Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work.

BACKGROUND: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.

Sudden Cardiac Death in Anabolic-Androgenic Steroid Users: A Literature Review.

Background and objectives: Anabolic-androgenic steroids (AASs) are a group of synthetic molecules derived from testosterone and its related precursors. AASs are widely used illicitly by adolescents and athletes, especially by bodybuilders, both for aesthetic uses and as performance enhancers to increase muscle growth and lean body mass. When used illicitly they can damage health and cause disorders affecting several functions. Sudden cardiac death (SCD) is the most common medical cause of death in athletes. SCD in athletes has also been associated with the use of performance-enhancing drugs. This review aimed to focus on deaths related to AAS abuse to investigate the cardiac pathophysiological mechanism that underlies this type of death, which still needs to be fully investigated. Materials and Methods: This review was conducted using PubMed Central and Google Scholar databases, until 21 July 2020, using the following key terms: "((Sudden cardiac death) OR (Sudden death)) AND ((androgenic anabolic steroid) OR (androgenic anabolic steroids) OR (anabolic-androgenic steroids) OR (anabolic-androgenic steroid))". Thirteen articles met the inclusion and exclusion criteria, for a total of 33 reported cases. Results: Of the 33 cases, 31 (93.9%) were males while only 2 (61%) were females. Mean age was 29.79 and, among sportsmen, the most represented sports activity was bodybuilding. In all cases there was a history of AAS abuse or a physical phenotype suggesting AAS use; the total usage period was unspecified in most cases. In 24 cases the results of the toxicological analysis were reported. The most detected AASs were nandrolone, testosterone, and stanozolol. The most frequently reported macroscopic alterations were cardiomegaly and left ventricular hypertrophy, while the histological alterations were foci of fibrosis and necrosis of the myocardial tissue. Conclusions: Four principal mechanisms responsible for SCD have been proposed in AAS abusers: the atherogenic model, the thrombosis model, the model of vasospasm induced by the release of nitric oxide, and the direct myocardial injury model. Hypertrophy, fibrosis, and necrosis represent a substrate for arrhythmias, especially when combined with exercise. Indeed, AAS use has been shown to change physiological cardiac remodeling of athletes to pathophysiological cardiac hypertrophy with an increased risk of life-threatening arrhythmias.

Toxicological Advancements in Cocaine Detection: A Review.

Cocaine, also known as methyl benzoylecgonine, is one of the most used drugs of abuse and one of the oldest; however, there has been a recent increase in the consumption of this substance. This trend has once again caught the attention of the scientific community. We discuss the current knowledge about this drug, focusing our attention on the forensic approach. Despite the fact that the cut-off of positivity to cocaine in drug tests is quite high, most current tests are able to detect much lower concentrations and could improve forensic sciences in both post-mortem investigations and in people screening. Immunological assays possessing substantial cross-reactivity to cocaine are particularly useful for screening oral fluid, hair, and post-mortem blood, where significant concentrations of the drug can be found. Liquid chromatography has now supplanted the previous techniques because it is very sensitive and specific and allows samples to be analyzed in a shorter time with only minimal sample preparation. Recent studies have focused on increased sensitivity, reduced processing times, and cheaper analysis.

The Impact of the COVID-19 Pandemic on the Practice of Forensic Medicine: An Overview.

During the COVID-19 pandemic, forensic sciences, on the one hand, contributed to gaining knowledge about different aspects of the pandemic, while on the other hand, forensic professionals were called on to quickly adapt their activities to respond adequately to the changes imposed by the pandemic. This review aims to clarify the state of the art in forensic medicine at the time of COVID-19, discussing the following: the influence of external factors on forensic activities, the impact of autopsy practice on COVID-19 and vice-versa, the persistence of SARS-CoV-2 RNA in post-mortem samples, forensic personnel activities during the SARS-CoV-2 pandemic, the global vaccination program and forensic sciences, forensic undergraduate education during and after the imposed COVID-19 lockdown, and the medico-legal implications in medical malpractice claims during the COVID-19 pandemic. The COVID-19 pandemic has greatly influenced different aspects of human life, and, accordingly, the practical activities of forensic sciences that are defined as multidisciplinary, involving different expertise. Indeed, the activities are very different, including crime scene investigation (CSI), external examination, autopsy, and genetic and toxicological examinations of tissues and/or biological fluids. At the same time, forensic professionals may have direct contact with subjects in life, such as in the case of abuse victims (in some cases involving children), collecting biological samples from suspects, or visiting subjects in the case of physical examinations. In this scenario, forensic professionals are called on to implement methods to prevent the SARS-CoV-2 infection risk, wearing adequate PPE, and working in environments with a reduced risk of infection. Consequently, in the pandemic era, the costs involved for forensic sciences were substantially increased.

