considered an important option for women in a subsequent pregnancy. AIMS: To analyse obstetric and neonatal outcomes in women in labour after caesarean section before and during the COVID-19 pandemic, and to determine factors associated with successful vaginal birth after caesarean (VBAC). METHODS: Observational cohort study of women in labour with history of caesarean section who gave birth between March 2019 and December 2020 in a tertiary hospital in southern Spain. Consecutive sampling was performed using the maternal birth database and a descriptive and inferential analysis of the study variables was carried out. Socio-demographic, obstetric and neonatal variables were compared between the pre-pandemic and pandemic periods. Multiple logistic regression analysis was performed to determine variables associated with VBAC success. FINDINGS: The VBAC success rate was 67.4%. The caesarean section rate was significantly higher during the COVID-19 pandemic period. Factors associated with VBAC success were: birth before the pandemic (OR 0.32) and at night (OR 0.45), use of epidural analgesia (OR 2.14), and having had a previous vaginal birth (OR 1.98). CONCLUSIONS: The success rate of VBAC was lower during the pandemic. Knowledge of the factors related to VBAC success is critical for practitioners when supporting women in decision-making about mode of birth after a previous caesarean section.

The impact of the state of alarm decreed by COVID-19 on educational Inclusion

The state of alarm decreed in most countries, due to Covid-19, forced schools to close. This meant an abrupt change in the way of teaching for which many of the teachers, families and students were unprepared. ITC took on a special role as they became the only way to access education. This situation came at a time when socio-economic differences maintained an open digital divide that prevents us from talking about equal opportunities in education and therefore educational inclusion. The aim of this study was to carry out a literature review in order to determine the consequences that this radical change in teaching has had on the process of educational inclusion, how it has affected the most vulnerable population and teachers, and what it has meant for the so-called digital divide. To this end, access has been gained to the different articles published on this field in the last year in different databases that refer to educational inclusion. The most relevant conclusions are based on the evidence of the importance of closing this digital divide that has left millions of students around the world without access to education and the great progress that has been made, in terms of experience and training of the educational community in general, in ITC and more active and autonomous methodologies for students. © 2021 North Caucasian Institute of Mining and Metallurgy, State Technological University. All rights reserved.

Clinical protocol for addressing mental health needs of healthcare professionals during COVID-19

Healthcare professionals are in the front line of care for patients with COVID-19, presenting greater risk of contagion and emotional distress. The aim of the study is to describe the results of a psychological intervention protocol for professionals;47 workers from Vall d'Hebron University Hospital who requested psychological support were included during the first month and a half of the crisis. Before and after the intervention a checklist of clinical symptoms, the Clinical Anxiety Scale and the Clinical Global Impression Scale were administered. Professionals who consulted were mostly women, nursing staff, and assistant nursing care technicians, presenting hyperconcern, sadness, sleep, and eating disturbances. Significant improvements were observed on clinical symptoms (z = 4.6, p <= .0001), acute stress (z = 2.5, p = .012), anxiety (z = 5.3, p <= .0001), and clinical impression (z = 4.1, p <= .0001). A brief psychological intervention, based on anxiety management, emotional regulation, and values oriented-behavior, was shown to be effective in reducing emotional symptoms in professionals.

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.