Search Results (22)

Peripheral nerve injuries represent a significant challenge in legal medicine, and their proper management and evaluation are at the intersection of clinical medicine, anatomical science, and legal medicine. In this review, we aimed to integrate current knowledge about the anatomy, physiology, clinical management, and paraclinical assessment of peripheral nerve injuries, targeted explicitly for medical–legal practice. We conducted a comprehensive review of the medical–legal evaluation framework needed to evaluate peripheral nerve injuries, with particular emphasis on anatomical variations, imaging techniques, and methods to assess the timing of injury. Peripheral nerve injuries should be analyzed using a complex approach, which includes anatomical characteristics, variants, microanatomy, physiopathology, imaging, and other paraclinical evaluations. The analysis of causation and timing of injury should be heavily based on objective criteria and should be performed using a reproducible, objective, and scientifically based approach. Full article

APOL1 Renal Risk Variants (APOL1RRVs, G1, and G2) are known to be toxic to glomerular podocytes and causally associated with an enhanced prevalence and progression of many different etiologies of chronic kidney disease (CKD), leading to the delineation of a new disease designation of APOL1-Mediated Kidney Disease (AMKD). Notably, APOL1RRVs have not consistently been shown to increase the prevalence or severity of diabetic kidney disease (DKD) progression, which is the most common cause of End-Stage Kidney Disease (ESKD). While this apparent discrepancy seems perplexing, its clarification should provide important mechanistic and therapeutic insights. Activation of the Renin–Angiotensin System (RAS) plays a critical role in the development and progression of DKD. Recent in vitro and in vivo studies also demonstrated that RAS activation contributes to kidney cell injury in AMKD experimental models. Both high glucose, as well as APOL1RRVs escalate the podocyte expression of miR193a, a known mediator of glomerulosclerosis, including idiopathic Focal Segmental Glomerular Sclerosis (FSGS) and DKD. We propose that either the RAS and/or miR193a levels in the diabetic milieu are already maximally conducive to kidney target cell injury and, therefore, are agnostic to further injury in response to APOL1RRVs. Similarly, the contributory role of hypertension (which is frequently reported as the second most common cause of ESKD) in the progression of AMKD remains a controversial issue. Since several clinical reports have shown that controlling hypertension does not consistently slow the progression of AMKD, this has led to a formulation wherein APOL1-RRVs primarily lead to kidney injury with accompanying hypertension. Notably, half a decade later, the notion that hypertension is not a cause but rather a consequence of kidney injury was contested by investigators analyzing the Mount Sinai BioMe repository, a comprehensive clinical and genetic database including participants with APOL1RRVs. These investigators observed that hypertension predated the observed decline in GFR in individuals with APOL1RRVs by ten years. In the present study, we discuss the mechanistic forces that may underpin the gaps in these clinical manifestations, which did not allow the temporal association of hypertension with AMKD to be translated into causation and may also dissociate DKD and AMKD. We have hypothesized models that need to be validated in future experimental studies. Full article

Background and Objectives: Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury with high mortality, characterized by hypoxemic respiratory failure and diffuse lung damage. Despite advancements in care, no definitive biomarkers have been established for ARDS diagnosis and prognostic stratification. Soluble receptor for advanced glycation end-products (sRAGE), a marker of alveolar epithelial injury, has shown promise as a prognostic indicator in ARDS. This study evaluates sRAGE’s utility in predicting 28-day mortality. Materials and Methods: A retrospective cohort study was conducted at a tertiary care ICU in Serbia from January 2021 to June 2023. Adult patients meeting the Berlin definition of ARDS were included. Exclusion criteria included pre-existing chronic respiratory diseases and prolonged mechanical ventilation before diagnosis. Serum sRAGE levels were measured within 48 h of ARDS diagnosis using enzyme-linked immunosorbent assay (ELISA). Clinical severity scores, laboratory markers, and ventilatory parameters were recorded. Logistic regression and survival analyses were used to assess the prognostic value of sRAGE for 28-day mortality. Results: A cohort of 121 patients (mean age 55.5 years; 63.6% male) was analyzed. Non-survivors exhibited higher median sRAGE levels than survivors (5852 vs. 4479 pg/mL, p = 0.084). The optimal sRAGE cut-off for predicting mortality was >16,500 pg/mL (sensitivity 30.4%, specificity 86.9%). Elevated sRAGE levels were associated with greater disease severity and an increased risk of 28-day mortality in ARDS patients, highlighting its potential as a prognostic biomarker. The main findings, while indicative of a trend toward higher sRAGE levels in non-survivors, did not reach statistical significance. Conclusions: The main findings, while indicative of a trend toward higher sRAGE levels in non-survivors, did not reach statistical significance (p = 0.084). sRAGE demonstrates potential as a prognostic biomarker in ARDS and has moderate correlation with 28-day mortality. Integrating sRAGE with other biomarkers could enhance risk stratification and guide therapeutic decisions. The retrospective design limits the ability to establish causation, underscoring the need for multicenter prospective studies. Full article

