Slideflow: deep learning for digital histopathology with real-time whole-slide visualization.

Deep learning methods have emerged as powerful tools for analyzing histopathological images, but current methods are often specialized for specific domains and software environments, and few open-source options exist for deploying models in an interactive interface. Experimenting with different deep learning approaches typically requires switching software libraries and reprocessing data, reducing the feasibility and practicality of experimenting with new architectures. We developed a flexible deep learning library for histopathology called Slideflow, a package which supports a broad array of deep learning methods for digital pathology and includes a fast whole-slide interface for deploying trained models. Slideflow includes unique tools for whole-slide image data processing, efficient stain normalization and augmentation, weakly-supervised whole-slide classification, uncertainty quantification, feature generation, feature space analysis, and explainability. Whole-slide image processing is highly optimized, enabling whole-slide tile extraction at 40x magnification in 2.5 s per slide. The framework-agnostic data processing pipeline enables rapid experimentation with new methods built with either Tensorflow or PyTorch, and the graphical user interface supports real-time visualization of slides, predictions, heatmaps, and feature space characteristics on a variety of hardware devices, including ARM-based devices such as the Raspberry Pi.

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.

The feasibility of three port endonasal, transorbital, and sublabial approach to the petroclival region: neurosurgical audit and multiportal anatomic quantitative investigation.

PURPOSE: The petroclival region represents the "Achille's heel" for the neurosurgeons. Many ventral endoscopic routes to this region, mainly performed as isolated, have been described. The aim of the present study is to verify the feasibility of a modular, combined, multiportal approach to the petroclival region to overcome the limits of a single approach, in terms of exposure and working areas, brain retraction and manipulation of neurovascular structures. METHODS: Four cadaver heads (8 sides) underwent endoscopic endonasal transclival, transorbital superior eyelid and contralateral sublabial transmaxillary-Caldwell-Luc approaches, to the petroclival region. CT scans were obtained before and after each approach to rigorously separate the contribution of each osteotomy and subsequentially to build a comprehensive 3D model of the progressively enlarged working area after each step. RESULTS: The addition of the contralateral transmaxillary and transorbital corridors to the extended endoscopic endonasal transclival in a combined multiportal approach provides complementary paramedian trajectories to overcome the natural barrier represented by the parasellar and paraclival segments of the internal carotid artery, resulting in significantly greater area of exposure than a pure endonasal midline route (8,77 cm2 and 11,14 cm2 vs 4,68 cm2 and 5,83cm2, extradural and intradural, respectively). CONCLUSION: The use of different endoscopic "head-on" trajectories can be combined in a wider multiportal extended approach to improve the ventral route to the most inaccessible petroclival regions. Finally, by combining these approaches and reiterating the importance of multiportal strategy, we quantitatively demonstrate the possibility to reach "far away" paramedian petroclival targets while preserving the neurovascular structures.

Proteomics: A New Research Frontier in Forensic Pathology.

Proteomics, the study of proteins and their functions, has revolutionized the field of forensic science by providing a powerful approach to identify and characterize proteins for various aims [...].

Exploring the Potential of Proteome Analysis as a Promising Tool for Evaluation of Sudden Cardiac Death (SCD) in Forensic Settings: A Literature Review.

Sudden cardiac death (SCD) represents a global emergency, with a high number of cases affecting all age groups every year. The prevention of these fatal events requires an accurate knowledge of etiology and pathogenesis, which can vary. Autopsy is an indispensable tool in cases of SCD for diagnostic purposes, as well as for judicial and preventive purposes for family members. Despite the completion of all routine post-mortem investigations, it is often complicated for the forensic pathologist to define the triggering cause of these events. The study of the proteome is proving to be extremely promising in the field of human cardiovascular disease. This paper aims to offer a literature review on the study of the proteome in post-mortem cadaveric biological samples obtained from SCD cases. The aim of this work is to outline the state of the art of the scientific advances that protein analysis can offer in the diagnosis of SCD and the limits that various studies have traced up to now. In conclusion, the work defines the future perspectives of this field in SCD, suggesting strategies to overcome the reported limits and improve the diagnostics of these events.

