"Actionable" host genetic markers for repurposing "add-on therapy" in COVID-19

Background/Objectives: COVID-19 still represents a lifethreatening disease in individuals with a specific genetic background. We successfully applied a new Machine Learning method on WES data to extract a set of coding variants relevant for COVID- 19 severity. We aim to identify personalized add-on therapy. Method(s): A subset of identified variants, "actionable" by repurposed drugs, were functionally tested by in vitro and in vivo experiments. Result(s): Males with either rare loss of function variants in the TLR7 gene or L412F polymorphism in the TLR3 gene benefit from IFN-gamma, which is specifically defective in activated PBMCs, restoring innate immunity. Females heterozygous for rare variants in the ADAMTS13 gene and males with D603N homozygous polymorphism in the SELP gene benefit from Caplacizumab, which reduces vWF aggregation and thrombus formation. Males with either the low-frequency gain of function variant T201M in CYP19A1 gene or with poly-Q repeats >=23 in the AR gene benefit from Letrozole, an aromatase inhibitor, which restores normal testosterone levels, reducing inflammation and which rescues male golden hamsters from severe COVID-19. Conclusion(s): By adding these commonly used drugs to standard of care of selected patients, the rate of intubation is expected to decrease consistently, especially in patients with high penetrance rare genetic markers, mitigating the effect of the pandemic with a significant impact on the healthcare system.

Care transition of older adults from hospital to home

Objective: To analyze the quality of care transition of older adults who were discharged from hospital to home. Methods: This is a cross-sectional observational study, conducted with 156 older adults after public hospital admission, located in the municipality of Piracicaba, state of Sao Paulo. Data were collected in patients' electronic medical records and by telephone calls with older adults, their relatives and/or caregivers, up to four weeks after hospital discharge. We used a questionnaire with sociodemographic data and the Care Transitions Measure, version validated for Brazil. Results: The mean duration of the last hospitalization was 8.27 days, mostly caused (72.44%) by COVID-19 and 75% of older adults had between 1 and 3 comorbidities, with hypertension (57.7%) being the most frequent. The mean CTM-15 score was 68.6. Factor 1, Management preparation, obtained the highest score (70.5), and Factor 4, Care plan, the lowest (59.14). There was a positive correlation between the 4 factors of Care Transitions Measure, also among these factors is the number of drugs used to treat older adults, according to the Anatomical Chemical Therapeutic Classification. Conclusion: We evidenced the quality of the transition of care in the hospital close to the value considered satisfactory, with two of the four factors with a score greater than 70;however, there is a need to adopt strategies to improve the discharge process from hospital to home, especially with regard to preferences imported and care plan for older adults.

Diagnostic Approach and Treatment of Lung Cancer Patients in Portugal: Portuguese Lung Cancer Study Group Survey

Introduction: In Portugal, in 2020, 5415 new lung cancer patients were diagnosed and 4797 deaths were caused by lung cancer. Lung cancer ranks third in terms of cancer incidence and is the leading cause of cancer mortality. Early diagnosis, complete and fast patient assessment and staging, multidisciplinary approach, access to personalized medicine, new treatment options and research are essential to improve survival and quality of life. Access to clinical trials is critical for this improvement.The aim of this study is to assess the techniques available to the diagnostic work-up, treatments, the waiting time and the needs perceived by physicians. Methods: The Portuguese Lung Cancer Study Group launched a survey in order to study the diagnostic approach and treatment of lung cancer patients in Portugal. An online survey with 47 questions was sent to all Portuguese hospitals that treat lung cancer, referring to the pre-COVID-19 pandemic experience. Results: Responses from 31 Portuguese hospitals were collected, between May and September 2020. Availability to bronchoscopy, image-guided transthoracic needle biopsy (TNB), endobronchial ultrasound- transbronchial needle aspiration (EBUS-TNBA), PET/CT, molecular biology testing is presented in table I. In 58% (n=18) the molecular biology test was performed as a "reflex test". About 68% (n=21) of hospitals used next generation sequencing. Two hospitals (7%) reported not having access to liquid biopsies.Video-assisted thoracoscopic surgery was the main surgical technique (61%;n=19). The waiting time for the first radiation oncology consultation was less than 15 days in 71% (n=26). About 61% (n=19) of hospitals had clinical trials. A wide majority of doctors (77%) would like to have more clinical trials. In 71% (n=22) of the hospitals, it was possible to refer patients to Palliative Care receiving systemic anticancer therapy. [Formula presented] Conclusions: Despite the limitations of the methods, this study allowed us to deepen our knowledge about the work-up technologies and treatments available for lung cancer patients in Portugal. It has also identified future opportunities, such as increasing accessibility to some diagnostic tools and clinical trials. Keywords: Diagnosis and treatment approach, Lung Cancer in Portugal, Health Services Research - Portugal

SARS-CoV-2 infection and return-to-play in junior competitive athletes: is systematic cardiac screening needed?