In traffic accidents, elderly individuals face a significantly higher risk of mortality compared with other age groups. To investigate the factors contributing to elderly pedestrian accidents and their impact on injury severity, 1420 motor vehicle/elderly pedestrian collisions from the 2019–2023 Chinese Traffic Accident Deep Investigation Database were analyzed using the FP-growth algorithm. This analysis identified 5594 association rules across 28 types of variables within 4 categories of influencing factors. Logistic regression results indicate that pedestrian age, collision speed, time of occurrence, and accident location are significant factors affecting the mortality rate of elderly pedestrians in traffic accidents. Specifically, pedestrian age and collision speed significantly influence mortality rates. As collision speed increases, the mortality rate rises markedly. For elderly pedestrians aged 60 and above, the mortality rate increases by 3.7% with each additional year of age. Moreover, accidents occurring at night, in suburban areas, or in villages are associated with a higher mortality rate. This study offers scientific support for the formulation of safety measures aimed at improving the traffic safety of elderly pedestrians. Full article

Myocardial infarction and reperfusion constitute a complex injury consisting of many distinct molecular stress patterns that influence cardiomyocyte survival and adaptation. Cell signalling, which is essential to cardiac development, also presents potential disease-modifying opportunities to recover and limit myocardial injury or maladaptive remodelling. Here, we hypothesized that Yap signalling could be sensitive to one or more molecular stress patterns associated with early acute ischemia. We found that Yap, and not Taz, expression patterns differed in a post-myocardial infarct compared to a peri-infarct region of rat hearts post-myocardial infarction, suggesting cell specificity that would be challenging to resolve for causation in vivo. Using H9c2 ventricular myotubes in vitro as a model, Yap levels were determined to be more sensitive to nutrient deprivation than other stress patterns typified by ischemia within the first hour of stress. Moreover, this is mediated by amino acid availability, predominantly L-isoleucine, and influences the expression of connective tissue growth factor (Ctgf)—a major determinant of myocardial adaptation after injury. These findings present novel opportunities for future therapeutic development and risk assessment for myocardial injury and adaptation. Full article

Persons with disabilities experience numerous barriers to healthcare access including vaccine accessibility. The purpose of this study was to determine COVID-19 vaccine uptake in the spinal cord injury and disease (SCI/D) population of Ontario and identify potential factors influencing C OVID-19 vaccine uptake. This was a retrospective closed-cohort study using administrative health data on individuals with SCI/D of traumatic and non-traumatic causes to examine the monthly number of COVID-19 vaccine doses received between December 2020 and December 2023. Logistic regression analysis was used to examine the potential association between socio-demographic, clinical, and neighbourhood characteristics with initial COVID-19 vaccine receipt and booster dose uptake. By the end of the observation period in December 2023, 82.9% received the full two-dose coverage and 65.6% received at least one additional booster dose in a cohort of 3574 individuals with SCI/D. SCI/D individuals showed a comparable COVID-19 vaccine uptake percentage to the general population. Sociodemographic, clinical, and neighbourhood characteristics were associated with COVID-19 vaccine uptake in the SCI/D population, including age, type of injury, number of comorbidities, mental health history, and neighbourhood characteristics such as income. Further investigation is necessary to determine the causation effects of these relationships with vaccine uptake to address health equity concerns. Full article

