Publications by authors named "Benjamin Ondruschka"

88 Publications

Bone mineral density modeling via random field: Normality, stationarity, sex and age dependence.

Comput Methods Programs Biomed 2021 Aug 19;210:106353. Epub 2021 Aug 19.

Department of Macroscopic and Clinical Anatomy, Medical University of Graz, Auenbruggerpl. 2, Graz 8036, Austria; Department of Orthopedic and Trauma Surgery, University of Leipzig, Leipzig, Germany; Fraunhofer Institute for Machine Tools and Forming Technology IWU, Nöthnitzer Straße 44, 01187, Dresden, Germany.

Background And Objective: Capturing the population variability of bone properties is of paramount importance to biomedical engineering. The aim of the present paper is to describe variability and correlations in bone mineral density with a spatial random field inferred from routine computed tomography data.

Methods: Random fields were simulated by transforming pairwise uncorrelated Gaussian random variables into correlated variables through the spectral decomposition of an age-detrended correlation matrix. The validity of the random field model was demonstrated in the spatiotemporal analysis of bone mineral density. The similarity between the computed tomography samples and those generated via random fields was analyzed with the energy distance metric.

Results: The random field of bone mineral density was found to be approximately Gaussian/slightly left-skewed/strongly right-skewed at various locations. However, average bone density could be simulated well with the proposed Gaussian random field for which the energy distance, i.e., a measure that quantifies discrepancies between two distribution functions, is convergent with respect to the number of correlation eigenpairs.

Conclusions: The proposed random field model allows the enhancement of computational biomechanical models with variability in bone mineral density, which could increase the usability of the model and provides a step forward in in-silico medicine.
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http://dx.doi.org/10.1016/j.cmpb.2021.106353DOI Listing
August 2021

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

Int J Legal Med 2021 Sep 6. Epub 2021 Sep 6.

III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

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.
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http://dx.doi.org/10.1007/s00414-021-02691-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418960PMC
September 2021

Heart Weight Is an Independent Factor Associated With, But Is a Poor Predictor for, Sudden Cardiac Death.

Am J Forensic Med Pathol 2021 Sep 2. Epub 2021 Sep 2.

From the Forensic and Analytical Science Service, NSW Health Pathology, New South Wales, Australia Northern Forensic Pathology Service of New Zealand, Auckland, New Zealand Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Abstract: An enlarged heart can cause electrical instability and impaired contractility, leading to fatal arrhythmia and acute heart failure, and is associated with sudden cardiac death. However, there is limited postmortem evidence on whether heart weight is an independent factor associated with sudden cardiac death. This 18-month retrospective study examined 108 adult heart weights in which all the hearts were weighed after dissection, blood and blood clots removed, rinsed in water, and pat dried. The multivariate logistic regression analysis showed heart weight was an independent factor associated with sudden cardiac death. However, after normalization, the heart weight was a poor predictor of sudden cardiac death with an area under the curve less than 0.7 in the plotted receiver operating characteristic curve.
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http://dx.doi.org/10.1097/PAF.0000000000000711DOI Listing
September 2021

The effects of drying the rinsed dissected heart on postmortem heart weight.

J Forensic Sci 2021 Aug 11. Epub 2021 Aug 11.

Northern Forensic Pathology Service of New Zealand, Auckland, New Zealand.

Blood and blood clots should be removed from the heart chambers before being weighed. The actual method in removing blood and blood clots may vary and can include manual removal with subsequent rinsing the heart in water. It is unclear whether drying the rinsed heart affects the heart weight. The objective of this article was to investigate the effects drying the rinsed dissected heart (residual rinsing water) on postmortem heart weight. The prospective study compared 44 dissected heart weights after being rinsed and after being pat dried. An average 18-20 g of residual rinsing water (4% of heart weight) was present in the dissected heart. The amount of residual rinsing water correlates positively with heart weight. The effects of drying the rinsed dissected heart were considered clinically insignificant. Although being clinically insignificant, this study highlights the lack of standardized approach in weighing the heart and the potential implications in interpreting heart weights.
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http://dx.doi.org/10.1111/1556-4029.14858DOI Listing
August 2021

Screening for Fatal Traumatic Brain Injuries in Cerebrospinal Fluid Using Blood-Validated CK and CK-MB Immunoassays.

Biomolecules 2021 07 20;11(7). Epub 2021 Jul 20.

Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, 22529 Hamburg, Germany.

