HCV spread among female incarcerated population and treatment pathways to viral elimination in Italian prison settings: clinical perspectives and medico legal aspects.

BACKGROUND: Hepatitis C virus (HCV) infection is more frequent among incarcerated people than in general population. In the DAAs era, the short schedules and the low risk of adverse reactions, increased the number of HCV treatments. However, the most part of literature reports lack of incarcerated women inclusion in studies on field. Our aim is to assess the screening execution, HCV prevalence, and DAAs treatment among incarcerated women. A focused insight on quick vs standard diagnosis and staging approach will be also provided. METHODS: Incarcerated women from 4 Italian regions' penitentiary institutes were included. HCV screening was executed with HCV saliva test (QuickOral Test®) or phlebotomy. Stage of liver fibrosis was evaluated with FIB-4 value or fibroscan®, based on physicians' decision. Treatment prescription followed national protocols. RESULTS: We included 156 women, 89 (57%) were Italian, mean age was 41 ± 10 years, and 28 (17.9%) were people who inject drugs (PWIDs). Overall, the HCV seroprevalence was 20.5%. Being PWID and on opioid substitution therapy (OST) were significantly associated with serological status (p-value < 0.001). Of them, the 75.5% of patients had active infection, the most frequent genotype was 3a (50%). Among them, 4 (16.6%) and 6 (25%) had psychosis or alcohol abuse history. The 62.5%, 25% and 12.5% had low, intermediate, and advanced fibrosis, respectively. Out of the 24 HCV-RNA positive patients, the 75% underwent to DAAs treatment. The sustained virological response (SVR12) was achieved in 88.8% of cases. When evaluating the influence of quick diagnosis and staging methods vs standard phlebotomy and fibroscan® on SVR12, FIB-4 use showed higher performance for retainment in treatment during prison staying (p = 0.015), while the use of quick saliva test had no influence on the outcome (p = 0.22). CONCLUSION: HCV seroprevalence and active infections are very high among incarcerated women. More tailored interventions should be focused on HCV diagnosis and treatment in female prison population. The use of quick staging methods (FIB-4) is useful to increase SVR12 achievement without delays caused by the fibroscan® awaiting.

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.

Human Brain Injury and miRNAs: An Experimental Study.

Brain damage is a complex dysfunction that involves a variety of conditions whose pathogenesis involves a number of mediators that lead to clinical sequelae. For this reason, the identification of specific circulating and/or tissue biomarkers which could indicate brain injury is challenging. This experimental study focused on microRNAs (miRNAs), a well-known diagnostic tool both in the clinical setting and in medico-legal investigation. Previous studies demonstrated that specific miRNAs (miR-21, miR-34, miR-124, miR-132, and miR-200b) control important target genes involved in neuronal apoptosis and neuronal stress-induced adaptation. Thus, in this experimental setting, their expression was evaluated in three selected groups of cadavers: drug abusers (cocaine), ischemic-stroke-related deaths, and aging damage in elder people who died from other neurological causes. The results demonstrated that the drug abuser group showed a higher expression of miR-132 and miR-34, suggesting a specific pathway in consumption-induced neurodegeneration. Instead, miR-200b and miR-21 dysregulation was linked to age-related cognitive impairment, and finally, stroke events and consequences were associated with an alteration in miR-200b, miR-21, and miR-124; significantly higher levels of this last expression are strongly sensitive for ischemic damage. Moreover, these results suggest that these expression patterns could be studied in other biological samples (plasma, urine) in subjects with brain injury linked to aging, drug abuse, and stroke to identify reliable biomarkers that could be applied in clinical practice. Further studies with larger samples are needed to confirm these interesting findings.

Haemorrhage from varicose veins and varicose ulceration: A systematic review.

Varicose veins (VVs) and varicose ulceration (VU) are usually considered non-life-threatening conditions, but in some cases they can lead to major complications such as fatal bleeding. The aim of this systematic review is to evidence the most updated information on bleeding from VV and VU. As evidence acquisition, we planned to include all the studies dealing with "Haemorrhage/Bleeding" and "VVs/VU". We excluded all the studies, which did not properly fit our research question, and with insufficient data. As evidence synthesis, of the 172 records found, after removing of duplicates, and after records excluded in title and abstract, 85 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 68 articles because of the following reasons: (1) not responding properly to our research questions; (2) insufficient data; the final set included 17 articles. From literature searching, we identify the following main issues to be discussed in the review: epidemiology and predisposing factors, pathophysiology and forensic aspects, first aid. It has been estimated that deaths for bleeding due to peripheral venous problems account up to 0.01% of autopsy cases. From a pathological point of view, venous bleeding may arise from either acute or chronic perforation of an enlarged vein segment through the weakened skin. From a forensic point of view, in cases of fatal haemorrhage the death scene can even simulate non-natural events, due to crime or suicide. In most cases, incorrect first aid led to fatal complications. Further investigation on epidemiology and prevention measures are needed.

Women Living with HIV in Italian Prison Settings: Results from the Gender-Specific ROSE Network.

BACKGROUND: Incarcerated women are a minority in the Italian prison population. The lack of prevention and awareness of HIV infection and the lack of access to treatment make the treatment path difficult. METHODS: we conducted a multi-center study including incarcerated women living with HIV (WLWH). RESULTS: The study included 85 WLWH with a mean age of 41.7 ± 8.7 years, and 58.8% (50/85) of them were Italian. Principally, HIV transmission was related to sexual intercourse, 47% of all patients were PWIDs, and 62.5% of them were on opioid substitution therapy (OST). Overall, 56.4% of the included patients had a CD4+ cell count of >500 cells/mmc. Among the participants, 92.9% were on antiretroviral therapy, 87.3% had treatment before incarceration, and 83.5% were virologically suppressed. Among the 13 non-virally-suppressed patients, 53.8% were unaware of their serological status before incarceration and had started HAART but were still not virologically suppressed; 46.2% (6/13) had a lack of compliance or had suspended the treatment before incarceration and restarted it after admission. All patients with chronic hepatitis C underwent treatment with direct-acting antivirals and reached a sustained virological response. CONCLUSIONS: the detention of these women could represent an occasion for the patients' healthcare provision and use, and the creation of a gender-specific network can be an effective strategy for reaching this population.

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.

Effectiveness and Safety of a New Nutrient Fixed Combination Containing Pollen Extract Plus Teupolioside, in the Management of LUTS in Patients with Benign Prostatic Hypertrophy: A Pilot Study.

Benign prostatic hyperplasia (BPH) is a common cause of male lower urinary tract symptoms (LUTS) that can reduce quality of life. Even if several drugs can be used in its treatment, the development of adverse drug reactions (ADRs) represents the most common cause of low adherence. In the present study, we evaluate both the efficacy and the safety of a new nutrient fixed combination of Pollen Extract plus Teupolioside, named Xipag®, in patients with LUTS. We conduct a pilot single center open label clinical study between 1 March 2020 and 30 June 2020 in patients with BPH referred to general practitioner's ambulatories. Male patients > 45 years, sexually active, with clinical symptoms of LUTS and with a diagnosis of HPB were enrolled and received one tablet/day of Xipag® (T0), for three months (T1: end of treatment). The IPSS and IIEF-5 questionnaires were carried out at T0 and T1 and represent the first end point, whereas the primary safety end point was considered the absence of ADR or of drug−drug interactions related to Xipag® administration. During the study period, 25 subjects aged 43 to 76 years (mean 62.7 ± 9) were enrolled and completed the study. The clinical evaluation in T1 documented that Xipag® induced a statistically significant improvement (p < 0.01) in symptoms, as documented by the IPSS questionnaire (range 22.7−88.9; mean 55.2 ± 23.6), without the development of ADRs. In conclusion, this is the first real-world study that showed the efficacy and the safety of Xipag® in the BPH patients with LUTS.

New evidence for a critical role of elastin in calcification of native heart valves: immunohistochemical and ultrastructural study with literature review.

AIMS: Calcific aortic stenosis is a progressive disease characterized by massive fibrosis andmineralization of the valve leaflets. The aim of this study was to determine whether the onset of native calcific aortic stenosis is associated primarily with matrix remodelling events, and particularly with elastin degradation. METHODS AND RESULTS: The immunohistochemical expression profile of matrix degradating enzymes and tenascin-C was investigated in both healthy and native calcified aortic valves. Collagen and elastic tissue were studied by light microscopy and electron microscopy. Immunophenotypic analysis of inflammatory cells was carried out by using monoclonal antibodies to macrophages, T and B lymphocytes. Immunoreactivity for tenascin-C and matrix metalloproteinase-12 (MMP-12) was associated with areas of dense mineralization, which were characterized by fibrosis, fragmentation and calcification of elastic fibres a positive reaction was also found around small islands of calcification. MMP-11 was not detected in the diseased valves. Osteopontin and osteonectin were also found at sites of mineralization. All calcified valves examined showed inflammatory cell infiltration. CONCLUSIONS: Our results demonstrate the direct involvement of MMP-12 in native aortic valve stenosis. MMP-mediated degradation of elastic fibres might contribute actively to valve mineralization by inducing calcium deposition onto fragmented elastin.