Functional and clinical outcomes after superior eyelid transorbital endoscopic approach for spheno-orbital meningiomas: illustrative case and literature review.

The pattern of growth of spheno-orbital meningiomas accounts for the main presenting symptoms, such as proptosis, eye motility deficit, visual impairment, diplopia. As these are benign tumors, the postoperative patient's quality of life is an important factor to consider during the preoperative planning. A detailed literature review of superior eyelid transorbital endoscopic approach for spheno-orbital meningiomas, including our own case, was made. A Medline search up to March 2022 in PubMed online electronic database was made using the following key phrases: "superior eyelid endoscopic transorbital approach spheno-orbital meningiomas," "superior eyelid endoscopic transorbital approach," "spheno-orbital meningiomas endoscopic approach." The inclusion criteria were surgical series, reviews, and case reports in English language, as well as papers written in other languages, but including the abstract in English. Cadaveric studies, multiportal combined approaches for SOM, were excluded. The literature review has disclosed five studies for a total of 65 patients, whose demographic, clinical, pathological, surgical, complications, and outcome data were analyzed. Functional and esthetic outcome data after superior eyelid transorbital approach are the following: improvement of proptosis (100%), of visual deficits (66.66%) and of ocular paresis (75%), with only 11 complications (4 trigeminal dysesthesia, 2 CSF leak, 2 wound complications, 1 upper eyelid necrosis, 1 hemorrhage of surgical field, 1 keratitis) reported, but at the expense of extent of resection (gross total resection 33.39%). Based on the outcome data, the superior eyelid transorbital endoscopic approach results in a suitable operative technique for selected spheno-orbital meningiomas.

An Unusual Case of Sudden Death: Is There a Relationship Between Thyroid Disorders and Fatal Pulmonary Thromboembolism? A Case Report and Review of Literature.

In adults, the most common cause of sudden death is coronary heart disease or defects in the cardiac conduction system; however, there are many cases of sudden death occurring from other causes such as fatal pulmonary thromboembolism. Several risk factors are recognized, including hospitalization, surgery, obesity, pregnancy, the use of oral contraceptives, traumatic fractures, and genetic conditions, which cause hypercoagulable states such as factor V Leiden mutations. Although many risk factors have been identified, the mortality rate is still high. An association between thyroid disease and coagulation disorders has previously been demonstrated. However, scientific literature does not yet agree on the association between thyroid diseases and pulmonary thromboembolism. Excessive thyroid hormones can determine an alteration in the hemostatic system through different mechanisms, which lead to a hypercoagulable state. In forensic literature, there are no reports of fatal thromboembolism in patients with thyroid disorders. We reported a case of a 41-year-old woman who died during sexual activity. The autopsy findings highlighted the presence of massive pulmonary embolism. Histopathological analysis showed structural anomalies of the thyroid gland. A retrospective analysis of her medical history and possible genetic alterations were performed.

A Case Report and Literature Review of Death by Potassium Chloride: Is it a Forensic Medicine Enigma?

The diagnosis of death from potassium chloride (KCl) injection is complex because it is a natural ion, so it is very difficult to trace the exogenous administration of drugs containing potassium. In these cases, it is important to perform a careful cadaver inspection, with the collection of circumstantial data on the scene, and proper autopsy investigations, in order to avoid errors regarding the reconstruction of the cause of death. The aim of this paper is to propose a forensic protocol, including evidence collected from the literature, that could help the medical examiner to perform the correct diagnosis, and also encourage control measures to avoid similar events, especially in nosocomial environments. This is important, especially for health professionals who can easily access drugs containing potassium. For this reason, we need to strengthen control measures of these drugs by proposing a double check in cases of pharmacological use, specifying the volume taken with a double authorization signature and the reasons for the withdrawal.

A Review of the Literature on Episodes of Acute Fentanyl Intoxication in Pediatric Age and Toxicological Applications.

Fentanyl is an opioid with powerful analgesic effects and a high speed of action. Due to its pharmacological properties, this molecule has therapeutic application as an anesthetic in surgery or as palliative therapy for cancer patients. Unfortunately, in recent years, the easy availability of this substance, the low cost and the illegal online market have favored the large-scale diffusion of fentanyl. Fentanyl is available in different forms, including nasal spray, oral patches, soluble capsules, aerosol or the new version of fentanyl mixed with other drugs, making its use very widespread. Subjects of various ages are involved in fentanyl consumption, including minors that have not yet reached adolescence. In this work, we performed a literature review using the search engines PubMed NCBI and SCOPUS regarding episodes of acute fentanyl intoxication occurring in those of a pediatric age using the Mesh Terms "fentanyl" AND "overdose" AND "children". The inclusion criteria were English papers published in the last 10 years regarding the cases of children under the age of 10. We evaluated the most frequent methods of intake and the circumstances of such episodes. In cases of death, we analyzed the autopsy, the toxicological findings and the investigations carried out. The review results show that in this age group (under < 10 y.o. s), it is possible to identify the risk factors for fentanyl intake, such as the presence of this molecule within the family unit due to drug addiction or medical therapy. The results also demonstrate a significant risk of underestimation of this phenomenon, since the molecule is often not investigated through adequate toxicological analysis. These results, therefore, suggest always carrying out toxicological investigations in the case of suspected fentanyl intoxication, both on patients or cadavers. The investigations must always include a urinary screening for opiates, and the request for a second level analysis with molecule dosage in cases of positivity or in cases of strong suspicion for assumption. In cases of intoxication in a family context of drug addiction, it is necessary to investigate the chronicity of the intake through hair analysis and evaluate the possible co-administration of other drugs. In conclusion, we suggest a protocol, applicable both on patients or cadavers, which can be useful for physicians and forensic pathologists in order to promptly identify these cases and allow for the reporting of them to the judicial authorities with the adoption of strict prevention and control measures.

The Role of Adrenomedullin as a Predictive Marker of the Risk of Death and Adverse Clinical Events: A Review of the Literature.

Adrenomedullin (ADM) is a vasodilatory peptide that plays a crucial role in maintaining cardiovascular health through its various biological functions. ADM was discovered in the acidic extract of human pheochromocytoma tissue and has been recognized for its significant effects on the vascular system. The main functions of ADM include vasodilation, controlling blood pressure and maintaining vascular integrity, although its role on cardiovascular health is broader. Research has shown that elevated levels of adrenomedullin have been observed in a large number of severe diseases, with high risk of death. In this work, we examined the role of ADM as a predictive molecule of the risk of mortality and adverse clinical outcome through a narrative review of the scientific literature. The results were divided based on the pathologies and anatomical districts examined. This review demonstrates how ADM shows, in many diseases and different systems, a close correlation with the risk of mortality. These results prove the value of ADM as a prognostic marker in various clinical contexts and diseases, with utility in the stratification of the risk of clinical worsening and/or death and in the evaluation of therapeutic efficacy. The results open new perspectives with respect to the concrete possibility that ADM enters clinical practice as an effective diagnostic and prognostic marker of death as well as a molecular target for therapies aimed at patient survival.

The Fascinating World of Forensic Sciences: Multidisciplinary Approaches in Human Remains and the Role of Forensic Pathology in Calabrian Experience.