A single, specific, sensitive biochemical biomarker that can reliably diagnose a traumatic brain injury (TBI) has not yet been found, but combining different biomarkers would be the most promising approach in clinical and postmortem settings. In addition, identifying new biomarkers and developing laboratory tests can be time-consuming and economically challenging. As such, it would be efficient to use established clinical diagnostic assays for postmortem biochemistry. In this study, postmortem cerebrospinal fluid samples from 45 lethal TBI cases and 47 controls were analyzed using commercially available blood-validated assays for creatine kinase (CK) activity and its heart-type isoenzyme (CK-MB). TBI cases with a survival time of up to two hours showed an increase in both CK and CK-MB with moderate (CK-MB: AUC = 0.788, < 0.001) to high (CK: AUC = 0.811, < 0.001) diagnostic accuracy. This reflected the excessive increase of the brain-type CK isoenzyme (CK-BB) following a TBI. The results provide evidence that CK immunoassays can be used as an adjunct quantitative test aid in diagnosing acute TBI-related fatalities.
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http://dx.doi.org/10.3390/biom11071061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301791PMC
July 2021

"Body stuffing" and "Body packing" - Forensic control of human excrements in police custody in Hamburg, Germany.

Leg Med (Tokyo) 2021 Jul 10;53:101940. Epub 2021 Jul 10.

Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Introduction: Different methods are used to confiscate evidence whenever suspected body packers or body stuffers are taken into custody. Among these, controlled defecation and analysis of drug toilets from suspects has proved to be safe given that no invasive or forceful procedures are applied.

Materials And Methods: All records of "drug toilet" evaluations done at the Hamburg Institute of Legal Medicine from January 1st 2018 to April 30th 2021 were descriptively analyzed for the individual's age, sex, country of origin, and whether the drug toilets contained any drug "balls", packages or containers. In case of a positive finding, the total number of balls found were recorded. Special cases are presented in detail for illustrative purposes.

Results: Drug toilets from 72 suspects were examined in the period under review. 98.6% (n = 71) of the suspects were males and relatively young with approximately two-thirds (62.5%, n = 45) aged 34 years or below (range 18-50 years). The majority of suspects originated from African countries (72.2%, n = 52). The typical drug balls or containers were found in 13 (18.1%) of the examined drug toilets.

Conclusion: Negative drug toilets might indeed indicate that the suspect had not ingested any drug packages at the time of arrest or while in custody. However, multiple excretions, voluntary delay of defecation, use of drugs to delay the excretion process or even individual differences in excretion times are possible, and therefore, a negative drug toilet should not always imply with certainty that the individual in question had not ingested any drugs.
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http://dx.doi.org/10.1016/j.legalmed.2021.101940DOI Listing
July 2021

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

Int J Legal Med 2021 Jul 22. Epub 2021 Jul 22.

Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

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.
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http://dx.doi.org/10.1007/s00414-021-02661-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295453PMC
July 2021

How Complex Is the Complex Innervation of the Hip Joint Capsular Complex?

Arthroscopy 2021 07;37(7):2022-2024

Institute of Macroscopic and Clinical Anatomy, University of Graz, Graz, Styria, Austria; Department of Orthopaedic, Trauma and Plastic Surgery, University of Leipzig, Leipzig, Saxony, Germany; Fraunhofer Institute for Machine Tools and Forming Technology, Division of Medical Technology, Dresden, Saxony, Germany.

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http://dx.doi.org/10.1016/j.arthro.2021.05.035DOI Listing
July 2021

Stellate ganglionitis in sudden cardiac death: A case report.

Auton Neurosci 2021 Sep 24;234:102837. Epub 2021 Jun 24.

Northern Forensic Pathology Service of New Zealand, Auckland, New Zealand; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand. Electronic address:

Sudden cardiac death (SCD) is the most common natural cause of death. The hypothesized mechanism of death is an arrhythmia precipitated by increased sympathetic outflow. The left stellate ganglion provides sympathetic innervation to the heart and plays a role in arrhythmogensis. We present a SCD with stellate ganglionitis in which the inflammatory cells were characterized. The case was 37-year-old man who died from ischemic and hypertensive heart disease. The left stellate ganglion showed lymphocytic inflammation with features of humoral immune response. This case report provides evidence that stellate ganglionitis can be seen in SCD and raises the possible association between the two.
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http://dx.doi.org/10.1016/j.autneu.2021.102837DOI Listing
September 2021

Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions.

Immunity 2021 07 9;54(7):1594-1610.e11. Epub 2021 Jun 9.

