Post-mortem genetic testing in sudden cardiac death and genetic screening of relatives at risk: lessons learned from a Czech pilot multidisciplinary study.

Sudden cardiac death (SCD) might have an inherited cardiac condition background. Genetic testing supports post-mortem diagnosis and screening of relatives at risk. Our aim is to determine the feasibility of a Czech national collaboration group and to establish the clinical importance of molecular autopsy and family screening. From 2016 to 2021, we have evaluated 100 unrelated SCD cases (71.0% males, age: 33.3 (12.8) years). Genetic testing was performed by next-generation sequencing utilizing a panel of 100 genes related to inherited cardiac/aortic conditions and/or whole exome sequencing. According to autopsy, cases were divided into cardiomyopathies, sudden arrhythmic death syndrome, sudden unexplained death syndrome, and sudden aortic death. We identified pathogenic/likely pathogenic variants following ACMG/AMP recommendations in 22/100 (22.0%) of cases. Since poor DNA quality, we have performed indirect DNA testing in affected relatives or in healthy parents reaching a diagnostic genetic yield of 11/24 (45.8%) and 1/10 (10.0%), respectively. Cardiological and genetic screening disclose 83/301 (27.6%) relatives at risk of SCD. Genetic testing in affected relatives as starting material leads to a high diagnostic yield offering a valuable alternative when suitable material is not available. This is the first multidisciplinary/multicenter molecular autopsy study in the Czech Republic which supports the establishment of this type of diagnostic tests. A central coordinator and proper communication among centers are crucial for the success of a collaboration at a national level.

Correlation between age, location, orientation, loading velocity and delamination strength in the human aorta.

Aortic dissection is a biomechanical phenomenon associated with a failure of internal cohesion, which manifests itself through the delamination of the aortic wall. The goal of this study is to deepen our knowledge of the delamination strength of the aorta. To achieve this, 661 peeling experiments were carried out with strips of the human aorta collected from 46 cadavers. The samples were ordered into groups with respect to (1) anatomical location, (2) orientation of the sample, and (3) extension rate used within the experiment. The obtained results are in accordance with the hypothesis that delamination resistance is not sensitive to the extension rates 0.1, 1, 10, and 50 mms-1. We arrived at this conclusion for all positions along the aorta investigated in our study. These were the thoracic ascending (AAs), thoracic descending (ADs), and the abdominal aorta (AAb), simultaneously considering both the longitudinal (L) as well as the circumferential (C) orientations of the samples. On the other hand, our results showed that the delamination strength differs significantly with respect to the anatomical position and orientation of the sample. The medians of the delamination strength were as follows, 4.1 in AAs-L, 3.2 in AAs-C, 3.1 in ADs-L, 2.4 in ADs-C, AAb-L in 3.6, and 2.7 in AAb-C case (all values are in 0.01·Nmm-1). This suggests that resistance to crack propagation should be an anisotropic property and that the aorta is inhomogeneous along its length from the point of view of delamination resistance. Finally, correlation analysis proved that the delamination strength of the human aorta significantly decreases with age.

A Morphologic Analysis of the Pubic Symphysis Using CT and MRI.

INTRODUCTION: The goal of this study was to investigate prevalence and morphometric parameters of pubic ligaments and the interpubic disk and its cavity using imaging methods for use in clinical medicine. METHODS: Pubic symphysis morphology was investigated in 652 patients (348 women and 304 men), from which 449 CT scans and 203 MR scans were available. The average age of men was 48 years and women 39 years. Investigated parameters included dimensions of the interpubic disk, visibility and width of the reinforcing ligaments, and visibility, dimensions, and location of the symphysial cavity. The results were compared with MR scans of 20 healthy volunteers and 21 dissected anatomic specimens. RESULTS: The craniocaudal, ventrodorsal, and mediolateral diameters of the pubic disk were 36 to 37.7, 14.8 to 15.2, and 2.2 to 4.2 mm in women and 42 to 42.3, 18.6 to 19, and 2.4 to 4.5 mm in men, respectively. Higher age correlated with shorter mediolateral diameter and larger craniocaudal and ventrodorsal diameters. The superior pubic ligament was visible in 93.1% of men (1.44 mm thick) and in 100% of women (1.7 mm); the inferior pubic ligament in 89.7% of men (1.74 mm) and 88% of women (1.95 mm), the anterior pubic ligament in 96.6% of men (1.5 mm) and 82% of women (1.34 mm); and the posterior pubic ligament in 65.5% of men (1.18 mm) and 63.7% of women (0.83 mm). A symphysial cavity was found in 24% of men and 22.9% of women, with craniocaudal, ventrodorsal, and mediolateral dimensions of 13, 10.7, and 3.2 mm in men and 9.5, 10.7, and 3 mm in women, respectively. CONCLUSION: The presented morphologic parameters provide an anatomic reference for diagnostics of pathologic conditions of the pubic symphysis. The following anatomic structures should be added to the official anatomic terminology: symphysial cavity (cavitas symphysialis), retropubic eminence (eminentia retropubica), anterior pubic ligament (ligamentum pubicum anterius), and posterior pubic ligament (ligamentum pubicum posterius). LEVEL OF EVIDENCE: II-III.