The centrality of amyloid-beta (Aβ) is an indisputable tenet of Alzheimer’s disease (AD). It was initially indicated by the detection (1991) of a mutation within Aβ protein precursor (AβPP) segregating with the disease, which served as a basis for the long-standing Amyloid Cascade Hypothesis (ACH) theory of AD. In the intervening three decades, this notion was affirmed and substantiated by the discovery of numerous AD-causing and AD-protective mutations with all, without an exception, affecting the structure, production, and intraneuronal degradation of Aβ. The ACH postulated that the disease is caused and driven by extracellular Aβ. When it became clear that this is not the case, and the ACH was largely discredited, a new theory of AD, dubbed ACH2.0 to re-emphasize the centrality of Aβ, was formulated. In the ACH2.0, AD is caused by physiologically accumulated intraneuronal Aβ (iAβ) derived from AβPP. Upon reaching the critical threshold, it triggers activation of the autonomous AβPP-independent iAβ generation pathway; its output is retained intraneuronally and drives the AD pathology. The bridge between iAβ derived from AβPP and that generated independently of AβPP is the neuronal integrated stress response (ISR) elicited by the former. The ISR severely suppresses cellular protein synthesis; concurrently, it activates the production of a small subset of proteins, which apparently includes components necessary for operation of the AβPP-independent iAβ generation pathway that are absent under regular circumstances. The above sequence of events defines “conventional” AD, which is both caused and driven by differentially derived iAβ. Since the ISR can be elicited by a multitude of stressors, the logic of the ACH2.0 mandates that another class of AD, referred to as “unconventional”, has to occur. Unconventional AD is defined as a disease where a stressor distinct from AβPP-derived iAβ elicits the neuronal ISR. Thus, the essence of both, conventional and unconventional, forms of AD is one and the same, namely autonomous, self-sustainable, AβPP-independent production of iAβ. What distinguishes them is the manner of activation of this pathway, i.e., the mode of causation of the disease. In unconventional AD, processes occurring at locations as distant from and seemingly as unrelated to the brain as, say, the knee can potentially trigger the disease. The present study asserts that these processes include traumatic brain injury (TBI), chronic traumatic encephalopathy, viral and bacterial infections, and a wide array of inflammatory conditions. It considers the pathways which are common to all these occurrences and culminate in the elicitation of the neuronal ISR, analyzes the dynamics of conventional versus unconventional AD, shows how the former can morph into the latter, explains how a single TBI can hasten the occurrence of AD and why it takes multiple TBIs to trigger the disease, and proposes the appropriate therapeutic strategies. It posits that yet another class of unconventional AD may occur where the autonomous AβPP-independent iAβ production pathway is initiated by an ISR-unrelated activator, and consolidates the above notions in a theory of AD, designated ACH2.0/E (for expanded ACH2.0), which incorporates the ACH2.0 as its special case and retains the centrality of iAβ produced independently of AβPP as the driving agent of the disease. Full article

Repeated regulatory incident investigations demonstrate the insufficiency of company risk assessments and the vulnerabilities that this exposes to the business and its duty holders who are, ultimately, culpable for the subsequent legislative breaches. While the epistemology and taxonomy of the traditional risk assessment are well established, there is a paucity of information that allows the verification and validation of the risk assessment content. Using evidence-based methodologies such as Content Analysis, Thematic Analysis, and validating the outputs using a survey, it became possible to “reverse engineer” the risk assessment content. This analysis of the published risk assessments, kindly supplied by six different Renewable Energy businesses, established that deterministic and behavioristic risk management methodologies had been adopted. These methodologies permitted and guided the use of vague and imprecise terminology and phraseology, numerical inconsistencies resulting in data ossification, and flawed assumptions. This analysis enables the duty holders to make informed and rational judgements about the adequacy of the risk assessment documents, and the process that permitted and guided their creation. Full article

In recent literature reviews, we concluded that the possibility that endometrial molecular aberrations are the sole or a necessary determinant of endometriosis and the Tissue Injury and Repair (TIAR) theory are yet to be convincingly proven. Here, we critically examine the theory that adenomyosis and endometriosis represent different phenotypes of a single disease. A common etiopathology for adenomyosis and endometriosis has been suggested because both conditions entail the presence of endometrial tissue at locations other than the lining of the uterus. There are wide differences in reported disease incidence and prevalence and, consequently, in estimates of the coexistence of both conditions. There are some similarities but also differences in their clinical features and predisposing factors. Each condition has a range of subtypes. These differences alone pose the question of whether subtypes of endometriosis and adenomyosis have different etiopathologies, and, in turn, this raises the question of whether they all share a common etiology. It is debatable whether the recognized differences between the eutopic endometrium in adenomyosis and endometriosis compared to those in unaffected women are the cause or the effect of the disease. The finding of common mutations, particularly of KRAS, lend support to the notion of shared predisposing factors, but this alone is insufficient evidence of causation. Full article