Pharmacological Abortion in a Pandemic: An Italian Medico-Legal Perspective.

The limitations caused by the spread of the SARS-CoV2 virus have had repercussions on the voluntary termination of pregnancy. During the pandemic, Italy issued updated guidelines regarding voluntary termination of pregnancy by means of mifepristone and prostaglandin. This included news concerning the time limit and location in which this procedure could be accessed: updates partially recognize women's needs, and they are into line with the European parliament's recent exhortations. However, these updates do not change the previously provided responsibilities that lie with doctors. This article aimed to compare regulations concerning medical abortion in Italy and other countries, with a focus on recent Italian updates in the context of pandemic.

Health in Prison: Does Penitentiary Medicine in Italy Still Exist?

Despite the detailed legislative developments that have occurred within the context of prison medicine in Italy, problems of a management nature continue to affect prisoner health and management, which in turn impact the prison system's ability to offer prisoners a real opportunity for rehabilitation. Certain behavioral aspects reported in prisons may alter and negatively impact the normal doctor-patient relationship, including elements that hinder the therapeutic alliance and impede proper clinical risk prevention and management. However, practical steps may be taken in connection with the analysis of flows and healthcare services that may enable prison administrations to bring about a true, modern restructure of the prison system.

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.

COVID-19 Pandemic and Equal Access to Vaccines.

The COVID-19 pandemic has evidenced the chronic inequality that exists between populations and communities as regards global healthcare. Vaccination, an appropriate tool for the prevention of infection, should be guaranteed by means of proportionate interventions to defeat such inequality in populations and communities affected by a higher risk of infection. Equitable criteria of justice should be identified and applied with respect to access to vaccination and to the order in which it should be administered. This article analyzes, as regards the worldwide distribution of anti-COVID-19 vaccines, the various ways the principle of equity has been construed and applied or even overlooked. The main obstacle to equal access to vaccines is vaccine nationalism. The perception of equity varies with the differing reference values adopted. Adequate response to needs appears to be the principal rule for achieving the criterion of equity in line with distributive justice. Priorities must be set equitably based on rational parameters in accordance with current needs. The entire process must be governed by transparency, from parameter identification to implementation. The issue of equal access to vaccination affects the entire world population, necessitating specific protective interventions. In light of this, the World Health Organization (WHO) has devised the COVAX plan to ensure that even the poorest nations of the world receive the vaccine; certain initiatives are also supported by the European Union (EU). This pandemic has brought to the fore the need to build a culture of equitable relationships both in each country's own domain and with the rest of the world.

The Difficult Balance between Ensuring the Right of Nursing Home Residents to Communication and Their Safety.

The COVID-19 epidemic has had a profound impact on healthcare systems worldwide. The number of infections in nursing homes for the elderly particularly is significantly high, with a high mortality rate as a result. In order to contain infection risks for both residents and employees of such facilities, the Italian government passed emergency legislation during the initial stages of the pandemic to restrict outside visitor access. On 30 November 2020, the Italian President of the Council of Ministers issued a new decree recognizing the social and emotional value of visits to patients from family and friends. In addition, it indicated prevention measures for the purposes of containing the infection risk within nursing homes for the elderly. This article comments on these new legislative provisions from the medicolegal perspective, providing indications that can be used in clinical practice.

Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases.