Faculty of Medicine, Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, University Medical Center Freiburg, Freiburg, Germany; Signalling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany. Electronic address:

COVID-19 can cause severe neurological symptoms, but the underlying pathophysiological mechanisms are unclear. Here, we interrogated the brain stems and olfactory bulbs in postmortem patients who had COVID-19 using imaging mass cytometry to understand the local immune response at a spatially resolved, high-dimensional, single-cell level and compared their immune map to non-COVID respiratory failure, multiple sclerosis, and control patients. We observed substantial immune activation in the central nervous system with pronounced neuropathology (astrocytosis, axonal damage, and blood-brain-barrier leakage) and detected viral antigen in ACE2-receptor-positive cells enriched in the vascular compartment. Microglial nodules and the perivascular compartment represented COVID-19-specific, microanatomic-immune niches with context-specific cellular interactions enriched for activated CD8 T cells. Altered brain T-cell-microglial interactions were linked to clinical measures of systemic inflammation and disturbed hemostasis. This study identifies profound neuroinflammation with activation of innate and adaptive immune cells as correlates of COVID-19 neuropathology, with implications for potential therapeutic strategies.
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http://dx.doi.org/10.1016/j.immuni.2021.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188302PMC
July 2021

Why heel spurs are traction spurs after all.

Sci Rep 2021 Jun 24;11(1):13291. Epub 2021 Jun 24.

Institute of Macroscopic and Clinical Anatomy, Medical University of Graz, Graz, Austria.

It is unclear whether plantar and posterior heel spurs are truly pathological findings and whether they are stimulated by traction or compression forces. Previous histological investigations focused on either one of the two spur locations, thereby potentially overlooking common features that refer to a uniform developmental mechanism. In this study, 19 feet from 16 cadavers were X-ray scanned to preselect calcanei with either plantar or posterior spurs. Subsequently, seven plantar and posterior spurs were histologically assessed. Five spur-free Achilles tendon and three plantar fascia entheses served as controls. Plantar spurs were located either intra- or supra-fascial whereas all Achilles spurs were intra-fascial. Both spur types consistently presented a trabecular architecture without a particular pattern, fibrocartilage at the tendinous entheses and the orientation of the spur tips was in line with the course of the attached soft tissues. Spurs of both entities revealed tapered areas close to their bases with bulky tips. Achilles and plantar heel spurs seem to be non-pathological calcaneal exostoses, which are likely results of traction forces. Both spur types revealed commonalities such as their trabecular architecture or the tip direction in relation to the attached soft tissues. Morphologically, heel spurs seem poorly adapted to compressive loads.
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http://dx.doi.org/10.1038/s41598-021-92664-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225903PMC
June 2021

[Infectiousness of SARS-CoV-2 positive corpses during external post mortem examination].

MMW Fortschr Med 2021 06;163(12):56-58

Institut für Rechtsmedizin, Universitätsklinikum Hamburg Eppendorf (UKE), Hamburg, Germany.

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http://dx.doi.org/10.1007/s15006-021-0084-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214379PMC
June 2021

GFAP positivity in neurons following traumatic brain injuries.

Int J Legal Med 2021 Jun 11. Epub 2021 Jun 11.

Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Glial fibrillary acidic protein (GFAP) is a well-established astrocytic biomarker for the diagnosis, monitoring and outcome prediction of traumatic brain injury (TBI). Few studies stated an accumulation of neuronal GFAP that was observed in various brain pathologies, including traumatic brain injuries. As the neuronal immunopositivity for GFAP in Alzheimer patients was shown to cross-react with non-GFAP epitopes, the neuronal immunopositivity for GFAP in TBI patients should be challenged. In this study, cerebral and cerebellar tissues of 52 TBI fatalities and 17 controls were screened for immunopositivity for GFAP in neurons by means of immunohistochemistry and immunofluorescence. The results revealed that neuronal immunopositivity for GFAP is most likely a staining artefact as negative controls also revealed neuronal GFAP staining. However, the phenomenon was twice as frequent for TBI fatalities compared to non-TBI control cases (12 vs. 6%). Neuronal GFAP staining was observed in the pericontusional zone and the ipsilateral hippocampus, but was absent in the contralateral cortex of TBI cases. Immunopositivity for GFAP was significantly correlated with the survival time (r = 0.306, P = 0.015), but no correlations were found with age at death, sex nor the post-mortem interval in TBI fatalities. This study provides evidence that the TBI-associated neuronal immunopositivity for GFAP is indeed a staining artefact. However, an absence post-traumatic neuronal GFAP cannot readily be assumed. Regardless of the particular mechanism, this study revealed that the artefact/potential neuronal immunopositivity for GFAP is a global, rather than a regional brain phenomenon and might be useful for minimum TBI survival time determinations, if certain exclusion criteria are strictly respected.
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http://dx.doi.org/10.1007/s00414-021-02568-1DOI Listing
June 2021

Dying of VOC-202012/01 - multimodal investigations in a death case of the SARS-CoV-2 variant.

Int J Legal Med 2021 Jun 5. Epub 2021 Jun 5.

Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Butenfeld 34, 22529, Hamburg, Germany.

The current pandemic with Severe acute respiratory syndrome-coronavirus-2 has been taking on new dynamics since the emergence of new variants last fall, some of them spreading more rapidly. Many countries currently find themselves in a race to ramp up vaccination strategies that have been initiated and a possible third wave of the pandemic from new variants, such as the Variant of Concern-202012/01 from the B.1.1.7 lineage. Until today, many investigations in death cases of Coronavirus-disease-19 have been conducted, revealing pulmonary damage to be the predominant feature of the disease. Thereby, different degrees of macroscopic and microscopic lung damage have been reported, most of them resembling an Acute Respiratory Distress Syndrome. Far more, systemic complications of the disease such as pulmonary embolisms have been described. However, neither morphologic nor virologic findings of patients dying of the new variants have yet been reported. Here, we report on a comprehensive analysis of radiologic, morphologic, and virologic findings in a fatal case of this variant.
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http://dx.doi.org/10.1007/s00414-021-02618-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178649PMC
June 2021

The handling of SARS-CoV-2 associated deaths - infectivity of the body.

Forensic Sci Med Pathol 2021 09 2;17(3):411-418. Epub 2021 Jun 2.

Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Butenfeld 34, 22529, Hamburg, Germany.

The body of a deceased with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is considered infectious. In this study, we present the results of infectivity testing of the body and testing of mortuary staff for SARS-CoV-2. We performed real-time quantitative polymerase chain reaction (RT-qPCR) for SARS-CoV-2 on 33 decedents with ante mortem confirmed SARS-CoV-2 infection. Swabs of the body surface from five different body regions and from the body bag or coffin were examined. A subset of the swabs was brought into cell culture. In addition, screening of 25 Institute of Legal Medicine (ILM) personnel for ongoing or past SARS-CoV-2 infection was performed at two different time points during the pandemic. Swabs from all locations of the body surface and the body environment were negative in cases of negative post mortem nasopharyngeal testing (n=9). When the post mortem nasopharyngeal swab tested positive (n=24), between 0 and 5 of the body surface swabs were also positive, primarily the perioral region. In six of the cases, the body bag also yielded a positive result. The longest postmortem interval with positive SARS-CoV-2 RT-qPCR at the body surface was nine days. In no case viable SARS-CoV-2 was found on the skin of the bodies or the body bags. One employee (autopsy technician) had possible occupational infection with SARS-CoV-2; all other employees were tested negative for SARS-CoV-2 RNA or antibody twice. Our data indicate that with adequate management of general safety precautions, transmission of SARS-CoV-2 through autopsies and handling of bodies is unlikely.
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http://dx.doi.org/10.1007/s12024-021-00379-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170863PMC
September 2021

The dynamic impact behavior of the human neurocranium.

Sci Rep 2021 May 31;11(1):11331. Epub 2021 May 31.

Institute of Macroscopic and Clinical Anatomy, Medical University of Graz, Graz, Austria.

Realistic biomechanical models of the human head should accurately reflect the mechanical properties of all neurocranial bones. Previous studies predominantly focused on static testing setups, males, restricted age ranges and scarcely investigated the temporal area. This given study determined the biomechanical properties of 64 human neurocranial samples (age range of 3 weeks to 94 years) using testing velocities of 2.5, 3.0 and 3.5 m/s in a three-point bending setup. Maximum forces were higher with increasing testing velocities (p ≤ 0.031) but bending strengths only revealed insignificant increases (p ≥ 0.052). The maximum force positively correlated with the sample thickness (p ≤ 0.012 at 2.0 m/s and 3.0 m/s) and bending strength negatively correlated with both age (p ≤ 0.041) and sample thickness (p ≤ 0.036). All parameters were independent of sex (p ≥ 0.120) apart from a higher bending strength of females (p = 0.040) for the 3.5 -m/s group. All parameters were independent of the post mortem interval (p ≥ 0.061). This study provides novel insights into the dynamic mechanical properties of distinct neurocranial bones over an age range spanning almost one century. It is concluded that the former are age-, site- and thickness-dependent, whereas sex dependence needs further investigation.
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http://dx.doi.org/10.1038/s41598-021-90322-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167104PMC
May 2021

[SARS-CoV‑2 incidental findings among Hamburg deaths: an epidemiological monitoring during the dynamic infection event in spring 2020].

Rechtsmedizin (Berl) 2021 Apr 20:1-7. Epub 2021 Apr 20.

Institut für Rechtsmedizin, Universitätsklinikum Hamburg-Eppendorf, Butenfeld 34, 22529 Hamburg, Deutschland.

Background: In the context of the COVID-19-pandemic, mortality and incidence are key determinants to assess the transmission dynamics and the resulting potential threat. Systematic microbiological monitoring of deaths provides a fundamental basis to particularly assess underrecording of community-acquired mortality. It should be further elucidated whether a death cohort of previously unreported cases may be structurally different from the cohort of officially registered cases.

Methods: A systematic reverse transcription (RT) qPCR testing for SARS-CoV‑2 infections from nasopharyngeal swab samples was carried out. A representative sample of corpses from crematoria and the Institute of Legal Medicine of the Federal State of Hamburg were included. A comparative analysis of primarily reported and unreported fatalities in an 8‑week period after occurrence of the first pandemic-related deaths in Hamburg was performed.

Results: A total of 1231 deaths were included, all of which were previously unsuspicious for SARS-CoV‑2 infection. Thereof 29 cases of previously unknown infections were recorded. In the first phase of the pandemic, incidental findings predominantly occurred among younger people from domestic environments with unclear or unnatural manner of death at the Institute of Legal Medicine. Over time, incidental findings investigated at the crematoria increased, mostly related to nursing home residents. The overall cohort showed no significant sociodemographic differences to a comparative collective of known SARS-CoV‑2-associated deaths. Primarily unreported cases showed a significantly lower proportion of COVID-19 as the underlying cause of death.

Conclusion: A systematic PCR-based monitoring of deaths allows a more targeted detection and classification of SARS-CoV‑2 positive cases. A preventive contribution can be made by disclosing unreported pandemic-related cases of death.
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http://dx.doi.org/10.1007/s00194-021-00481-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056197PMC
April 2021

Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury.

Int J Legal Med 2021 Jul 24;135(4):1525-1535. Epub 2021 Apr 24.

Institute of Forensic Medicine, University of Wuerzburg, Versbacher Str. 3, 97078, Wuerzburg, Germany.

The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.
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http://dx.doi.org/10.1007/s00414-021-02606-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205912PMC
July 2021

Deaths associated with newly launched SARS-CoV-2 vaccination (Comirnaty®).

Leg Med (Tokyo) 2021 Jul 17;51:101895. Epub 2021 Apr 17.

Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Butenfeld 34, 22529 Hamburg, Germany.

Since 27th December 2020, a mRNA vaccine from BioNTech / Pfizer (Comirnaty®) has been used across Germany. As of 12th March 2021, 286 fatalities of vaccinated German individuals were registered at the Paul-Ehrlich-Institute with time intervals after vaccination between one hour to 40 days. From our catchment area in northern Germany, we have so far become aware of 22 deaths in connection with vaccination in a 5 week period (range: 0-28 days after vaccination). Three death cases after vaccination with Comirnaty®, which were autopsied at the Institute of Legal Medicine Hamburg, are presented in more detail. All three deceased had severe cardiovascular diseases, among other comorbidities, and died in the context of these pre-existing conditions, while one case developed a COVID-19 pneumonia as cause of death. Taking into account the results of the postmortem examination a causal relation between the vaccination and the death was not established in any case. If there are indications of an allergic reaction, histological and postmortem laboratory examinations should be performed subsequent to the autopsy (tryptase, total IgE, CRP, interleukin-6, complement activity C3/C5).
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http://dx.doi.org/10.1016/j.legalmed.2021.101895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052499PMC
July 2021

Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators.

Am J Pathol 2021 07 21;191(7):1193-1208. Epub 2021 Apr 21.

Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts, and the Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts. Electronic address:

Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-β1 and tumor necrosis factor-α, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.
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http://dx.doi.org/10.1016/j.ajpath.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059259PMC
July 2021

Classifying Microscopic Acute and Old Myocardial Infarction Using Convolutional Neural Networks.

Am J Forensic Med Pathol 2021 Sep;42(3):230-234

Department of Medicine, Section of Forensic Medicine, University of Udine, Udine, Italy.

Abstract: Convolutional neural network (CNN) has advanced in recent years and translated from research into medical practice, most notably in clinical radiology and histopathology. Research on CNNs in forensic/postmortem pathology is almost exclusive to postmortem computed tomography despite the wealth of research into CNNs in surgical/anatomical histopathology. This study was carried out to investigate whether CNNs are able to identify and age myocardial infarction (a common example of forensic/postmortem histopathology) from histology slides. As a proof of concept, this study compared 4 CNNs commonly used in surgical/anatomical histopathology to identify normal myocardium from myocardial infarction. A total of 150 images of the myocardium (50 images each for normal myocardium, acute myocardial infarction, and old myocardial infarction) were used to train and test each CNN. One of the CNNs used (InceptionResNet v2) was able to show a greater than 95% accuracy in classifying normal myocardium from acute and old myocardial infarction. The result of this study is promising and demonstrates that CNN technology has potential applications as a screening and computer-assisted diagnostics tool in forensic/postmortem histopathology.
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http://dx.doi.org/10.1097/PAF.0000000000000672DOI Listing
September 2021

Determinants of health care use among homeless individuals: evidence from the Hamburg survey of homeless individuals.

BMC Health Serv Res 2021 Apr 7;21(1):317. Epub 2021 Apr 7.

Department of Health Economics and Health Services Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: To identify the determinants of health care use among homeless individuals.

Methods: Data were taken from the Hamburg survey of homeless individuals (n = 100 individuals in the here used model, mean age 44.8 years, SD 12.5) focusing on homeless individuals in Hamburg, Germany. The number of physician visits in the past 3 months and hospitalization in the preceding 12 months were used as outcome measures. Drawing on the Andersen model of health care use as a conceptual framework, predisposing characteristics, enabling resources and need factors as well as psychosocial variables were included as correlates.

Results: Negative binomial regressions showed that increased physician visits were associated with being female (IRR: 4.02 [95% CI: 1.60-10.11]), absence of chronic alcohol consume (IRR: 0.26 [95% CI: 0.12-0.57]) and lower health-related quality of life (IRR: 0.97 [95% CI: 0.96-0.98]). Furthermore, logistic regressions showed that the likelihood of hospitalization was positively associated with lower age (OR: 0.93 [95% CI: 0.89-0.98]), having health insurance (OR: 8.11 [2.11-30.80]) and lower health-related quality of life (OR: 0.97 [95% CI: 0.94-0.99]).

Conclusions: Our study showed that predisposing characteristics (both age and sex), enabling resources (i.e., health insurance) and need factors in terms of health-related quality of life are main drivers of health care use among homeless individuals. This knowledge may assist in managing health care use.
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http://dx.doi.org/10.1186/s12913-021-06314-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026095PMC
April 2021

Loneliness among Homeless Individuals during the First Wave of the COVID-19 Pandemic.

Int J Environ Res Public Health 2021 03 16;18(6). Epub 2021 Mar 16.

Department of Health Economics and Health Services Research, University Medical Center Hamburg-Eppendorf, 22529 Hamburg, Germany.

The feeling of loneliness is a major public health concern associated with multiple somatic and psychiatric illnesses. Studies have shown increasing incidence of loneliness in the general population during the first wave of the COVID-19 pandemic. Homeless individuals are a particularly vulnerable group; however, little is known about loneliness among homeless individuals. We therefore aimed to examine the prevalence of loneliness among homeless individuals during the pandemic. Furthermore, we estimated the association between loneliness and sociodemographic and lifestyle factors, as well as the self-perceived risk of contracting COVID-19. Data from the Hamburg survey of homeless individuals were used, including 151 homeless individuals that were recruited in spring of 2020. Loneliness was measured by the 3- item version of the UCLA-3 Loneliness Scale. To summarize, 48.5% of the participants experienced loneliness. Multiple linear regressions showed increased loneliness to be associated with male gender (β = 1.07, = 0.01), being single (β = 1.33, = 0.00), originating from Germany (β = 1.48, = 0.00), high frequency of sharing a sleeping space with more than three people (β = 0.42, = 0.02) and a higher self-perceived risk of contracting COVID-19 (β = 0.41, = 0.02). On the contrary, there was no association of loneliness with age, educational level, chronic alcohol consumption or frequently sharing a sleeping space. In conclusion, the magnitude of loneliness among homeless individuals during the pandemic was highlighted. Description of factors determining loneliness may help to identify homeless individuals at risk.
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http://dx.doi.org/10.3390/ijerph18063035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999173PMC
March 2021

A systematic review and meta-analysis of the hip capsule innervation and its clinical implications.

Sci Rep 2021 Mar 5;11(1):5299. Epub 2021 Mar 5.

Institute of Macroscopic and Clinical Anatomy, University of Graz, Graz, Styria, Austria.

Detailed understanding of the innervation of the hip capsule (HC) helps inform surgeons' and anaesthetists' clinical practice. Post-interventional pain following radiofrequency nerve ablation (RFA) and dislocation following total hip arthroplasty (THA) remain poorly understood, highlighting the need for more knowledge on the topic. This systematic review and meta-analysis focuses on gross anatomical studies investigating HC innervation. The main outcomes were defined as the prevalence, course, density and distribution of the nerves innervating the HC and changes according to demographic variables. HC innervation is highly variable; its primary nerve supply seems to be from the nerve to quadratus femoris and obturator nerve. Many articular branches originated from muscular branches of the lumbosacral plexus. It remains unclear whether demographic or anthropometric variables may help predict potential differences in HC innervation. Consequently, primary targets for RFA should be the anterior inferomedial aspect of the HC. For THA performed on non-risk patients, the posterior approach with capsular repair appears to be most appropriate with the lowest risk of articular nerve damage. Care should also be taken to avoid damaging vessels and muscles of the hip joint. Further investigation is required to form a coherent map of HC innervation, utilizing combined gross and histological investigation.
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http://dx.doi.org/10.1038/s41598-021-84345-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935927PMC
March 2021

Levels of haemolysis have no effect on femoral vein post-mortem tryptase levels.

