Layering of stomach contents in drowning cases in post-mortem computed tomography compared to forensic autopsy.

BACKGROUND: In forensic autopsy, the analysis of stomach contents is important when investigating drowning cases. Three-layering of stomach contents may be interpreted as a diagnostic hint to drowning due to swallowing of larger amounts of water or other drowning media. The authors experienced frequent discrepancies of numbers of stomach content layering in drowning cases between post-mortem computed tomography (PMCT) and autopsy in forensic casework. Therefore, the goal of this study was to compare layering of stomach contents in drowning cases between PMCT and forensic autopsy. METHODS: Drowning cases (n = 55; 40 male, 15 female, mean age 45.3 years; mean amount of stomach content 223 ml) that received PMCT prior to forensic autopsy were retrospectively analyzed by a forensic pathologist and a radiologist. Number of layers of stomach content in PMCT were compared to number of layers at forensic autopsy. RESULTS: In 28 of the 55 evaluated drowning cases, a discrepancy between layering of stomach contents at autopsy compared to PMCT was observed: 1 layer at autopsy (n = 28): 50% discrepancy to PMCT, 2 layers (n = 20): 45% discrepancy, and 3 layers (n = 7): 71.4% discrepancy. Sensitivity of correctly determining layering (as observed at forensic autopsy) in PMCT was 52% (positive predictive value 44.8%). Specificity was 46.6% (negative predictive value 53.8%). In a control group (n = 35) of non-drowning cases, three-layering of stomach contents was not observed. CONCLUSION: Discrepancies of observed numbers of stomach content layers between PMCT and forensic autopsy are a frequent finding possibly due to stomach content sampling technique at autopsy and movement of the corpse prior to PMCT and autopsy. Three-layering in PMCT, if indeed present, may be interpreted as a hint to drowning.

Hounsfield unit values of liver pathologies in unenhanced post-mortem computed tomography.

BACKGROUND: The goal of this study was to evaluate if unenhanced PMCT HU values of liver pathologies differ from post-mortem HU values of non-pathologic liver tissue. METHODS: Liver HU values were measured in five liver segments in PMCT unenhanced datasets of 214 forensic cases (124 male, 90 female, mean age 54.3 years). Liver HU values were compared with corresponding histologic liver findings. HU values of non-pathologic livers were compared to HU values of liver pathologies. RESULTS: A total of 64 non-pathologic livers (mean HU 58.32, SD 8.91) were assessed. Histologic diagnosed liver pathologies were as follows: steatosis (n = 121 (grade I n = 61, grade II n = 37, grade III n = 23)), fibrosis (n = 10), and cirrhosis (n = 19). HU values of the livers exhibiting severe steatosis (mean HU 32.44, SD 13.76), fibrosis (mean HU 44.7, SD 16.31), and cirrhosis (mean HU 50.59, SD 9.42) significantly differed to HU values of non-pathologic livers at ANOVA testing. CONCLUSION: PMCT unenhanced liver HU value measurements may be used as an additional method to detect unspecific liver-pathology. Values below 30 HU may specifically indicate severe steatosis.

Distortion of the temporary cavity and its influence on staining in firearm barrels.

After contact shots to the head, biological traces can be found inside the barrel of the firearm. Experimental protocols to generate this sort of staining, using 12 cm gelatin cubes containing thin foil bags filled with acrylic paint, human blood, and radiocontrast agent, have been developed. Previous research on shots fired at a distance has shown the underlay sustaining these gelatin cubes has an influence on experimental results. This study was conducted to investigate the role of the sustaining base of the gelatin blocks during contact shots, and its influence on the staining result inside firearm barrels. Eighteen contact shots were performed using 22 LR, 32 ACP (7.65 Browning) and 9 mm Luger semi-automatic pistols. With each pistol, shots were fired onto six gelatin cubes; three placed upon a rigid platform and three upon an elastic underlay. The shots were recorded by a high-speed video camera as they penetrated the gelatin cube. Any staining present inside the firearm barrels after the shots were fired was documented by endoscopy. Cross sections of the gelatin blocks were then compared to the high-speed video. It was found that the nature of the staining inside the barrel was not influenced by the underlay sustaining the target model. In the experiment using a 9 mm Luger, the rigid counterfort provoked a visible distortion of the temporary cavity, but, cross sectional analysis of the gelatin cubes did not reveal a relevant influence of the sustaining underlay on the crack length in the gelatin. This could be explained by a secondary expansion of the temporary cavity left by the projectile as a consequence of subsequent inflow of muzzle gases.

The truth lies within: the reconstructive value of inner livores in a homicide case.

Through the widespread use of postmortem computed tomography, inner livores of the lungs have become a frequently observed phenomenon in the field of forensic medicine. Yet their time-dependent development, notably in comparison with the widely studied external livores, remains poorly understood. We present a unique homicide case where the victim was discovered in supine position with correspondent external livores fixed exclusively on the rear side. Yet upon postmortem computed tomography, the victim presented pronounced inner livores within the depending dorsal areas of both lungs but also vertical sedimentation levels solely within the right lung, suggesting an initial right-hand side position and a postmortem re-positioning of the body. Interestingly, this was consistent with tangible hints of postmortem manipulation on-site. It is likely that this repositioning occurred sometime during the early postmortem interval (<6 h) as the external livores have completely rearranged to the final supine position. The presented case suggests different development patterns of inner and outer livores, highlighting the necessity for controlled studies that explore the formation and fixation processes of livor mortis in internal organs. A better understanding of these issues can prove useful in forensic examinations.

