Learning from the past in the COVID-19 era: rediscovery of quarantine, previous pandemics, origin of hospitals and national healthcare systems, and ethics in medicine.

After the dramatic coronavirus outbreak at the end of 2019 in Wuhan, Hubei province, China, on 11 March 2020, a pandemic was declared by the WHO. Most countries worldwide imposed a quarantine or lockdown to their citizens, in an attempt to prevent uncontrolled infection from spreading. Historically, quarantine is the 40-day period of forced isolation to prevent the spread of an infectious disease. In this educational paper, a historical overview from the sacred temples of ancient Greece-the cradle of medicine-to modern hospitals, along with the conceive of healthcare systems, is provided. A few foods for thought as to the conflict between ethics in medicine and shortage of personnel and financial resources in the coronavirus disease 2019 era are offered as well.

The long-term cardiovascular impairment of COVID 19: need for clarity in definition and terminology.

Clinical experience and several large studies in the field have found that SARS-CoV-2 infection can cause long-term persistent cardiovascular (CV) impairment beyond the acute phase of the disease. This has resulted in a major public health concern worldwide. Regarding COVID-related long-term involvement of various organs and systems, using specific definitions and terminology is crucial to point out time relationships, lingering damage, and outcome, mostly when symptoms and signs of CV disease persist beyond the acute phase. Due to a lack of a common standardized definition, investigators have used interchangeable terms such as "long COVID," "post-COVID," or "post-acute sequelae of COVID-19" to describe CV involvement, thus causing some confusion. For the sake of clarity, the aim of this paper is to discuss the definition and terminology used in defining sequelae after the acute phase of COVID-19, thus pointing out the meaning of definitions like acute cardiac injury, post-acute sequelae of COVID-19, long COVID syndrome, and increased risk of atherosclerotic cardiovascular disease.

Pediatric Hypertension: A Condition That Matters.

Systemic hypertension has been considered mainly as an adult health issue for a long time, but it is now being increasingly acknowledged as a significant problem also among pediatric patients. The frequency of pediatric hypertension has grown mostly because of increases in childhood obesity and sedentary lifestyles, but secondary forms of hypertension play a role as well. Considering that unaddressed hypertension during childhood can result in enduring cardiovascular complications, timely identification and intervention are essential. Strategies for addressing this disease encompass not only lifestyle adjustments, but also the use of medications when needed. Lifestyle modifications entail encouraging a nutritious diet, consistent physical activity, and the maintenance of a healthy weight. Moreover, educating both children and their caregivers about monitoring blood pressure at home can aid in long-term management. Thus, the aim of this review is to discuss the etiologies, classification, and principles of the treatment of hypertension in pediatric patients.

Repaired Tetralogy of Fallot: Have We Understood the Right Timing of PVR?

Despite many advances in surgical repair during the past few decades, the majority of tetralogy of Fallot patients continue to experience residual hemodynamic and electrophysiological abnormalities. The actual issue, which has yet to be solved, is understanding how this disease evolves in each individual patient and, as a result, who is truly at risk of sudden death, as well as the proper timing of pulmonary valve replacement (PVR). Our responsibility should be to select the most appropriate time for each patient, going above and beyond imaging criteria used up to now to make such a clinically crucial decision. Despite several studies on timing, indications, procedures, and outcomes of PVR, there is still much uncertainty about whether PVR reduces arrhythmia burden or improves survival in these patients and how to appropriately manage this population. This review summarizes the most recent research on the evolution of repaired tetralogy of Fallot (from adolescence onwards) and risk factor variables that may favor or delay PVR.

Familial Hypercholesterolaemia in Children and Adolescents: Current and Future Perspectives.

Familial hypercholesterolemia (FH) is a genetic disease, the underlying cause of which is represented by mutations capable of influencing the metabolism of low-density lipoproteins (LDL). The distinguishing characteristic of FH has increased LDL cholesterol blood levels since birth, triggering early development of atherosclerosis-related diseases. Diagnosis of FH is frequently either missed or made with a considerable delay. Prompt identification of the disease is pivotal in implementing early prevention measures. Safe and effective drugs have been approved for use in children and adolescents, with statins, with or without ezetimibe, representing first-line therapy. At times, however, these medications may not be sufficient to achieve the therapeutic target, particularly in homozygous FH patients. Lipoprotein apheresis, which has proved safe and efficient, is strongly suggested in such cases. New drugs still at the investigational stage may represent a promising and personalised therapy. Lowering cholesterol levels in childhood hampers the formation of arterial atherosclerotic plaques, thus reducing cardiovascular events later in life. Accordingly, early detection, diagnosis, and therapy in FH subjects are priority aims.

Non-Invasive Imaging Assessment in Patients with Aortic Coarctation: A Contemporary Review.

Coarctation of the aorta (CoA) is a congenital abnormality characterized by a narrowing of the aortic lumen, which can lead to significant morbidity and mortality if left untreated. Even after repair and despite significant advances in therapeutic management, these patients have overall reduced long-term survival due to the consequences of chronic afterload increase. Cardiovascular imaging is key from the first diagnosis to serial follow-up. In recent years, novel imaging techniques have emerged, increasing accessibility to advanced imaging modalities and enabling early and non-invasive identification of complications after repair. The aim of this paper is to provide a comprehensive review of the role of different imaging techniques in the evaluation and management of patients with native or repaired CoA, highlighting their unique strengths and limitations.

Cardiovascular prevention in childhood: a consensus document of the Italian Society of Cardiology Working Group on Congenital Heart Disease and Cardiovascular Prevention in Paediatric Age.

Cardiovascular diseases (CVD) may be manifested from a very early age. Genetic and environmental (epigenetic) factors interact to affect development and give rise to an abnormal phenotypical expression of genetic information, although not eliciting changes in the nucleotide sequence of DNA. It has been scientifically proven that increased oxidative stress (OS) caused by disease (overweight, obesity, diabetes), nutritional imbalances, unhealthy lifestyles (smoking, alcohol, substance abuse) in the mother during pregnancy may induce placental dysfunction, intrauterine growth restriction, prematurity, low birth weight, postnatal adiposity rebound, metabolic alterations and consequent onset of traditional cardiovascular risk factors. OS represents the cornerstone in the onset of atherosclerosis and manifestation of CVD following an extended asymptomatic period. OS activates platelets and monocytes eliciting the release of pro-inflammatory, pro-atherogenic and pro-oxidising substances resulting in endothelial dysfunction, decrease in flow-mediated arterial dilatation and increase in carotid intima-media thickness. The prevention of CVD is defined as primordial (aimed at preventing risk factors development), primary (aimed at early identification and treatment of risk factors), secondary (aimed at reducing risk of future events in patients who have already manifested a cardiovascular event), and tertiary (aimed at limiting the complex outcome of disease). Atherosclerosis prevention should be implemented as early as possible. Appropriate screening should be carried out to identify children at high risk who are apparently healthy and implement measures including dietary and lifestyle changes, addition of nutritional supplements and, lastly, pharmacological treatment if risk profiles fail to normalise. Reinstating endothelial function during the reversible stage of atherosclerosis is crucial.

Primary and secondary paediatric hypertension.

High blood pressure (BP) or hypertension is a well known risk factor for developing heart attack, stroke, atrial fibrillation and renal failure. Although in the past hypertension was supposed to develop at middle age, it is now widely recognized that it begins early during childhood. As such, approximately 5-10% of children and adolescents are hypertensive. Unlike that previously reported, it is now widely accepted that primary hypertension is the most diffuse form of high BP encountered even in paediatric age, while secondary hypertension accounts just for a minority of the cases. There are significant differences between that outlined by the European Society of Hypertension (ESH), the European Society of Cardiology (ESC), and the last statement by the American Academy of Pediatrics (AAP) concerning the BP cut-offs to identify young hypertensive individuals. Not only that, but the AAP have also excluded obese children in the new normative data. This is undoubtedly a matter of concern. Conversely, both the AAP and ESH/ESC agree that medical therapy should be reserved just for nonresponders to measures like weight loss/salt intake reduction/increase in aerobic exercise. Secondary hypertension often occurs in aortic coarctation or chronic renal disease patients. The former can develop hypertension despite early effective repair. This is associated with significant morbidity and is arguably the most important adverse outcome in about 30% of these subjects. Also, syndromic patients, for example those with Williams syndrome, may suffer from a generalized aortopathy, which triggers increased arterial stiffness and hypertension. This review summarizes the state-of-the-art situation regarding primary and secondary paediatric hypertension.

Need for resuming sports and physical activity for children and adolescents following COVID-19 infection.

Introduction: A decline in sports activities among children and adolescents was noted during the stay-at-home restrictions imposed by COVID-19. With the easing of restrictions, physical activities are being resumed. Evidence acquisition: A data search was conducted to identify the role of parents in resuming sporting activities, the risks and benefits of doing so, the physical examination to be conducted prior to physical activity, the existence of guidelines/protocols for return to sports and physical activity, the role of comorbidities in influencing the restart of the same. Evidence synthesis: Parents should consult the child's physician prior to allowing he/she to resume physical exercise. In preparation for this, a careful physical examination should be performed. Children with COVID-19, even if asymptomatic, should not resume any physical activity until at least 10 days after testing positive. Those with moderate or severe COVID-19 should be referred for cardiological evaluation. The level of activity should be resumed gradually, as per the GRTP protocol. Athletes with a positive COVID-19 test in the presence of concomitant medical conditions (diabetes, cardiovascular or respiratory or renal disease) should undergo medical evaluation prior to adhering to a GRTP. Those with complicated COVID19 infection or long Covid may need additional investigations. Conclusions: While there is no doubt that it will bring multiple benefits in terms of general health, returning to play sport should be gradual and preceded by an accurate physical examination in those young subjects previously affected by the coronavirus disease, especially when their heart and/or lungs and/or kidneys were affected.

COVID-19 Vaccine-Induced Pro-thrombotic Immune Thrombocytopenia (VIPIT): State of the Art.

In 2020, as the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic spread rapidly throughout the world, scientists worked relentlessly to develop and test the safety and effectiveness of potential vaccines. Usually, the vaccine development process involves years of investigation and testing prior to gaining approval for use in practice. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, may be manifested following the administration of viral vector vaccines. It leads to severe clot formation at unusual sites approximately in 1 out of 110.000 vaccinated persons. This side effect, although rare, represents a newly devastating clotting phenomenon manifested in otherwise healthy young adults, who are often female. An in-depth description of the specific biological mechanisms implicated in the syndrome is here summarized.

Concerning the unexpected prothrombotic state following some coronavirus disease 2019 vaccines.

Currently, the world is coping with the COVID-19 pandemic with a few vaccines. So far, the European Medicine Agency has approved four of them. However, following widespread vaccination with the recombinant adenoviral vector-based Oxford-AstraZeneca vaccine, available only in the United Kingdom and Europe, many concerns have emerged, especially the report of several cases of the otherwise rare cerebral sinus vein thrombosis and splanchnic vein thrombosis. The onset of thrombosis particularly at these unusual sites, about 5--14 days after vaccination, along with thrombocytopenia and other specific blood test abnormalities, are the main features of the vaccine side effects. The acronym vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) has been coined to name this new condition, with the aim of highlighting the difference from the classic heparin-induced thrombocytopenia (HIT). VIPIT seems to primarily affect young to middle-aged women. For this reason, the vaccine administration has been stopped or limited in a few European countries. Coagulopathy induced by the Oxford-AstraZeneca vaccine (and probably by Janssen/Johnson & Johnson vaccine as well in the USA) is likely related to the use of recombinant vector DNA adenovirus, as experimentally proven in animal models. Conversely, Pfizer and Moderna vaccines use mRNA vectors. All vaccine-induced thrombotic events should be treated with a nonheparin anticoagulant. As the condition has some similarities with HIT, patients should not receive any heparin or platelet transfusion, as these treatments may potentially worsen the clinical course. Aspirin has limited rational use in this setting and is not currently recommended. Intravenous immunoglobulins may represent another potential treatment, but, most importantly, clinicians need to be aware of this new unusual postvaccination syndrome.

Cerebral Venous Sinus Thrombosis following COVID-19 Vaccination: Analysis of 552 Worldwide Cases.

To date, billions of vaccine doses have been administered to restrain the current COVID-19 pandemic worldwide. Rare side effects, including intravascular blood clots, were reported in the general population after vaccination. Among these, cerebral venous sinus thrombosis (CVST) has been considered the most serious one. To shed further light on such an event, we conducted a literature search for case descriptions of CVST in vaccinated people. Findings were analyzed with emphasis on demographic characteristics, type of vaccine, site of thrombosis, clinical and histopathological findings. From 258 potential articles published till September 2021, 41 studies were retrieved for a total of 552 patients. Of these, 492 patients (89.1%) had received AZD1222/Vaxzevria, 45 (8.2%) BNT162b2/CX-024414 Spikevax, 15 (2.7%) JNJ-78436735, and 2 (0.3%) Covishield vaccine. CVST occurred in 382 women and 170 men (mean aged 44 years), and the median timing from the shot was 9 days (range 2-45). Thrombi were predominantly seen in transverse (84%), sigmoid (66%), and/or superior sagittal (56%) sinuses. Brain injury (chiefly intracranial bleeding) occurred in 32% of cases. Of 426 patients with detailed clinical course, 63% were discharged in good clinical conditions, at times with variable neurological sequelae, whereas 37% deceased, largely due to brain injury. This narrative review confirmed CVST as a rare event after (adenoviral vector) COVID-19 vaccination, with a women/men rate ratio of 2.25. Though the pathogenesis of thrombosis is still under discussion, currently available histopathological findings likely indicate an underlying immune vasculitis.

Does Oxygen Content Play a Role in Spontaneous Closure of Perimembranous Ventricular Septal Defects?

(1) Background: the impact of a series of laboratory parameters (haemoglobin, haematocrit, foetal haemoglobin, peripheral oxygen saturation, iron, transferrin, ferritin, and albumin) on perimembranous ventricular septal defects spontaneous healing was tested. (2) Methods: one hundred and seven patients were enrolled in the study (57% males; mean age 2.1 ± 0.4 years) and were subsequently subdivided into two groups: self-healing (n = 36) and in need of intervention (n = 71). Self-healing subjects were defined on the basis of an absence of residual shunts at colorDoppler across the previous defect. (3) Results: no statistically significant differences were reported in the size of perimembranous ventricular septal defects between the two groups (p = ns). Conversely, prevalence of anaemia was significantly higher in those requiring intervention than in the self-healing group (p < 0.03), while haemoglobin, iron, ferritin, and albumin levels were lower (p < 0.001, p < 0.05, p < 0.02, p < 0.007, respectively). In multivariable linear regression analysis, only haemoglobin and albumin were found to be associated with spontaneous closure (p < 0.005 and p < 0.02, respectively). In multiple logistic regression analysis, haemoglobin independently increased the probability of self-healing of perimembranous ventricular septal defects (p = 0.03). All patients needing an interventional closure of perimembranous ventricular septal defects presented with haemoglobin <12.7 g/dL. (4) Conclusion: the self-resolution of perimembranous ventricular septal defects seems to rely on numerous factors, including oxygen content, which is likely to promote cell proliferation as well as tissue regeneration. Haemoglobin blood concentration seems to influence the natural history of perimembranous ventricular septal defects and improvement of anaemia by supplementation of iron intake might represent a simple and reliable method to promote self-healing.

Pulmonary hypertension in pediatrics. A feasible approach to bridge the gap between real world and guidelines.

