Association between the intake of cocaine and a strong physical and emotional stress: a case report of a sudden death

Cocaine is a powerful sympathomimetic agent, that determines its effects either by inhibiting synaptic re-uptake of noradrenaline or through the direct stimulation of the release of catecholamines from the adrenal gland. Cocaine abuse is associated with various cardiovascular events including ventricular arrhytmias, systemic hypertension, myocardial infarction and left ventricular hypertrophy. These effects are independent of the dose and route of administration of the substance and can be noticeably enhanced by the synergistic action of factors such as stress, smoking and alcoholism. The case that we report has involved a 48 year old man, who died of acute myocardial infarction, which arose as the result of an intake of a large amount of cocaine and a strong physical and emotional stress

Accuracy of MRI skeletal age estimation for subjects 12–19. Potential use for subjects of unknown age

In forensic practice, there is a growing need for accurate methods of age estimation, especially in the cases of young individuals of unknown age. Age can be estimated through somatic features that are universally considered associated with chronological age. Unfortunately, these features do not always coincide with the real chronological age: for these reasons that age determination is often very difficult. Our aim is to evaluate accuracy of skeletal age estimation using Tomei's MRI method in subjects between 12 and 19 years old for forensic purposes. Two investigators analyzed MRI images of the left hand and wrist of 77 male and 74 female caucasian subjects, without chronic diseases or developmental disorders, whose age ranged from 12 to 19 years. Skeletal maturation was determined by two operators, who analyzed all MRI images separately, in blinded fashion to the chronological age. Inter-rater agreement was measured with Pearson (R (2)) coefficient. One of the examiners repeated the evaluation after 6 months, and intraobserver variation was analyzed. Bland-Altman plots were used to determine mean differences between skeletal and chronological age. Inter-rater agreement Pearson coefficient showed a good linear correlation, respectively, 0.98 and 0.97 in males and females. Bland-Altman analysis demonstrated that the differences between chronological and skeletal age are not significant. Spearman's correlation coefficient showed good correlation between skeletal and chronological age both in females (R (2) = 0.96) and in males (R (2) = 0.94). Our results show that MRI skeletal age is a reproducible method and has good correlation with chronological age

Genomic landscape of clinically advanced KRAS wild-type pancreatic ductal adenocarcinoma

IntroductionKRAS mutation is a common occurrence in Pancreatic Ductal Adenocarcinoma (PDA) and is a driver mutation for disease development and progression. KRAS wild-type PDA may constitute a distinct molecular and clinical subtype. We used the Foundation one data to analyze the difference in Genomic Alterations (GAs) that occur in KRAS mutated and wild-type PDA.MethodsComprehensive genomic profiling (CGP) data, tumor mutational burden (TMB), microsatellite instability (MSI) and PD-L1 by Immunohistochemistry (IHC) were analyzed.Results and discussionOur cohort had 9444 cases of advanced PDA. 8723 (92.37%) patients had KRAS mutation. 721 (7.63%) patients were KRAS wild-type. Among potentially targetable mutations, GAs more common in KRAS wild-type included ERBB2 (mutated vs wild-type: 1.7% vs 6.8%, p <0.0001), BRAF (mutated vs wild-type: 0.5% vs 17.9%, p <0.0001), PIK3CA (mutated vs wild-type: 2.3% vs 6.5%, p <0.001), FGFR2 (mutated vs wild-type: 0.1% vs 4.4%, p <0.0001), ATM (mutated vs wild-type: 3.6% vs 6.8%, p <0.0001). On analyzing untargetable GAs, the KRAS mutated group had a significantly higher percentage of TP53 (mutated vs wild-type: 80.2% vs 47.6%, p <0.0001), CDKN2A (mutated vs wild-type: 56.2% vs 34.4%, p <0.0001), CDKN2B (mutated vs wild-type: 28.9% vs 23%, p =0.007), SMAD4 (mutated vs wild-type: 26.8% vs 15.7%, p <0.0001) and MTAP (mutated vs wild-type: 21.7% vs 18%, p =0.02). ARID1A (mutated vs wild-type: 7.7% vs 13.6%, p <0.0001 and RB1(mutated vs wild-type: 2% vs 4%, p =0.01) were more prevalent in the wild-type subgroup. Mean TMB was higher in the KRAS wild-type subgroup (mutated vs wild-type: 2.3 vs 3.6, p <0.0001). High TMB, defined as TMB > 10 mut/mB (mutated vs wild-type: 1% vs 6.3%, p <0.0001) and very-high TMB, defined as TMB >20 mut/mB (mutated vs wild-type: 0.5% vs 2.4%, p <0.0001) favored the wild-type. PD-L1 high expression was similar between the 2 groups (mutated vs wild-type: 5.7% vs 6%,). GA associated with immune checkpoint inhibitors (ICPIs) response including PBRM1 (mutated vs wild-type: 0.7% vs 3.2%, p <0.0001) and MDM2 (mutated vs wild-type: 1.3% vs 4.4%, p <0.0001) were more likely to be seen in KRAS wild-type PDA