Understanding the Relationship between Fetal Alcohol Spectrum Disorder (FASD) and Criminal Justice: A Systematic Review.

Prenatal alcohol exposure is considered one of the main causes of preventable birth disorders; however, it represents the main form of developmental delay in the world. Among the so-called secondary disabilities related to fetal alcohol spectrum disorder (FASD), there is a close connection with criminal behavior. This systematic review aims to provide up-to-date information about the relationship between FASD subjects and criminal justice analyzing different aspects. In light of the results of this review, a further goal is to provide several suggestions in order to reduce the public cost impact of FASD. A systematic review of the literature was conducted according to the PRISMA guidelines, producing 20 articles that met the inclusion criteria. Based on the results published in the selected studies, fetal alcohol syndrome (FAS) is a leading cause of preventable birth disorders and developmental disabilities in newborns. Moreover, these subjects seem to be more inclined to criminal acts compared to others. In conclusion, it should be pointed out that FASD entails high public health costs, both regarding the support measures provided to the affected individual and to their family, as well as the cost and social impact of any criminal offenses committed.

The Risk of COVID-19 Infection in Prisons and Prevention Strategies: A Systematic Review and a New Strategic Protocol of Prevention.

Health risks within prisons are well known and have worsened with the 2019 coronavirus pandemic (COVID-19), becoming a public health emergency. To date, there are more than 10 million inmates in the world; in most cases, conditions are bad and health care is scarce. A SARS-CoV-2 outbreak inside a prison is extremely rapid. The aim of this systematic review was to analyze all possible prevention techniques to reduce the risk of COVID-19 related infection within prisons. A systematic review of the literature was performed according to the PRISMA guidelines. Scopus, Web of Science, PubMed, and Google Scholar were used as search engines from 1 January 2020 to 1 November 2021 to evaluate the prevention of COVID-19 in prisoners. A total of 1757 articles were collected. Of them, 486 duplicates were removed. A total of 1250 articles did not meet the inclusion criteria. In conclusion, 21 articles were included in the present systematic review. From this analysis, it emerged that the most common COVID-19 prevention methods were the screening of the entire population (prisoners and workers) inside the prison through swab analysis and the reduction in overcrowding in prisons. Few studies concerned the prevention of COVID-19 infection through vaccination and the implementation of quarantine. To our knowledge, this is the first systematic review that evaluates the prevention of COVID-19 within jails and the real effectiveness of all possible methods used and published in the literature. Finally, a very useful strategic protocol is provided to reduce the incidence of infection and to control and manage COVID-19 in prisons.

Protection of Prisoners with Mental Health Disorders in Italy: Lights and Shadows after the Abolition of Judicial Psychiatric Hospitals.

In Italy, a person suffering from a mental disorder who commits a crime will be given a custodial security order and serve the period of admission at a Residenza per la esecuzione delle misure di sicurezza (REMS) (Residence for the Execution of Security Measures, hereinafter "REMS"). These institutions have been established recently and though equipped with the necessary safety measures, the focus is on psychiatric therapy. Despite being present on a national scale, access is very limited in terms of capacity. Immediate remedial measures are needed, so much so that the European Court of Human Rights recently condemned Italy for this very reason. This article, through a review of the constitutive principles of these institutions, shows how they have very positive aspects such as the attention to necessary psychotherapy in order to protect the right to health and the real taking charge of the fragility of the subjects; however, it is seen how there are many negative aspects linked above all to the scarce availability of places in these structures. The article provides suggestions on a more comprehensive strategy for facilities for detainees with mental disorders.

