Postmortem CT Angiography Compared with Autopsy: A Forensic Multicenter Study.

Purpose To determine if postmortem computed tomography (CT) and postmortem CT angiography help to detect more lesions than autopsy in postmortem examinations, to evaluate the strengths and weaknesses of each method, and to define their indications. Materials and Methods Postmortem CT angiography was performed on 500 human corpses and followed by conventional autopsy. Nine centers were involved. All CT images were read by an experienced team including one forensic pathologist and one radiologist, blinded to the autopsy results. All findings were recorded for each method and categorized by anatomic structure (bone, organ parenchyma, soft tissue, and vascular) and relative importance in the forensic case (essential, useful, and unimportant). Results Among 18 654 findings, autopsies helped to identify 61.3% (11 433 of 18 654), postmortem CT helped to identify 76.0% (14 179 of 18 654), and postmortem CT angiography helped to identify 89.9% (16 780 of 18 654; P < .001). Postmortem CT angiography was superior to autopsy, especially at helping to identify essential skeletal lesions (96.1% [625 of 650] vs 65.4% [425 of 650], respectively; P < .001) and vascular lesions (93.5% [938 of 1003] vs 65.3% [655 of 1003], respectively; P < .001). Among the forensically essential findings, 23.4% (1029 of 4393) were not detected at autopsy, while only 9.7% (428 of 4393) were missed at postmortem CT angiography (P < .001). The best results were obtained when postmortem CT angiography was combined with autopsy. Conclusion Postmortem CT and postmortem CT angiography and autopsy each detect important lesions not detected by the other method. More lesions were identified by combining postmortem CT angiography and autopsy, which may increase the quality of postmortem diagnosis. Online supplemental material is available for this article.

Conditional loss of hepatocellular Hedgehog signaling in female mice leads to the persistence of hepatic steroidogenesis, androgenization and infertility.

The Hedgehog signaling pathway is known to be involved in embryogenesis, tissue remodeling, and carcinogenesis. Because of its involvement in carcinogenesis, it seems an interesting target for cancer therapy. Indeed, Sonidegib, an approved inhibitor of the Hedgehog receptor Smoothened (Smo), is highly active against diverse carcinomas, but its use is also reported to be associated with several systemic side effects. Our former work in adult mice demonstrated hepatic Hedgehog signaling to play a key role in the insulin-like growth factor axis and lipid metabolism. The current work using mice with an embryonic and hepatocyte-specific Smo deletion describes an adverse impact of the hepatic Hedgehog pathway on female fertility. In female SAC-KO mice, we detected androgenization characterized by a 3.3-fold increase in testosterone at 12 weeks of age based on an impressive induction of steroidogenic gene expression in hepatocytes, but not in the classic steroidogenic organs (ovary and adrenal gland). Along with the elevated level of testosterone, the female SAC-KO mice showed infertility characterized by juvenile reproductive organs and acyclicity. The endocrine and reproductive alterations resembled polycystic ovarian syndrome and could be confirmed in a second mouse model with conditional deletion of Smo at 8 weeks of age after an extended period of 8 months. We conclude that the down-regulation of hepatic Hedgehog signaling leads to an impaired hormonal balance by the induction of steroidogenesis in the liver. These effects of Hedgehog signaling inhibition should be considered when using Hedgehog inhibitors as anti-cancer drugs.

Frequency and clinical course of cerebral embolism in patients undergoing transcatheter left atrial appendage closure.

AIMS: The aim of this study was to assess silent and clinically apparent cerebral embolic events in patients undergoing transcatheter left atrial appendage closure. METHODS AND RESULTS: In this prospective single-centre study, 28 patients underwent percutaneous closure of the left atrial appendage. In all patients, a diffusion-weighted magnetic resonance imaging (DW-MRI) study was performed before, the day after the procedure, and during routine follow-up after 45 days. All patients underwent neurological assessment at the time of DW-MRI. Additionally, transcranial Doppler ultrasound monitoring (TCD) for the detection of microembolic material during the procedure was performed. The procedure was successfully completed in all patients. New embolic lesions were detected in nine patients (32%) after the procedure, of which three (33%) were detectable as gliotic lesions at follow-up. One (3.6%) new lesion was observed at 45-day follow-up. Neurological assessment showed no neurological deficits. We observed no relationship between the numbers of microembolic signals on TCD monitoring and the occurrence of cerebral infarctions on DW-MRI. CONCLUSIONS: New cerebral embolic events occur after transcatheter closure of the left atrial appendage. However, most of the lesions demonstrate no gliotic transformation at follow-up. In all patients, the cerebral lesions were clinically unapparent.