Forensic sciences play a vital role in the criminal justice system by providing insights into the identity of victims and suspects, causes of death, and other crucial pieces of evidence. In this research paper, we will explore the utility of forensic sciences, its techniques and applications, and the critical role of the forensic pathologist in analyzing human remains. For this purpose, we have analyzed a series of human remains and cadavers found in a state of decomposition, illustrating the medico-legal investigations carried out. Specifically, 50 cases from Calabrian experience are reported from 2003 to 2023 in different contexts of both judicial and archaeological interest and discovered by chance. In any case, anthropological, odontological, genetic, entomological, and forensic radiological investigations were carried out with the supervision of the forensic pathologist in all cases. The varied composition of the sample made it possible to understand the methods and the various specialists involved in such diversified cases. Furthermore, a review of the scientific literature on the topic of human remains was carried out. In particular, by delving into these topics, we aim to provide a comprehensive understanding of forensic anthropology and forensic sciences and their significance in the criminal justice system.

A Multidisciplinary Approach to a Complex Fatal Attack Due to a Pack of Maremma Sheepdogs: Is It Always an Accident?

Deaths due to dog attacks are a worldwide issue. Fatal dog attacks may occur in various environments, including the dog owner's property. A lot of difficulties emerge when the attack involves a pack of dogs, of different species and sizes. In this case, it becomes much more difficult for forensic investigators to evaluate the event, especially regarding the identification of the dog or dogs that caused the death as well as the identification of the owner and the reconstruction of the dynamics for forensic purposes. In this paper, we analyze a specific case of an attack by a herd of Maremma sheepdogs. A crime scene investigation has been carried out. In the first phase of this case, the victim interacted with dogs that had non-aggressive attitudes. Then, after an escape attempt, she was assaulted by about 20 Maremma dogs of different sizes, leading to multiple injuries all over her body. The greatest difficulty was precisely that of reconstructing the dynamics due to the numerous injuries and dogs involved in the attack. The dynamics were divided into several stages following the analysis of the injuries found on the victim. This case study highlights how the forensic multidisciplinary approach has made it possible to precisely reconstruct the event. The analysis of the dogs' state of malnutrition and their suddenly aggressive attitude towards the victim revealed profiles of responsibility of the owner attributable to improper management and training of the animals to defend their property.

Multimodal Use of Contact Endoscopy in Neurosurgery: Case Series with Technical Note and Literature Review.

BACKGROUND: Originally adopted for the cytological screening of cervical and uterine cancer, contact endoscopy (CE) is now widely used in several fields of oncological surgery. The CE method, with magnification power up to 150x, was designed to enhance visualization and identify microscopic changes indicative of precancerous and cancerous lesions at early stages. In this pilot study, we evaluated the multimodal applications of CE during different endoscopic intracranial neurosurgical procedures. METHODS: Twenty patients with skull base lesions underwent surgery using different minimally invasive endoscopic approaches (endonasal, transorbital, and supraorbital). CE was used to distinguish the pathology from the surrounding healthy tissue by positioning the endoscope either in proximity or directly onto the target tissue. Special attention was given to the visualization of the margins of the lesion to differentiate compression/displacement from infiltration of the normal surrounding tissue. RESULTS: With its unprecedented range of magnification, CE could clearly identify the microvascular pattern and cytological architecture of a tissue not detectable by simple white light endoscopy, with no reported damage due to heat transmission or iatrogenic injuries. All the lesions diagnosed as "presumed neoplastic tissue" by CE were confirmed by histopathology. The most promising results were observed in surgeries for meningioma and pituitary adenoma, as these lesions exhibit distinctive microvascular networks. CONCLUSIONS: CE represents a new and effective technique for the in vivo identification of pathological microvascular and tissue features, allowing preservation of normal tissue during different endoscopic approaches. The use of CE could improve diagnostic accuracy and assist in intraoperative decision-making, becoming a key tool in various applications in neurosurgical field.

Evaluation of Major Pathologic Response and Pathologic Complete Response as Surrogate End Points for Survival in Randomized Controlled Trials of Neoadjuvant Immune Checkpoint Blockade in Resectable in NSCLC.

