The Role of Molecular Investigations in Estimating the Time since Deposition (TSD) of Bloodstains: A Systematic Review of the Literature.

At many crime scenes, investigators are able to trace and find traces of blood. For many years, it was believed that such traces could only be subjected to genetic investigations, such as those aimed at comparing DNA profiling with a suspect to verify his identity, and that it was therefore not possible to backdate the traces. In recent years, various works have used experimental models to investigate the possibility of identifying markers and methodologies for estimating the time since deposition (TSD) of bloodstains. Despite the results, these methods are still not part of standard procedures, and there is no univocal analysis methodology. In this work we carried out a systematic literature review of all the papers published in the last ten years on this topic, comparing the experimental models created. This review demonstrates the potential that different molecular approaches, such as transcriptomics, metabolomics, proteomics, and spectrometry, can have in the analysis of TSD, with notable sensitivity and specificity. This paper also analyzes the intrinsic and extrinsic limits of these models and emphasizes the need to continue research work on this topic, considering the importance that this parameter can assume in forensic investigations against a suspect.

Oxidative Stress in Sepsis: A Focus on Cardiac Pathology.

This study aims to analyze post-mortem human cardiac specimens, to verify and evaluate the existence or extent of oxidative stress in subjects whose cause of death has been traced to sepsis, through immunohistological oxidative/nitrosative stress markers. Indeed, in the present study, i-NOS, NOX2, and nitrotyrosine markers were higher expressed in the septic death group when compared to the control group, associated with also a significant increase in 8-OHdG, highlighting the pivotal role of oxidative stress in septic etiopathogenesis. In particular, 70% of cardiomyocyte nuclei from septic death specimens showed positivity for 8-OHdG. Furthermore, intense and massive NOX2-positive myocyte immunoreaction was noticed in the septic group, as nitrotyrosine immunostaining intense reaction was found in the cardiac cells. These results demonstrated a correlation between oxidative and nitrosative stress imbalance and the pathophysiology of cardiac dysfunction documented in cases of sepsis. Therefore, subsequent studies will focus on the expression of oxidative stress markers in other organs and tissues, as well as on the involvement of the intracellular pattern of apoptosis, to better clarify the complex pathogenesis of multi-organ failure, leading to support the rationale for including therapies targeting redox abnormalities in the management of septic patients.

The Expression of FOXO3a as a Forensic Diagnostic Tool in Cases of Traumatic Brain Injury: An Immunohistochemical Study.

Traumatic brain injury (TBI) is one of the most well-known causes of neurological impairment and disability in the world. The Forkhead Box class O (FOXO) 3a is a transcription factor that is involved in different molecular processes, such as cell apoptosis regulation, neuroinflammation and the response to oxidative stress. This study is the first to evaluate the post-mortem immunohistochemical (IHC) positivity of FOXO3a expression in human cases of TBI deaths. The autopsy databases of the Legal Medicine and Forensic Institutes of the "Sapienza" University of Roma and the University of Pisa were retrospectively reviewed. After analyzing autopsy reports, 15 cases of TBI deaths were selected as the study group, while the other 15 cases were chosen among non-traumatic brain deaths as the control group. Decomposed bodies and those with initial signs of putrefaction were excluded. Routine histopathological studies were performed using hematoxylin-eosin (H&E) staining. Furthermore, an IHC investigation on cerebral samples was performed. To evaluate FOXO3a expression, anti-FOXO3a antibodies (GTX100277) were utilized. Concerning the IHC analysis, all 15 samples of TBI cases showed positivity for FOXO3a in the cerebral parenchyma. All control cerebral specimens showed FOXO3a negativity. In addition, the longer the survival time, the greater the positivity to the reaction with FOXO3a was. This study shows the important role of FOXO3a in neuronal autophagy and apoptosis regulation and suggests FOXO3a as a possible potential pharmacological target.

miRNAs and Substances Abuse: Clinical and Forensic Pathological Implications: A Systematic Review.

Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.

6-Monoacetylmorphine-antibody distribution in tissues from heroin-related death cases: An experimental study to investigate the distributive response.

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6-diacetyl ester of morphine (diacetylmorphine). The post-mortem diagnosis of heroin-related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post-mortem anti-6-MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin-related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post-mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications.

Post-mortem computer tomography in ten cases of death while diving: a retrospective evaluation.

INTRODUCTION: Self-contained underwater breathing apparatus (SCUBA) diving deaths have always been a challenge for forensic pathologists. Post-mortem computer tomography (PMCT) allows intracorporeal gas visualization, contributing to identify the cases in which the cause of death is arterial gas embolism (AGE). However, in the literature, it is indicated to perform the radiological examination within 24 h after death. MATERIALS AND METHODS: In this retrospective study, 32 cases of death who had undergone PMCT 24-48 h after death/corpse finding between January 2011 and March 2021 were analyzed, including ten cases of SCUBA divers who died of AGE. All cases' radiological images were reviewed to localize the intracorporeal gas distribution alongside other findings that are usually related to SCUBA diving death. A semi-quantitative evaluation was also performed. RESULTS: Most of the divers showed gas within the left heart and the arteries. In addition, the semi-quantitative evaluation revealed that the divers presented a higher mean amount of intraarterial gas compared to the fresh corpses. On the other hand, the putrefied corpses presented gas within the portal system and generalized subcutaneous emphysema with higher frequency and quantity than the divers and fresh corpses. CONCLUSION: Our cases suggested that the PMCT, even when performed 24-48 h after death, remains a valuable tool to diagnose AGE in cases of SCUBA diving deaths. In addition, with the limit of the small sample size, our data showed that at least a medium quantity of intraarterial gas, when not associated with a high amount of gas within the portal system and subcutaneous emphysema, could be considered a diagnostic criterion of AGE.

Clinical Management of Complications Following Filler Injection.

AIM: Dermal fillers have been progressively used for cosmetic procedures. Concurrently, the rates of filler complications have also increased. The aim of this study is to describe the clinical management and treatment we performed in patients with complications occurred after filler injection. METHODS: From March 2000 to February 2020, 197 patients have been evaluated for complications due to filler injection. For each patient type of material, symptoms and signs were recorded. Ultrasound evaluation was used to obtain information about the type, amount and location of the injected material. Magnetic Resonance Imaging was performed in those patients who were candidate for surgery. Based on the clinical manifestations, we performed a targeted therapy. RESULTS: The local and systemic medical therapy allowed us a complete remission of the clinical signs and symptoms in all patients presented with edema and erythema. We obtained optimal results with surgery, where a complete removal of the injected material was possible. In all the cases in which the complete removal of the infiltrated area could have led to functional impairments, we performed partial removal with poor outcomes. CONCLUSION: We observed complex clinical manifestations in the patients subjected to permanent fillers. An accurate knowledge upon the effects of the materials on tissues, a specific instrumental evaluation and a targeted therapy are crucial. We suggest the use of absorbable fillers. Patient should be subjected to filler implant in authorized structures by an expert specialist with experience in filler injection and with a thorough knowledge of the anatomical structures. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Glymphatic System a Window on TBI Pathophysiology: A Systematic Review.

BACKGROUND: In recent years, the attention of the scientific world has focused on a clearance system of brain waste metabolites, called the glymphatic system, based on its similarity to the lymphatic system in peripheral tissue and the relevant role of the AQP4 glial channels and described for the first time in 2012. Consequently, numerous studies focused on its role in organ damage in cases of neuropathologies, including TBI. METHODS: To evaluate the role that the glymphatic system has in the pathogenesis of TBI, on 23 March 2022, a systematic review of the literature according to PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, resulting in 12 articles after the selection process. DISCUSSION AND CONCLUSION: The present review demonstrated that an alteration of AQP4 is associated with the accumulation of substances S100b, GFAP, and NSE, known markers of TBI in the forensic field. In addition, the alteration of the functionality of AQP4 favors edema, which, as already described, constitutes alterations of secondary brain injuries. Moreover, specific areas of the brain were demonstrated to be prone to alterations of the glymphatic pathway, suggesting their involvement in post-TBI damage. Therefore, further studies are mandatory. In this regard, a study protocol on cadavers is also proposed, based on the analyzed evidence.