Contribution of asthma in opiate deaths

Purpose Several studies showed an association between asthma and opiate abuse. This retrospective study aimed to analyze the demographic, toxicologic, and seasonal differences in asthmatic and non-asthmatic subjects who died of opiates. In addition, the relationship between toxicological levels of opiates and histologic grade of lung inflammation was examined, to understand if it was possible to determine a predominance of drug vs. asthma in the mechanism of death. Methods Deaths from 2013 to 2018 involving opiates as the primary cause of death in Cook County were reviewed. Twenty-six cases of opiate deaths of individuals with a history of asthma and lung histology slides available were identified. In comparison, 40 cases of deaths due to opiates only were reviewed. A check-list system for the evaluation of the grade of microscopic inflammation in asthma was developed. Results Statistically significant differences were found between the groups concerning demography and toxicology. Our results suggest that the association between asthma and opiate in the determination of death may not be linked to the quantity of drug administered and the grade of inflammation in the lung tissue. Conclusion Our results confirm the importance of encouraging all asthmatic people to refrain from using opiates, regardless of the route of administration. The results of this study could be helpful for the forensic pathologists, showing the importance of histologic examination in all the autopsies on suspected opiate-related deaths and the necessity to include asthma in the death certificate whenever this condition is observed histologically

Fatal bleeding caused by a ruptured varicose vein.

Chronic venous insufficiency is generally not lethal, but massive bleeding from ruptured varicose veins can be fatal. A 79-year-old woman was found dead in her apartment in Rome. Pools of blood and contact pattern bloodstains were observed around the body. She lived alone and suffered from vascular dementia. On the medial aspect of the right leg, a circular ulcer communicating with the lumen of a varicose vein was noted. Death was attributed to hypovolemic shock caused by bleeding from the rupture of the varicose vein. Our case confirms that varicose veins rupture is a potentially fatal medical emergency. Conditions such as dementia may lead to failure to understand the gravity of the bleeding and to seek help. Recognition of this issue is important especially when the care of people suffering from mental illness is involved

Dyskeratosis congenita

Dyskeratosis congenita (DC) is a genetic syndrome with progressive multisystem involvement classically characterized by the clinical triad of oral leukoplakia, nail dystrophy, and reticular hyperpigmentation. Frequent complications are bone marrow failure, increased rate of malignancy, lung and liver diseases. DC results from an anomalous progressive shortening of telomeres resulting in DNA replication problems inducing replicative senescence. We report a death due to DC in a 16-year-old male with bone marrow failure and multiple organ dysfunction. At autopsy, nail dystrophy and skin hypopigmentation were observed. Gross and microscopic examinations of the internal organs showed cardiac hypertrophy, multiple lung consolidations and prominent interstitial fibrosis, liver cirrhosis, and fibrosis. Multiple foci of extramedullary hematopoiesis were identified, including on the epidural surface of the dura, that is an infrequent location, mimicking a focal area of epidural hemorrhage. Only a few autopsy studies about DC are reported in the literature. Further research should be done to understand the pathophysiology of the disease and its complications

THE OUTBREAK OF FENTANYL-RELATED DEATHS IN COOK COUNTY, ILLINOIS. A RETROSPECTIVE STUDY AND A COMPARISON WITH PREVIOUS DATA

The National Institute on Drug Abuse in the U.S. has observed an increase in the deaths from synthetic opioids (mainly fentanyl) in recent years. Several epidemics related to the illicit abuse of fentanyl and its analogs have been reported in the Country: one of those happened in Cook County in 2005-2007 (350 individuals). Another outbreak of fentanyl death occurred in 2015-2017 in the same area. The electronic database of the Cook County Medical Examiner’s Office in Chicago was searched for cases of death involving fentanyl and fentanyl analogs toxicity between October 2015 and December 2017. A total of 27,131 deaths were identified in the studied period. Among these, 1,244 cases (4.5%) satisfied the requirements of the study. The population was divided into two subpopulations: 927 deaths involving fentanyl and 317 deaths involving fentanyl analogs (without fentanyl). Most of the cases involved Caucasian males. The mean age was 44 years old, and the study population ranged between 14 and 77 years. The mean fentanyl concentration in post-mortem peripheral blood was 18.19 ng/ml (range: 0.11-464). A progressively increasing number of cases/year was observed from 2015 to 2017: 56 in October-December 2015, 540 in 2016 and 648 in 2017. In the vast majority of 2015-2017 fentanyl cases, fentanyl was associated with other products: the most common drug used with fentanyl was heroin, followed by cocaine and ethanol. Statistical comparisons with the 2005-2007 population were performed, showing an increase in the number of cases by 2.6 times. In both the 2005-2007 and 2015-2017 populations, the majority of deaths involved males, but a significant increase in the number of females was observed in the 2015-2017 group. Regarding the race of the decedents, in 2005-2007 the majority of deaths occurred among African Americans, while in 2015-2017 the majority of deaths involved Caucasians. In addition, some combinations of drugs were significantly more common in specific demography subgroups (male/females; Caucasian/African American; certain age groups): this could be due to an increased use/choice of these combinations in these groups, or to a possible greater susceptibility of these groups to the effect of some specific drugs association. Knowledge about the new fentanyl outbreak could be useful for public health in monitoring and quickly diagnosing and treating acute intoxication when fentanyl is involved. Moreover, the analysis of the recreational drugs usually combined with fentanyl can contribute to a better-informed public policy that helps reduce the risk for drug abusers

Autopsy features in a newborn baby affected by a central congenital diaphragmatic hernia

Congenital diaphragmatic hernia is a congenital malformation of the diaphragm, resulting in the herniation of the abdominal organs into the thoracic cavity. The most common types of congenital diaphragmatic hernia are Bochdalek hernia (postero-lateral hernia), Morgagni hernia (anterior defect), and diaphragm eventration (abnormal displacement of part or all of an otherwise intact diaphragm into the chest cavity). Congenital diaphragmatic hernia is a life-threatening pathology in infants, and a major cause of death due to pulmonary hypoplasia and pulmonary hypertension. We present a fatal case of congenital diaphragmatic hernia in a newborn. At the autopsy, a central defect of the diaphragm was found, 8 × 5 cm in size, that led to a herniation of the small intestine, the right lobe of the liver, and the right adrenal gland into the thorax. An esophageal atresia was associated with the congenital diaphragmatic hernia. The lungs showed severe hypoplasia and atelectasia. Physicians should pay attention to a prenatal diagnosis of congenital diaphragmatic hernia in order to prevent newborn fatalities

Atypical Enostoses—Series of Ten Cases and Literature Review

Bone islands (BI; enostoses) may be solitary or occur in the setting of osteopoikilosis (multiple bone islands) and are sometimes associated with Gardner’s Syndrome (osteopoikilosis and colonic polyposis). Characteristic features of bone islands are (1) absence of pain or local tenderness, (2) typical radio dense central appearance with peripheral radiating spicules (rose thorn), (3) Mean CT (computerized tomography) attenuation values above 885 Hounsfield units (HU) (4) absence of uptake on bone scan and (5) radiographic stability over time. However, when enostoses display atypical features of pain, unusual radiographic appearance, aberrant HU, increased radiotracer uptake, and/or enlargement, they can be difficult to differentiate from more sinister bony lesions such as osteoblastic metastasis, low grade central osteosarcoma, osteoid osteoma and osteoblastoma. In this retrospective case series, the demographic, clinical, radiographic, treatment and outcome for ten patients with eleven atypical bone islands (ABI) are presented, some showing associated pain (5), some with atypical radiographic appearance (3), some with increased activity on BS (4), some with documented enlargement over time (7), one with abnormal CT attenuation value, some in the setting of osteopoikilosis (2), one in the setting of Gardner’s Syndrome and one osteoid osteoma simulating a bone island. This series represents the spectrum of presentations of ABI. Comprehensive review of the literature reveals that the previous largest series of ABI showing enlargement as the atypical feature was in younger patients with jaw BI. Hence, this represents one of the largest series reported of ABI of all types in adults