A simple method for inducing estrous cycle stage-specific morphological changes in the vaginal epithelium of immature female mice.

The vaginal epithelium of the adult female laboratory rodent changes from mucous secretion to cornification over the course of the estrous cycle. The morphophysiological changes occur with such regularity, accuracy and precision that the specific stage of the estrous cycle in the rat can be determined by inspection of the vaginal opening and/or exfoliative vaginal cytology. However, in the mouse, post-mortem vaginal histology is often required to determine the estrous cycle stage for ensuring the required level of reliability. Consequently, an excess number of female adult mice are needed to allow for the delivery of sufficient numbers of mice in a desired estrous cycle stage. In this study, we demonstrate that the standard procedure for oocyte superovulation and collection in the laboratory mouse (e.g. injection of equine chorionic gonadotropin followed 48 h later by human chorionic gonadotropin) can also be reliably used to induce changes in the epithelium of 3.5-week-old mouse vaginas in an estrous cycle stage-specific manner (e.g. establishment and replacement of a mucous secreting epithelium with a cornified epithelium; induction of cornification-associated loricrin expression). The superovulation protocol thus allows for the efficient and economic induction of estrous cycle stage-specific characteristics in the Müllerian duct-derived vagina thereby avoiding the necessity of post-mortem identification of the estrous cycle stage. In addition, our study indicates that the laboratory mouse vagina is an excellent organ for studying the sequence of events leading to cornification.

Acute aortic dissection caused by Clostridium septicum aortitis.

Clostridium septicum aortitis is a rare cause of aortic dissection. So far, only 28 cases have been described in literature before. Most of these cases occurred in elderly patients and an association to colonic neoplasms and/or atherosclerosis has been witnessed frequently. Here we report the case of a 32-year-old man with fatal aortic dissection due to aortic infection with C. septicum. Beside a case of a 22-year-old man who died of aortic dissection due to C. septicum aortitis this is the second case of C. septicum aortitis in a young individual with no signs of colonic neoplasms or atherosclerosis.

Unstable EEG-vigilance in patients with cancer-related fatigue (CRF) in comparison to healthy controls.

OBJECTIVES: Cancer-related fatigue (CRF) is associated with tiredness and sleepiness. It remains unclear, whether such complaints are associated with neurophysiological signs of sleep proneness or a state of neurophysiological hyperarousal in which the patient finds it difficult to relax and to initiate sleep. Therefore the goal of this study is to compare the electroencephalographic (EEG)-vigilance regulation of patients with CRF and healthy controls. METHODS: A 15-min resting EEG with eyes closed was recorded in 22 patients with CRF and 22 matched healthy controls. Consecutive 1-s segments were classified into seven different vigilance stages ranging from high alertness to relaxed wakefulness (stage 0, A1, A2, A3) and further on to drowsiness (B1, B2/3) and sleep onset (stage C). RESULTS: Results showed that patients with CRF revealed a higher number of vigilance stages A3 (mean 15.26 vs. 6.67%, P = 0.004) dropped significantly earlier to vigilance levels A3 (drop after 130.8 vs. 533.3 s, P = 0.000) and B2/3&C (407.8 vs. 604.1 s, P = 0.035) and showed significantly more transitions between vigilance stages (46.0 vs. 31.1%, P = 0.003) in comparison to healthy controls. CONCLUSIONS: These findings suggest an unstable vigilance regulation in patients with CRF and provide a neurophysiological framework for the reported efficacy of psychostimulants in CRF.