Pharmacogenetics and Forensic Toxicology: A New Step towards a Multidisciplinary Approach.

Pharmacogenetics analyzes the individual behavior of DNA genes after the administration of a drug. Pharmacogenetic research has been implemented in recent years thanks to the improvement in genome sequencing techniques and molecular genetics. In addition to medical purposes, pharmacogenetics can constitute an important tool for clarifying the interpretation of toxicological data in post-mortem examinations, sometimes crucial for determining the cause and modality of death. The purpose of this systematic literature review is not only to raise awareness among the forensic community concerning pharmacogenetics, but also to provide a workflow for forensic toxicologists to follow in cases of unknown causes of death related to drug use/abuse. The scientific community is called on to work hard in order to supply evidence in forensic practice, demonstrating that this investigation could become an essential tool both in civil and forensic contexts. The following keywords were used for the search engine: (pharmacogenetics) AND (forensic toxicology); (pharmacogenetics) AND (post-mortem); (pharmacogenetics) AND (forensic science); and (pharmacogenetics) AND (autopsy). A total of 125 articles were collected. Of these, 29 articles were included in this systematic review. A total of 75% of the included studies were original articles (n = 21) and 25% were case reports (n = 7). A total of 78% (n = 22) of the studies involved deceased people for whom a complete autopsy was performed, while 22% (n = 6) involved people in good health who were given a drug with a subsequent pharmacogenetic study. The most studied drugs were opioids (codeine, morphine, and methadone), followed by antidepressants (tricyclic antidepressants and venlafaxine). Furthermore, all studies highlighted the importance of a pharmacogenetics study in drug-related deaths, especially in cases of non-overdose of drugs of abuse. This study highlights the importance of forensic pharmacogenetics, a field of toxicology still not fully understood, which is of great help in cases of sudden death, deaths from overdose, deaths after the administration of a drug, and also in cases of complaint of medical malpractice.

Sudden Death in Adults: A Practical Flow Chart for Pathologist Guidance.

The medico-legal term "sudden death (SD)" refers to those deaths that are not preceded by significant symptoms. SD in apparently healthy individuals (newborn through to adults) represents a challenge for medical examiners, law enforcement officers, and society as a whole. This review aims to introduce a useful flowchart that should be applied in all cases of SD. Particularly, this flowchart mixes the data obtained through an up-to-date literature review and a revision of the latest version of guidelines for autopsy investigation of sudden cardiac death (SCD) in order to support medico-legal investigation. In light of this review, following the suggested flowchart step-by-step, the forensic pathologist will be able to apply all the indications of the scientific community to real cases. Moreover, it will be possible to answer all questions relative to SD, such as: death may be attributable to cardiac disease or to other causes, the nature of the cardiac disease (defining whether the mechanism was arrhythmic or mechanical), whether the condition causing SD may be inherited (with subsequent genetic counseling), the assumption of toxic or illicit drugs, traumas, and other unnatural causes.

Autopsy Findings and Causality Relationship between Death and COVID-19 Vaccination: A Systematic Review.

The current challenge worldwide is the administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Considering that the COVID-19 vaccination represents the best possibility to resolve this pandemic, this systematic review aims to clarify the major aspects of fatal adverse effects related to COVID-19 vaccines, with the goal of advancing our knowledge, supporting decisions, or suggesting changes in policies at local, regional, and global levels. Moreover, this review aims to provide key recommendations to improve awareness of vaccine safety. All studies published up to 2 December 2021 were searched using the following keywords: "COVID-19 Vaccine", "SARS-CoV-2 Vaccine", "COVID-19 Vaccination", "SARS-CoV-2 Vaccination", and "Autopsy" or "Post-mortem". We included 17 papers published with fatal cases with post-mortem investigations. A total of 38 cases were analyzed: 22 cases were related to ChAdOx1 nCoV-19 administration, 10 cases to BNT162b2, 4 cases to mRNA-1273, and 2 cases to Ad26.COV2.S. Based on these data, autopsy is very useful to define the main characteristics of the so-called vaccine-induced immune thrombotic thrombocytopenia (VITT) after ChAdOx1 nCoV-19 vaccination: recurrent findings were intracranial hemorrhage and diffused microthrombi located in multiple areas. Moreover, it is fundamental to provide evidence about myocarditis related to the BNT162B2 vaccine. Finally, based on the discussed data, we suggest several key recommendations to improve awareness of vaccine safety.

Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review.

Introduction: The World Health Organization declared the COVID-19 pandemic in March 2020. COVID-19 still represents a worldwide health emergency, which causesa severe disease that has led to the death of many patients. The pathophysiological mechanism of SARS-CoV-2 determining the tissue damage is not clear and autopsycan be auseful tool to improve the knowledge of this infection and, thus, it can help achieve a timely diagnosis and develop an appropriate therapy. This is an overview of the main post-mortem findings reporting data on the infection effects on several organs. Methods: A systematic literature search was conducted in the PubMed database searching for articles from 1 January to August 31, 2020. Thearticles were selected identifying words/concepts in the titles and/or abstracts that indicated the analysis of the morphological/pathological tissue injuries related to SARS-CoV-2 disease by several investigations. Results: A total of 63 articles were selected. The main investigated tissue was the lung showing a diffuse alveolar damage (DAD) frequently associated with pulmonary thrombotic microangiopathy. Inflammatory findings and vascular damage were observed in other organs such as heart, liver, kidney, brain, spleen, skin and adrenal gland. The immunohistochemical analysis showed tissue inflammatory cells infiltrates. The virus presence was detected by several investigations such as RT-PCR, immunohistochemistry and electron microscope, showing the effect ofSARS-CoV-2not exclusively in the lung. Discussion: The evidence emerging from this review highlighted the importance of autopsy to provide a fundamental base in the process of understanding the consequences ofSARS-CoV-2 infection. COVID-19 is strictly related to a hyper inflammatory state that seems to start with DAD and immuno-thrombotic microangiopathy. Massive activation of the immune system and microvascular damage might also be responsible for indirect damage to other organs, even if the direct effect of the virus on these tissues cannot be excluded.

Effectiveness of Antipsychotics in Reducing Suicidal Ideation: Possible Physiologic Mechanisms.

Background: The aim of this study is to evaluate whether any specific antipsychotic regimen or dosage is effective in managing suicidal ideation in schizophrenia. Four comparisons were conducted between: (1) clozapine and other antipsychotics; (2) long-acting injectable and oral antipsychotics; (3) atypical and typical antipsychotics; (4) antipsychotics augmented with antidepressants and antipsychotic treatment without antidepressant augmentation. Methods: We recruited 103 participants diagnosed with schizophrenia spectrum disorders. Participants were followed for at least six months. The Beck Scale for Suicidal Ideation (BSS) was used to assess the severity of suicidal ideation at each visit. We performed a multiple linear regression model controlling for BSS score at study entry and other confounding variables to predict the change in the BSS scores between two visits. Results: Overall, there were 28 subjects treated with clozapine (27.2%), and 21 subjects with depot antipsychotics (20.4%). In our sample, 30 subjects experienced some suicidal ideation at study entry. When considering the entire sample, there was a statistically significant decrease in suicidal ideation severity in the follow-up visit compared to the study entry visit (p = 0.043). Conclusions: To conclude, our preliminary analysis implies that antipsychotics are effective in controlling suicidal ideation in schizophrenia patients, but no difference was found among alternative antipsychotics' classes or dosages.

Do We Really Need Hazard Prevention at the Expense of Safeguarding Death Dignity in COVID-19?

