Concordance between MITS and conventional autopsies for pathological and virological diagnoses.

In pandemics or to further study highly contagious infectious diseases, new strategies are needed for the collection of post-mortem tissue samples to identify the pathogen as well as its morphological impact. In this study, an ultrasound-guided minimally invasive tissue sampling (MITS) protocol was developed and validated for post-mortem use. The histological and microbiological qualities of post-mortem specimens were evaluated and compared between MITS and conventional autopsy (CA) in a series of COVID-19 deaths. Thirty-six ultrasound-guided MITS were performed. In five cases more, specimens for histological and virological examination were also obtained and compared during the subsequently performed CA. Summary statistics and qualitative interpretations (positive, negative) were calculated for each organ tissue sample from MITS and CA, and target genes were determined for both human cell count (beta-globin) and virus (SARS-CoV-2 specific E gene). There are no significant differences between MITS and CA with respect to the detectability of viral load in individual organs, which is why MITS can be of utmost importance and an useful alternative, especially during outbreaks of infectious diseases.

Minimally Invasive Tissue Sampling via Post Mortem Ultrasound: A Feasible Tool (Not Only) in Infectious Diseases-A Case Report.

In the past years the number of hospital autopsies have declined steadily, becoming almost excluded from medical training. Medicolegal (forensic) autopsies account for almost all autopsies, whereas hospital autopsies are becoming increasingly rare. Minimally invasive tissue sampling (MITS) using post mortem ultrasound offers the opportunity to increase the number of post mortem examinations in a clinical and even forensic context. MITS is a needle-based post mortem procedure that uses (radiological) imaging techniques to examine major organs of the body, acquire tissue samples and aspirate fluid from the body cavities or hollow organs. In this study, MITS was used to determine the presence of other co-existing diseases in a deceased infected 97-year-old woman with severe acute respiratory syndrome coronavirus 2. The examination of her body was carried out using ultrasound as an imaging tool and to gather ultrasound-guided biopsies as conventional autopsy was rejected by the next of kin. Ultrasound and histology identified an intravesical mass leading to an obstruction of the urinary outlet resulting in bilateral hydronephrosis and purulent pyelonephritis, which was unknown during her lifetime. Histopathological examination revealed the tumor mass to be a squamous cell carcinoma. This study has shown that MITS can be used to determine the cause of death and the presence of concomitant diseases in the infectious deceased.

Sacrospinous and sacrotuberous ligaments influence in pelvis kinematics.

The alteration in mechanical properties of posterior pelvis ligaments may cause a biased pelvis deformation which, in turn, may contribute to hip and spine instability and malfunction. Here, the effect of different mechanical properties of ligaments on lumbopelvic deformation is analyzed via the finite element method. First, the improved finite element model was validated using experimental data from previous studies and then used to calculate the sensitivity of lumbopelvic deformation to changes in ligament mechanical properties, load magnitude, and unilateral ligament resection. The deformation of the lumbopelvic complex relative to a given load was predominant in the medial plane. The effect of unilateral resection on deformation appeared to be counterintuitive, suggesting that ligaments have the ability to redistribute load and that they play an important role in the mechanics of the lumbopelvic complex.

Robotic Tissue Sampling for Safe Post-Mortem Biopsy in Infectious Corpses.

In pathology and legal medicine, the histopathological and microbiological analysis of tissue samples from infected deceased is a valuable information for developing treatment strategies during a pandemic such as COVID-19. However, a conventional autopsy carries the risk of disease transmission and may be rejected by relatives. We propose minimally invasive biopsy with robot assistance under CT guidance to minimize the risk of disease transmission during tissue sampling and to improve accuracy. A flexible robotic system for biopsy sampling is presented, which is applied to human corpses placed inside protective body bags. An automatic planning and decision system estimates optimal insertion point. Heat maps projected onto the segmented skin visualize the distance and angle of insertions and estimate the minimum cost of a puncture while avoiding bone collisions. Further, we test multiple insertion paths concerning feasibility and collisions. A custom end effector is designed for inserting needles and extracting tissue samples under robotic guidance. Our robotic post-mortem biopsy (RPMB) system is evaluated in a study during the COVID-19 pandemic on 20 corpses and 10 tissue targets, 5 of them being infected with SARS-CoV-2. The mean planning time including robot path planning is 5.72±167s. Mean needle placement accuracy is 7.19± 422mm.

