The brain tissue reaction to blunt trauma: a field of possible cooperation between neuroanatomists and forensic pathologists

The goal of this presentation is to describe, through the histological examination, the evolution over time of the biological processes, at the cellular and molecular level, in the neurological tissue after a blunt trauma. The origin of the secondary ischemia, that often occurs after a brain trauma, leading to death the patient, is almost studied on animal models and is not well known yet. It is presumed that hemorrhages and contusions result in brain ischemia, and that also brain edema arises intra-cranial pressure producing ischemia. Forensic pathology deals everyday with cases of traumatic deaths, and is therefore able to study the inflammatory reaction to trauma in a human casuistry giving information to other disciplines like neuroanatomy. The time-dependent appearance of different leucocyte subtypes can contribute to a forensic wound age estimation but, in contrast to peripheral tissue, the cellular reaction in the CNS is characterized by a minimal neutrophil exsudation and a delayed increase in mononuclear cell numbers. 62 deaths due to head injury with a survival time from few minutes till 30 days were studied. Samples of brain tissue were stained with immunohistochemistry using selectin P and E, GFAP, HIF1-α, CD 117 (c-kit), LCA. The schematic information about chronology of head trauma are given as follows: survival of a few minutes, of 1 hour, of 2-4 hours, of 4-12 horus, of 12-24 hours, 24-48 hours, 2-6 days, 6-14 days, 15-30 days. The number of platelets microthrombi increases with TBI age up to 3 days, afterward leukocytes start to take their place. Platelets aggregates may impair cerebral circulation causing ischemia. Cerebral ischemia plays an important role in SBD. There is also an involvement of CD 117+ cells and HIF-1 α in the modulation and progression of the brain injury. After brain injury a cascade of events occurs leading sometime to a brain secondary ischemic injury. Thanks to the availability of injured human brain tissues, forensic histopathologists might work together with neuroanatomists in order to help in the identification of glial cells and leukocytes communication with endothelial cells, and on the post-traumatic ischemic process that causes the death in prolonged survival time after brain injury

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Planned and unplanned complex suicides: Casuistry of the Institute of Legal Medicine of Parma (Italy)

Complex suicide is performed using more harmful methods, simultaneously or consecutively. In these cases, the distinction between suicide and homicide represents a challenge for forensic pathologists. In literature, complex suicide is divided in two subgroups: â\u80\u9cplanned complex suicideâ\u80\u9d or â\u80\u9cunplanned complex suicideâ\u80\u9d depending from forensic features and often related to psychiatric variables. Aim of this study was to show the casuistry of complex suicide in Parma's Forensic service analyzing, for each case, the forensic medical problems (type and site of lesions on the body), and the supplementary data [Police's inspection report, toxicological analysis and psychiatric anamnesis (when available)], trying, through a multidisciplinary approach, to determine a possible correlation between the victim's mood and suicide's method chosen, whether planned or unplanned. Our results showed the importance of all the elements collected on the crime scene to distinguish suicide from homicide, and the correlation between bipolar disorder, borderline personality disorder and schizophrenia with unplanned complex suicide (because of the impulsiveness), and major depression disorder and anxiety disorder with planned complex suicide. Being able to understand the causes behind this extreme gesture may become important not only for forensic pathologists and judicial authority, but also, and above all, for the family as well

Determination of methadone and eight new psychoactive substances in hair samples by gas chromatography/mass spectrometry