To date, little is known regarding the transmission risks of SARS-CoV-2 infection for subjects involved in handling, transporting, and examining deceased persons with known or suspected COVID-19 positivity at the time of death. This experimental study aims to define if and/or how long SARS-CoV-2 persists with replication capacity in the tissues of individuals who died with/from COVID-19, thereby generating infectious hazards. Sixteen patients who died with/from COVID-19 who underwent autopsy between April 2020 and April 2021 were included in this study. Based on PMI, all samples were subdivided into two groups: 'short PMI' group (eight subjects who were autopsied between 12 to 72 h after death); 'long PMI' (eight subjects who were autopsied between 24 to 78 days after death). All patients tested positive for RT-PCR at nasopharyngeal swab both before death and on samples collected during post-mortem investigation. Moreover, a lung specimen was collected and frozen at -80 °C in order to perform viral culture. The result was defined based on the cytopathic effect (subjective reading) combined with the positivity of the RT-PCR test (objective reading) in the supernatant. Only in one sample (PMI 12 h), virus vitality was demonstrated. This study, supported by a literature review, suggests that the risk of cadaveric infection in cases of a person who died from/with COVID-19 is extremely low in the first hours after death, becoming null after 12 h after death, confirming the World Health Organization (WHO) assumed in March 2020 and suggesting that the corpse of a subject who died from/with COVID-19 should be generally considered not infectious.

Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review.

Anabolic-androgenic steroids (AASs) are a large group of molecules including endogenously produced androgens, such as testosterone, as well as synthetically manufactured derivatives. AAS use is widespread due to their ability to improve muscle growth for aesthetic purposes and athletes' performance, minimizing androgenic effects. AAS use is very popular and 1-3% of US inhabitants have been estimated to be AAS users. However, AASs have side effects, involving all organs, tissues and body functions, especially long-term toxicity involving the cardiovascular system and the reproductive system, thereby, their abuse is considered a public health issue. The aim of the proposed review is to highlight the most recent evidence regarding the mechanisms of action of AASs and their unwanted effects on organs and lifestyle, as well as suggesting that AAS misuse and abuse lead to adverse effects in all body tissues and organs. Oxidative stress, apoptosis, and protein synthesis alteration are common mechanisms involved in AAS-related damage in the whole body. The cardiovascular system and the reproductive system are the most frequently involved apparatuses. Epidemiology as well as the molecular and pathological mechanisms involved in the neuropsychiatric side-effects of AAS abuse are still unclear, further research is needed in this field. In addition, diagnostically reliable tests for AAS abuse should be standardized. In this regard, to prevent the use of AASs, public health measures in all settings are crucial. These measures consist of improved knowledge among healthcare workers, proper doping screening tests, educational interventions, and updated legislation.

Drug-Drug Interactions in Vestibular Diseases, Clinical Problems, and Medico-Legal Implications.

Peripheral vestibular disease can be treated with several approaches (e.g., maneuvers, surgery, or medical approach). Comorbidity is common in elderly patients, so polytherapy is used, but it can generate the development of drug-drug interactions (DDIs) that play a role in both adverse drug reactions and reduced adherence. For this reason, they need a complex kind of approach, considering all their individual characteristics. Physicians must be able to prescribe and deprescribe drugs based on a solid knowledge of pharmacokinetics, pharmacodynamics, and clinical indications. Moreover, full information is required to reach a real therapeutic alliance, to improve the safety of care and reduce possible malpractice claims related to drug-drug interactions. In this review, using PubMed, Embase, and Cochrane library, we searched articles published until 30 August 2021, and described both pharmacokinetic and pharmacodynamic DDIs in patients with vestibular disorders, focusing the interest on their clinical implications and on risk management strategies.

Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects.

Vestibular disorders may generate complex signs and symptoms, which may alter patients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/usefulness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) pharmacodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs.

The Role of a Good Quality Autopsy in Pediatric Malpractice Claim: A Case Report of an Unexpected Death in an Undiagnosed Thymoma.

Thymomas are extremely rare in the first 20 years of life, with different clinical presentations: from asymptomatic mediastinal masses to compressive and paraneoplastic syndromes. In pediatric population, the respiratory disorders have a higher incidence. The overall thymoma mortality rate is described as 40% and metastasized tumors are more aggressive. This case report describes a compressive syndrome caused by a thymoma in which symptoms were exacerbated by a concurrent pulmonary infection, thus leading an affected infant to sudden death despite medical treatment. In this case, patient's death occurred just before the differential diagnostic process got completed. Malpractice claim was based on the missing diagnosis as well as the suspect of inadequate provided care. Consequently, autopsy played a crucial post-mortem role to find out the cause of death, and to exclude any professional liability. Despite modern diagnostic techniques, autopsies are still the best available forensic tool. It is useful to remember that death is a fact of life, therefore not always preventable.