Expression of MicroRNAs in Sepsis-Related Organ Dysfunction: A Systematic Review.

Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to microbial pathogens. Such processes lead to an abnormal inflammatory response and multi-organ failure. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of gene regulation. This means that miRNAs are involved in multiple intracellular pathways and thus contribute to or inhibit inflammation. As a result, their variable expression in different tissues and organs may play a key role in regulating the pathophysiological events of sepsis. Thanks to this property, miRNAs may serve as potential diagnostic and prognostic biomarkers in such life-threatening events. In this narrative review, we collect the results of recent studies on the expression of miRNAs in heart, blood, lung, liver, brain, and kidney during sepsis and the molecular processes in which they are involved. In reviewing the literature, we find at least 122 miRNAs and signaling pathways involved in sepsis-related organ dysfunction. This may help clinicians to detect, prevent, and treat sepsis-related organ failures early, although further studies are needed to deepen the knowledge of their potential contribution.

State-of-the-Art on Wound Vitality Evaluation: A Systematic Review.

The vitality demonstration refers to determining if an injury has been caused ante- or post-mortem, while wound age means to evaluate how long a subject has survived after the infliction of an injury. Histology alone is not enough to prove the vitality of a lesion. Recently, immunohistochemistry, biochemistry, and molecular biology have been introduced in the field of lesions vitality and age demonstration. The study was conducted according to the preferred reporting items for systematic review (PRISMA) protocol. The search terms were "wound", "lesion", "vitality", "evaluation", "immunohistochemistry", "proteins", "electrolytes", "mRNAs", and "miRNAs" in the title, abstract, and keywords. This evaluation left 137 scientific papers. This review aimed to collect all the knowledge on vital wound demonstration and provide a temporal distribution of the methods currently available, in order to determine the age of lesions, thus helping forensic pathologists in finding a way through the tangled jungle of wound vitality evaluation.

Cytokine Storm in COVID-19: Immunopathogenesis and Therapy.

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease.

Neutropenic Enterocolitis and Sepsis: Towards the Definition of a Pathologic Profile.

Background: Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. Case report: A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. Literature Review: To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. Conclusions: Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic "neutropenic enterocolitis and sepsis" appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.

Autopsy findings in COVID-19-related deaths: a literature review.

Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus disease. The need for postmortem information is urgent to improve patient management of mild and severe illness, and treatment strategies. The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. A systematic literature search and a critical review of the collected studies were conducted. An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from database inception to June 2020 was performed. We found 28 scientific papers; the total amount of cases is 341. The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels. It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed. A uniform COVID-19 post-mortem diagnostic protocol has not yet been developed. In a time in which international collaboration is essential, standardized diagnostic criteria are fundamental requirements.

MicroRNAs and Sepsis-Induced Cardiac Dysfunction: A Systematic Review.

Sepsis is a severe condition characterized by systemic inflammation. One of the most involved organs in sepsis is the heart. On the other hand, heart failure and dysfunction are some of the most leading causes of death in septic patients. miRNAs are short single-strand non-coding ribonucleic acids involved in the regulation of gene expression on a post-transcriptional phase, which means they are a part of the epigenetic process. Recently, researchers have found that miRNA expression in tissues and blood differs depending on different conditions. Because of this property, their use as serum sepsis biomarkers has also been explored. A narrative review is carried out to gather and summarize what is known about miRNAs' influence on cardiac dysfunction during sepsis. When reviewing the literature, we found at least 77 miRNAs involved in cardiac inflammation and dysfunction during sepsis. In the future, miRNAs may be used as early sepsis-induced cardiac dysfunction biomarkers or as new drug targets. This could help clinicians to early detect, prevent, and treat cardiac damage. The potential role of miRNAs as new diagnostic tools and therapeutic strategies worth deepening the complex network between non-coding RNA and biological pathways. Additional studies are needed to further investigate their role in sepsis-induced myocardium injury.