Postmortem CT versus forensic autopsy: frequent discrepancies of tracheobronchial content findings.

In their daily forensic casework, the authors experienced discrepancies of tracheobronchial content findings between postmortem computed tomography (PMCT) and autopsy to an extent previously unnoticed in the literature. The goal of this study was to evaluate such discrepancies in routine forensic cases. A total of 327 cases that underwent PMCT prior to routine forensic autopsy were retrospectively evaluated for tracheal and bronchial contents according to PMCT and autopsy findings. Hounsfield unit (HU) values of tracheobronchial contents, causes of death, and presence of pulmonary edema were assessed in mismatching and matching cases. Comparing contents in PMCT and autopsy in each of the separately evaluated compartments of the respiratory tract low positive predictive values were assessed (trachea, 38.2%; main bronchi, 40%; peripheral bronchi, 69.1%) indicating high discrepancy rates. The majority of tracheobronchial contents were viscous stomach contents in matching cases and low radiodensity materials (i.e., HU < 30) in mismatching cases. The majority of causes of death were cardiac related in the matching cases and skull/brain trauma in the mismatching cases. In mismatching cases, frequency of pulmonary edema was significantly higher than in matching cases. It can be concluded that discrepancies in tracheobronchial contents observed between PMCT and routine forensic autopsy occur in a considerable number of cases. Discrepancies may be explained by the runoff of contents via nose and mouth during external examination and the flow back of tracheal and main bronchial contents into the lungs caused by upright movement of the respiratory tract at autopsy.

Interleukin-10 and prostaglandin E2 have complementary but distinct suppressive effects on Toll-like receptor-mediated dendritic cell activation in ovarian carcinoma.

Dendritic cells (DC) have the potential to instigate a tumour-specific immune response, but their ability to prime naïve lymphocytes depends on their activation status. Thus, for tumour immunotherapy to be effective, the provision of appropriate DC activation stimuli such as Toll-like receptor (TLR) agonists is crucial in order to overcome immunosuppression associated with the tumour microenvironment. To address this, we investigated how ovarian carcinoma (OC)-associated ascites impedes activation of DC by TLR agonists. Our results show that ascites reduces the TLR-mediated up-regulation of CD86 and partially inhibits the production of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-12 and tumour necrosis factor α (TNFα) in monocyte-derived DC from healthy controls. We further observe an impaired T cell stimulatory capacity of DC upon activation with TLR agonists in the presence of ascites, indicating that their functionality is affected by the immunosuppressive factors. We identify IL-10 and prostaglandin E2 (PGE2) as the pivotal immunosuppressive components in OC-associated ascites compromising TLR-mediated DC activation. Interestingly, IL-10 is present in both ascites from patients with malignant OC and in peritoneal fluid from patients with benign ovarian conditions and both fluids have similar ability to reduce TLR-mediated DC activation. However, depletion of IL-10 from ascites revealed that the presence of paracrine IL-10 is not crucial for ascites-mediated suppression of DC activation in response to TLR activation. Unlike IL-10, PGE2 is absent from peritoneal fluid of patients with benign conditions and selectively reduces TNFα induction in response to TLR-mediated activation in the presence of OC-associated ascites. Our study highlights PGE2 as an immunosuppressive component of the malignant OC microenvironment rendering PGE2 a potentially important target for immunotherapy in OC.

Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells.

Special AT-rich sequence-binding protein 1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating major histocompatibility complex class II (MHC II) expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46(+) inflammatory DCs that infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. In vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but continuous Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression.

Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation.

The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.

Nucleic acids and endosomal pattern recognition: how to tell friend from foe?

The innate immune system has evolved endosomal and cytoplasmic receptors for the detection of viral nucleic acids as sensors for virus infection. Some of these pattern recognition receptors (PRR) detect features of viral nucleic acids that are not found in the host such as long stretches of double-stranded RNA (dsRNA) and uncapped single-stranded RNA (ssRNA) in case of Toll-like receptor (TLR) 3 and RIG-I, respectively. In contrast, TLR7/8 and TLR9 are unable to distinguish between viral and self-nucleic acids on the grounds of distinct molecular patterns. The ability of these endosomal TLR to act as PRR for viral nucleic acids seems to rely solely on the mode of access to the endolysosomal compartment in which recognition takes place. The current dogma states that self-nucleic acids do not enter the TLR-sensing compartment under normal physiological conditions. However, it is still poorly understood how dendritic cells (DC) evade activation by self-nucleic acids, in particular with regard to specific DC subsets, which are specialized in taking up material from dying cells for cross-presentation of cell-associated antigens. In this review we discuss the current understanding of how the immune system distinguishes between foreign and self-nucleic acids and point out some of the key aspects that still require further research and clarification.