Pulmonary hypertension (PH) is quite infrequent in pediatric age and its most common etiologies include idiopathic pulmonary arterial hypertension, PH related to congenital heart diseases, bronchopulmonary dysplasia (chronic lung disease), persistence of pulmonary hypertension of the newborn, and congenital diaphragmatic hernia. The developed for adult patients PH classification shows limitations when applied to pediatric subjects since the underlying causes are markedly different between the two ages. In 2011, the Pulmonary Vascular Research Institute Panama Task Force outlined the first specific pediatric pulmonary hypertensive vascular disease diagnostic classification, including 10 main categories and 109 subcategories, thus testifying PH complex pathophysiology during newborns/children growth and development. The unique, distinctive features of pediatric PH were recognized also during the fifth World Symposium on pulmonary hypertension in 2013 and then confirmed in the recent 2018 sixth World Symposium. For the sake of uniformity, an attempt to adapt the adult classification to pediatric patients was made. However, all these commendable classifications are very complex and maybe not of quick comprehension for clinicians. A clinical simpler and simplified method is now suggested, comprising only five groups: neonatal, cardiac, developmental, idiopathic, and syndromic PH. This approach is not aimed at replacing the already existing classifications but is mainly based on the kind of specialized physician (neonatologist, pediatric cardiologist, pediatrician, pulmonologist, general practitioner) who first faces and looks after the child with suspected PH. What is dramatically known is that pediatric PH is a severe disease which, when untreated or undertreated, may lead to increased morbidity and mortality.

[High blood pressure in children and adolescents: lights and shadows in the American Academy of Pediatrics clinical practice guidelines]. / La pressione elevata nei bambini e negli adolescenti: luci ed ombre nelle linee guida per la pratica clinica dell'Accademia Americana di Pediatria.

High blood pressure in pediatric age is meeting a growing interest owing to the possible aftermaths in adult age in terms of public health. In fact, children and adolescents with high blood pressure values are likely to become hypertensive adults, thus developing cardiovascular diseases. Over the last decade, numerous studies have been conducted in this field. That is the reason why the American Academy of Pediatrics in 2017 published un update on the previous recommendations of the United States Fourth Working Group on pediatric blood pressure. This update includes a new classification of hypertension, the endorsement of the 24-hour ambulatory blood pressure monitoring and the reduction in the blood pressure target for both chronic kidney disease and non-chronic kidney disease hypertensive children. This review discusses strengths and weaknesses of the recent practical guidelines of the American Academy of Pediatrics.

COVID 19 Vaccine for Adolescents. Concern about Myocarditis and Pericarditis.

The alarming onset of some cases of myocarditis and pericarditis following the administration of Pfizer-BioNTech and Moderna COVID-19 mRNA-based vaccines in adolescent males has recently been highlighted. All occurred after the second dose of the vaccine. Fortunately, none of patients were critically ill and each was discharged home. Owing to the possible link between these cases and vaccine administration, the US and European health regulators decided to continue to investigate the potential causal relationship between COVID-19 mRNA vaccines and myocarditis. In any case, none of the patients fulfilled the criteria for multi-system inflammatory syndrome or Kawasaki-like disease and there was no evidence of acute SARS-CoV-2 infection.

Adult congenital heart disease: Special considerations for COVID-19 and vaccine allocation/prioritization.

Individuals with the highest risk for adverse outcomes of COVID-19 should be prioritized by the vaccine allocation policies. We have conducted a literature review of published studies, which comprehend congenital heart disease (CHD) and COVID-19, in order to present the overall evidences of both exposure and clinical risk of patients with adult congenital heart disease (ACHD) and to propose a risk profile schema for those patients to be incorporated into vaccine distribution decisions.

The Deadly Quartet (Covid-19, Old Age, Lung Disease, and Heart Failure) Explains Why Coronavirus-Related Mortality in Northern Italy Was So High.

Since its outbreak in China at the end of 2019, the new coronavirus disease (COVID-19) was characterized by both easy spreading and high mortality. The latter proved to be way more elevated in the North of Italy -with a peak of 18.4% in region Lombardia and even 31% in the city of Bergamo and surrounding county- than in the rest of the world. In an attempt to conceptualize the reasons for such a dramatic situation, four key elements have been identified: COVID-19 itself, old age, lung disease, and heart failure. Their harmful combination has been named "The deadly quartet". The underlying risk factors, among which a lot of them are distinctive features of the population in northern Italy, have been summarized as "unmodifiable", "partially modifiable", and "modifiable", for the sake of clarity. Up-to-date scientific evidence in this field has been described in the form of a narrative and easy-to-read review.