Many new psychoactive substances (NPSs) with different chemical structures have emerged in the illicit drug market in the last decade. The present work was aimed at the development of a simple method in gas chromatography/mass spectrometry (MS) for the determination of NPS of different classes, the use of cannabinoids, and, at the same time, the evaluation of methadone therapy in hair matrix, within our routine analysis control for methadone treatment or from autopsy cases. The determination of synthetic cannabinoids and methadone therapy used an extraction method based on incubation in concentrated sodium hydroxide (NaOH) solution, providing a dissolution of the keratin matrix. The described method was applied on 15 authentic specimens from our cases: five showed the presence of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). The described method can be useful not only in the forensic investigation of NPS-related addiction histories but also in epidemiological and retrospective studies on the spread of NPS among specific safety-sensitive social workers. The GC instrument was an Agilent 7820A (Agilent Technologies, Santa Clara, CA, USA), and the detection system was an Agilent 5977B single quadrupole MS operating in selective ion monitoring mode. Validation parameters such as limit of detections (LODs), limit of quantifications (LOQs), repeatability, accuracy, and linearity were satisfactory for its application on real specimens. LODs, LOQs, R%CV, standard deviation, and the mean concentration for the analyzed compounds are reported in Table 1b. Accuracy and repeatability were acceptable for all the analytes at their respective LOQs. Recovery experiments varied from 58.3% to 103.0%, thus allowing the application on authentic specimens. The described method can be useful not only in the forensic investigation of NPS-related addiction histories but also in epidemiological and retrospective studies on the spread of NPS among specific safety-sensitive social workers, such as drivers

Safe drugs in drug facilitated crimes and acute intoxications in Northern Italy

Toxicological analyses are often performed in drug-facilitated sexual assaults (DFSA), when the victim shows or reports impaired consciousness and reduced ability. However, in other crimes or fatalities, especially in cases of concurrent natural disease or when another likely cause of death has been established, the involvement of drugs can be overlooked. The aim of this study is to report a series of cases of (i) victims of drug-facilitated crimes (DFC) other than DFSA and (ii) victims of acute intoxications, in which \u201clicit\u201d psychoactive drugs were found in blood samples, with the aim of understanding in which circumstances and to what extent prescription drugs have been used for non-medical purposes in recent Italian casuistry. Circumstantial, autopsy, and toxicological data were collected through a retrospective analysis performed between 2013 and 2017 in the Forensic Toxicology Unit of the University of Bologna. Cases of \u201cDFC other than DFSA\u201d and \u201cAcute Intoxication\u201d in which \u201cpsychoactive drugs\u201d or \u201cprescription drugs\u201d or \u201clicit drugs\u201d were found in the blood samples of the victims were included in the study. Nine cases of DFC other than DFSA, and 11 cases of acute intoxication, were identified. Different categories of \u201clicit\u201d psychoactive drugs (e.g. hypnotics, antipsychotics, antidepressants, anticonvulsants) had been used to facilitate diverse types of crime (homicide, robberies, elder abuse, fatal poisoning) or acute intoxication (suicide, attempted suicide, accidental death). The circumstances of these cases, as well as toxicological findings in blood samples and other relevant forensic elements, are reported, summarized and discussed in this paper. The non-medical use of pharmaceuticals has been identified by recent forensic literature and the present study as a significant and growing phenomenon, and its implication in fatalities should be taken into consideration and accurately investigated through appropriate toxicological analysis. Our study presents an overview of the circumstances of non-medical use of prescription drugs, usually considered \u201csafe drugs\u201d, and their involvement in cases of DFC, suicides and accidental intoxication. In order to estimate the real incidence of these medications in DFC and acute intoxication, and thus collect more analytical and contextual data, further studies are needed, along with effective cooperation among police officers, clinicians, forensic pathologists, and toxicologists

Posture and gait in the early course of schizophrenia.

While correlations between postural stability deficits and schizophrenia are well documented, information on dynamic motor alterations in schizophrenia are still scarce, and no data on their onset are available yet. Therefore, the aim of this study was i) to measure gait pattern(s) in patients with schizophrenia; ii) to identify posture and gait alterations which could potentially be used as a predictive clinical tool of the onset of the disorder. Body composition, posture and gait parameters were assessed in a group of 30 patients with schizophrenia and compared to 25 healthy subjects. Sway area was significantly higher in the schizophrenia group compared to controls regardless of whether the participants were in eyes open or eyes closed condition. Gait cadence and speed were significantly lower in patients with schizophrenia, while stride length was similar. We concluded that the combination of an increased sway area (independent from eye closure) and a gait cadence reduction-in the presence of normal gait speed and stride length-might be considered peculiar postural and gait profile characteristic of early schizophrenia

