Francesco Ventura

Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition.

Background Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with AAA in comparison with matched controls. Methods TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dG). Results and Conclusions Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed.

The timing of perinatal hypoxia/ischemia events in term neonates: A retrospective autopsy study. HSPs, ORP-150 and COX2 are reliable markers to classify acute, perinatal events

BackgroundThe understanding of the cellular responses implicated in perinatal brain damages and the characterization of the various mechanisms involved might open new horizons for understanding the time of onset of a brain hypoxic-ischemic lesion and for effective therapeutic strategies.MethodsWe performed an immunohistochemical investigation on brain and brainstem sections of 47 peripartum deaths. The gradation and localization of the expression of antibodies such as TNFα, IL-1β, IL-6, HSPs, β APP, anti-TrypH, GAP43, GFAP, COX2, ORP-150, could be correlated with an hypoxic-ischemic damage to document a significant correlation between response and the time of onset acute (≤8 hs) or non-acute (≥8 hs ≤48 hs).Results and DiscussionsIn non-acute cases HSP70 reaction was prominent in the neuron cytoplasm, while in acute cases a mild reaction was evident in sporadic fields. HSP90 exhibited a similar pattern of positivity as HSP70. In acute group, ORP150 expressed an intense reaction showing a granular pattern in the cytoplasm of the neurons in the cortex of the infarcted areas. In non-acute group the positive reaction was more intense in astrocytes and less extended in neurons. COX2 reaction exhibited the strongest positive reaction in the neuronal cell bodies of acute cases, while a immunolabeling was prominent in the glial cytoplasm in the non-acute cases.ConclusionsChaperones HSP70 and 90, ORP-150 reaction, and COX2 protein, have provided very interesting results. These results would suggest to the clinicians to extend the differential diagnosis of a too large perinatal hypoxic-ischemic insult category to delineate a more accurate chronological judgement.

Suicide with the latest type of slaughterer's gun.

The authors describe a case of suicide by a single shot to the head from the latest type of captive bolt pistol (which has lateral instead of frontal gas outlets), with the aim of finding criteria to identify correctly the lesions caused by this type of weapon correctly and to distinguish them from those caused by typical firearms.

Arrhythmogenesis and diagnosis of cardiac sarcoidosis. An immunohistochemical study in a sudden cardiac death.

We present an uncommon case of sudden cardiac death in a 34-year-old white woman. She was found lifeless at home by her parents. Three months before death she was recovered at the Emergency Room for chest pain, palpitation and loss of consciousness. Subsequent cardiological evaluation with ECG showed sinusal rhythm, QRS deviation to the left, QS aspect, asymmetric and rounded T waves and slight length of QT. During hospitalization she presented some episodes of supraventricular paroxysmal tachycardia and non-sustained ventricular tachycardia. No echocardiography alterations were found. An anti-arrhythmic treatment was prescribed. Autopsy revealed some fibrotic scarring in the myocardium of left ventricle. The histological examination of the heart revealed diffuse and extensive fibrosis with non-caseating sarcoid granulomas. The lungs, kidneys and lymph node also showed the same non-caseating granulomas. The diagnosis of sarcoidosis with massive and extensive cardiac involvement was established as cause of death.

Fatal pulmonary thromboembolism. A retrospective autopsy study: Searching for genetic thrombophilias (Factor V Leiden (G1691A) and FII (G20210A) gene variants) and dating the thrombus

The accuracy of antemortem diagnosis of pulmonary embolism is within the range of just 10-30%, so representing one of the most frequent missed diagnosis in sudden, unexpected death. We describe 43 fatal cases of pulmonary embolism as confirmed by post-mortem examination. The aim of our study was to verify the systematic search for the most common genetic thrombophilias (Factor V Leiden (G1691A) and FII (G20210A) gene variants) and dating the thrombus. As a whole, 41 patients (95.3%) had at least one risk factor. Pre-existing symptoms are described just before fatal embolism in 18 (41.9%) out 43 patients. In 18 out of 43 (41.9%) it was not possible to find the thrombotic site. In 24 out of the remaining 25 cases the involvement of the deep veins of one leg was shown; in 1 case the thrombus was localised in the inferior caval vein. 10 (41.7%) were iliac vein thromboses, 7 (29.1%) femoral, 2 (8.3%) popliteal, 3 (12.6%) posterior-tibial, 1 (4.1%) anterior-tibial and 1 (4.1%) peroneal vein thromboses. In our cohort of patients, 4 (10%) out of 40 cases carried the 20210A prothrombin gene variant in heterozygosis. One (2.5%) out of 40 carried the Factor V Leiden (G1691A) gene variant in heterozygosis. Patients carrying these gene variants in homozygosis or carrying both were not present in our case-series. We strongly underline the relevance of a complete methodological approach, integrating clinical data by means of autopsy findings and histological study. On the contrary, investigating common inherited thrombophilia is not warranted.

Cerebrospinal fluid PCR analysis and biochemistry in bodies with severe decomposition

The aim of this study was to assess whether Neisseria meningitidis, Listeria monocytogenes, Streptococcus pneumoniae and Haemophilus influenzae can be identified using the polymerase chain reaction technique in the cerebrospinal fluid of severely decomposed bodies with known, noninfectious causes of death or whether postmortem changes can lead to false positive results and thus erroneous diagnostic information. Biochemical investigations, postmortem bacteriology and real-time polymerase chain reaction analysis in cerebrospinal fluid were performed in a series of medico-legal autopsies that included noninfectious causes of death with decomposition, bacterial meningitis without decomposition, bacterial meningitis with decomposition, low respiratory tract infections with decomposition and abdominal infections with decomposition. In noninfectious causes of death with decomposition, postmortem investigations failed to reveal results consistent with generalized inflammation or bacterial infections at the time of death. Real-time polymerase chain reaction analysis in cerebrospinal fluid did not identify the studied bacteria in any of these cases. The results of this study highlight the usefulness of molecular approaches in bacteriology as well as the use of alternative biological samples in postmortem biochemistry in order to obtain suitable information even in corpses with severe decompositional changes.

Elder abuse in Europe’s “most elderly” city: an assessment of the phenomenon and an analysis of the data from the Penal Court of Genoa from 2010 to 2015

IntroductionIn Italy, 5% of the elderly are estimated to have suffered abuse. While the Penal Code refers to generic types of abuse, such as physical and psychological maltreatment, abandonment and financial fraud, it does not specifically protect the elderly as a category.AimsTo assess the frequency and modalities of elder abuse in Genoa and its Province, and to compare these data with those reported in the literature, in order to provide a picture of the current situation that can be used by the authorities to combat this phenomenon.MethodsWe analysed the first-degree verdicts issued by the Court of Genoa regarding accusations of physical, psychological and moral abuse and maltreatment of elderly subjects (over 65 years) in the period 2010–2015.ResultsOnly 85 of the 4028 court verdicts analysed involved elderly persons: 19 cases of domestic maltreatment, 3 of abuse of the means of correction or discipline, 18 of personal injury, 5 of abandonment and 40 of circumvention (deceiving someone, especially an elderly or mentally impaired person, to obtain a profit).Discussion and conclusionsA gap was observed between the number of crimes reported to the judicial authorities (tip of the iceberg) and the estimated prevalence of the phenomenon in the literature. There is a need both to create a network of protection for the elderly involving medical and judicial specialists and to train healthcare professionals to better recognise and report cases of maltreatment.

Sudden death during medical thoracoscopy

Medical thoracoscopy (or pleuroscopy) is a valuable diagnostic tool in patients with pleural pathology, being minimally invasive, inexpensive and relatively easy to learn. Complications may occur, depending on the complexity of the case, and mainly include broncho-pleural fistulas, chest infections, arrhythmia, severe hemorrhage due to blood vessel injury, and air or gas embolism. Death is very rare. The present report describes the peculiar case of a 72-year-old woman affected by a pleural empyema who suddenly and unexpectedly died during medical thoracoscopy. On autopsy, three small perforations of the right lung were found, without involvement of major vessels or bronchial ramifications. After a brief overview of medical thoracoscopy and its complications, the fatality and its possible pathophysiological mechanisms are analyzed through a review of the literature.

A fatal case of streptococcal and meningococcal meningitis in a 2-years-old child occurring as Waterhouse–Friderichsen Syndrome

We report a fatal case of streptococcal and meningococcal meningitis in a previously healthy 2-year-old child, a simultaneous co-infection of both pathogens that is poorly reported in the reviewed literature. The lack of a clinical diagnosis in addition to the medico-legal aspects arising from possible professional liability for the emergency service doctor who had failed to recognize the childs symptoms led to a forensic autopsy within 48 h after the death. After external and internal examination, Waterhouse-Friderichsen Syndrome (WFS) was suspected. Consequently, cerebrospinal fluid, whole blood, nasal and pharyngeal swab and pleural liquid samples were selected and collected for microbiological studies. All tested samples resulted Neisseria meningitidis DNA and Streptococcus pneumoniae DNA positive. The NM genotyping Real-Time PCR resulted positive for NM serotype C. Microscopic histological study confirmed these findings. We underline that when a patient presents fever and petechiae (50-60% of patients), WFS must be considered, even when the patient has a non-toxic appearance. Due to its rapid progression and often devastating consequences, therapy should be started as soon as WFS is suspected. Emphasis should also be placed on the importance of public education programs and on broadening protection against meningitis through new vaccines. In such cases, from a forensic point of view, there is a strong need for a robust, multidisciplinary approach in order to reach the correct post-mortem diagnosis.