Post-Traumatic Meningitis Is a Diagnostic Challenging Time: A Systematic Review Focusing on Clinical and Pathological Features.

Post-traumatic meningitis is a dreadful condition that presents additional challenges, in terms of both diagnosis and management, when compared with community-acquired cases. Post-traumatic meningitis refers to a meningeal infection causally related to a cranio-cerebral trauma, regardless of temporal proximity. The PICO (participants, intervention, control, and outcomes) question was as follows: "Is there an association between traumatic brain injury and post-traumatic meningitis?" The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. Studies examining post-traumatic meningitis, paying particular attention to victims of traumatic brain injury, were included. Post-traumatic meningitis represents a high mortality disease. Diagnosis may be difficult both because clinical signs are nonspecific and blurred and because of the lack of pathognomonic laboratory markers. Moreover, these markers increase with a rather long latency, thus not allowing a prompt diagnosis, which could improve patients' outcome. Among all the detectable clinical signs, the appearance of cranial cerebrospinal fluid (CSF) leakage (manifesting as rhinorrhea or otorrhea) should always arouse suspicion of meningitis. On one hand, microbiological exams on cerebrospinal fluid (CSF), which represent the gold standard for the diagnosis, require days to get reliable results. On the other hand, radiological exams, especially CT of the brain, could represent an alternative for early diagnosis. An update on these issues is certainly of interest to focus on possible predictors of survival and useful tools for prompt diagnosis.

Fatal Epstein-Barr virus infection in an immunocompetent host: a postmortem diagnosis.

Meningoencephalitis is the most common neurological complication related to Epstein-Barr virus (EBV), and in immunocompetent adults, it is most commonly self-limited. We describe a case of fatal EBV infection characterized by meningoencephalitis, foci of myocarditis and interstitial nephritis in an immunocompetent 74-year-old man. The postmortem diagnosis was made based on the presence of EBV DNA in the cerebrospinal fluid and by immunohistochemical assay that showed spots of intracellular positivity to anti-EBV antibody in brain tissue.

miR-1, miR-499 and miR-208 are sensitive markers to diagnose sudden death due to early acute myocardial infarction.

MicroRNAs (miRNAs) are strongly up-regulated under pathological stress and in a wide range of diseases. In recent years, miRNAs are under investigation for their potential use as biomarkers in cardiovascular diseases. We investigate whether specific cardio-miRNAs are overexpressed in heart samples from subjects deceased for acute myocardial infarction (AMI) or sudden cardiac death (SCD), and whether miRNA could help differentiate between them. Forty four cases of death due to cardiovascular disease were selected, respectively, 19 cases categorized as AMI and 25 as SCD. Eighteen cases of traumatic death without pathological cardiac involvement were selected as control. Immunohistochemical investigation was performed for CD15, IL-15, Cx43, MCP-1, tryptase, troponin C and troponin I. Reverse transcription and quantitative real-time PCR were performed for miR-1, miR-133, miR-208 and miR-499. In AMI group, stronger immunoreaction for the CD15, IL-15 and MCP-1 antibodies was detectable compared with SCD and control. Cx43 showed a negative reaction with respect to the other groups. Real-time PCR results showed a down-regulation of all miRNAs in the AMI group compared with SCD and control. The selected miRNAs presented high accuracy in discriminating SCD from AMI (miR-1 and miR-499) and AMI from control (miR-208) representing a potential aid for both clinicians and pathologists for differential diagnosis.

Post-mortem computed tomography (PMCT) radiological findings and assessment in advanced decomposed bodies.

PURPOSE: The aim of the study is to report radiological findings and features in advanced decomposed bodies obtained by post-mortem computed tomography (PMCT) with autopsy correlation. MATERIALS AND METHODS: This retrospective descriptive multicentric study included 41 forensic cases examined between May 2013 and November 2016. All the bodies were PMCT-scanned prior to autopsy, and internal putrefactive state was determined using the radiological alteration index (RAI) by a radiologist with expertise in forensic radiology and a forensic pathologist trained in forensic imaging. After PMCT scans, grade of external putrefaction (GEP) was assigned during the external examination and the complete autopsy was performed by forensic pathologists. RESULTS: The PMCT images evaluation revealed that the RAI index was > 61 in all bodies, corresponding to a moderate-massive presence of putrefactive gas. The gas grade was > II in correspondence of the major vessels, heart cavities, liver parenchyma, vertebra L3 and subcutaneous pectoral tissues, and varied from I to III in correspondence of the kidney. Cadaveric external examination revealed the presence of advanced transformative phenomena, with a GEP3 and GEP4 in most of the cases, with body swelling, eyes and tongue protrusion, body fluids expulsion and fat liquefaction. CONCLUSION: Radiological imaging by PMCT as an adjunct to autopsy in advanced decomposed bodies represents a useful tool in detecting post-mortem gas, even in very small amounts. A correct interpretation process of the PMCT data is essential to avoid images pitfalls, due to natural decomposition that can be mistaken for pathologic processes.

Postmortem computed tomography angiography (PMCTA) and traditional autopsy in cases of sudden cardiac death due to coronary artery disease: a systematic review and meta-analysis.

INTRODUCTION: Several studies have been performed to assess the efficacy of postmortem computed tomography angiography (PMCTA) in solving cases of sudden cardiac death, even in comparison with the traditional autopsy. However, the results were often inconsistent and inconclusive. Therefore, a global discussion on the subject through a systematic review of the literature and a meta-analysis is necessary. METHODS: A systematic search of PubMed was performed up to April 23, 2018. Studies exploring the role of PMCTA in cases of sudden cardiac death and the accuracy of this method in diagnosing the cause of death compared to traditional autopsy were included. RESULTS: The overall sensitivity and specificity of the seven included studies, using conventional autopsy as a reference standard, were 92% and 95%, respectively. The positive and negative likelihood ratios were, respectively, 20.76 (95% CI 1.16-370.2) and 0.08 (95% CI 0.03-0.17), showing that PMCTA represents a strong indicator of the posttest probability of disease. The diagnostic odds ratio and the area under the curve were, respectively, 261.54 (95% CI 1.87-5760.53) and 0.93 (95% CI 0.90-0.95), indicating a high diagnostic power of the test. CONCLUSION: PMCTA demonstrated a high accuracy in the diagnosis of parietal and luminal coronary changes but was less effective in detecting myocardial ischemia and necrosis. Therefore, the only radiological investigation is often insufficient to determine the cause of sudden death and the conventional autopsy remains the gold standard. However, PMCTA can improve the performance of the autopsy, serving as an aid and guide in the sampling phase for histopathological investigations.

Sudden death in acrogeria Gottron type.

In this paper, we describe the case of a 29-year-old Caucasian male who was reported dead in his home. In 2010, a diagnosis of acrogeria, Gottron type was obtained by genetic analysis of a COL3A1 gene mutation. External examination showed typical characteristics of acrogeria, Gottron type. Autopsy showed a full-thickness laceration in the inferior vena cava wall, which caused hemorrhage and death. Samples of inferior vena cava were processed by Masson trichrome staining, which revealed a reduction in vessel wall thickness and a decrease in the amount of elastic fibers. An antibody reaction with BCL-2 was intensely positive. Our case is extremely rare in the medical field and in the world of scientific literature, both because the patient had a variant of acrogeria, Gottron type and because of the cause of death, which is not typical of Ehlers-Danlos syndrome. To the best of our knowledge, this very rare event has not previously been reported in the international scientific literature.