This review focuses on SARS-CoV-2 infection in placental and fetal tissues. Viremia is rare in infected pregnant women, and the virus is seldom amplified from placental tissues. Definite and probable placental infection requires the demonstration of viral RNA or proteins using in situ hybridization (ISH) and immunohistochemistry (IHC). Small subsets (1.0–7.9%, median 2.8%) of placentas of SARS-CoV-2-positive women showed definite infection accompanied by a characteristic histopathology named SARS-CoV-2 placentitis (SP). The conventionally accepted histopathological criteria for SP include the triad of intervillositis, perivillous fibrin deposition, and trophoblast necrosis. SP was shown to be independent of the clinical severity of the infection, but associated with stillbirth in cases where destructive lesions affecting more than 75% of the placental tissue resulted in placental insufficiency and severe fetal hypoxic–ischemic injury. An association between maternal thrombophilia and SP was shown in a subset of cases, suggesting a synergy of the infection and deficient coagulation cascade as one of the mechanisms of the pathologic accumulation of fibrin in affected placentas. The virus was amplified from fetal tissues in approximately 40% of SP cases, but definite fetal involvement demonstrated using ISH or IHC is exceptionally rare. The placental pathology in SARS-CoV-2-positive women also includes chronic lesions associated with placental malperfusion in the absence of definite or probable placental infection. The direct viral causation of the vascular malperfusion of the placenta in COVID-19 is debatable, and common predispositions (hypertension, diabetes, and obesity) may play a role. Full article

Incidents are caused by a variety of factors, and there are correlations between incident causative factors. How to effectively clarify the importance of incidental injury-causing factors and their correlations is the current technical challenge in the field of incident causation analysis. This paper takes the study of injury-causing factors and their relationships between object-striking incidents in the process of construction as an example, and it statistically analyzes the incident investigation reports of 126 cases of object-striking incidents in construction projects in China from 2016 to 2022; it screens out 52 categories of incident-causing factors. The Apriori algorithm and FP-growth algorithm are used to data mine the influencing factors obtained from the 126 object-striking incidents: 28 main incident causative items of object-striking incidents and the respective correlation degree between each factor are obtained. By analyzing the support degree of the main incident causation items, as well as comparing and analyzing the results of the incident causation support degree and association rules with Bayesian inference, 9 key injury-causing factors of object-striking incidents are identified. The research results put forward a new research idea for the analysis of the injury factors of object-striking incidents in construction, which can provide theoretical reference for improving the pertinence and effectiveness of incident prevention measures. Full article

Governments and authorities worldwide consider road traffic crashes (RTCs) to be a major concern. These crashes incur losses in terms of productivity, property, and life. For a country to establish its road and action plans, it is crucial to comprehend the reasons for and consequences of traffic collisions. The main objective of this research study was to evaluate and rank the important and supporting factors influencing traffic crashes on the road. To identify the most significant accident causation elements, the proportion-based analytic hierarchy process (PBAHP) was used to order the factors in terms of their relative importance. In this study, the city of Al-Ahsa, located in the eastern province of Saudi Arabia, was used as a case study, since this city is the highest RTC-prone area in the region. PBAHP was used to calculate relative importance/weights for different crash types and reasons in terms of their impact on crash severity. It was found that vehicle-overturned collisions which result in fatal crashes have the most weight, whereas “hit motorcycle” crashes result in serious injury crashes. When vehicles (two or more) collide with one another while they are moving, it appears that the likelihood of a fatality in a collision increases. The highest weights for serious injury crashes came from “driver distraction”, “leaving insufficient safe distance”, and “speeding”, which also generated similar and relatively high weights for fatal crashes. Weights from the PBAHP approach were also used to develop utility functions for predicting the severity of crashes. This approach could assist decision-makers in concentrating on the key elements affecting road traffic crashes and enhancing road safety. Full article

As understanding their pathogenesis remains elusive, both endometriosis and adenomyosis are often referred to as “enigmatic diseases”. The uncertainty and heightened interest are reflected in the range of expressed views and opinions. There is a sense of urgency because of the entailed patient suffering. The plethora of opinions calls for a critical analysis of proposed theories, both old and new. A series of papers published since 2009 proposed that both endometriosis and adenomyosis originate from the same aberrations occurring within the uterus. This came to be recognized as the tissue injury and repair theory, and the newly coined term “archimetrosis” posits that the two diseases share the same origin. While the theory opens an interesting channel for exploration, its claim as a unifying theory necessitates a critical appraisal. We, thus, undertook this review of the theory and analyzed its underpinnings based on a comprehensive review of the literature. Our appraisal indicates that the theory is open to a range of criticisms. Chief among these is the need for confirmatory evidence of features of abnormal uterine contractility and the lack of data addressing the question of causality. In addition, the theory has, as yet, no supporting epidemiological evidence, which is a major weakness. The theory suffers as it is not open to the test of falsifiability, and it lacks the ability to make useful predictions. It has not addressed the questions, such as why only a small percentage of women develop adenomyosis or endometriosis, given the ubiquity of uterine peristalsis. On the other hand, the triggers and prevention of hyper- or dys-peristalsis become critical to a theory of causation. We conclude that additional supportive evidence is required for the theory to be accepted. Full article

The two-hit model has been proposed to explain the effects of diabetes on mothers who are already in a putative subclinical damaged state and then undergo neuronal damage during the delivery process. However, the anatomical and pathophysiological mechanisms are not well understood. Our overarching hypothesis in this review paper is that pregnant women who are diabetic have a damaged peripheral nervous system, constituting the “first hit” hypothesis. The delivery process itself—the “second hit”—can produce neurological damage to the mother. Women with diabetes mellitus (DM) are at risk for neurological damage during both hits, but the cumulative effects of both “hits” pose a greater risk of neurological damage and pathophysiological changes during delivery. In our analysis, we introduce the different steps of our concept paper. Subsequently, we describe each of the topics. First, we outline the mechanisms by which diabetes acts as a detrimental variable in neuropathy by focusing on the most common form of diabetic neuropathy, diabetic distal symmetrical polyneuropathy, also known as distal sensorimotor neuropathy. The possible role of macrosomia in causing diabetic neuropathy and obstetric neurological injury is discussed. Second, we describe how vaginal delivery can cause various obstetrical neurological syndromes and pathophysiological changes. Third, we highlight the risk of obstetric neuropathy and discuss anatomical sites at which lesions may occur, including lesions during delivery. Fourth, we characterize the pathophysiological pathways involved in the causation of diabetic neuropathy. Finally, we highlight diabetic damage to sensory vs. motor nerves, including how hyperglycemia causes different types of damage depending on the location of nerve cell bodies. Full article

The rapid identification of patients at risk for massive blood transfusion is of paramount importance as uncontrolled exsanguination may lead to death within 2 to 6 h. The aim of this study was to analyze a cohort of severe trauma patients to identify risk factors associated with massive transfusion requirements and hypocalcemia. All major trauma (ISS > 16) presented directly from the scene to the Niguarda hospital between 1 January 2015 and 31 December 2021 were analyzed. A total of 798 patients were eligible out of 1586 screened. Demographic data showed no significant difference between hypocalcemic (HC) and normocalcemic (NC) patients except for the presence of crush trauma, alcohol intake (27% vs. 15%, p < 0.01), and injury severity score (odds ratio 1.03, p = 0.03). ISS was higher in the HC group and was an independent, even if weak, predictor of hypocalcemia (odds ratio 1.03, p = 0.03). Prehospital data showed a lower mean systolic arterial pressure (SAP) and a higher heart rate (HR) in the HC group (105 vs. 127, p < 0.01; 100 vs. 92, p < 0.001, respectively), resulting in a higher shock index (SI) (1.1 vs. 0.8, p < 0.001). Only retrospective studies such as ours are available, and while hypocalcemia seems to be an independent predictor of mortality and massive transfusion, there is not enough evidence to support causation. Therefore, randomized prospective studies are suggested. Full article