Background: SARS-CoV-2 infection might be associated with cardiac complications in low-risk populations, such as in competitive athletes. However, data obtained in adults cannot be directly transferred to preadolescents and adolescents that are less susceptible to adverse clinical outcomes and are often asymptomatic. Purpose: We conducted this prospective multi-centre study to describe the incidence of cardiovascular complications following SARS-CoV-2 infection in a large cohort of junior athletes and to examine the effectiveness of a screening protocol for a safe return-to-play. Methods: Junior competitive athletes suffering from asymptomatic or mildly symptomatic SARS-CoV-2 infection underwent cardiac screening, including physical examination, 12-lead resting electrocardiogram (ECG), echocardiogram, and exercise ECG testing. Further investigations were performed in cases of abnormal findings. Results: A total of 571 competitive junior athletes (14.3±2.5 years) were evaluated. About half of the population (50.3%) was mildly symptomatic during SARS-CoV-2 infection, and the average duration of symptoms was 4±1 days. Pericardial involvement was found in 3.2% of junior athletes: small pericardial effusion (2.6%), moderate pericardial effusion (0.2%), and pericarditis (0.4%). No relevant arrhythmias or myocardial inflammation were found in subjects with pericardial involvement. Athletes with pericarditis or moderate pericardial effusion were temporarily disqualified, and a gradual return-to-play was achieved after complete clinical resolution. Conclusions: The prevalence of cardiac involvement was low in junior athletes after asymptomatic or mild SARS-CoV-2 infection. A screening strategy primarily driven by cardiac symptoms, ECG abnormalities and arrhythmias at rest and/or during exercise should detect cardiac involvement from SARS-CoV-2 infection in most junior athletes. Systematic echocardiographic screening is not recommended in junior athletes. (Figure Presented).

Early multidisciplinary evaluation in a case of refractory cardiogenic shock

A 19-year-old man was centralized in our cardiac intensive care unit due to refractory cardiogenic shock and multiorgan failure (MOF).At the admission he presented with hypotension, tachycardia and severe metabolic acidosis (pH 6.8,lac 18),ECG showed sinus tachycardia with left branch block, the echocardiography showed dilated left ventricle,with normal thickness (no edema), EF 15% with diffuse hypokinesia and right ventricle dysfunction (TAPSE 12 mm,S' 8,FAC 25%).He had elevated levels of transaminases and severe reduction of liver synthesis (INR 3.7,ATIII 19%,fibrinogen 53 mg/dl). From patient's history emerged a familiarity for an unspecific heart disease and some months ago fever (SARS-CoV2 tests negative) and progressive symptoms of right ventricle heart failure appeared.After the admission the patients was supported with ino-vasopressors,then bicarbonate and coagulation factors were administered and ventilation was optimized. Patient had a cardiogenic shock stage D and MOF,therefore a mechanical circulatory support (MCS) would have been indicated but from heart team discussion emerged fear of vascular complications or systemic bleeding during MCS support,due to the severe alteration of the caogulative state. Furthermore there were no adjunctive indications for veno- arterial ECMO support such as severe hypoxemia or ventricular arrhythmias.Multiparameter monitoring continued and two femoral sheath were positioned for a possible MCS implantation. After few hours systemic pressure stabilized. with norepinephrine and dobutamine, diuresis was adequate, blood gas improved, lactate reached 24 mmol/l and then slowly decrease for a concomitant liver dysfunction. After levosimendan infusion right ventricle contractility improved and after 5 days the patient was extubated. Acute or subacute myocarditis was excluded because of cardiac MRI did not show edema but bilateral fibrosis, myocardial biopsy showed little fibrosis,no lympho-monocitary infiltrates,no viral inclusion,no accumulation. Serological tests excluded viral hepatitis, Chagas disease, ceruloplasmin levels were normal. The patient was discharged after execution of check-list for heart transplantation, moreover CRT-D was implanted. Genetical exams are ongoing. Conclusion: Rapid patient centralization and discussion with heart team,assessing hemodynamic laboratory and metabolic parameters,allowed us to avoid an early MCS implantation and to observe the positive effects of pharmacological and support therapy (Figure Presented).

ANMCO POSITION PAPER: Considerations on in-hospital cardiological consultations and cardiology outpatient clinics during the COVID-19 pandemic

Infections by SARS CoV2-COVID-19 have become in a short time a worldwide health emergency. Due to cardiovascular implications of COVID-19 and to very frequent previous cardiovascular disorders of COVID-19 patients, it is presently crucial that Cardiologists are fully aware of COVID-19 related epidemiological, pathophysiological and therapeutic problems, in order to manage at best the present emergency by appropriate protocols developed on the basis of the competences acquired and shared on the field. The aim of this document is to propose algorithms for the management of cardiovascular diseases during COVID-19 emergency with the objective of providing patients with optimal care, minimizing contagion risk and appropriately managing personal protective equipment.