Risk Management and Recommendations for the Prevention of Fatal Foreign Body Aspiration: Four Cases Aged 1.5 to 3 Years and Mini-Review of the Literature.

(1) Background: Foreign body aspiration (FBA) is a significant public health concern among the pediatric population, and fatalities are dramatic for families. It typically involves organic foreign bodies (mainly food) aspirated by children under three years old, usually at home or school. This review aimed to focus on the preventive measures around four actual cases of fatal foreign body aspiration, emphasizing the correct execution of the Heimlich maneuver and cardiopulmonary resuscitation, supervised mealtimes, and high-risk foods. (2) Methods: Four fatal cases of foreign body aspiration in children are presented here. The children were in a free environment, such as school, home, and the countryside, and were in the presence of teachers, parents, and a grandmother who did not supervise the children adequately. A literature review was performed via the MEDLINE database using the key terms: "foreign body aspiration," "infant choking, 1.5 to 3 years," "food and foreign body aspiration," "common household," "prevention of foreign body aspiration," "guidelines," "recommendations," "training of caregivers (parents, educators)," "resuscitation," "Heimlich maneuver," and "disengagement of the upper airways." We focused on the prevention of foreign body aspiration. (3) Results: a complete postmortem examination was performed. In three cases, the foreign bodies were food (mozzarella cheese, pear, or raw bean), while in one case, the foreign body was a pebble. (4) Conclusions: This review aimed to discuss recent scientific literature and provide a perspective on the benefits of a dedicated approach to the management of fatal foreign body aspiration in children by caregivers who usually have no experience with the best ways of supervising children in a safe environment, especially regarding the correct execution of resuscitation maneuvers, such as the Heimlich maneuver. Recommendation updates could improve healthcare quality in a pediatric setting and reduce medico-legal implications.

A case of suicide using a home-modified gun.

The problem of the possibility of modifying blank cartridge dummy firearms to make them fire a real bullet has long been known, but the phenomenon has been constantly on the increase in the recent years. In Italy, there are no restrictions on the purchase of an inoffensive weapon. However, few modifications are frequently enough to transform the inoffensive weapon into a harmful one: a procedure is often undertaken to avoid the mandatory control and registration of firearms. We describe a case of suicide of a man in Trieste, Italy, in 2002, with a blank cartridge dummy pistol that had been modified to fire homemade bullets.

Effects of Very Low Calorie Ketogenic Diet on the Orexinergic System, Visceral Adipose Tissue, and ROS Production.

BACKGROUND: Caloric restriction is a valid strategy to reduce the visceral adipose tissue (VAT) content in obese persons. Hypocretin-1 (orexin-A) is a neuropeptide synthesized in the lateral hypothalamus that strongly modulates food intake, thus influencing adipose tissue accumulation. Therapeutic diets in obesity treatment may combine the advantages of caloric restriction and dietary ketosis. The current study aimed to evaluate the effect of a very low calorie ketogenic diet (VLCKD) in a population of obese patients. METHODS: Adiposity parameters and orexin-A serum profiling were quantified over an 8 week period. The effect of the VLCKD on reactive oxygen species (ROS) production and cell viability was evaluated, in vitro, by culturing Hep-G2 cells in the presence of VLCKD sera. RESULTS: Dietary intervention induced significant effects on body weight, adiposity, and blood chemistry parameters. Moreover, a selective reduction in VAT was measured by dual-energy X-ray absorptiometry. Orexin-A levels significantly increased after dietary treatment. Hep-G2 cell viability was not affected after 24, 48, and 72 h incubation with patients' sera, before and after the VLCKD. In the same model system, ROS production was not significantly influenced by dietary treatment. CONCLUSION: The VLCKD exerts a positive effect on VAT decrease, ameliorating adiposity and blood chemistry parameters. Furthermore, short-term mild dietary ketosis does not appear to have a cytotoxic effect, nor does it represent a factor capable of increasing oxidative stress. Finally, to the best of our knowledge, this is the first study that shows an effect of the VLCKD upon the orexinergic system, supporting the usefulness of such a therapeutic intervention in promoting obesity reduction in the individual burden of this disease.