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Background/Objectives: While post-acute COVID-19 syndrome is well known and extensively studied, the post-acute COVID vaccination syndrome (PACVS) is a more recent nosological entity that is poorly defined at the immunopathological level, although it shares many symptoms with the sequelae of viral infections. Methods: This single-center retrospective study reports a case series of 17 subjects vaccinated with mRNA or adenoviral vector vaccines who were healthy before vaccination and had never been infected with SARS-CoV-2 but who presented with symptoms similar to PACVS for a median time of 20 months (min 4, max 32). The medical records of all patients referred to our outpatient clinic over a one-year period were retrospectively analyzed. Results: In this group, serological tests showed that, in addition to positivity for anti-spike protein antibodies, a high percentage of subjects were positive for antibodies against G protein-coupled receptors and molecules involved in the response to SARS-CoV-2. In a panel of 16 autoantibodies tested, a few were positively associated with some of the symptoms reported by patients: anti-ATR1 with lymphadenopathy and/or tonsillitis; anti-ACE2 with skin symptoms such as ecchymosis, skin oedema, and rash; anti-MAS1 with widespread burning sensation; and anti-STAB1 with skin oedema and rash. Anti-ADRA2A were negatively associated with memory loss and/or mental fog. ACE2 correlated with the serum levels of anti-S antibodies, supporting the hypothesis of an anti-idiotype mechanism in the immunopathogenesis of PACVS. Conclusions: This exploratory analysis suggests that the levels of autoantibodies directed against ACE2, and probably also MAS1 and STAB1, may serve as biomarkers for PACVS. [ABSTRACT FROM AUTHOR]

Despite all the progress made by science in the prevention and treatment of cardiovascular diseases and cancers, these are still the main reasons for hospitalizations and death in the Western world. Among the possible causes of this situation, disorders related to hyperinsulinemia and insulin resistance (Hyperin/IR) are still little-known topics. An analysis of the literature shows that this condition is a multiple risk factor for type 2 diabetes, cardiovascular diseases, cellular senescence and cancer, and neurodegenerative diseases. Hyperin/IR is progressively increasing worldwide, and its prevalence has now exceeded 50% of the general population and in overweight children. Asymptomatic or poorly symptomatic, it can last for many years before manifesting itself as diabetes, cardiovascular disease, neoplasm, cognitive deficit, or dementia, therefore leading to enormous social and healthcare costs. For these reasons, a screening plan for this pathology should be implemented for the purpose of identifying people with Hyperin/IR and promptly starting them on preventive treatment. [ABSTRACT FROM AUTHOR]

Peripheral insulin resistance (IR) is a well-documented, independent risk factor for the development of type 2 diabetes, cardiovascular disease, cancer and cellular senescence. Recently, the brain has also been identified as an insulin-responsive region, where insulin acts as regulator of the brain metabolism. Despite the clear link between IR and the brain, the exact mechanisms underlying this relationship remain unclear. Therapeutic intervention in patients showing symptoms of neurodegenerative diseases has produced little or no results. It has been demonstrated that insulin resistance plays a significant role in the pathogenesis of neurodegenerative diseases, particularly cognitive decline. Peripheral and brain IR may represent a modifiable state that could be used to prevent major brain disorders. In this review, we will analyse the scientific literature supporting IR as a risk factor for Alzheimer's disease and suggest some therapeutic strategies to provide a new proposal for the prevention of brain IR and its consequences. [ABSTRACT FROM AUTHOR]

Unfortunately, cardiovascular diseases and cancers are still the leading causes of death in developed and developing countries despite the considerable progress made in the prevention and treatment of diseases. Maybe we missed something? Insulin resistance (IR) with associated hyperinsulinemia (Hypein) is a silent pandemic whose prevalence is continually growing in developed and developing countries, now exceeding 51% of the general population. IR/Hypein, despite the vast scientific literature supporting its adverse action on the development of type 2 diabetes, cardiovascular alterations, tumors, neurological disorders, and cellular senescence, is not yet considered an independent risk factor and, therefore, is not screened in the general population and adequately treated. There are now numerous substances, drugs, and natural substances that, in association with the correction of a wrong lifestyle, can help to reduce IR/Hypein. We are convinced that the time has come to implement a prevention plan against this critical risk factor. Therefore, this manuscript aims to highlight IR/Hypein as an independent risk factor for type 2 diabetes, cardiovascular diseases, cancers, cellular senescence, and neuropsychiatric disorders, supporting our conviction with the available scientific literature on the topic. [ABSTRACT FROM AUTHOR]

Heart failure (HF) has become a subject of continuous interest since it was declared a new pandemic in 1997 because of the exponential increase in hospitalizations for HF in the latest years. HF is the final state to which all heart diseases of different etiologies lead if not adequately treated. It is highly prevalent worldwide, with a progressive increase with age, reaching a prevalence of 10% in subjects over the age of 65 years. During the last two decades, it was possible to see that the prevalence of heart failure with preserved ejection fraction (HFpEF) was increasing while that of heart failure with reduced ejection fraction (HFrEF) was decreasing. HFpEF is typically characterized by concentric remodeling of the left ventricle (LV) with impaired diastolic function and increased filling pressures. Over the years, also the prevalence of insulin resistance (IR)/hyperinsulinemia (Hyperins) in the general adult population has progressively increased, primarily due to lifestyle changes, particularly in developed and developing countries, with a range that globally ranges between 15.5% and 46.5%. Notably, over 50% of patients with HF also have IR/Hyperins, and the percentage is even higher in those with HFpEF. In the scientific literature, it has been well highlighted that the increased circulating levels of insulin, associated with conditions of insulin resistance, are responsible for progressive cardiovascular alterations over the years that could stimulate the development and/or the worsening of HFpEF. The aim of this manuscript was to review the scientific literature that supports a pathophysiologic connection between IR/Hyperins and HFpEF to stimulate the scientific community toward the identification of hyperinsulinemia associated with insulin resistance as an independent cardiovascular risk factor in the development and worsening of HF, believing that its adequate screening in the general population and an appropriate treatment could reduce the prevalence of HFpEF and improve its progression. [ABSTRACT FROM AUTHOR]

The editorial in the journal "Biomedicines" discusses the role of insulin resistance (IR) and hyperinsulinemia in the development and progression of heart failure (HF), particularly HF with preserved ejection fraction (HFpEF). The article highlights the complex interplay between metabolic dysregulation and cardiac function, emphasizing the detrimental effects of chronic hyperinsulinemia on the cardiovascular system. It also explores potential therapeutic strategies, such as targeting IR with substances like metformin and berberine, to improve patient outcomes in HF management. The authors call for further research to better understand the mechanisms of IR in different HF subtypes and to develop tailored therapeutic approaches based on underlying pathophysiology. [Extracted from the article]

This opinion article highlights the potential alterations caused by insulin resistance and hyperinsulinemia on the cardiovascular system and their negative impact on heart failure (HF), and describes the potential benefits of an early screening with consequent prompt treatment. HF is the final event of several different cardiovascular diseases. Its incidence has been increasing over the last decades because of increased survival from ischemic heart disease thanks to improvements in its treatment (including myocardial revascularization interventions) and the increase in life span. In particular, incidence of HF with preserved ejection fraction (HFpEF) is significantly increasing, and patients with HFpEF often are also affected by diabetes mellitus and insulin resistance (IR), with a prevalence > 45%. Concentric left ventricular (LV) remodeling and diastolic dysfunction are the main structural abnormalities that characterize HFpEF. It is well documented in the literature that IR with chronic hyperinsulinemia, besides causing type 2 diabetes mellitus, can cause numerous cardiovascular alterations, including endothelial dysfunction and increased wall thicknesses of the left ventricle with concentric remodeling and diastolic dysfunction. Therefore, it is conceivable that IR might play a major role in the pathophysiology and the progressive worsening of HF. To date, several substances have been shown to reduce IR/hyperinsulinemia and have beneficial clinical effects in patients with HF, including SGLT2 inhibitors, metformin, and berberine. For this reason, an early screening of IR could be advisable in subjects at risk and in patients with heart failure, to promptly intervene with appropriate therapy. Future studies aimed at comparing the efficacy of the substances used both alone and in association are needed. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial dysfunction and cardiovascular disease. While diabetes care is fairly well standardized, the prevention and treatment of IR lacks a single pharmaceutical approach and many lifestyle and dietary interventions have been proposed, including a wide range of food supplements. Among the most interesting and well-known natural remedies, alkaloid berberine and the flavonol quercetin have particular relevance in the literature, while silymarin—the active principle of the Silybum marianum thistle—was traditionally used for lipid metabolism disorders and to sustain liver function. This review describes the major defects of insulin signaling leading to IR and the main properties of the three mentioned natural substances, their molecular targets and synergistic action mechanisms. The actions of berberine, quercetin and silymarin are partially superimposable as remedies against reactive oxygen intermediates generated by a high-lipid diet and by NADPH oxidase, which is triggered by phagocyte activation. Furthermore, these compounds inhibit the secretion of a battery of pro-inflammatory cytokines, modulate intestinal microbiota and are especially able to control the various disorders of the insulin receptor and post-receptor signaling systems. Although most of the evidence on the effects of berberine, quercetin and silymarin in modulating insulin resistance and preventing cardiovascular disease derive from experimental studies on animals, the amount of pre-clinical knowledge strongly suggests the need to investigate the therapeutic potential of these substances in human pathology. [ABSTRACT FROM AUTHOR]

Recently, in Italy, a flowchart to be used by General Practitioners for the at-home treatment of patients with COVID-19, has been released. It states that early at-home treatment for SARS-CoV-2 infection is possible due to the availability of specific antiviral drugs to be used in at-risk patients, and that non-steroidal anti-inflammatory drugs (NSAIDs) have an important function in combating the virus. Therefore, the use of NSAIDs is not only rational but also effective in cases that cannot be treated using antivirals. These seemingly simple concepts have been applied in Italy since the beginning of the pandemic by doctors that belong to Italian groups created in order to help COVID-19 patients early at home, at a time of organizational difficulties within Italian health institutions and government. However, this approach was largely boycotted by both the Italian Ministry of Health and medical institutions, which mainly suggested the use of paracetamol as symptomatic, and a wait-and-watch approach for the first three days from the onset of symptoms. In this article, we analyze the rationale for the use of NSAIDs and, in particular, the multi-targeted approach including indomethacin in synergism with flavonoids and low-dose aspirin, as early at-home treatment of patients with COVID-19. Applying these simple concepts from the beginning could have reduced the high lethality of the disease during the first two years of the pandemic and prevented hospital overload. In perspective, it is still necessary to systematically address the comparison between different therapeutic approaches to this viral disease on an experimental basis. [ABSTRACT FROM AUTHOR]