Anmco position paper: The role of cardiology in the management of the health needs in the post-Covid-19 era

At the end of 2019 a new Coronavirus appeared in China and, from there, it spread to the rest of the world. On 24th May, 2020, the confirmed cases in the world were more than 5 million and the deaths almost 350.000. At the end of May, Italy reported more than 27.000 cases among healthcare professionals and 163 deaths among physicians. The National Health Systems from almost all over the world, including Italy's, were unprepared for this pandemic, and this generated important consequences of organizational nature. All elective and urgent specialized activities were completely reorganized, and many hospital units were partially or completely converted to the care of the COVID-19 patients. A significant reduction in hospital admissions for acute heart disease were recorded during the SARS-CoV-2 pandemic and, in order to gradually resume hospital activities, the Italian National Phase 2 Plan for the partial recovery of activities, must necessarily be associated with a Phase 2 Health Plan. In regards to the cardiac outpatient activities we need to identify short term goals, i.e. reschedule the suspended outpatient activities, revise the waiting lists, review the 'timings' of the bookings. This will reduce the number of available examinations compared to the pre-Covid-19 era. The GP's collaboration could represent an important resource, a structured telephone follow-up plan is advisable with the nursing staff's involvement. It is equally important to set medium-long term goals, the pandemic could be an appropriate moment for making a virtue of necessity. It is time to reason on prescriptive appropriateness, telemedicine implementation intended as integration to the traditional management. It is time to restructure the cardiological units related to the issue of structural adjustment to the needs for functional isolation. Moreover, the creation of 'grey zones' with multidisciplinary management according to the intensity of care levels seems to be necessary as well as the identification of Covid dedicated cardiologies. Finally, the pandemic could represent the opportunity for a permanent renovation of the cardiological and territorial medicine activities. © 2020 Oxford University Press. All rights reserved.

ANMCO POSITION PAPER: Network Organization for the Treatment of Acute Coronary Syndrome Patients during the Emergency COVID-19 Pandemic

The COVID-19 pandemic has become a global health emergency. In Italy, the number of people infected by SARS-COVID-2 is rapidly increasing and what emerges from the current data is that the majority do not present any symptoms or only minor flu-like symptoms. In about 20% of the patients, the disease progresses towards more complex forms (interstitial pneumonia to acute respiratory distress and multiple organ failure) with the need of hospitalization in CICU and advanced ventilator assistance. The transmission of the virus occurs very easily from the symptomatic patient s droplets from coughing and sneezing and from direct contact with persons or surfaces. In a patient presenting with ST elevation (STEMI) myocardial infarction or STEMI-like, if positive to COVID-19, the reperfusion therapeutic strategy depends on the local organization and on the possibility to access without delay a PCI COVID Center, on the basis, obviously, of the risk/benefit assessment of the individual case. However, we advise to try pursuing, in the first instance, the mechanical revascularization strategy, according to the available local possibilities.

Prognostic bioindicators in severe COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. MATERIALS AND METHODS: Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. RESULTS: In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. CONCLUSIONS: Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.

What is the role of rapid diagnostic tests for covid-19 igm/igg in the pre-operative period of cosmetic plastic surgery?

Introduction: The disease by the new coronavirus 2019 (COVID-19) emerged in China and spread globally with sustained worldwide transmission from human to human. The COVID-19 IgM/IgG rapid diagnostic tests performed at the time of hospital admission, before elective surgery, are among the most widely used pre-operative screening methods. Objectives: This study aims to evaluate the role of the rapid test of COVID-19 antibodies as screening in outpatients in aesthetic plastic surgery. Methods: A systematic review was carried out for studies published since December 2019, with several search terms related to the rapid antibody test for COVID-19 and SARS-CoV-2. The relevant articles were selected through the evaluation of titles and abstracts. Relevant articles have been revised. Data on the level of evidence, sensitivity, and specificity were collected. Results: The review strategy produced 409 manuscripts. A total of 357 studies were duplicated or proved to be irrelevant to the research question. Among the remaining articles, 28 were studies without precision information, and 24 were manuscripts describing precision measures. The sensitivity varied from 18.4 to 100%;the positive predictive value between 19.7 and 100%;specificity between 94 and 100%;and the negative predictive value between 20 and 100%. Conclusion: COVID-19 IgM / IgG rapid diagnostic tests may be inaccurate. We found no evidence to support the rapid antibody test COVID-19 or SARS-CoV-2 for outpatients in cosmetic plastic surgery. © 2021, Sociedade Brasileira de Cirurgia Plastica (SBCP). All rights reserved.