Med Sci Law 2021 Mar 2:25802421998851. Epub 2021 Mar 2.

Department of Forensic Pathology, LabPLUS, Auckland City Hospital, New Zealand.

Haemolysis is reported to be an artefact that may alter post-mortem tryptase levels. However, previous studies did not sample peripheral blood using newly standardised methods. Recent studies have shown that some previously recognised peri- and post-mortem confounders can be muted by careful sample collection with first clamping and then sampling the femoral vein. This prospective study investigated the relationship between the degree of haemolysis of the blood samples and femoral vein post-mortem tryptase levels when sampled using this recommended method. Seventy consecutive post-mortem tryptase levels in non-anaphylactic deaths were compared to the degree of haemolysis of these samples, and results showed no significant correlation between them. The mean post-mortem tryptase level was 9.5 μg/L. This study demonstrated that the effects of haemolysis on femoral vein post-mortem tryptase was negligible when the blood was sampled using the recommended sampling method. Future studies on post-mortem tryptase as well as other typically used blood markers in forensics are recommended to adopt this method of blood sampling in routine practice.
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http://dx.doi.org/10.1177/0025802421998851DOI Listing
March 2021

Topographical mapping of the mechanical characteristics of the human neurocranium considering the role of individual layers.

Sci Rep 2021 Feb 12;11(1):3721. Epub 2021 Feb 12.

Institute of Macroscopic and Clinical Anatomy, University of Graz, Graz, Austria.

The site-dependent load-deformation behavior of the human neurocranium and the load dissipation within the three-layered composite is not well understood. This study mechanically investigated 257 human frontal, temporal, parietal and occipital neurocranial bone samples at an age range of 2 to 94 years, using three-point bending tests. Samples were tested as full-thickness three-layered composites, as well as separated with both diploë attached and removed. Right temporal samples were the thinnest samples of all tested regions (median < 5 mm; p < 0.001) and withstood lowest failure loads (median < 762 N; p < 0.001). Outer tables were thicker and showed higher failure loads (median 2.4 mm; median 264 N) than inner tables (median 1.7 mm, p < 0.001; median 132 N, p = 0.003). The presence of diploë attached to outer and inner tables led to a significant reduction in bending strength (with diploë: median < 60 MPa; without diploë: median > 90 MPa, p < 0.001). Composites (r = 0.243, p = 0.011) and inner tables with attached diploë (r = 0.214, p = 0.032) revealed positive correlations between sample thickness and age. The three-layered composite is four times more load-resistant compared to the outer table and eight times more compared to the inner table.
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http://dx.doi.org/10.1038/s41598-020-80548-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881109PMC
February 2021

A comparison on the detection accuracy of ante mortem computed tomography vs. autopsy for the diagnosis of pelvic ring injury in legal medicine.

J Forensic Sci 2021 May 29;66(3):919-925. Epub 2021 Jan 29.

Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

A detailed knowledge on the exact morphology of pelvic injuries provided crucial information in understanding the mechanisms of injury and has influence on the natural course and subsequent mortality. However, forensic medical literature investigating pelvic fractures in detail is scarce to date. This case series aims to compare the accuracy in detecting pelvic injuries using autopsy and ante mortem computed tomography (CT). Nineteen deceased patients with CT scans of pelvic fractures were included retrospectively. Pelvic injuries were independently assessed by a board-certified radiologist (R) and a board-certified trauma surgeon (T), both using the ante mortem CT scans, and by a board-certified forensic pathologist using autopsy (A) results without knowledge of the CT scan findings. No patient had died causatively from a pelvic fracture. Most injuries of the pelvis were present in the pubic rami (16/18) and sacral bone (13/18), followed by the sacroiliac joint (9/18) and iliac bone fractures (8/18). Ilium fractures (A:100%;R:67%;T:67%) and injuries of the sacroiliac joint (A:83%;R:50%;T:42%) were best detected via autopsy. The diagnosis of sacral fractures (A:19%;R:94%;T:88%) and fractures of the pubic rami (A:67%;R:96%;T:96%) were most often missed in autopsy. The results show deficits in the assessment of the pelvic injury for both CT and autopsy. Autopsy was superior in detecting injuries of the sacroiliac joint, but inferior in detecting sacral and pubic bone fractures. For an encompassing evaluation of ligamento-skeletal pelvic injuries, the complementary use of both CT and autopsy is recommended.
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http://dx.doi.org/10.1111/1556-4029.14677DOI Listing
May 2021

Biomechanical characterization of human temporal muscle fascia in uniaxial tensile tests for graft purposes in duraplasty.

