Healthcare Workers: Heroes or Victims? Context of the Western World and Proposals to Prevent Violence.

Episodes of direct violence against healthcare workers and social workers represent a worrying and widespread phenomenon in Western countries. These violent attacks, whether verbal or physical, occur in various work environments, targeting professionals working in private facilities, medical practices, or those employed within the National Health System facilities. We conducted a search using a single search engine (PubMed) using the terms "violence against healthcare workers AND Western" for the period 2003-2023, identifying 45 results to which we added to the literature through hand searching. Our review thus analyzed the sector literature to highlight the phenomenon of violence against healthcare workers, particularly in Western countries. We began with an analysis of the problem and then focused on the true purpose of the study, which is to propose new solutions to protect healthcare workers in all work settings. Consequently, we aim to improve both the working environment for healthcare professionals and to enhance the overall healthcare and public health outcomes.

The "Criminal Shield": Criminal Liability for Healthcare Professionals during the COVID-19 Pandemic.

The Sars-CoV-2 pandemic has had important economic, health, political, and jurisprudential implications all over the world. According to innovations already introduced by Law 24/2017, with Decree Law no. 44 of 1 April 2021 and the subsequent conversion law no. 71 of 2021, Italy is the only country in which ad hoc rules have been introduced to limit the professional liability of healthcare professionals during the health emergency. The "criminal shield" can be defined as the Legislator response to the extreme pressure on healthcare professionals during the pandemic.

Learning from the Past to Improve the Future-Vaccine Hesitancy Determinants in the Italian Population: A Systematic Review.

WHO identifies vaccine hesitancy (VH) as one of the ten threats to global health. The authors bring to the international scientific community an Italian episode that offers the opportunity to renew the discussion on the extent of the VH matter. The purpose of this systematic review is to analyze the factors determining vaccine hesitancy in the Italian population, to understand its roots, and suggest potential strategies to mitigate it. A systematic review of the literature according to the PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, using the following strategy: (COVID-19 vaccines) AND (vaccination hesitancy) AND (Italy). After the selection process, 36 articles were included in this systematic review. The most frequently detected factors associated with VH in the Italian population can be grouped as vaccine-related factors, socio-cultural factors, and demographic factors. Currently, we are facing a gap between the population and science, governments, and institutions. To heal this breach, it is necessary to strengthen the trust of the population through the implementation of health communication and public education strategies, while scientific literacy must continue to support families and individuals in discerning evidence from opinions to recognize the real risks and balance them with the benefits.

Histopathological Features of SARS-CoV-2 in Extrapulmonary Organ Infection: A Systematic Review of Literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health concern responsible for the ongoing pandemic. Histopathological pieces of evidence on COVID-19 are not fully investigated. This review aims to provide, through microscopy investigations, a histopathological overview of COVID-19 structural and ultrastructural alterations in different organs and tissues, excluding the respiratory system. The authors systematically reviewed the literature over the period February 2020-July 2022. Selected databases were PubMed, Scopus, and Google Scholar. The search strategy included the following terms: "COVID-19" or SARS-CoV-2 and "histopathology" or "pathology"; and "microscopy" and "liver", "myocardium"," spleen", "testis", and "placenta". Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Thirty-one articles included in this systematic review demonstrated, at a histopathological level, that COVID-19 exerts detrimental effects on tissues, often promoting degenerative processes. Even if COVID-19 shows a histopathological tropism for the respiratory system, other tissues, from cardiovascular to reproductive, are affected by COVID-19. Therefore, this paper provides an up-to-date view of histopathological observations of the structural and ultrastructural alterations associated with COVID-19 and may contribute to a better knowledge of the physiopathological bases of this disease.

Defensive Medicine in the Management of Cesarean Delivery: A Survey among Italian Physicians.

BACKGROUND AND OBJECTIVES: This study aims to contribute to the definition of the defensive medicine phenomenon between obstetricians and gynecologists, as well as to possible effects on the frequency of deliveries performed by cesarean sections (CS). MATERIALS AND METHODS: a digital questionnaire was administered through a mail-list including 600 gynecological specialists (of these 168 doctors completed the test), both in public and private settings. It was made of twenty multiple choice questions, concerning their awareness about the practice of defensive medicine and the planning and execution of CS. All doctors involved received clear and complete information about the purpose of this study and about the organizations that received their answers. Analyses of variance and regression were performed to describe differences between groups and to estimate the relationships between variables. The value of p < 0.5 was considered statistically relevant. RESULTS: our analysis revealed that most respondents are confident with the defensive medicine definition and characteristics. This survey confirmed that gynecologists fear legal actions promoted by their patients and therefore modulate their choices by implementing professional behaviors of so-called "defensive medicine". This relates to a greater number of medical liability judgements, which more often concern omission or delayed execution of cesarean section, rather than unskillful surgical procedures. CONCLUSIONS: there are few data to support a relation between the high rate of CS and defensive medicine. Numerous scientific studies associated this CS rate with the phenomenon of defensive medicine. This practice is constantly growing in all medical areas, especially in high-risk specialties such as obstetrics and gynecology. Our study highlights physicians' awareness of adopting defensive medicine behaviors in their clinical practice, affecting the choice of the type of delivery to be performed.

Traumatic brain injury: Estimate of the age of the injury based on neuroinflammation, endothelial activation markers and adhesion molecules.

Studies on traumatic brain injury (TBI) are applicable not only in the clinical context, but also in the forensic field. Over time, the literature has accumulated scientific evidence supporting the use of specific histopathological tests in dating traumatic brain injuries. In primary damage, cell death occurs by necrosis/apoptosis. In secondary injury, the underlying mechanisms are inflammation and ischemia. The inflammatory response of the central nervous system (CNS) follows the common steps of the innate response. In head injury, the blood brain barrier (BBB) undergoes both functional damage and, subsequently, finer structural changes. Scientific evidence has shown modifications of the junctional-endothelial system that favors the extravasation of immunocompetent cells. The histological evaluation of the subdural hematoma, of the cerebral contusions, of the diffuse axonal damage can certainly bring useful elements, with limitations, to the chronological evaluation of the lesions. Many markers have been used to better define the dating of the head injury. Several authors also analyzed the usefulness of secondary damage markers in brain tissue. The progress achieved with immunohistochemistry is significant compared to the use of routine staining. With immunohistochemistry it is possible to identify much narrower and more precise time intervals and, above all, with greater probative reliability. Recently attention has been paid to the modification of structural proteins and miRNAs. Future research is already started and entrusted to multidisciplinary teams that know how to combine their specific skills in search of a reproducible standard of known and sufficient accuracy.

Multidisciplinary approach to suspected sudden unexpected infant death caused by milk-aspiration: A case report.

BACKGROUND: The term sudden unexpected infant death (SUID) is not always properly invoked. It refers to a broad range of conditions that sometimes defy classification. There is not only a strong emotional impact on the family, but such cases are also quite complex. Underlying causes may be multiple, not always readily apparent, and have potential repercussions, especially in terms of forensics. CASE SUMMARY: A 5-month-old male baby was pronounced dead following acute lung failure and cardiopulmonary arrest. The parents had immediately rushed their child to the hospital, stating the baby was found prone and not breathing. Total-body postmortem computed tomography (PMCT) was performed, revealing a hypodense material of indeterminate nature within the main airways and areas of ground-glass parenchymal change. At autopsy, the respiratory tract mucosa appeared edematous and was coated with a whitish stringy material. There was widespread airspace reduction due to parenchymal collapse. Alveolar sacs and bronchial openings contained abundant amorphous material admixed with white blood cells. Immunohistochemical studies were performed, targeting CD15, CD68, and alpha-lactalbumin. Ultimately, the focus was on alpha-lactalbumin (milk protein), which showed marked immunopositivity within alveolar spaces. Cytoplasmic staining of macrophages was also particularly prominent. CONCLUSION: Postmortem investigations are thus essential to identify causes of death and surrounding circumstances. PMCT is a useful tool in this setting, given the frequent dearth of autopsy findings and ambiguity as to cause of death in SUID cases. These findings, later confirmed by immunohistochemical investigations, were indicative of active pneumonia due to aspirated milk. The present account illustrates the importance a broad diagnostic approach to SUID in cases of forensic concern. PMCT is a very valuable aid in cases of forensic interest, as it can provide useful information in all those situations in which the cause of death is uncertain or there are no suggestive dynamics or lesions.

Mast cells activation and high blood tryptase levels due to paclitaxel administration. Is Cremophor EL the culprit?: A case report.

RATIONALE: Although the cancer incidence continues to rise, cancer mortality has declined over the past decade, in large part due to more efficacious chemotherapeutic regimens thus, the ability to use first-line chemotherapeutic agents in the treatment of patients with cancer is crucial. Antineoplastic agents can potentially cause toxic and/or hypersensitivity reactions, that can have serious consequences. Anaphylaxis is a big pitfall in oncological patients; the most important aspect in diagnosing anaphylaxis is to precisely identify the offending agent to prevent future events. Paclitaxel (Taxol) is widely used as antitumor medication in the ovarian, breast, non-small-cell lung, and other cancers. Paclitaxel hypersensitivity reactions are frequently described in the literature, but fatalities are rarely reported. Due to the low solubility of paclitaxel, the compound requires dissolution in Cremophor EL, a derivative of castor oil. PATIENT CONCERNS: A 79-year-old man was affected by high-grade non-papillary urothelial carcinoma and underwent a radical cystectomy and prostatectomy with locoregional lymphadenectomy. DIAGNOSIS: Eight months later, relapse was detected, and penis amputation and left nephrostomy were performed. Multiple metastases to lymph nodes were detected. INTERVENTIONS: Palliative chemotherapy was started with Paclitaxel (110 mg) infused at a rate of 50 mL/h. Despite premedication with cetirizine dihydrochloride, dexamethasone, ondansetron, ranitidine, 20 min after Paclitaxel infusion starts, the patient developed general distress, followed by cardiac arrest. OUTCOMES: The mechanism of fatal paclitaxel-associated hypersensitivity reaction is uncertain and its solvent vehicle Cremophor EL may be involved. Several mechanisms have been postulated: an IgE-mediated mast cell degranulation induced by paclitaxel or Cremophor EL, a non-IgE-mediated idiosyncratic mast cell degranulation by paclitaxel or by Cremophor EL, and complement activation. Severe hypersensitivity reactions with fatal outcome are considered rare. LESSONS: The unpredictability and often dramatic reactions of Taxol cause substantial anxiety for doctors and caretakers. They also represent a significant logistic and financial burden on hospitals. Despite premedication, skin testing, and desensitization protocols administration of taxane-based, chemotherapy cannot be considered safe and severe to fatal hypersensitivity reactions cannot be prevented.

MicroRNAs: The New Challenge for Traumatic Brain Injury Diagnosis.

The acronym TBI refers to traumatic brain injury, an alteration of brain function, or an evidence of brain pathology, that is caused by an external force. TBI is estimated to become the third leading cause of permanent disability and mortality worldwide. TBI-related injuries can be classified in many ways, according to the degree of severity or the pathophysiology of brain injury (primary and secondary damage). Numerous cellular pathways act in secondary brain damage: excitotoxicity (mediated by excitatory neurotransmitters), free radical generation (due to mitochondrial impairment), neuroinflammatory response (due to central nervous system and immunoactivation) and apoptosis. In this scenario, microRNAs are implicated in the regulation of almost all genes at the post-transcriptional level. Several microRNAs have been demonstrated to be specifically expressed in particular cerebral areas; moreover, physiological changes in microRNA expression during normal cerebral development upon the establishment of neural networks have been characterized. More importantly, microRNAs show profound alteration in expression in response to brain pathological states, both traumatic or not. This review summarizes the most important molecular networks involved in TBI and examines the most recent and important findings on TBI-related microRNAs, both in animal and clinical studies. The importance of microRNA research holds promise to find biomarkers able to unearth primary and secondary molecular patterns altered upon TBI, to ultimately identify key points of regulation, as a valuable support in forensic pathology and potential therapeutic targets for clinical treatment.

Atopic Eczema: Genetic Analysis of COL6A5, COL8A1, and COL10A1 in Mediterranean Populations.

To date, the genes associated with susceptibility to Atopic Eczema (AE) are mainly implicated in immunity, inflammation, and maintenance of skin barrier. Little is known about the possible relationship between genes modulating Extra-Cellular Matrix (ECM) and AE etiopathogenesis. In this regard, the primary objective of the present study has been the investigation of susceptibility biomarkers localized within genes encoding collagen proteins. Several studies have shown that polymorphisms within the genes encoding such proteins may generate abnormal connective tissues, making them more susceptible to mechanical stress, loss of epidermal integrity, and aging. We therefore decided to investigate three polymorphisms located in COL6A5, COL8A1, and COL10A1 as potential susceptibility biomarkers for AE in a cohort of 1470 subjects of Mediterranean origin. The genes of interest have been selected considering that the ECM and immune/inflammatory response are strongly dysregulated in AE and other complex disorders. The study confirmed that the susceptibility to AE depends on a complex interaction between latitude, geographical localization, and the differential distribution of genetic variants among populations exposed to similar environmental factors.

Digenic Inheritance of Shortened Repeat Units of the D4Z4 Region and a Loss-of-Function Variant in SMCHD1 in a Family With FSHD.

Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder which is typically transmitted by an autosomal dominant pattern, although reduced penetrance and sporadic cases caused by de novo mutations, are often observed. FSHD may be caused by a contraction of a repetitive element, located on chromosome 4 (4q35). This locus is named D4Z4 and consists of 11 to more than 100 repeated units (RU). The D4Z4 is normally hypermethylated and the genes located on this locus are silenced. In case of FSHD, the D4Z4 region is characterized by 1-10 repeats and results in the region being hypomethylated. However, 5% of FSHD cases do not carry the short allele of D4Z4 region. To date, two forms of FSHD (FSHD1 and FSHD2) are known. FSHD2 is usually observed in patients without the D4Z4 fragment contraction and carrying variants in SMCHD1 (18p11.32) gene. We report the case of a young adult patient who shows severe symptoms of FSHD. Preliminary genetic analysis did not clarify the phenotype, therefore we decided to study the family members by genetic and epigenetic approaches. The analysis of D4Z4 fragment resulted to be 8 RU in the affected proband and in his father; 26 RU in the mother and 25 RU in the maternal uncle. SMCHD1 analysis revealed a heterozygous variation within the exon 41. The variant was detected in the proband, her mother and the uncle. Furthermore, epigenetic analysis of CpG6 methylation regions showed significant hypomethylation in the affected patient (54%) and in the mother (56%), in contrast to the father (88%) and the uncle (81%) carrying higher methylation levels. The analysis of DR1 methylation levels reported hypomethylation for the proband (19%), the mother (11%), and the uncle (16%). The father showed normal DR1 methylation levels (>30%). Given these results, the combined inheritance of SMCHD1 variant and the short fragment might explain the severe FSHD phenotype displayed by the proband. On this subject, SMCHD1 analysis should be promoted in a larger number of patients, even in presence of D4Z4 contractions, to facilitate the genotype-phenotype correlation as well as, to enable a more precise diagnosis and prognosis of the disease.

Identification of Duchenne/Becker muscular dystrophy mosaic carriers through a combined DNA/RNA analysis.

OBJECTIVE: The Duchenne/Becker muscular dystrophy (DMD) carrier screening includes the evaluation of mutations in DMD gene, and the most widely used analysis is the multiplex ligation-dependent probe amplification (MLPA) for the DMD deletions/duplications detection. The high frequency of de novo mutations permits to estimate a risk up to 20% of mosaicisms for mothers of sporadic DMD children. The purpose of this study is to evaluate alternative analytical strategy for the detection of mosaics carrier women, in order to improve the recurrence risk estimation. METHOD: Different DNA and RNA analyses were conducted on samples from a woman that conceived a DMD fetus without previous family history of dystrophynopathy. RESULTS: Standard MLPA analysis failed to identify mosaicism, even if MLPA doses suggested it. Electrophoresis and direct sequencing conducted on RNA permitted to detect two different amplicons of cDNAs, demonstrating the presence of somatic mosaicism. Subsequent detection of a second affected fetus confirmed the mosaic status on the mother. CONCLUSION: The implementation of RNA analysis in diagnostic algorithm can increase the sensitivity of carrier test for mothers of sporadic affected patients, permitting detection of mosaic status. A revision of analytical guidelines is needed in order to improve the recurrence risk estimation and support prenatal genetic counseling.

A Case of Herpes Simplex Virus-1 Encephalitis from a Medicolegal Point of View.

We present a case of herpes simplex virus-1 encephalitis (HSVE) and discuss the difficulty of early diagnosis and the possibility of a wrong or delayed diagnosis and treatment of this encephalitis. We show the importance of considering HSVE to pursue every case of suspicious medical liability.