Insight into the incidence of acute aortic dissection in the German region of Berlin and Brandenburg.

BACKGROUND: Stanford acute type A aortic dissection (ATAAD) is a potentially lethal condition. Epidemiology studies show a statistical incidence in Europe of approximately 2-16 cases/100,000 inhabitants/year. In Germany, the estimated incidence (here subsumed under "thoracic aortic dissection" with 4.63 cases/100,000 inhabitants/year) is mainly extracted from medical death certificates by the German Federal Statistical Office. The prehospital incidence of ATAAD deaths is largely unknown. Since patients often die in the pre-hospital setting, the incidence of ATAAD is therefore likely to be higher than current estimates. MATERIAL AND METHODS: For the period from 2010 to 2014, we retrospectively analyzed all in-hospital ATAAD data from two of the largest cardiac surgical centers that treat ATAAD in the Berlin-Brandenburg region. In addition, autopsy reports of all forensic medicine institutes and of one large pathological provider in the region were analyzed to identify additional non-hospitalized ATAAD patients. Based on these findings, the regional incidence of ATAAD was calculated. RESULTS: In addition to in-hospital ATAAD patients (n=405), we identified additional 145 lethal ATAAD cases among 14,201 autopsy reports. The total of 550 ATAAD cases led to an estimated incidence of 11.9 cases/100,000 inhabitants/year for the whole Berlin-Brandenburg region. Arterial hypertension, pre-existing aortic dilatation, and hereditary connective tissue disorder were found in, respectively, 62.7%, 10%, and 1.8% of patients. CONCLUSION: ATAAD is more frequent than previously reported. Our results show that when patients who die outside of cardiac surgery centers are included, the incidence of ATAAD significantly exceeds the rate reported by the Federal Statistical Office.

[Deaths from propofol abuse : Survey of institutes of forensic medicine in Germany, Austria and Switzerland]. / Todesfälle durch Propofolmissbrauch : Befragung in rechtsmedizinischen Instituten in Deutschland, Österreich und der Schweiz.

Previous references suggesting a high mortality of propofol addiction in medical personnel were mostly based on surveys of the heads of medical departments or case reports; therefore, a questionnaire was sent to 48 forensic medicine departments in Germany, Austria and Switzerland concerning the number of autopsies carried out between 2002-2112 on medical personnel with the suspicion of abuse of propofol or other analgesics. The response rate was 67%. In 16 out of the 32 responding departments 39 deaths (27 males) were observed with previous connections to anesthesiology, intensive care or emergency departments of which 22 were physicians, 13 nurses, 2 other personnel and 2 were unknown. Propofol was the major cause of death in 33 cases (85%), in 8 cases including 7 with propofol, an unintentional accident was recorded and 29 were determined to be suicide. In 14 cases chronic abuse was denied but actually excluded by toxicological analysis in only 2 cases. In 11 cases involving suicide the question of abuse was not investigated. This survey confirmed previous data about the central role of propofol for the fatal outcome of addiction and suicide of anesthetists and other medical personnel. A dual prevention strategy with low-threshold offers for persons at risk and strategies for early detection is urgently needed including a stricter control of dispensing, improvement in forensic medical documentation and the use of toxicological investigations in every case of suspected abuse.

[Mortui vivos docent : The dead teach the living]. / Mortui vivos docent : Die Toten lehren die Lebenden.

There are considerable similarities and intersections between forensic medicine and emergency medicine. This applies especially to frustraneously resuscitated patients or other lethal clinical courses of traumatized patients who are subject to latter forensic autopsy. Cooperation between departments of emergency and forensic medicine not only has emergency medical training potential, but also the possibility of retrospective evaluation of medical emergency measures - both in individual cases and with regard to epidemiological aspects. In particular, the widespread registration of autopsied pre-hospital trauma deaths that occurred despite on-scene resuscitation attempts is useful. The pre-hospital situation represents a hotspot, but also a blind spot in the overall trauma mortality. In recent clinical registers, preclinical deaths go mostly unrecorded, despite the undisputed benefits of clinical registers.

[Tension pneumomediastinum and tension pneumothorax following tracheal perforation during cardiopulmonary resuscitation]. / Spannungspneumomediastinum und -pneumothorax nach Trachealperforation während Reanimation.

Tension pneumothorax can occur at any time during cardiopulmonary resuscitation (CPR) with external cardiac massage and invasive ventilation either from primary or iatrogenic rib fractures with concomitant pleural or parenchymal injury. Airway injury can also cause tension pneumothorax during CPR. This article presents the case of a 41-year-old woman who suffered cardiopulmonary arrest after undergoing elective mandibular surgery. During CPR the upper airway could not be secured by orotracheal intubation due to massive craniofacial soft tissue swelling. A surgical airway was established with obviously unrecognized iatrogenic tracheal perforation and subsequent development of tension pneumomediastinum and tension pneumothorax during ventilation. Neither the tension pneumomediastinum nor the tension pneumothorax were decompressed and accordingly resuscitation efforts remained unsuccessful. This case illustrates the need for a structured approach to resuscitate patients with ventilation problems regarding decompression of tension pneumomediastinum and/or tension pneumothorax during CPR.

LPS-induced effects on angiotensin I-converting enzyme expression and shedding in human pulmonary microvascular endothelial cells.

Angiotensin I-converting enzyme (kininase II, ACE, and CD143) availability is a determinant of local angiotensin and kinin concentrations and their physiological actions. Until now, it is unclear whether the decrease of pulmonary ACE activity in sepsis-described in clinical studies-is due to an enzyme compensatory downregulation (reduced ACE-mRNA expression) to shedding of ACE or endothelial damage. To address these questions, ACE distribution under septic conditions was studied in vitro by treating pulmonary microvascular endothelial cells (HPMEC) and human umbilical vein endothelial cells (HUVEC) with lipopolysaccharide from Escherichia coli (LPS). Primary isolated HUVEC and HPMEC were compared by detecting ACE activity, membrane-bound ACE, as well as shedding and mRNA production of ACE with and without LPS (1 ng/ml-1 µg/ml). ACE mRNA expression was detected by real-time PCR, and shedded ACE was measured in cell culture supernatant by ELISA. Additionally, membrane-bound protein expression was investigated by immunohistochemistry in situ. In septic ARDS, the distribution of ACE protein was significantly reduced in all lung endothelial cells (p<0.001). After stimulation with LPS, cultivated HPMEC showed more markedly than HUVEC, a concentration-dependent reduction of ACE protein expression compared to the respective untreated controls. Real-time PCR demonstrated a reduced ACE mRNA expression after LPS stimulation, predominantly in HPMEC. Specifically, in HPMEC, a concentration-dependent increase of shedded ACE was shown 24 h after LPS treatment. HPMEC cultures are an apt model for the investigation of pulmonary ACE expression in sepsis. This study suggests that reduced pulmonary microvascular endothelial ACE expression in septic ARDS is caused by two processes: (initial) increased shedding of ACE accompanied by a compensatory downregulation of ACE-mRNA and membrane-bound protein expression.

Trauma-related preventable deaths in Berlin 2010: need to change prehospital management strategies and trauma management education.

BACKGROUND: Fatal trauma is one of the leading causes of death in Western industrialized countries. The aim of the present study was to determine the preventability of traumatic deaths, analyze the medical measures related to preventable deaths, detect management failures, and reveal specific injury patterns in order to avoid traumatic deaths in Berlin. MATERIALS AND METHODS: In this prospective observational study all autopsied, direct trauma fatalities in Berlin in 2010 were included with systematic data acquisition, including police files, medical records, death certificates, and autopsy records. An interdisciplinary expert board judged the preventability of traumatic death according to the classification of non-preventable (NP), potentially preventable (PP), and definitively preventable (DP) fatalities. RESULTS: Of the fatalities recorded, 84.9 % (n = 224) were classified as NP, 9.8 % (n = 26) as PP, and 5.3 % (n = 14) as DP. The incidence of severe traumatic brain injury (sTBI) was significantly lower in PP/DP than in NP, and the incidence of fatal exsanguinations was significantly higher. Most PP and NP deaths occurred in the prehospital setting. Notably, no PP or DP was recorded for fatalities treated by a HEMS crew. Causes of DP deaths consisted of tension pneumothorax, unrecognized trauma, exsanguinations, asphyxia, and occult bleeding with a false negative computed tomography scan. CONCLUSIONS: The trauma mortality in Berlin, compared to worldwide published data, is low. Nevertheless, 15.2 % (n = 40) of traumatic deaths were classified as preventable. Compulsory training in trauma management might further reduce trauma-related mortality. The main focus should remain on prevention programs, as the majority of the fatalities occurred as a result of non-survivable injuries.

Changes to the cell, tissue and architecture levels in cranial suture synostosis reveal a problem of timing in bone development.

Premature fusion of cranial sutures is a common problem with an incidence of 3-5 per 10,000 live births. Despite progress in understanding molecular/genetic factors affecting suture function, the complex process of premature fusion is still poorly understood. In the present study, corresponding excised segments of nine patent and nine prematurely fused sagittal sutures from infants (age range 3-7 months) with a special emphasis on their hierarchical structural configuration were compared. Cell, tissue and architecture characteristics were analysed by transmitted and polarised light microscopy, 2D-histomorphometry, backscattered electron microscopy and energy-dispersive-x-ray analyses. Apart from wider sutural gaps, patent sutures showed histologically increased new bone formation compared to reduced new bone formation and osseous edges with a more mature structure in the fused portions of the sutures. This pattern was accompanied by a lower osteocyte lacunar density and a higher number of evenly mineralised osteons, reflecting pronounced lamellar bone characteristics along the prematurely fused sutures. In contrast, increases in osteocyte lacunar number and size accompanied by mineralisation heterogeneity and randomly oriented collagen fibres predominantly signified woven bone characteristics in patent, still growing suture segments. The already established woven-to-lamellar bone transition provides evidence of advanced bone development in synostotic sutures. Since structural and compositional features of prematurely fused sutures did not show signs of pathological/defective ossification processes, this supports the theory of a normal ossification process in suture synostosis - just locally commencing too early. These histomorphological findings may provide the basis for a better understanding of the pathomechanism of craniosynostosis, and for future strategies to predict suture fusion and to determine surgical intervention.

Copy number aberrations of BCL2 and CDKN2A/B identified by array-CGH in thymic epithelial tumors.

The molecular pathology of thymic epithelial tumors (TETs) is largely unknown. Using array comparative genomic hybridization (CGH), we evaluated 59 TETs and identified recurrent patterns of copy number (CN) aberrations in different histotypes. GISTIC algorithm revealed the presence of 126 significant peaks of CN aberration, which included 13 cancer-related genes. Among these peaks, CN gain of BCL2 and CN loss of CDKN2A/B were the only genes in the respective regions of CN aberration and were associated with poor outcome. TET cell lines were sensitive to siRNA knockdown of the anti-apoptotic molecules BCL2 and MCL1. Gx15-070, a pan-BCL2 inhibitor, induced autophagy-dependent necroptosis in TET cells via a mechanism involving mTOR pathways, and inhibited TET xenograft growth. ABT263, an inhibitor of BCL2/BCL-XL/BCL-W, reduced proliferation in TET cells when administered in combination with sorafenib, a tyrosine kinase inhibitor able to downregulate MCL1. Immunohistochemistry on 132 TETs demonstrated that CN loss of CDKN2A correlated with lack of expression of its related protein p16(INK4) and identified tumors with poor prognosis. The molecular markers BCL2 and CDKN2A may be of potential value in diagnosis and prognosis of TETs. Our study provides the first preclinical evidence that deregulated anti-apoptotic BCL2 family proteins may represent suitable targets for TET treatment.

Ceramide mediates nanovesicle shedding and cell death in response to phosphatidylinositol ether lipid analogs and perifosine.

Anticancer phospholipids that inhibit Akt such as the alkylphospholipid perifosine (Per) and phosphatidylinositol ether lipid analogs (PIAs) promote cellular detachment and apoptosis and have a similar cytotoxicity profile against cancer cell lines in the NCI60 panel. While investigating the mechanism of Akt inhibition, we found that short-term incubation with these compounds induced rapid shedding of cellular nanovesicles containing EGFR, IGFR and p-Akt that occurred in vitro and in vivo, while prolonged incubation led to cell detachment and death that depended on sphingomyelinase-mediated generation of ceramide. Pretreatment with sphingomyelinase inhibitors blocked ceramide generation, decreases in phospho-Akt, nanovesicle release and cell detachment in response to alkylphospholipids and PIAs in non-small cell lung cancer cell lines. Similarly, exogenous ceramide also decreased active Akt and induced nanovesicle release. Knockdown of neutral sphingomyelinase decreased, whereas overexpression of neutral or acid sphingomyelinase increased cell detachment and death in response to the compounds. When transferred in vitro, PIA or Per-induced nanovesicles increased ceramide levels and death in recipient cells. These results indicate ceramide generation underlies the Akt inhibition and cytotoxicity of this group of agents, and suggests nanovesicle shedding and uptake might potentially propagate their cytotoxicity in vivo.

The diagnostic value of synovial membrane hemorrhage and bloody discoloration of synovial fluid ("inner knee sign") in autopsy cases of fatal hypothermia.

We describe and discuss autopsy findings of synovial membrane hemorrhage and bloody discoloration of synovial fluid ("inner knee sign") within a study population comprising 36 cases of fatal hypothermia and 300 control cases. Synovial membrane hemorrhage and bloody discoloration of synovial fluid of the knees were seen in 27 cases of fatal hypothermia (75%). Though we are not dealing here with an obligatory autopsy finding in fatal hypothermia, the detection of the inner knee sign might be used as another corroborative sign of vital hypothermia after considering all differential diagnostic aspects. However, the absence of this finding does not exclude death due to hypothermia.

Post-mortem decapitation by domestic dogs: three case reports and review of the literature.

Post-mortem animal depredation is not an uncommon phenomenon in routine forensic autopsies. We present three cases of complete post-mortem decapitation by domestic German shepherd dogs. In two cases, the head had been bitten off, defleshed and left lying near the body, while in one case it had been completely devoured by two dogs; only small skull fragments and crowned teeth could be found. Two of the three bodies were putrefied; all dog bite injuries had been inflicted after death. The cause of death was drug toxicity in two cases and fatal hemorrhage from ruptured esophageal varices in one case. These rare injuries due to post-mortem animal depredation are discussed in the light of earlier studies and case reports.

Pulmonary periarterial inflammation in fatal asthma.

BACKGROUND: To date, little information has been available about pulmonary artery pathology in asthma. The pulmonary artery supplies the distal parts of the lungs and likely represents a site of immunological reaction in allergic inflammation. The objective of this study was to describe the inflammatory cell phenotype of pulmonary artery adventitial inflammation in lung tissue from patients who died of asthma. METHODS: We quantified the different inflammatory cell types in the periarterial region of small pulmonary arteries in lung tissue from 22 patients who died of asthma [fatal asthma (FA)] and 10 control subjects. Using immunohistochemistry and image analysis, we quantified the cell density for T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), eosinophils, mast cells (chymase and tryptase), and neutrophils in the adventitial layer of pulmonary arteries with a diameter smaller than 500 microm. RESULTS: Our data (median/interquartile range) demonstrated increased cell density of mast cells [FA=271.8 (148.7) cells/mm2; controls=177.0 (130.3) cells/mm2, P=0.026], eosinophils [FA=23.1 (58.6) cells/mm2; controls=0.0 (2.3) cells/mm2, P=0.012], and neutrophils [FA=50.4 (85.5) cells/mm2; controls=2.9 (30.5) cells/mm2, P=0.009] in the periarterial space in FA. No significant differences were found for B and T lymphocytes or CD4+ or CD8+ subsets. Chymase/tryptase positive (MCCT) mast cells predominated over tryptase (MCT) mast cells in the perivascular arterial space in both asthma patients and controls [MCCT/(MCCT+MCT)=0.91 (0-1) in FA and 0.75 (0-1) in controls, P=0.86]. CONCLUSIONS: Our results show that the adventitial layer of the pulmonary artery participates in the inflammatory process in FA, demonstrating increased infiltration of mast cells, eosinophils, and neutrophils, but not of T and B lymphocytes.

[Iatrogenic trauma following resuscitation measures]. / Iatrogene Traumata nach frustraner Reanimation.

Resuscitation attempts require invasive iatrogenic manipulations on the patient. On the one hand, these measures are essential for successful survival of the patient, but on the other hand can damage the patient. We differentiate between frequent and rare injuries. Factors of influence are duration and intensity of the resuscitation attempts, age of the patient as well as a coagulate-inhibiting medication.

Can post-mortem blood be used for DNA profiling after peri-mortem blood transfusion?

The question of whether blood transfusions can affect DNA profiling is still a contentious issue throughout the forensic community. It is hypothesised that donor leucocytes present in the administered blood will be detected upon examination of recipient blood. In order to resolve this issue, a selection of theoretical experiments were carried out to determine how much donor DNA must be present for its detection in blood components. Five casework examples of material collected from individuals after massive transfusion, including a case of whole organ transplantation, were also investigated. The results indicated that filtration processes used during blood production do not allow the passage of enough donor leucocytes for detection using current forensic profiling techniques. No evidence of secondary profile alleles were found in any case, indicating that peri-mortem blood transfusion does not affect DNA profiling.

[Spontaneous ruptures of the urinary bladder in the routine forensic examination]. / Spontane Harnblasenrupturen im Rechtsmedizinischen Untersuchungsgut.

This article analyses three cases of death following a spontaneous rupture of the urinary bladder. One case is based on an extensive tamponade of the bladder eight days after a transurethral resection of the prostate gland. Two other cases of death by spontaneous rupture resulted from increased alcohol consumption. The paper presents an overview of pathomorphological findings such as the typical intraperitoneal rupture localisation at the posterior wall of the urinary bladder or bladder dome and the subsequent diagnosed causes of death. In addition predisposing (anamnestic) influencing factors such as chronic alcoholism are highlighted and their relevance for the clinical urologist and the forensic pathologist are discussed.