Severe starvation and restraint in a 47-year-old woman: Clinical, autopsy and histopathological evidence of abuse and neglect.

The recognition of abuse and/or neglect still represents a challenge for both clinicians and forensic pathologists. Whereas abusive behaviors have been largely described among pediatric and elderly populations, adults' abuse and neglect is less frequently encountered, and therefore investigated. We report a case of a middle-aged woman without any known organic or psychiatric disorders who died of a multiple organ failure (MOF) due to extreme cachexia and bed-resting syndrome. The integration of all clinical, autopsy and histopathological data highlighted a picture of severe malnutrition, restraint, and widespread traumatic injuries related to abuse and neglect. We believe that the case here presented could be useful for both clinicians and forensic pathologists as it underlines once again the importance of collecting and integrating all medical evidence (both in the ante- and post-mortem settings) for reconstructing the most probable pathophysiology of disorders and injuries, comparing that reconstruction with the allegations of the caregivers, and thus identifying any potential abuse and/or neglect behaviors.

Dying at home during the SARS-CoV-2 endemic: The importance of defining the exact mechanism of death.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) has become endemic in Europe thanks to the presence of less deadly and more infectious variants and to the existence of a significant portion of unvaccinated people among the general population. SARS-Cov-2 related deaths are probably going to fade in the next years, but Covid-19 should still be considered a potential cause of death in the out-of-hospital setting in the next future. MATERIAL AND METHODS: Three (3) cases of unexpected death at home are here presented. Each case has been investigated with the same methodological approach: death scene investigation (DSI), complete autopsy with histology, immunohistochemistry, RNA in situ hybridization for SARS-CoV-2 spike protein in lung tissue, toxicology and microbiology. RESULTS AND DISCUSSION: All three cases had a COVID + post-mortem nasopharyngeal swab. Histology and immunohistochemistry revealed a SARS-CoV-2 lung involvement in only two of the cases (Cases 2 and 3), while a septic bacterial pneumonia was found in Case 1, where RNA-in situ hybridization for viral spike protein showed no reactivity in pneumocytes. The integration of all postmortem evidence allowed to attribute a different role of SARS-Cov-2 in the determinism of the death. CONCLUSION: In the current post-pandemic context, SARS-CoV-2 remains a possible cause of death when investigating out-of-hospital unexpected deaths. Since a positive post-mortem swab does not automatically imply a COVID-19-related death, histology and immunohistochemistry are helpful for identifying SARS-CoV-2 lung involvement and, therefore, its potential active role in the determinism of death.

Necrotizing fasciitis: case series and review of the literature on clinical and medico-legal diagnostic challenges.

Necrotizing fasciitis (NF) is a life-threatening infection of soft tissues spreading along the fasciae to the surrounding musculature, subcutaneous fat and overlying skin areas that can rapidly lead to septic shock and death. Due to the pandemic increase of medical malpractice lawsuits, above all in Western countries, the forensic pathologist is frequently asked to investigate post-mortem cases of NF in order to determine the cause of death and to identify any related negligence and/or medical error. Herein, we review the medical literature dealing with cases of NF in a post-mortem setting, present a case series of seven NF fatalities and discuss the main ante-mortem and post-mortem diagnostic challenges of both clinical and forensic interests. In particular, we address the following issues: (1) origin of soft tissue infections, (2) micro-organisms involved, (3) time of progression of the infection to NF, (4) clinical and histological staging of NF and (5) pros and cons of clinical and laboratory scores, specific forensic issues related to the reconstruction of the ideal medical conduct and the evaluation of the causal value/link of any eventual medical error.

Circulating miRNAs expression profiling in drug-resistant epilepsy: Up-regulation of miR-301a-3p in a case of sudden unexpected death.

Sudden and unexpected death in epilepsy (SUDEP) represents one of the most challenging fields for clinical, forensic and preventative pathology. Several authors have emphasized the search of innovative biomarkers related to drug-resistance for an appropriate risk stratification in these patients. However, no reliable biomarker has been implemented into clinical practice, so far. Herein, we present a case of SUDEP due to drug-resistant mesial temporal lobe epilepsy (MTLE) in which we performed miRNA expression profiling (miR-301a-3p, miR-194-5p, miR-30b-5p, mIR-342-5p, and miR-4446-3p) from both the plasma and the temporal lobe in comparison to ten autopsies for traumatic or asphyxia deaths. A significant up-regulation of miR-301a-3p in both the plasma (2.3 increase vs. controls) and the hippocampus (3.2-fold increase vs. controls) was evidenced, whereas the other tested miRNAs showed no significant expression differences between case and controls. Even preliminary, our results support miRNAs as an innovative class of biomarkers compatible with an adequate analysis of biospecimens obtained from forensic autopsies.

Looking at the missing brain: hydranencephaly case series and literature review.

Hydranencephaly is a severe congenital condition where most of the cerebral hemispheres are replaced by a membranous sac. Despite the growing amount of case reports, most pathogenic, phenotypic, and prognostic aspects of hydranencephaly remain controversial. By matching the recent literature data with the findings of our own series (four cases: two fetuses at the twelfth gestational week, a 32-year-old man, and a 14-year-old female), we attempted to date back the insult leading to hydranencephaly to understand its pathogenesis and to explain the basis of its protean phenotype. The variable detection of cerebral remnants seems to mirror the developmental pathway of cerebral arteries. Moreover, fetal and postnatal neuroimaging data and histopathologic findings point toward an early bilateral internal carotid artery occlusion, mostly occurring between the eighth and twelfth gestational weeks, as the main pathogenic mechanism of hydranencephaly.

Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype.

OBJECTIVE: To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype. DESIGN: Description of a novel phenotype associated with a presenilin 1 mutation. SETTING: The subject was an outpatient who was diagnosed at the local referral center. PATIENT: A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected. MAIN OUTCOME MEASURES: We analyzed the processing of Abeta precursor protein in vitro as well as the Abeta species in brain tissue. RESULTS: The PSEN1 S170F mutation induced a 3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60% increase of secreted Abeta precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated Abeta species ending at both residues 40 and 42. CONCLUSION: These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the Abeta aggregates' composition.