Systematic review and meta-analysis of the biomechanical properties of the human dura mater applicable in computational human head models.

Accurate biomechanical properties of the human dura mater are required for computational models and to fabricate artificial substitutes for transplantation and surgical training purposes. Here, a systematic literature review was performed to summarize the biomechanical properties of the human dura mater that are reported in the literature. Furthermore, anthropometric data, information regarding the mechanically tested samples, and specifications with respect to the used mechanical testing setup were extracted. A meta-analysis was performed to obtain the pooled mean estimate for the elastic modulus, ultimate tensile strength, and strain at maximum force. A total of 17 studies were deemed eligible, which focused on human cranial and spinal dura mater in 13 and 4 cases, respectively. Pooled mean estimates for the elastic modulus (n = 448), the ultimate tensile strength (n = 448), and the strain at maximum force (n = 431) of 68.1 MPa, 7.3 MPa and 14.4% were observed for native cranial dura mater. Gaps in the literature related to the extracted data were identified and future directions for mechanical characterizations of human dura mater were formulated. The main conclusion is that the most commonly used elastic modulus value of 31.5 MPa for the simulation of the human cranial dura mater in computational head models is likely an underestimation and an oversimplification given the morphological diversity of the tissue in different brain regions. Based on the here provided meta-analysis, a stiffer linear elastic modulus of 68 MPa was observed instead. However, further experimental data are essential to confirm its validity.

Assessing Protein Biomarkers to Detect Lethal Acute Traumatic Brain Injuries in Cerebrospinal Fluid.

Diagnosing traumatic brain injury (TBI) from body fluids in cases where there are no obvious external signs of impact would be useful for emergency physicians and forensic pathologists alike. None of the previous attempts has so far succeeded in establishing a single biomarker to reliably detect TBI with regards to the sensitivity: specificity ratio in a post mortem setting. This study investigated a combination of body fluid biomarkers (obtained post mortem), which may be a step towards increasing the accuracy of biochemical TBI detection. In this study, serum and cerebrospinal fluid (CSF) samples from 30 acute lethal TBI cases and 70 controls without a TBI-related cause of death were evaluated for the following eight TBI-related biomarkers: brain-derived neurotrophic factor (BDNF), ferritin, glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6), lactate dehydrogenase, neutrophil gelatinase-associated lipocalin (NGAL), neuron-specific enolase and S100 calcium-binding protein B. Correlations among the individual TBI biomarkers were assessed, and a specificity-accentuated threshold value analysis was conducted for all biomarkers. Based on these values, a decision tree modelling approach was performed to assess the most accurate biomarker combination to detect acute lethal TBIs. The results showed that 92.45% of acute lethal TBIs were able to be diagnosed using a combination of IL-6 and GFAP in CSF. The probability of detecting an acute lethal TBI was moderately increased by GFAP alone and considerably increased by the remaining biomarkers. BDNF and NGAL were almost perfectly correlated (p = 0.002; R2 = 0.944). This study provides evidence that acute lethal TBIs can be detected to a high degree of statistical accuracy using forensic biochemistry. The high inter-individual correlations of biomarkers may help to estimate the CSF concentration of an unknown biomarker, using extrapolation techniques.

Prospective postmortem evaluation of 735 consecutive SARS-CoV-2-associated death cases.

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. 84.1% (n = 618) were classified as COVID-19 deaths, 6.4% (n = 47) as non-COVID-19 deaths, 9.5% (n = 70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n = 283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%; n = 187). Thromboses were found in 39.2% (n = 62/158 cases), pulmonary embolism in 22.1% (n = 56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n = 618) represented COVID-19 deaths. Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.

Multiorgan tropism of SARS-CoV-2 lineage B.1.1.7.