CPR-related injuries after non-traumatic out-of-hospital cardiac arrest: Survivors versus non-survivors.

AIM: There have been no direct comparisons of cardiopulmonary resuscitation (CPR)-related injuries between those who die during CPR and those who survive to intensive care unit (ICU) admission. This study aimed to compare the incidence, severity, and impact on survival rate of these injuries and potential influencing factors. METHOD: This retrospective multicenter study analyzed autopsy reports of patients who experienced out-of-hospital cardiac arrest (OHCA) and were not admitted to hospital. CPR-related injuries were compared to OHCA patients with clinical suspicion of CPR-related injury confirmed on imaging when admitted to the ICU. RESULTS: A total of 859 out-of-hospital cardiac arrests (OHCA) were divided into 2 groups: those who died during CPR and underwent autopsy (DEAD [n = 628]); and those who experienced return of spontaneous circulation and admitted to the ICU (ICU [n = 231]). Multivariable analyses revealed that independent factors of 30-day mortality included no bystander arrest, cardiac etiology, no shockable rhythm, and CPR-related injury. Trauma was independently associated with older age, bystander CPR, cardiac etiology, duration of CPR, and no defibrillation. CPR-related injury occurred in 30 (13%) patients in the ICU group and 547 (87%) in the DEAD group (p < 0.0001). Comparison of injuries revealed that those in the DEAD group experienced more thoracic injuries, rib(s) and sternal fractures, and fewer liver injuries compared to those in the ICU group, without differences in injury severity. CONCLUSION: CPR-related injuries were observed more frequently in those who died compared with those who survived to ICU admission. Injury was an independent factor of 30-day mortality.

A plea for extension of the anatomical nomenclature: Vessels.

This article is the fourth and last part of a series aimed at extending and correcting the anatomical nomenclature. Because of the rapid development of internet and the use of electronic formats in communication in anatomy, embryology, histology, medical education, and clinical medicine, an appropriate, precise, and concise anatomical nomenclature is required. Such tool enables to avoid any potential confusion and possible scientific/medical mistakes. The up-to-date official anatomical terminology, Terminologia Anatomica, is available longer than 20 years and needs to be refined and extended. The authors have collected and listed 210 terms and completed them with definitions and/or explanations. We aimed to start a discussion about their potential incorporation into the new revised version of the Terminologia Anatomica. This article is primarily focused on the vessels of the human body (arteries, veins, and lymphatic system).

The role of vascularization on changes in ligamentum flavum mechanical properties and development of hypertrophy in patients with lumbar spinal stenosis.

BACKGROUND CONTEXT: Ligamentum flavum (LF) induced lumbar spinal stenosis (LSS) is conditioned not only by its "gathering" but especially by hypertrophy. Previous studies have examined the pathophysiology and biochemical changes that cause the hypertrophy. Some studies have described a link between chronic LF inflammation and neovascularization but others have reported highly hypovascular LF tissue in LSS patients. Currently, there is no practical application for our knowledge of the pathophysiology of the LF hypertrophy. Considerations for future treatment include influencing this hypertrophy at the level of tissue mediators, which may slow the development of LSS. To our knowledge, there is no study of micromechanical properties of native LF to date. PURPOSE: (1) To clarify the changes in vascularization, chondroid metaplasia, and the presence of inflammatory cell infiltration in LF associated with LSS. (2) To quantify changes in the micromechanical properties associated with LF degenerative processes. STUDY DESIGN/SETTING: Vascular density analysis of degenerated and healthy human LF combined with measurement of micromechanical properties. METHODS: The study involved 35 patients who underwent surgery between November 1, 2015 and October 1, 2016. The LSS group consisted of 20 patients and the control group consisted of 15 patients. LF samples were obtained during the operation and were used for histopathological and nanoindentation examinations. Sample vascularization was examined as microvascular density (Lv), which was morphometrically evaluated using semiautomatic detection in conjunction with NIS-Elements AR image analysis software. Samples were also histologically examined for the presence of chondroid metaplasia and inflammation. Mechanical properties of native LF samples were analyzed using the Hysitron TI 950 TriboIndenter nanomechanical testing system. RESULTS: Vascular density was significantly lower in the LSS group. However, after excluding the effect of age, the difference was not significant. There was high association between Lv and age. With each increasing year of age, Lv decreased by 11.5 mm2. Vascular density decreased up to the age of 50. Over the age of 50, changes were no longer significant and Lv appeared to stabilize. No correlation was observed between Lv and the presence of inflammation or metaplasia; however, LSS patients had a significantly increased incidence of chondroid metaplasia and inflammatory signs. The mechanical properties of control group samples showed significantly higher stiffness than those samples obtained from the LSS group. CONCLUSION: This study showed that Lv changes were not dependent on LSS but were age-dependent. Vascular density was found to decrease up to the age of 50. A significantly higher incidence of chondroid metaplasia and inflammation was observed in LSS patients. The mechanical property values measured by nanoindentation showed high microstructural heterogeneity of the tested ligaments. Our results showed that healthy ligaments were significantly stiffer than LSS ligaments. CLINICAL SIGNIFICANCE: Prevention of the loss of LF vascularization during aging may influence stiffness of LF which in turn may slow down the LF degenerative processes and delay onset of LSS.