Nattokinase (NK) is a serine protease enzyme with fibrinolytic activity. Even if it could be used for the treatment of several diseases, no data have been published supporting its use patients who underwent vascular surgery. In this study, we evaluated both the efficacy and the safety of nattokinase (100 mg/day per os) in patients admitted to vascular surgery. Patients were of both sexes, >18 years of age, with vascular diseases (i.e., deep vein thrombosis, superficial vein thrombosis, venous insufficiency), and naïve to specific pharmacological treatments (anticoagulants or anti-platelets). Patients were divided into three groups. Group 1: patients with deep vein thrombosis, treated with fondaparinux plus nattokinase. Group 2: patients with phlebitis, treated with enoxaparin plus nattokinase. Group 3: patients with venous insufficiency after classical surgery, treated with nattokinase one day later. During the study, we enrolled 153 patients (age 22-92 years), 92 females (60.1%) and 61 males (39.9%;), and documented that nattokinase was able to improve the clinical symptoms (p < 0.01) without the development of adverse drug reactions or drug interactions. Among the enrolled patients, during follow-up, we did not record new cases of vascular diseases. Attention to patients' clinical evolution, monitoring of the INR, and timely and frequent adjustment of dosages represent the cornerstones of the safety of care for patients administered fibrinolytic drugs as a single treatment or in pharmacological combination. Therefore, we can conclude that the use of nattokinase represents an efficient and safe treatment able to both prevent and treat patients with vascular diseases.

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.

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.

Autopsy Findings in Case of Fatal Scorpion Sting: A Systematic Review of the Literature.

Scorpion sting is a public health issue in several countries, particularly in America, the Middle East, India and Africa. The estimated annual global incidence of scorpion envenomings is about 1.5 million, resulting in 2600 deaths. Scorpions are Arthropoda characterized by a tail ending in a terminal bulbous (telson) containing paired venom glands and the stinger. There are 19 known families of scorpions and more than 2200 species, of which about 50 from the families of Buthidae, Hemiscorpiidae and Scorpionidae are harmful to humans. Scorpion venom is a complex structure composed of neurotoxic proteins, salts, acidic proteins and organic compounds, thereby having neurologic, cardiovascular, hematologic and renal side effects, in addition to local effects such as redness, pain, burning and swelling. When the sting is fatal, the mechanism of death is often related to cardiotoxicity with terminal pulmonary edema. However, the cholinergic excess or the neuromuscular excitation can provoke respiratory failure. Sometimes, death is due to an anaphylactic reaction to the envenoming. The purpose of this literature review is to evaluate the autopsy findings in scorpion sting-related deaths in order to better understand the pathophysiological mechanisms underlying them, thus helping pathologists in defining the correct diagnosis.

Take-Home Messages from the COVID-19 Pandemic: Strengths and Pitfalls of the Italian National Health Service from a Medico-Legal Point of View.

The World Health Organization (WHO) declared the outbreak of the Coronavirus disease-2019 (COVID-19) infection a pandemic on 11 March 2020. As of the end of October 2020, there were 50 million cases of infection and over one million deaths recorded worldwide, over 45,000 of which occurred in Italy. In Italy, the demand for intensive care over the course of this pandemic crisis has been exceptionally high, resulting in a severe imbalance between the demand for and availability of the necessary resources. This paper focuses on elements of preventive medicine and medical treatments in emergency and non-emergency situations which, based on the international scientific literature, may prove to be useful to physicians on a behavioral level and avert professional liability problems. In order to achieve this objective, we have performed a search on MEDLINE to find published articles related to the risks associated with the pandemic that contain useful suggestions and strategies for mitigating risks and protecting the safety of the population. The results have been collocated in line with these specific study areas.

Traumatic Brain Injury: A Forensic Approach: A Literature Review.

Traumatic brain injury (TBI) is the principal cause of invalidity and death in the population under 45 years of age worldwide. This mini-review aims to systematize the forensic approach in neuropathological studies, highlighting the proper elements to be noted during external, radiological, autoptical, and histological examinations with particular attention paid to immunohistochemistry and molecular biology. In the light of the results of this mini-review, an accurate forensic approach can be considered mandatory in the examination of suspected TBI with medico-legal importance, in order to gather all the possible evidence to corroborate the diagnosis of a lesion that may have caused, or contributed to, death. From this point of view, only the use of an evidence-based protocol can reach a suitable diagnosis, especially in those cases in which there are other neuropathological conditions (ischemia, neurodegeneration, neuro-inflammation, dementia) that may have played a role in death. This is even more relevant when corpses, in an advanced state of decomposition, are studied, where the radiological, macroscopic and histological analyses fail to give meaningful answers. In these cases, immune-histochemical and molecular biology diagnostics are of fundamental importance and a forensic neuropathologist has to know them. Particularly, MiRNAs are promising biomarkers for TBI both for brain damage identification and for medico-legal aspects, even if further investigations are required to validate the first experimental studies. In the same way, the genetic substrate should be examined during any forensic examination, considering its importance in the outcome of TBI.