INTRODUCTION: Controversy remains as to whether pathologic complete response (pCR) and major pathologic response (MPR) represent surrogate end points for event-free survival (EFS) and overall survival (OS) in neoadjuvant trials for resectable NSCLC. METHODS: A search of PubMed and archives of international conference abstracts was performed from June 2017 through October 31, 2023. Studies incorporating a neoadjuvant arm with immune checkpoint blockade alone or in combination with chemotherapy were included. Those not providing information regarding pCR, MPR, EFS, or OS were excluded. For trial-level surrogacy, log ORs for pCR and MPR and log hazard ratios for EFS and OS were analyzed using a linear regression model weighted by sample size. The regression coefficient and R2 with 95% confidence interval were calculated by the bootstrapping approach. RESULTS: Seven randomized clinical trials were identified for a total of 2385 patients. At the patient level, the R2 of pCR and MPR with 2-year EFS were 0.82 (0.66-0.94) and 0.81 (0.63-0.93), respectively. The OR of 2-year EFS rates by response status was 0.12 (0.07-0.19) and 0.11 (0.05-0.22), respectively. For the 2-year OS, the R2 of pCR and MPR were 0.55 (0.09-0.98) and 0.52 (0.10-0.96), respectively. At the trial level, the R2 for the association of OR for response and HR for EFS was 0.58 (0.00-0.97) and 0.61 (0.00-0.97), respectively. CONCLUSIONS: Our analyses reveal a robust correlation between pCR and MPR with 2-year EFS but not OS. Trial-level surrogacy was moderate but imprecise. More mature follow-up and data to assess the impact of study crossover are needed.

The Effects of COVID-19 Pandemic on Public Mental Health: State of Art and Future Perspectives.

The COVID-19 pandemic has radically changed our lives in every way [...].

The Risk of Suicide in the Post-COVID-19 Emergency Era: Psychological and Forensic Implications.

The emergence of the coronavirus disease 2019 (COVID-19) pandemic brought numerous challenges, including the management of psychological and psychiatric disorders, leading to an increased risk of suicide. At the end of the COVID-19 emergency, we wonder what the impact of the pandemic has been, and still is, on the state of public mental health with respect to the phenomenon of suicide. Therefore, this review aims to explore the psychological and forensic aspects of suicide in the post-COVID-19 emergency era. The paper will delve into the various psychiatric disorders associated in the literature with COVID-19, the risk factors for suicide during the pandemic, and measures that can be taken to prevent suicide in the post-COVID-19 era. Additionally, the paper will look at how forensic experts investigate suicide cases due to COVID-19 and the legal implications of suicide due to the pandemic. The findings of this study will provide insights into the psychological and forensic aspects of suicide in the post-COVID era, and emphasize interventions and policy development to address this growing public health concern.

Clinical and Forensic Investigation Protocols for Diagnosing Abusive Head Trauma: A Literature Review.

Abusive head trauma (AHT) represents a very serious global public health problem. Prevention of these episodes is essential to reduce the morbidity and mortality of this phenomenon. All healthcare professionals should be able to recognize the signs of abuse. However, diagnosis is very complex as the signs are often blurred and cannot be recognized with certainty without carrying out adequate instrumental investigations. It has been calculated that approximately one-third of AHT cases remain undetected and require more than one medical visit to be correctly interpreted and diagnosed. On the other hand, the literature has recently also emphasized the problems related to possible false diagnoses of abuse and the numerous family and personal repercussions that follow from this issue. For these reasons, correct and timely recognition is essential to avoid the risk of recurrence of AHT and to start proper forensic investigations, in order to identify the offender or exonerate a suspect. The present work explores the most recent evidence of recent years in the field of AHT diagnostics through a literature review. The purpose of this article is to provide forensic pathologists with clear tools for diagnosis based on the literature. To this end, the review suggests clinical and forensic protocols aimed at the timely diagnosis of AHT in order to prevent abuse from remaining undetected.

Sudden Death of a Young Man Due to Massive Haemoptysis Associated With Pulmonary Tuberculosis: A Rare Case.