Terminologia Histologica 10 years on: some disputable terms in need of discussion and recent developments.

At first sight, the issue of morphological terminology may seem to be a "closed and unchanging chapter", as many of the structures within the human body have been known for decades or even centuries. However, the exact opposite is true. The initial knowledge of the microscopic structure of the human body has been continuously broadening thanks to the development of new specialized staining techniques, discovery of the electron microscope, or later application of histochemical and immunohistochemical methods into routine tissue examination. Contrary to popular belief, histology has a status of constantly developing scientific discipline, with continuous influx of new knowledge, resulting in an unavoidable necessity to revise the histological nomenclature at regular intervals. The team of experts of the Federative International Programme on Anatomical Terminology, a working group of the International Federation of Associations of Anatomists, published in 2008 the First Edition of Terminologia Histologica. Terminologia Histologica (TH) is the best and most extensive of all the histological nomenclatures ever issued. However, here we suggest that several terms of important histological structures are still missing while several other terms are disputable. First, we present some clinically important terms of cells and tissue structures for inclusion in the next TH and, in a second part, we refer to some new terms in the current edition of the TH which are not yet mentioned in current histology textbooks (e.g., fusocellular connective tissue, bundle bone as the third type of bone tissue, spongy layer of vagina or arteria vaginata from the splenic white pulp). With this article we hope to start a wide scientific discussion which will lead to an inambiguous definition and demonstration of typical examples of all terms in the TH, with the result that the new edition of the Terminologia Histologica will become an internationally accepted communication tool for all practitioners and teachers of histology alike.

A plea for an extension of the anatomical nomenclature: Organ systems.

This article is the third part of a series aimed at correcting and extending the anatomical nomenclature. Communication in clinical medicine as well as in medical education is extensively composed of anatomical, histological, and embryological terms. Thus, to avoid any confusion, it is essential to have a concise, exact, perfect and correct anatomical nomenclature. The Terminologia Anatomica (TA) was published 20 years ago and during this period several revisions have been made. Nevertheless, some important anatomical structures are still not included in the nomenclature. Here we list a collection of 156 defined and explained technical terms related to the anatomical structures of the human body focusing on the digestive, respiratory, urinary and genital systems. These terms are set for discussion to be added into the new version of the TA.

The Terminologia Histologica after 10years: Inconsistencies, mistakes, and new proposals.

This article details our experience with the Terminologia Histologica (TH) and its utility in the teaching of histology, cytology, and clinical medicine (e.g., pathology and hematology). Latin histological nomenclature has been used for 43years, and the latest version of the TH has been in use for 15years (although it was only issued publicly within the past 10years). The following findings and ensuing proposals allow us to discuss key points pertaining to the TH and make important suggestions for potential changes to the TH (such as the exclusion and inclusion of various terms). We classify these changes into six groups: 1.) mistakes in the TH, 2.) discrepancies among various Terminologiae, 3.) discrepancies within the TH, 4.) the repetition of terms, 5.) synonyms in the TH, and 6.) missing terms in the TH. Surprisingly, unlike the anatomical nomenclature, the histological nomenclature has been neglected in the literature. This article addresses this problem by reviewing and summarizing the state of this field, pointing out key discrepancies, offering solutions, and highlighting topics for further discussion.

A plea for an extension of the anatomical nomenclature: The locomotor system.

Anatomical nomenclature is the main tool of communication in morphology, anatomy and other medical disciplines as well as in medical education, and thus needs to be exact, flawless, elaborate and correct. The Terminologia Anatomica (TA) is a thorough and extensive list of anatomical terms and their definitions, and the current standard for human anatomical terminology. Although several revisions to the TA have been made in the last 20 years, some important anatomical structures are still not included. This article is aimed at correcting and extending the anatomical nomenclature described in the TA. We gathered and presented a list of anatomical terms, with their definitions and explanations, to provoke a discussion about correcting and extending the TA. Our list comprises of 96 terms related to the locomotor system of the human body, i.e., the bones, joints, muscles and related structures.