Sci Rep 2021 01 22;11(1):2127. Epub 2021 Jan 22.

Department of Macroscopic and Clinical Anatomy, Medical University of Graz, Graz, Austria.

The human temporal muscle fascia (TMF) is used frequently as a graft material for duraplasty. Encompassing biomechanical analyses of TMF are lacking, impeding a well-grounded biomechanical comparison of the TMF to other graft materials used for duraplasty, including the dura mater itself. In this study, we investigated the biomechanical properties of 74 human TMF samples in comparison to an age-matched group of dura mater samples. The TMF showed an elastic modulus of 36 ± 19 MPa, an ultimate tensile strength of 3.6 ± 1.7 MPa, a maximum force of 16 ± 8 N, a maximum strain of 13 ± 4% and a strain at failure of 17 ± 6%. Post-mortem interval correlated weakly with elastic modulus (r = 0.255, p = 0.048) and the strain at failure (r =  - 0.306, p = 0.022) for TMF. The age of the donors did not reveal significant correlations to the TMF mechanical parameters. Compared to the dura mater, the here investigated TMF showed a significantly lower elastic modulus and ultimate tensile strength, but a larger strain at failure. The human TMF with a post-mortem interval of up to 146 h may be considered a mechanically suitable graft material for duraplasty when stored at a temperature of 4 °C.
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http://dx.doi.org/10.1038/s41598-020-80448-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822884PMC
January 2021

Surface coating and speckling of the human iliotibial tract does not affect its load-deformation properties.

Sci Rep 2020 11 27;10(1):20747. Epub 2020 Nov 27.

Department of Macroscopic and Clinical Anatomy, Medical University of Graz, Graz, Austria.

Stochastic surface patterns form an important requirement to facilitate digital image correlation and to subsequently quantify material properties of various tissues when loaded and deformed without artefacts arising from material slippage. Depending on the samples' natural colour, a surface pattern is created by speckling with colour or dye only, or it requires combined surface coating and speckling before to enhance the contrast, to facilitate high-quality data recording for mechanical evaluation. However, it is unclear to date if the colours deployed for coating and speckling do significantly alter the biomechanical properties of soft tissues. The given study investigated the biomechanical properties of 168 human iliotibial tract samples as a model for collagen-rich soft tissues, separated into four groups: untreated, graphite speckling only, water-based coating plus graphite speckling and solvent-based coating plus graphite speckling following a standardized approach of application and data acquisition. The results reveal that elastic modulus, ultimate tensile strength and strain at maximum force of all groups were similar and statistically non-different (p ≥ 0.69). Qualitatively, the speckle patterns revealed increasing contrast differences in the following order: untreated, graphite speckling only, water-based coating plus graphite speckling and solvent-based coating plus graphite speckling. Conclusively, both coating by water- and solvent-based paints, as well as exclusive graphite speckling, did not significantly influence the load-deformation parameters of the here used human iliotibial tract as a model for collagen-rich soft tissues. In consequence, water- and solvent-based coating paints seem equally suitable to coat collagen-rich soft tissues for digital image correlation, resulting in suitable speckle patterns and unbiased data acquisition.
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http://dx.doi.org/10.1038/s41598-020-77299-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695729PMC
November 2020

Metabolomics in postmortem cerebrospinal fluid diagnostics: a state-of-the-art method to interpret central nervous system-related pathological processes.

Int J Legal Med 2021 Jan 12;135(1):183-191. Epub 2020 Nov 12.

Institute of Forensic Medicine, University of Wuerzburg, Versbacher Str. 3, 97078, Wuerzburg, Germany.

In the last few years, quantitative analysis of metabolites in body fluids using LC/MS has become an established method in laboratory medicine and toxicology. By preparing metabolite profiles in biological specimens, we are able to understand pathophysiological mechanisms at the biochemical and thus the functional level. An innovative investigative method, which has not yet been used widely in the forensic context, is to use the clinical application of metabolomics. In a metabolomic analysis of 41 samples of postmortem cerebrospinal fluid (CSF) samples divided into cohorts of four different causes of death, namely, cardiovascular fatalities, isoIated torso trauma, traumatic brain injury, and multi-organ failure, we were able to identify relevant differences in the metabolite profile between these individual groups. According to this preliminary assessment, we assume that information on biochemical processes is not gained by differences in the concentration of individual metabolites in CSF, but by a combination of differently distributed metabolites forming the perspective of a new generation of biomarkers for diagnosing (fatal) TBI and associated neuropathological changes in the CNS using CSF samples.
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http://dx.doi.org/10.1007/s00414-020-02462-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782422PMC
January 2021
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