Asphyxia includes a large number of possible causes and mechanisms, such as infectious diseases of the lungs. Among these, tuberculosis (TB) is one of the main infectious causes of death worldwide. The burden of TB is very high, by virtue of antibiotic resistance and the risk of other concomitant infections, such as HIV. A major problem is related to the omitted diagnosis of TB infection which, in some cases, may remain completely unknown to the patient, with a significant increase in mortality and morbidity risk. There has been a decrease in the reported cases of sudden death due to TB, especially that associated with hemoptysis and aspiration of blood. In this report, we describe a case of sudden death that occurred in a young male in the workplace, under unclear circumstances. The autopsy detected acute asphyxia due to a massive pulmonary hemorrhage in the individual, who was apparently suffering from TB. The autopsy proved to be essential for understanding the cause of death and investigating the adequacy of the health surveillance measures carried out on the individual.

Liver injury associated with high value of D-dimer plasmatic level in COVID-19 patients.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causal agent of the coronavirus disease (COVID-19), has infected millions of people worldwide. Currently, the scientific community debates on the direct viral responsibility of liver damage or whether the observed changes are secondary manifestations of systemic inflammation triggered by COVID-19. The hepatic involvement is associated with worse clinical outcomes and higher risk of COVID-19 related morbidity and mortality. Furthermore, SARS-CoV-2 infection may predispose patients to thrombotic disease due to excessive inflammation, platelet activation, and endothelial dysfunction. METHODS: In this paper, we reported a cross-sectional analysis of five patients affected by a severe form of COVID-19, who died between April 11 and May 1, 2020. Each patient has been subjected to a medico-legal autopsy in which both gross and histological liver changes were evaluated, as well as the correlation with the related coagulation profile. RESULTS: In three cases of our cohort, the thromboembolism was recognized as cause of death. Furthermore, a significant statistical difference between D-dimer values at hospital admission and death among enrolled patients (P=0.033), was evaluated. No patient has recorded a pre-existing liver disease. CONCLUSIONS: Our results support the evidence that hepatic damage in subjects with severe form of COVID-19 is related to the changes in coagulative and fibrinolytic pathways. Hence, the evaluation of D-dimer blood levels may be useful in clinical practice to predict the involvement of the liver and the prognosis of these patients. This data highlights the fundamental role of coagulation balance in subjects with advanced form of COVID-19.

Concomitant, Single Burr Hole Endoscopic Third Ventriculostomy and Tumor Biopsy for Pineal Lesions: Feasibility, Safety, and Benefits.

Obtaining a prompt diagnosis, avoiding indwelling ventriculoperitoneal shunt, and enhancing the predictive value of pathologic examinations are only some of the advantages conferred by a simultaneous third ventriculostomy and tumor biopsy in patients with pineal region tumors. The objective of this study was to retrospectively search the literature on concomitant, single burr hole endoscopic third ventriculostomy (ETV) and tumor biopsy (TB) for pineal region tumors and to analyze the feasibility, surgical safety, and benefits of these 2 combined procedures. Consequently, a comprehensive, systematic literature search was performed in compliance with the updated PRISMA 2020 guidelines within electronic databases MEDLINE/PubMed, EMBASE, PLOS, and Cochrane Library. Statistical analysis was performed with IBM SPSS 28.0.1.1(14), using Kendall's and Spearman's tests, with a P < 0.05 considered significant. A total of 25 studies were selected and included in this review, for a total of 368 patients (mean age 20.6 years; range 1-86 years; SD 17.5). More than two-thirds of the procedures were operated with a rigid endoscope and 27.6% were performed with either a flexible endoscope, a combination of the 2, or not otherwise specified. Germinoma represented the most frequent diagnosis (20.1%) followed by astrocytoma (12.9%) and pineocytoma (9.9%). The single-entry approach allowed a correct histologic diagnosis in 88.7% of the examined cases. Summing up, concomitant ETV and TB represent a valuable option for the management of non-communicating hydrocephalus and the initial assessment of pineal region tumors. The histologic confirmation rate was 88.7% in the examined cohort, with only 10% of the biopsies yielding inconclusive results.