Due to the development of novel functionalities, distinct SARS-CoV-2 variants such as B.1.1.7 fuel the current pandemic. B.1.1.7 is not only more transmissible, but may also cause an increased mortality compared to previous SARS-CoV-2 variants. Human tissue analysis of the SARS-CoV-2 lineage B.1.1.7 is urgently needed, and we here present autopsy data from 7 consecutive SARS-CoV-2 B.1.1.7 cases. The initial RT-qPCR analyses from nasopharyngeal swabs taken post mortem included typing assays for B.1.1.7. We quantitated SARS-CoV-2 B.1.1.7 viral load in autopsy tissue of multiple organs. Highest levels of SARS-CoV-2 B.1.1.7 copies normalized to ß-globin were detected in the respiratory system (lung and pharynx), followed by the liver and heart. Importantly, SARS-CoV-2 lineage B.1.1.7 was found in 100% of cases in the lungs and in 85.7% in pharynx tissue. Detection also in the kidney and brain highlighting a pronounced organ tropism. Comparison of the given results to a former cohort of SARS-CoV-2 deaths during the first wave in spring 2020 showed resembling organ tropism. Our results indicate that also SARS-CoV-2 B.1.1.7 has a relevant organ tropism beyond the respiratory tract. We speculate that B.1.1.7 spike protein's affinity to human ACE2 facilitates transmission, organ tropism, and ultimately morbidity and mortality. Further studies and larger cohorts are obligatory to proof this link.

Ultrasound in legal medicine-a missed opportunity or simply too late? A narrative review of ultrasonic applications in forensic contexts.

OBJECTIVES: Conventional autopsies remain the gold standard of postmortem healthcare quality assurance and help gathering extended knowledge on diseases. In answer to constantly declining autopsy rates non- or minimally invasive autopsy methods were introduced. Ultrasound is a well-established tool for imaging commonly used in clinical practice. This narrative review aims to summarize the current literature regarding the feasibility and validity of ultrasound in a forensic context. MATERIAL AND METHODS: A PubMed database search was carried out. Abstracts were scanned for pre-defined ex- and inclusion criteria, followed by a snowball search procedure applied to the primarily included articles. RESULTS: Forty-five publications met our inclusion criteria. The selected articles concern the feasibility of ultrasound in pre- or postmortem settings, forensic age estimation, and minimally invasive approaches. For imaging, ultrasound was deemed a reliable tool for the examination of epiphyses und superficial wounds, with limitations regarding internal organs and image quality due to postmortem changes. Ultrasound-guided minimally invasive approaches yielded higher success rates for adequate tissue sampling. Many investigations were carried out in low- and middle-income countries focusing on infectious diseases. CONCLUSION: Ultrasound seems a promising but underutilized imaging tool in legal medicine to date. Promising approaches on its feasibility have been conducted. Especially for minimally invasive methods, ultrasound offered significant improvements on qualified biopsy sampling and thus appropriate diagnostics. Moreover, ultrasonic evaluation of epiphyses for age estimation offered valuable results. Nevertheless, further assessment of ultrasonic feasibility in forensic contexts is needed.

Subthalamic nucleus volumes are highly consistent but decrease age-dependently-a combined magnetic resonance imaging and stereology approach in humans.

The subthalamic nucleus (STN) is a main target structure of deep brain stimulation (DBS) in idiopathic Parkinson's disease. Nevertheless, there is an ongoing discussion regarding human STN volumes and neuron count, which could potentially have an impact on STN-DBS. Moreover, a suspected functional subdivision forms the basis of the tripartite hypothesis, which has not yet been morphologically substantiated. In this study, it was aimed to investigate the human STN by means of combined magnetic resonance imaging (MRI) and stereology. STN volumes were obtained from 14 individuals (ranging from 65 to 96 years, 25 hemispheres) in 3 T MRI and in luxol-stained histology slices. Neuron number and cell densities were investigated stereologically over the entire STN and in pre-defined subregions in anti-human neuronal protein HuC/D-stained slices. STN volumes measured with MRI were smaller than in stereology but appeared to be highly consistent, measuring on average 99 ± 6 mm3 (MRI) and 132 ± 20 mm3 (stereology). The neuron count was 431,088 ± 72,172. Both STN volumes and cell count decreased age-dependently. Neuron density was different for the dorsal, medial and ventral subregion with significantly higher values ventrally than dorsally. Small variations in STN volumes in both MRI and stereology contradict previous findings of large variations in STN size. Age-dependent decreases in STN volumes and neuron numbers might influence the efficacy of STN-DBS in a geriatric population. Though the study is limited in sample size, site-dependent differences for the STN subregions form a morphological basis for the tripartite theory. Hum Brain Mapp 38:909-922, 2017. © 2016 Wiley Periodicals, Inc.