Postmortem imaging of blunt chest trauma using CT and MRI: comparison with autopsy

OBJECTIVE: Postmortem examination of chest trauma is an important domain in forensic medicine, which is today performed using autopsy. Since the implementation of cross-sectional imaging methods in forensic medicine such as computed tomography (CT) and magnetic resonance imaging (MRI), a number of advantages in comparison with autopsy have been described. Within the scope of validation of cross-sectional radiology in forensic medicine, the comparison of findings of postmortem imaging and autopsy in chest trauma was performed. METHODS: This retrospective study includes 24 cases with chest trauma that underwent postmortem CT, MRI, and autopsy. Two board-certified radiologists, blind to the autopsy findings, evaluated the radiologic data independently. Each radiologist interpreted postmortem CT and MRI data together for every case. The comparison of the results of the radiologic assessment with the autopsy and a calculation of interobserver discrepancy was performed. RESULTS: Using combined CT and MRI, between 75% and 100% of the investigated findings, except for hemomediastinum (70%), diaphragmatic ruptures (50%; n=2) and heart injury (38%), were discovered. Although the sensitivity and specificity regarding pneumomediastinum, pneumopericardium, and pericardial effusion were not calculated, as these findings were not mentioned at the autopsy, these findings were clearly seen radiologically. The averaged interobserver concordance was 90%. CONCLUSION: The sensitivity and specificity of our results demonstrate that postmortem CT and MRI are useful diagnostic methods for assessing chest trauma in forensic medicine as a supplement to autopsy. Further radiologic-pathologic case studies are necessary to define the role of postmortem CT and MRI as a single examination modality.

A pedigree with autosomal dominant thrombocytopenia, red cell macrocytosis, and an occurrence of t(12:21) positive pre-B acute lymphoblastic leukemia

Sampling and analyzing new families with inherited blood disorders are major steps contributing to the identification of gene(s) responsible for normal and pathologic hematopoiesis. Familial occurrences of hematological disorders alone, or as part of a syndromic disease, have been reported, and for some the underlying genetic mutation has been identified. Here we describe a new autosomal dominant inherited phenotype of thrombocytopenia and red cell macrocytosis in a four-generation pedigree. Interestingly, in the youngest generation, a 2-year-old boy presenting with these familial features has developed acute lymphoblastic leukemia characterized by a t(12;21) translocation. Tri-lineage involvement of platelets, red cells and white cells may suggest a genetic defect in an early multiliear progenitor or a stem cell. Functional assays in EBV-transformed cell lines revealed a defect in cell proliferation and tubulin dynamics. Two candidate genes, RUNX1 and FOG1, were sequenced but no pathogenic mutation was found. Identification of the underlying genetic defect(s) in this family may help in understanding the complex process of hematopoiesis.

Venous thromboembolism and occult malignancy: simultaneous detection during pulmonary CT angiography with CT venography

OBJECTIVE: We explored the potential for patients with proven venous thromboembolism or pulmonary embolism (PE) to have occult malignancies detected during the same CT examination. To verify this, we compared the presence of occult malignancies identified on pulmonary artery CT angiography (CTA) and CT venography (CTV) when venous thromboembolism (VTE) was present. SUBJECTS AND METHODS: Pulmonary artery CTA combined with CTV was performed on a 16-MDCT scanner on 186 adult patients suspected of having pulmonary embolism without any known malignancies. CTV was performed from the diaphragm to the knee 180 seconds after CTA. Two radiologists evaluated the presence of VTE, that is PE or deep venous thrombosis (DVT), and tumor lesions on both examinations in consensus. The malignant nature of the possibly identified tumors was confirmed by pathologic examination. RESULTS: VTE was found in 49 patients (26%). Malignant tumors were detected in 24 patients (13%). Eleven patients with malignant tumors had VTE (46% of patients with malignant tumors; 22% with VTE and 6% of all patients). There was correlation with presence of malignancies between both and DVT and DVT associated with PE but not between presence of malignancies and PE only. Patients with DVT and those with DVT associated with PE had a risk ratio of 3.2 and 3.3, respectively, for having a malignant tumor discovered simultaneously. CONCLUSION: A high number of malignant tumors can be incidentally discovered on pulmonary artery CTA, even more so with additional CTV. Radiologists should scrutinize scans to pick up unknown malignancies, especially in patients with identified VTE.

Fenestrated and branched endografts: why we need them now

Standard endovascular repair of abdominal aortic aneurysm (AAA) has been shown to be associated with significant advantages compared with conventional surgery in the perioperative time frame related to the minimally invasive nature of the procedure. Given the encouraging long-term results of endovascular AAA repair, this method is increasingly applied to patients with complex AAA anatomies. The present article reviews the indications for branched and fenestrated endografts in various aortic pathologic processes.

Gene and stem cell therapy in peripheral arterial occlusive disease

Peripheral arterial occlusive disease (PAOD) is a manifestation of systemic atherosclerosis strongly associated with a high risk of cardiovascular morbidity and mortality. In a considerable proportion of patients with PAOD, revascularization either by endovascular means or by open surgery combined with best possible risk factor modification does not achieve limb salvage or relief of ischaemic rest pain. As a consequence, novel therapeutic strategies have been developed over the last two decades aiming to promote neovascularization and remodelling of collaterals. Gene and stem cell therapy are the main directions for clinical investigation concepts. For both, preclinical studies have shown promising results using a wide variety of genes encoding for growth factors and populations of adult stem cells, respectively. As a consequence, clinical trials have been performed applying gene and stem cell-based concepts. However, it has become apparent that a straightforward translation into humans is not possible. While several trials reported relief of symptoms and functional improvement, other trials did not confirm this early promise of efficacy. Ongoing clinical trials with an improved study design are needed to confirm the potential that gene and cell therapy may have and to prevent the gaps in our scientific knowledge that will jeopardize the establishment of angiogenic therapy as an additional medical treatment of PAOD. This review summarizes the experimental background and presents the current status of clinical applications and future perspectives of the therapeutic use of gene and cell therapy strategies for PAOD.

Frequency of spontaneous ventricular tachycardia in a pediatric population

Few data exist on the incidence of spontaneously occurring ventricular tachycardia (VT) in an unselected pediatric population. The aim of this study was to define the incidence and outcomes of VT in a general pediatric population. A retrospective analysis was performed of all documented episodes of VT in children referred to a single center during a 10-year study period ending in December 2005. The study center drains a stable referral area with 252,000 children aged <16 years, with no other pediatric cardiologic or pediatric intensive care services available. Twenty-seven patients with spontaneously occurring episodes of VT were observed, accounting for a VT incidence of 1.1 episodes/100,000 childhood years. Thirteen patients had VT in the absence of structural heart disease, and 14 had VT in the presence of a wide range of underlying cardiac disease. Overall mortality was 5 of 27 patients (19%), but mortality was seen exclusively in patients with underlying heart disease; for this subgroup of patients, mortality was 36%. Idiopathic VT in children with structurally normal hearts carried a good prognosis, and treatment was required in a minority (20%) of these patients. In conclusion, this study highlights that VT in childhood is rare, and outcomes are highly dependent on the underlying pathologic substrate.

Severe structural damage of the seemingly non-diseased infrarenal aortic aneurysm neck

OBJECTIVE: The success of open and endovascular repair of abdominal aortic aneurysms (AAA) is hampered by postoperative dilatation of the anatomical neck of the AAA, which is used for graft attachment. The purpose of this study was to determine whether the macroscopically non-diseased infrarenal aortic neck of AAA is histologically and biochemically altered at the time of operative repair. METHODS: We harvested full-thickness aortic wall samples as longitudinal stripes spanning from AAA neck to aneurysmal sac in 22 consecutive patients undergoing open surgical AAA repair. Control tissue was obtained from five organ donors and five deceased subjects undergoing autopsy without evidence of aneurysmal disease. We assessed aortic media thickness, number of intact elastic lamellar units, media destruction, and neovascularization grade and performed immunohistochemistry for matrix metalloproteinase (MMP)-9 and phosphorylated c-Jun N-terminal kinase (p-JNK). MMP-9 and p-JNK protein expressions were quantified using Western Blots. RESULTS: The median thickness of the aortic media was 1150 mum in control tissue (range, 1000-1300), 510 mum in aortic necks (250-900), and 200 mum in aortic sacs (50-500, P from nonparametric test for trend <.001). The number of intact elastic lamellar units was 33 in controls (range, 33-55), 12 in aortic necks (0-31) and three in aortic sacs (0-10, P < .001). The expression of MMP-9 and p-JNK as assessed by Western Blots (P = .007 and .061, respectively) and zymography (P for trend <.001) were up regulated in both the AAA neck and sac compared with controls. Except for p-JNK expression, differences between tissues were similar after the adjustment for age, gender, and type of sampling. CONCLUSION: The seemingly non-diseased infrarenal AAA neck in patients with AAA undergoing surgical repair shows histological signs of destruction and upregulation of potential drug targets.

Prediction of spatial orientation and morphology of calcaneonavicular coalitions

BACKGROUND: Calcaneonavicular coalitions (CNC) have been reported to be associated with anatomical aberrations of either the calcaneus and/or navicular bones. These morphological abnormalities may complicate accurate surgical resection. Three-dimensional analysis of spatial orientation and morphological characteristics may help in preoperative planning of resection. MATERIALS AND METHODS: Sixteen feet with a diagnosis of CNC were evaluated by means of 3-D CT modeling. Three angles were defined that were expressed in relation to one reproducible landmark (lateral border of the calcaneus): the dorsoplantar inclination, anteroposterior inclination, and socket angle. The depth and width of the coalitions were measured and calculated to obtain the estimated contact surface. Three-dimensional reconstructions of the calcanei served to evaluate the presence, distortion or absence of the anterior calcaneal facet and presence of a navicular beak. The interrater correlations were assessed in order to obtain values for the accuracy of the measurement methods. Sixteen normal feet were used as controls for comparison of the socket angle; anatomy of the anterior calcaneal facet and navicular beak as well. RESULTS: The dorsoplantar inclination angle averaged 50 degrees (+/-17), the anteroposterior inclination angle 64 degrees (+/-15), and the pathologic socket angle 98 degrees (+/-11). The average contact area was 156 mm(2). Ninety-four percent of all patients in the CNC group revealed a plantar navicular beak. In 50% of those patients the anterior calcaneal facet was replaced by the navicular portion and in 44% the facet was totally missing. In contrast, the socket angle in the control group averaged 77 degrees (+/-18), which was found to be statistically different than the CNC group (p = 0.0004). Only 25% of the patients in the control group had a plantar navicular beak. High, statistically significant interrater correlations were found for all measured angles. CONCLUSION: Computer-aided CT analysis and reconstructions help to determine the spatial orientations of CNC in space and provide useful information in order to anticipate morphological abnormalities of the calcaneus and navicular.

Ultrasonography for depiction of brachial plexus injury

Recent development of ultrasonographic equipment has allowed improved spatial resolution for visualizing normal and pathologic conditions of peripheral nerves. Regarding the brachial plexus, only ultrasonographic studies that have described the normal appearance have been reported. To the best of our knowledge, no case report regarding the ultrasonographic description of a brachial plexus lesion has been published. We report the ultrasonographic findings of a brachial plexus injury after extirpation of a suspected enlarged supraclavicular lymph node.

Ultrasound of the pediatric female pelvis

Pelvic pain is a common indication for ultrasound examinations in female pediatric patients. Many pathological processes affect the female pelvis in childhood. Knowledge of the normal ultrasound appearance of the pelvic organs is the basis for the recognition of pathologic findings. Pelvic pain in children is a nonspecific clinical finding often prompting use of ultrasound. Other indications for pelvic ultrasound in female children include workup of cysts seen on fetal ultrasound, urogenital malformations in newborns, precocious puberty, vaginal discharge or abnormal bleeding, and amenorrhea. Knowledge of differential diagnosis for disease processes of the female pelvic organs is essential. Ultrasound is the imaging modality of choice for evaluating the pediatric female pelvis.

VEGF-A stimulates ADAM17-dependent shedding of VEGFR2 and crosstalk between VEGFR2 and ERK signaling

Vascular endothelial growth factor (VEGF)-A and the VEGF receptors are critical for regulating angiogenesis during development and homeostasis and in pathological conditions, such as cancer and proliferative retinopathies. Most effects of VEGF-A are mediated by the VEGFR2 and its coreceptor, neuropilin (NRP)-1. Here, we show that VEGFR2 is shed from cells by the metalloprotease disintegrin ADAM17, whereas NRP-1 is released by ADAM10. VEGF-A enhances VEGFR2 shedding by ADAM17 but not shedding of NRP-1 by ADAM10. VEGF-A activates ADAM17 via the extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase pathways, thereby also triggering shedding of other ADAM17 substrates, including tumor necrosis factor alpha, transforming growth factor alpha, heparin-binding epidermal growth factor-like growth factor, and Tie-2. Interestingly, an ADAM17-selective inhibitor shortens the duration of VEGF-A-stimulated ERK phosphorylation in human umbilical vein endothelial cells, providing evidence for an ADAM17-dependent crosstalk between the VEGFR2 and ERK signaling. Targeting the sheddases of VEGFR2 or NRP-1 might offer new opportunities to modulate VEGF-A signaling, an already-established target for treatment of pathological neovascularization.

Verteporfin therapy in occult with no classic CNV due to AMD: results of the Photodynamic Therapy in Occult-Only Lesions study

PURPOSE: To provide further information on verteporfin photodynamic therapy in occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: Verteporfin therapy was administered at baseline and then at months 3, 6, and 9, if fluorescein leakage from CNV was evident on angiography. RESULTS: Of 202 patients enrolled, 184 completed 12 months. Each patient was treated in one eye only. All study eyes received verteporfin therapy at baseline, with a progressive decrease in the number treated at subsequent visits (mean 2.5 treatments during 12 months). The mean change in visual acuity letter score from baseline to month 12 was -11.9. At month 12, 164 eyes (82.4%) had lost <30 letters of visual acuity, 123 eyes (61.8%) had lost <15 letters, 78 eyes (39.2%) had lost <5 letters, 31 (15.6%) had >5-letter increase, and 7 (3.5%) had >15-letter improvement. The percentage of eyes with fluorescein leakage from CNV decreased from 75.5% at month 3 to 25.1% at month 12. Adverse events were documented for 54% patients. Few patients had treatment-associated adverse events (7%). Acute severe visual acuity decrease occurred in two eyes (1%), one of which had visual acuity that returned to baseline by the next follow-up visit. CONCLUSIONS: This study provides additional evidence that over 12 months, verteporfin is generally well tolerated and maintains or improves visual acuity in over one-third of eyes containing occult-only CNV. Verteporfin also improved anatomical outcomes by reducing leakage from CNV in at least two-thirds of eyes.

Conventional radiographs to assess femoroacetabular impingement

Femoroacetabular impingement (FAI) is a pathologic condition of the hip joint in young adults that, if untreated, leads to end-stage osteoarthritis. It is characterized by early pathologic contact between primary osseous prominences of the acetabular rim (so-called pincer FAI) and/or the femoral head-neck junction (cam FAI). Conventional radiographs are often considered normal because classic radiographic signs of osteoarthritis are not present initially. The physician should be aware of the radiographic features for both types of impingement to recognize subtle pathologies.

Cell death in allergic diseases

Apoptosis, the most common form of cell death, is a key mechanism in the build up and maintenance of both innate and adaptive immunity. Central to the apoptotic process is a family of intracellular cysteine proteases with aspartate-specificity, called caspases. Caspases are counter-regulated by multiple anti-apoptotic molecules, and the expression of the latter in leukocytes is largely dependent on survival factors. Therefore, the physiologic rates of apoptosis change under pathologic conditions. For instance, in inflammation, the expression of survival factors is usually elevated, resulting in increased cell survival and consequently in the accumulation of the involved immune cells. In many allergic diseases, eosinophil apoptosis is delayed contributing to both blood and tissue eosinophilia. Besides eosinophils, apoptosis of other leukocytes is also frequently prevented or delayed during allergic inflammatory processes. In contrast to inflammatory cells, accelerated cell death is often observed in epithelial cells, a mechanism, which amplifies or at least maintains allergic inflammation. In conclusion, deregulated cell death is a common phenomenon of allergic diseases that likely plays an important role in their pathogenesis. Whether the apoptosis is too little or too much depends on the cell type. In this review, we discuss the regulation of the lifespan of the participating leukocytes in allergic inflammatory responses.

Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds

BACKGROUND: Clinical observations are suggesting accelerated granulation tissue formation in traumatic wounds treated with vacuum-assisted closure (VAC). Aim of this study was to determine the impact of VAC therapy versus alternative Epigard application on local inflammation and neovascularization in traumatic soft tissue wounds. METHODS: Thirty-two patients with traumatic wounds requiring temporary coverage (VAC n = 16; Epigard n = 16) were included. At each change of dressing, samples of wound fluid and serum were collected (n = 80). The cytokines interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 were measured by ELISA. Wound biopsies were examined histologically for inflammatory cells and degree of neovascularization present. RESULTS: All cytokines were found to be elevated in wound fluids during both VAC and Epigard treatment, whereas serum concentrations were negligible or not detectable. In wound fluids, significantly higher IL-8 (p < 0.001) and VEGF (p < 0.05) levels were detected during VAC therapy. Furthermore, histologic examination revealed increased neovascularization (p < 0.05) illustrated by CD31 and von Willebrand factor immunohistochemistry in wound biopsies of VAC treatment. In addition, there was an accumulation of neutrophils as well as an augmented expression of VEGF (p < 0.005) in VAC wound biopsies. CONCLUSION: This study suggests that VAC therapy of traumatic wounds leads to increased local IL-8 and VEGF concentrations, which may trigger accumulation of neutrophils and angiogenesis and thus, accelerate neovascularization.