Petechial hemorrhages, ethanol, and opioids in victims from intoxication.

Petechial hemorrhages are of interest to forensic pathologists because of their association with pressure on the neck. This study shows the associations between ethanol, opioids in blood and the risk of petechiae in conjunctivae and eye lids of 865 medico-legally examined victims from intoxication, 112 (12.9 %) with petechiae. Livor mortis on the front, face down body position, higher body weight, and younger age of the victims were independently associated with higher risk of petechiae. These variables were used for adjustment in the logistic regression analyzes. We found associations between ethanol, opioids, and the risk of petechiae when analyzed simultaneously. The association between ethanol and the risk of petechiae differed in opioid negative and positive victims (interaction, p = 0.028). In the opioid negative group, the association was J-formed, victims with low to medium level ethanol having lower risk (OR = 0.77) than those without ethanol or opioids, whereas high ethanol level gave a 4-fold higher risk (OR = 3.97). In the opioid positive group, the J-formed pattern was reversed. Victims with low to medium level ethanol had more than 4 times higher risk (OR = 4.65), whereas high level ethanol gave a slightly elevated risk (OR = 1.34) only compared to no ethanol or opioids. The results suggest that ethanol and opioids have a complex association with the risk of petechiae independent of livor mortis, initial body position, body weight, and age in victims from intoxication. Of practical value for the post-mortem examination is that the pathologist must consider both the ethanol level and the presence of opioids when judging the significance of petechiae in the eye regions.

Asphyxiation death caused by oxygen-depleting cargo on a ship.

The extreme danger associated with entering enclosed spaces loaded with oxygen-depleting organic cargo in ships and tanks is obviously underestimated, both among crew and management. We present a case report to highlight this occupational hazard and to increase the knowledge about the imperative precautions, in order to prevent future accidents. An experienced customs officer was found lifeless at the bottom of the unattended cargo hold on a ship loaded with woodchips. The oxygen content in the cargo atmosphere was below 2%, which is incompatible with life. Forensic autopsy revealed injuries related to the fall, and there were no positive toxicological findings in blood, lung or urine. Management and workers must be taught about the extreme rapidity of developing unconsciousness and asphyxiant death when entering enclosed spaces loaded with oxygen-depleting cargo. Even a single inhalation can result in unconsciousness and death. Dozens of annual deaths and severe injuries can easily be prevented if simple precautions are followed.

Genomic Evolution of Breast Cancer Metastasis and Relapse.

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.

Petechial Hemorrhages and Ethanol in Deaths from Intoxication.

Petechiae in conjunctivae and in the palpebrae/skin of the eyelids are of particular interest for the forensic pathologist, because of their association with pressure on the neck. They have been described in the eyelids of intoxicated persons both in case reports and in text books of forensic pathology. We studied 590 deaths caused by intoxication, and 75 had petechiae either in the conjunctivae, the eyelids, or in both locations. We examined the influence of drugs and ethanol on the location of the petechial hemorrhages in these deaths. Deaths with ethanol in blood and in urine/vitreous humor more often had petechiae in both locations than those without. This association was statistically significant, independent of body position and livor mortis. No association between the location of petechiae, medicinal drugs, or narcotics was found. These results suggest that ethanol may contribute to the development of petechial hemorrhages in deaths from intoxication.

Subclonal diversification of primary breast cancer revealed by multiregion sequencing.

The sequencing of cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and late in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer.