Diagnosis of fatal pulmonary fat embolism with minimally invasive virtual autopsy and post-mortem biopsy

We report a case of a 78-year-old female with a proximal femur fracture caused by an accidental fall who died suddenly 1h after orthopaedic prosthesis insertion. Post-mortem computed tomography (CT) scan and histological examination of samples obtained with post-mortem percutaneous needle biopsies of both lungs were performed. Analysis of the medical history and the clinical scenario immediately before death, imaging data, and biopsy histology established the cause of death without proceeding to traditional autopsy. It was determined to be acute right ventricular failure caused by massive pulmonary fat embolism. Although further research in post-mortem imaging and post-mortem tissue sampling by needle biopsies is necessary, we conclude that the use of CT techniques and percutaneous biopsy, as additional tools, can offer a viable alternative to traditional autopsy in selected cases and may increase the number of minimally invasive forensic examinations performed in the future.

The contribution of surface residues to membrane binding and ligand transfer by the -tocopherol transfer protein ( -TTP)

Previous work has shown that the -tocopherol transfer protein ( -TTP) can bind to vesicular or immobilized phospholipid membranes. Revealing the molecular mechanisms by which -TTP associates with membranes is thought to be critical to understanding its function and role in the secretion of tocopherol from hepatocytes into the circulation. Calculations presented in the Orientations of Proteins in Membranes database have provided a testable model for the spatial arrangement of -TTP and other CRAL-TRIO family proteins with respect to the lipid bilayer. These calculations predicted that a hydrophobic surface mediates the interaction of -TTP with lipid membranes. To test the validity of these predictions, we used site-directed mutagenesis and examined the substituted mutants with regard to intermembrane ligand transfer, association with lipid layers and biological activity in cultured hepatocytes. Substitution of residues in helices A8 (F165A and F169A) and A10 (I202A, V206A and M209A) decreased the rate of intermembrane ligand transfer as well as protein adsorption to phospholipid bilayers. The largest impairment was observed upon mutation of residues that are predicted to be fully immersed in the lipid bilayer in both apo (open) and holo (closed) conformations such as Phe165 and Phe169. Mutation F169A, and especially F169D, significantly impaired -TTP-assisted secretion of -tocopherol outside cultured hepatocytes. Mutation of selected basic residues (R192H, K211A, and K217A) had little effect on transfer rates, indicating no significant involvement of nonspecific electrostatic interactions with membranes.

Postmortem imaging-guided biopsy as an adjuvant to minimally invasive autopsy with CT and postmortem angiography: a feasibility study

Although postmortem CT suffices for diagnosing most forms of traumatic death, the examination of natural death is, to date, very difficult and error prone. The introduction of postmortem angiography has led to improved radiologic diagnoses of natural deaths. Nevertheless, histologic changes to tissues, an important aspect in traditional examination procedures, remain obscure even with CT and CT angiography. For this reason, we examined the accuracy of a minimally invasive procedure (i.e., CT angiography combined with biopsy) in diagnosing major findings and the cause of death in natural deaths.

Clinical radiology and postmortem imaging (Virtopsy) are not the same: Specific and unspecific postmortem signs

The aim of this article is to disclose the characteristics of postmortem forensic imaging; give an overview of the several possible findings in postmortem imaging, which are uncommon or new to clinical radiologists; and discuss the possible pitfalls. Unspecific postmortem signs are enlisted and specific signs shall be presented, which are typical for one cause of death. Unspecific signs. Livor mortis may not only be seen from the outside, but also inside the body in the lungs: in chest CT internal livor mortis appear as ground glass opacity in the dependent lower lobes. The aortic wall is often hyperdense in postmortem CT due to wall contraction and loss of luminal pressure. Gas bubbles are very common postmortem due to systemic gas embolism after major open trauma, artificial respiration or initial decomposition; in particular putrefaction produces gas bubbles globally. Specific signs. Intracranial bleeding is hyperattenuating both in radiology and in postmortem imaging. Signs of strangulation are hemorrhage in the soft tissue of the neck like skin, subcutaneous tissue, platysma muscle and lymph nodes. The "vanishing" aorta is indicative for exsanguination. Fluid in the airways with mosaic lung densities and emphysema (aquosum) is typical for fresh-water drowning.

Can MRI of the neck compete with clinical findings in assessing danger to life for survivors of manual strangulation? A statistical analysis

The aim of the study was to examine the clinical forensic findings of strangulation according to their ability to differentiate between life-threatening and non-life-threatening strangulation, compare clinical and MRI findings of the neck and discuss a simple score for life-threatening strangulation (SLS).

[A dead man with a light reddish skin]

A 40-year-old man was found dead in his bathroom with a light reddish skin. The cause of death was asphyxia due to CO-intoxication.

Adjuvant radiotherapy in the treatment of invasive intraductal papillary mucinous neoplasm of the pancreas: an analysis of the surveillance, epidemiology, and end results registry

Management and outcomes of patients with invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas are not well established. We investigated whether adjuvant radiotherapy (RT) improved cancer-specific survival (CSS) and overall survival (OS) among patients undergoing surgical resection for invasive IPMN.

Surgical pathology in sub-Saharan Africa--volunteering in Malawi

The breadth of material found in surgical pathology services in African countries differs from the common spectrum of "the West". We report our experience of a voluntary work in the pathology departments of Blantyre and Lilongwe, Malawi. During a 6-week period, 405 cases (378 histology and 27 cytology cases) were processed. The vast majority showed significant pathological findings (n = 369; 91.1 %): 175 cases (47.4 %) were non-tumoral conditions with predominance of inflammatory lesions, e.g., schistosomiasis (n = 11) and tuberculosis (n = 11). There were 39 (10.6 %) benign tumors or tumor-like lesions. Intraepithelial neoplasia of the cervix uteri dominated among premalignant conditions (n = 15; 4.1 %). The large group of malignancies (n = 140; 37.9 %) comprised 11 pediatric tumors (e.g., rhabdomyosarcoma, small blue round cell tumors) and 129 adult tumors. Among women (n = 76), squamous cell carcinomas (SCCs) of the cervix uteri predominated (n = 25; 32.9 %), followed by breast carcinomas (n = 12; 15.8 %) and esophageal SCC (n = 9; 11.8 %). Males (n = 53) most often showed SCC of the esophagus (n = 9; 17.0 %) and of the urinary bladder (n = 7; 13.2 %). Lymphomas (n = 7) and Kaposi's sarcomas (n = 6) were less frequent. Differences compared to the western world include the character of the conditions in general, the spectrum of inflammatory lesions, and the young age of adult tumor patients (median 45 years; range 18-87 years). Providing pathology service in a low-resource country may be handicapped by lack of personnel, inadequate material resources, or insufficient infrastructure. Rotating volunteers offer a bridge for capacity building of both personnel and the local medical service; in addition, the volunteer's horizons are broadened professionally and personally.

Quantification of network perfusion in ASL cerebral blood flow data with seed based and ICA approaches

Independent component analysis (ICA) or seed based approaches (SBA) in functional magnetic resonance imaging blood oxygenation level dependent (BOLD) data became widely applied tools to identify functionally connected, large scale brain networks. Differences between task conditions as well as specific alterations of the networks in patients as compared to healthy controls were reported. However, BOLD lacks the possibility of quantifying absolute network metabolic activity, which is of particular interest in the case of pathological alterations. In contrast, arterial spin labeling (ASL) techniques allow quantifying absolute cerebral blood flow (CBF) in rest and in task-related conditions. In this study, we explored the ability of identifying networks in ASL data using ICA and to quantify network activity in terms of absolute CBF values. Moreover, we compared the results to SBA and performed a test-retest analysis. Twelve healthy young subjects performed a fingertapping block-design experiment. During the task pseudo-continuous ASL was measured. After CBF quantification the individual datasets were concatenated and subjected to the ICA algorithm. ICA proved capable to identify the somato-motor and the default mode network. Moreover, absolute network CBF within the separate networks during either condition could be quantified. We could demonstrate that using ICA and SBA functional connectivity analysis is feasible and robust in ASL-CBF data. CBF functional connectivity is a novel approach that opens a new strategy to evaluate differences of network activity in terms of absolute network CBF and thus allows quantifying inter-individual differences in the resting state and task-related activations and deactivations.

Laparoscopic appendectomy outcomes on the weekend and during the week are no different: a national study of 151,774 patients

The "weekend effect" is defined as increased morbidity and mortality for patients admitted on weekends compared with weekdays. It has been observed for several diseases, including myocardial infarction and renal insufficiency; however, it has not yet been investigated for laparoscopic appendectomy in acute appendicitis-one of the most prevalent surgical diagnoses.

Cholecystectomy concomitant with laparoscopic gastric bypass: a trend analysis of the nationwide inpatient sample from 2001 to 2008

Gallstone formation is common in obese patients, particularly during rapid weight loss. Whether a concomitant cholecystectomy should be performed during laparoscopic gastric bypass surgery is still contentious. We aimed to analyze trends in concomitant cholecystectomy and laparoscopic gastric bypass surgery (2001-2008), to identify factors associated with concomitant cholecystectomy, and to compare short-term outcomes after laparoscopic gastric bypass with and without concomitant cholecystectomy.

Concomitant Vascular Reconstruction During Pancreatectomy for Malignant Disease: A Propensity Score-Adjusted, Population-Based Trend Analysis Involving 10 206 Patients

OBJECTIVE To assess trends in the frequency of concomitant vascular reconstructions (VRs) from 2000 through 2009 among patients who underwent pancreatectomy, as well as to compare the short-term outcomes between patients who underwent pancreatic resection with and without VR. DESIGN Single-center series have been conducted to evaluate the short-term and long-term outcomes of VR during pancreatic resection. However, its effectiveness from a population-based perspective is still unknown. Unadjusted, multivariable, and propensity score-adjusted generalized linear models were performed. SETTING Nationwide Inpatient Sample from 2000 through 2009. PATIENTS A total of 10 206 patients were involved. MAIN OUTCOME MEASURES Incidence of VR during pancreatic resection, perioperative in-hospital complications, and length of hospital stay. RESULTS Overall, 10 206 patients were included in this analysis. Of these, 412 patients (4.0%) underwent VR, with the rate increasing from 0.7% in 2000 to 6.0% in 2009 (P < .001). Patients who underwent pancreatic resection with VR were at a higher risk for intraoperative (propensity score-adjusted odds ratio, 1.94; P = .001) and postoperative (propensity score-adjusted odds ratio, 1.36; P = .008) complications, while the mortality and median length of hospital stay were similar to those of patients without VR. Among the 25% of hospitals with the highest surgical volume, patients who underwent pancreatic surgery with VR had significantly higher rates of postoperative complications and mortality than patients without VR. CONCLUSIONS The frequency of VR during pancreatic surgery is increasing in the United States. In contrast with most single-center analyses, this population-based study demonstrated that patients who underwent VR during pancreatic surgery had higher rates of adverse postoperative outcomes than their counterparts who underwent pancreatic resection only. Prospective studies incorporating long-term outcomes are warranted to further define which patients benefit from VR.

Differential distribution of vasa vasorum in different vascular beds in humans

OBJECTIVE: Vasa vasorum (VV) have been implicated to play a role in the pathogenesis of atherosclerosis. This study was designed to describe the distribution of VV density in different vascular beds in humans and to investigate the association between VV density and the known distribution of atherosclerosis in human arteries. METHODS: Forty-two human arteries, harvested at autopsy or after explantation, were analyzed by three-dimensional microscopic-computed tomography (micro-CT). VV density, endothelial-surface-fraction (Sigma VV endothelial-surface-area/vessel-wall-volume) and vascular-area-fraction (Sigma VV area/vessel-wall-area) were calculated for coronary, renal and femoral arteries. Representatively five coronary, renal and femoral arteries were stained for endothelial cells (von Willebrand-Factor), macrophages (CD68), vascular endothelial growth factor (VEGF) and collagen (Sirius Red). RESULTS: Coronary arteries showed a higher VV density compared to renal and femoral arteries (2.12+/-0.26 n/mm(2) versus 0.61+/-0.06 n/mm(2) and 0.66+/-0.11 n/mm(2); P<0.05 for both) as well as a higher endothelial-surface-fraction and vascular-area-fraction. Histology showed a positive correlation between histologically derived VV density and CD68-positive cells/area (r=0.54, P<0.01), VEGF-immunoreactivity/area (r=0.55, P<0.01) and a negative correlation between VV density and collagen I content (r=0.66, P<0.05). CONCLUSION: This micro-CT study highlights a higher VV density in coronary than in peripheral arteries, supporting the relation between VV density and the susceptibility to atherosclerosis in different vascular beds in humans.

Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function

In protein folding and secretion disorders, activation of endoplasmic reticulum (ER) stress signaling (ERSS) protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs) during endochondral bone formation. In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del), misfolded alpha1(X) chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophic-like state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant collagen II and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia.