Discrimination and Calibration of Predictive Scores of Mortality in Ecmo for Patients with Covid-19

INTRODUCTION: The criteria for the COVID-19 patients' selection that benefit most from ECMO therapy are yet to be defined. In this study, we evaluate the predictive performance of the ECMO mortality predictive models in patients with COVID-19. METHOD(S): A retrospective study was performed in two high-complexity hospitals between March 18, 2020, and December 31, 2021. We included patients over 18 years old with COVID-19 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) who received V-V ECMO due to COVID-19-related ARDS. We evaluated the predictive performance (discrimination, calibration, and accuracy) of death prediction of the following predictive models: i) Prediction of Death due to Severe ARDS in V-V ECMO score (PRESERVE);ii) The Respiratory Extracorporeal Membrane Oxygenation Survival Score (RESP) score;iii) Prediction of Survival on ECMO Therapy- Score (PRESET) score, to predict death. Also, we perform a cost-benefit analysis using the health-related quality of life reported by the CESAR TRIAL and the US life expectancy. Besides, we add the mortality predicted probability calculated with the best predictive model to the cost-benefit analysis. Therefore, the cost/QALY formula was: cost/QALY = cost / age-specific life expectancy*health utilitiesz.ast;survival probability. RESULT(S): We included 38 adult patients who received ECMO due to COVID-19. The PRESET score had the highest discrimination (AUROCs 0.81 [CI95% 0.67-0.94]) and the best calibration (Hosmer-Lemeshow test, p=0.6). The optimal threshold for this score was 7 (sensitivity 67%, specificity 89%, accuracy 78%). The cost per QALY in the USA, adjusted to life expectancy, was higher than UDS 100,000 in patients older than 45 years with a PRESET>10. CONCLUSION(S): The PRESET score had the highest predictive performance and could help in the patient's selection that benefits most from this resource-demanding and highly invasive therapy. Also, the addition of the costbenefit analysis output can help decide which patient to place on ECMO therapy, especially in low-resource settings.

Surfactant protein D (SP-D) as biomarker of SARSCOV-2 infection

Beside lowering the surface tension at air-liquid interface in the alveoli, the pulmonary surfactant has a pivotal role in triggering the elimination of pathogens or any hazardous materials introduced with breathing. Among the components of the pulmonary surfactant, surfactant protein-D (SP-D) is a low abundant (0.6%) hydrophilic protein that is able to promote pathogens clearance binding highly conserved glycosidic residues on their surface. SP-D also cooperates in the maintenance of lung homeostasis by directly modulating immune system activity. Previous investigations on acute respiratory distress syndrome (ARDS) patients demonstrated a significant increment of SP-D serum level compared with healthy donors. Since in physiological condition SP-D is not permeable to alveoli-capillary membrane and poorly express by other tissues, this enhancement is likely due to an impairment of the pulmonary barrier caused by prolonged inflammation. In view of the above, the present work aims to investigate SP-D as diagnostic and/or prognostic marker for COVID-19. In particular, a retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio (i.e., 79 mild cases plus 123 severe cases) was conducted to assess differences of the hematic levels of this biomarker among COVID-19 patients and healthy donors and if SP-D serum levels resulted a risk factor for disease severity and mortality. The performed analyses, using an Anova-Mixed model, showed a significant difference in the mean of log SP-D between COVID-19 patients and healthy donors: 150 ng/mL was identified as threshold value to best discriminate the mentioned groups. Significant differences were also found between dead vs survived patients, as well among severe vs non-severe cases. In all cases, SP-D serum levels presented significantly higher values for COVID-19 patients, dead and severe cases.Moreover, further analysis conducted with Logistic Mixed models, highlighted that SP-D, in a model with Age, C-reactive protein and cancer status, resulted the strongest significant risk factor of mortality (model predictive accuracy, AUC=0.826), and in a lesser extent for risk of severity.The overall data suggest that SP-D can be a predictive marker of COVID-19 disease and its outcome.

The Inclusion of Students With Disabilities: Challenges for Italian Teachers During the Covid-19 Pandemic

In March 2020 all schools in Italy were closed due to the Covid-19 pandemic, and the novelty of distance learning was introduced. During the 2020-2021 school year, pre-primary and primary schooling was carried out in situ, while secondary education was re-organized into a mixed system, with students spending 50% of their time attending classes from home, in distance learning. This reconfiguration was a challenge to students, teachers, and parents, affecting the learning experience of the most vulnerable students and students with disabilities, particularly. It necessarily brought into question Italy's "progressive" legal framework for "school inclusion." The scope of the present article is to analyze the teaching activities carried out with students with disabilities in Italy during the first wave of the emergency lockdown and their consequent challenges for school inclusiveness. An overview of the Italian inclusive model in education and the national measures adopted to guarantee the right to education during times of school closure/restriction is outlined. We have sought to test the hypothesis that distance learning may introduce many risks for inclusion (resulting in a "downgrading inclusion," that is, a decline of the level of inclusion already reached for students with disabilities), but it may also present an improvement in how teachers address these students and their needs. To this end, after reporting data from the available studies on this target, we provide insights from a web questionnaire submitted to a non-probabilistic sample of nearly 150 primary and (lower and upper) secondary school teachers. Results showcase that, though with a general worsening of school inclusion, in some cases, teachers were actually able to support students with disabilities and their families in a new, customized, empathetic, and more attentive manner.

Development of an integrated environmental monitoring protocol for SARS-CoV-2 contamination. Applications at the IRCSS San Martino Polyclinic Hospital in Genoa, Italy.

SCIENTIFIC BACKGROUND: Environmental sampling of SARS-CoV-2 is a fundamental tool for evaluating the effectiveness of non-specific prophylaxis measures in counteracting virus spread. The purpose of our work was to evaluate the effectiveness of the different sampling methods in the hospital setting to assess their correlation with the structural, functional, and operational situation of the monitored departments and to define the dynamics of the spread of the virus in indoor environments. METHODS: The monitoring (air bubbling sampling, surface wipe test) was carried out at the San Martino Polyclinic Hospital (Genoa, Italy) in the period since April 2020 to June 2021. The presence of viral RNA in the collected samples was evaluated by qPCR. The infection capacity of the samples collected was also evaluated by an in vitro challenge test on cells sensitive to SARS-CoV-2 infection. RESULTS: The percentage of positivity with respect to the number of tests performed (sensitivity) were air bubbler 50%, wipe test 17%, and challenge test 11%. Only 20% of the samples tested positive in the wipe test and 43% of the samples tested positive in the bubbler sampling were also positive in the challenge test. All the positivity obtained was detected at a distance of less than 2 m and height of less than 1.5 from COVID-19 patients. CONCLUSIONS: Environmental contamination from SARS-CoV-2 detected at the San Martino Polyclinic Hospital is found lower than similar assessments performed in other hospitals both in Italy and abroad. Our study predicted that environmental monitoring of SARS-CoV-2 must be carried out in an integrated way by not using a single sampling method, as each individual test has a different biological significance and performance. However, the virus detected by wipe test only is often a degraded viral fragment and not an intact infecting virion.

New Older Users’ Attitudes Toward Social Networking Sites and Loneliness: The Case of the Oldest-Old Residents in a Small Italian City

Older adults make little use of social networking sites (SNS). SNS has become essential for maintaining social contacts and countering loneliness in the current era marked by the Covid-19 pandemic. This study explores the attitudes of the oldest-old on SNS after attending a training course on SNS use. The study’s goals are to investigate their personal experiences, choices of use and to survey their views on the usefulness of SNS and its effects on mitigating loneliness for older people. The interviews were conducted in the context of the “Ageing in a Networked Society—Social Experiment Study.” The participants, who were randomly selected for the course on SNS use, agreed to be interviewed during the post-intervention evaluation (N = 39). Results show SNS are mainly and productively used with relatives and friends. A positive view is reported for the potential impact of using SNS to counter loneliness, but mainly for socially isolated older individuals, while only a few find online contact futile. Intergenerational communication and a perspective of SNS as a leisure activity were identified as motivational factors for SNS use. Rare use or non-use are mainly related to privacy and security issues and technical difficulties. This is also the reason underlying the majority’s preference for WhatsApp over Facebook. These findings confirm the need for widespread SNS-focused online communication training interventions for seniors. On the speculative level, these results complement the existing literature by delving deeper into the perceptions of new older SNS users, a poorly studied segment of the population. © The Author(s) 2021.

Antiandrogen therapy and TMPRSS2 status: How prostate cancer patients are protected from COVID-19 pandemic

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into target cells by exploiting the cellular transmembrane protease serine 2 (TMPRSS2) for spike protein cleavage. Male gender, age, obesity, diabetes, hypertension are some of the factors related to coronavirus disease 2019 (COVID-19) severity and mortality. Prostate cancer (PCa) patients (pts) are expected to be at higher risk for COVID-19 due to age and disease related comorbidities. TMPRSS2 transcription depends on androgens and androgen receptor and it is significantly downregulated by hormone therapies commonly used to treat PCa in different settings. Supposing that in PCa pts androgen deprivation therapy (ADT) could hamper SARS-CoV-2 cell entry, we aim to evaluate if the presence of single nucleotide polymorphisms (SNPs) in the androgen responsive elements (AREs) in the TMPRSS2 promoter is associated to COVID-19 outcomes. Trial design: The present exploratory biological study is part of an ongoing retrospective-prospective multicenter cohort trial designed to verify whether PCa pts on ADT develop milder clinical presentation of COVID-19 than the general male population. The cohort trial collects real world data since February 2020 through regional databases that identified 200,000 potential pts to be enrolled to compare the clinical outcome of COVID-19 between PCa pts on active therapy (Study Group) and non-PCa pts (Control Group). Within the Study Group, we will compare the COVID-19 outcome between treatment subgroups: ADT alone, ADT plus antiandrogens, CYP17 inhibitors or chemotherapy. To identify SNPs in AREs of the TMPRSS2 gene and to describe possible associations with COVID-19 outcome, blood samples will be collected from 50 PCa pts treated at selected centers. Pts will participate voluntarily and sign an informed consent approved by local ethical committees. We will centrally perform PBMCs isolation and DNA extraction by using quiagen QIAamp DNA Mini Kit. SNPs will be evaluated with the Axiom™ Human Genotyping SARS-CoV-2 array. The effect of ADT will be corrected depending on identified SNPs and associated to COVID-19 outcome. The study is ongoing: we processed blood samples from 21 pts. Final results are awaited by the end of 2021. Legal entity responsible for the study: The authors. Funding: Fondazione IRCCS Istituto Nazionale Tumori di Milano. Disclosure: All authors have declared no conflicts of interest.

COVID-19: Vademecum for gastrointestinal endoscopy

Since the novel coronavirus disease (COVID-19) outbreak has been spreading globally, Italy and other nations worldwide have been adopting very strict measures to protect populations from the infection. However, the number of infected people is growing exponentially and the COVID-19 disease has been declared a pandemic by the World Health Organization. Endoscopy units (EUs) face significant risk for diffusion of respiratory diseases that can be spread via an airborne route, including aspiration of oral and fecal material via endoscopes. The purpose of this article is to discuss the potential impact of COVID-19 infections on EUs and to show how they should contribute to fighting the spread of this infection, protecting both patients and healthcare personnel. Further, we briefly report data on the current burden of the COVID-19 outbreak on EUs across Italy.

Immunometabolic Status of COVID-19 Cancer Patients.

Cancer patients appear to be more likely to be diagnosed with coronavirus disease 2019 (COVID-19). This is supported by the understanding of immunometabolic pathways that intersect patients with infection and cancer. However, data derived by case series and retrospective studies do not offer a coherent interpretation, since data from China suggest an increased risk of COVID-19, while data from the United States and Italy show a prevalence of COVID-19 in cancer patients comparable with the general population. Noteworthy, cancer and COVID-19 exploit distinct patterns of macrophage activation that promote disease progression in the most severe forms. In particular, the alternative activation of M2-polarized macrophages plays a crucial role in cancer progression. In contrast, the macrophage-activation syndrome appears as the source of M1-related cytokine storm in severe COVID-19 disease, thus indicating macrophages as a source of distinct inflammatory states in the two diseases, nonetheless as a common therapeutic target. New evidence indicates that NAMPT/NAD metabolism can direct both innate immune cell effector functions and the homeostatic robustness, in both cancer and infection. Moreover, a bidirectional relationship exists between the metabolism of NAD and the protective role that angiotensin converting enzyme 2, the COVID-19 receptor, can play against hyperinflammation. Within this immunometabolic framework, the review considers possible interference mechanisms that viral infections and tumors elicit on therapies and provides an overview for the management of patients with cancer affected by COVID-19, particularly for the balance of risk and benefit when planning normally routine cancer treatments and follow-up appointments.