Sulphurous thermal water inhalation impacts respiratory metabolic parameters in heavy smokers

Sulphurous thermal water inhalations have been traditionally used in the treatment of airway diseases. In vivo and in vitro studies reported that they ameliorate mucus rheology, mucociliary clearance and reduce inflammation. Cigarette smoking induces an inflammatory damage, with consequent remodeling of respiratory airways, which in turn affect pulmonary functions. Despite the anti-inflammatory effects of H2S are clinically documented in several airway inflammatory diseases, data on the effects of sulphurous thermal water treatment on pulmonary function and biomarkers of airways inflammation in smokers are still scant. Therefore, we investigated whether a conventional cycle of sulphurous thermal water inhalation produced changes in markers of respiratory inflammation and function. A cohort of 504 heavy current and former smokers underwent 10-day cycles of sulphurous thermal water inhalation. Pulmonary function and metabolic analyses on exhaled breath condensate were then performed at day 0 and after the 10-day treatment. Spirometric data did not change after spa therapy, while exhaled breath condensate analysis revealed that a single 10-day cycle of sulphurous water inhalation was sufficient to induce a statistically significant increase of citrulline levels along with a decrease in ornithine levels, thus shifting arginine metabolism towards a reduced nitric oxide production, i.e. an anti-inflammatory profile. Overall, sulphurous thermal water inhalation impacts on arginine catatabolic intermediates of airways cells, shifting their metabolic balance towards a reduction of the inflammatory activity, with potential benefits for smokers

A Clinico-pathological "Bird's-Eye" View of Left Atrial Myocardial Fibrosis in 121 Patients with Persistent Atrial Fibrillation: Developing Architecture and Main Cellular Players

Background - Scientific research on atrial fibrosis in atrial fibrillation (AF) has mainly focused on quantitative and/or molecular features. The purpose of this study was to perform a clinico-architectural/structural investigation of fibrosis to provide one key to understanding the electrophysiological/clinical aspects of AF. Methods - We characterized the fibrosis (amount, architecture, cellular components, and ultrastructure) in left atrial biopsies from 121 patients with persistent/long-lasting persistent AF (Group 1) (59 males; 60±11 years; 91 mitral disease-related AF, 30 non-mitral disease-related AF) and from 39 patients in sinus rhythm with mitral-valve regurgitation (Group 2; 32 males; 59±12 years). Ten autopsy hearts served as controls. Results - Qualitatively, the fibrosis exhibited the same characteristics in all cases and displayed particular architectural scenarios (which we arbitrarily subdivided into four stages) ranging from isolated foci to confluent sclerotic areas. The percentage of fibrosis was larger and at a more advanced stage in Group 1 vs. Group 2 and, within Group 1, in patients with rheumatic disease vs. non-rheumatic cases. In AF patients with mitral disease and no rheumatic disease, the percentage of fibrosis and the fibrosis stages correlated with both left atrial volume index and AF duration. The fibrotic areas mainly consisted of type I collagen with only a minor cellular component (especially fibroblasts/myofibroblasts; average value range 69-150 cells/mm2, depending on the areas in AF biopsies). A few fibrocytes-circulating and bone marrow-derived mesenchymal cells-were also detectable. The fibrosis-entrapped cardiomyocytes showed sarcolemmal damage and connexin 43 redistribution/internalization. Conclusions - Atrial fibrosis is an evolving and inhomogeneous histological/architectural change which progresses through different stages ranging from isolated foci to confluent sclerotic zones which - seemingly - constrain impulse conduction across restricted regions of electrotonically-coupled cardiomyocytes. The fibrotic areas mainly consist of type I collagen extracellular matrix and, only to a lesser extent, mesenchymal cells