Single Nuclei Sequencing Reveals Novel Insights Into the Regulation of Cellular Signatures in Children With Dilated Cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of death in children with heart failure. The outcome of pediatric heart failure treatment is inconsistent, and large cohort studies are lacking. Progress may be achieved through personalized therapy that takes age- and disease-related pathophysiology, pathology, and molecular fingerprints into account. We present single nuclei RNA sequencing from pediatric patients with DCM as the next step in identifying cellular signatures. METHODS: We performed single nuclei RNA sequencing with heart tissues from 6 children with DCM with an age of 0.5, 0.75, 5, 6, 12, and 13 years. Unsupervised clustering of 18 211 nuclei led to the identification of 14 distinct clusters with 6 major cell types. RESULTS: The number of nuclei in fibroblast clusters increased with age in patients with DCM, a finding that was confirmed by histological analysis and was consistent with an age-related increase in cardiac fibrosis quantified by cardiac magnetic resonance imaging. Fibroblasts of patients with DCM >6 years of age showed a profoundly altered gene expression pattern with enrichment of genes encoding fibrillary collagens, modulation of proteoglycans, switch in thrombospondin isoforms, and signatures of fibroblast activation. In addition, a population of cardiomyocytes with a high proregenerative profile was identified in infant patients with DCM but was absent in children >6 years of age. This cluster showed high expression of cell cycle activators such as cyclin D family members, increased glycolytic metabolism and antioxidative genes, and alterations in ß-adrenergic signaling genes. CONCLUSIONS: Novel insights into the cellular transcriptomes of hearts from pediatric patients with DCM provide remarkable age-dependent changes in the expression patterns of fibroblast and cardiomyocyte genes with less fibrotic but enriched proregenerative signatures in infants.

A Fatal Case of Cardiac Contusion After Blunt Chest Injury.

ABSTRACT: In this article, we report the autopsy findings of a 48-year-old man who sustained blunt trauma to the thorax. A medical record review revealed no history of cardiac disease. He presented to the hospital with a computed tomography-verified fracture of the left fourth and fifth ribs, and pulmonary and cardiac contusion. He was released from the hospital in stable condition at his own request 7 days later. Because of sudden deterioration, he was readmitted to the hospital the next day. Electrocardiogram detected cardiac arrhythmia on the 15th day after chest trauma. Electrocardiography detected pericardial effusion and severe mitral insufficiency resulting in left ventricular failure. Death was attributed to diffuse alveolar damage-complicating pneumonia due to cardiac contusion with mitral insufficiency occurring 25 days after hospital admission. Internal examination revealed diffuse fibrinous pericarditis, left atrial tear right above the anterior mitral valve leaflet with intrapericardial granulation tissue, and no sign of myocardial damage. Immunohistochemistry showed significantly more CD68-positive macrophages within tissue taken from the heart, a finding indicative of previous atrial and ventricular myocardial contusion. This case report demonstrates that routine hematoxylin and eosin staining may not always reveal significant myocardial damage.

Arrhythmogenic Ventricular Cardiomyopathy Associated With Fibromuscular Dysplasia of Ostial Right Main Coronary Artery.

In this article, we report the autopsy findings of a 23-year-old woman, who was found unconscious at home by her relatives. During the transportation to the hospital, the woman was handed over to the ambulance personnel, who were the first to provide cardiopulmonary resuscitation. In the hospital, after an hour-lasting asystole, the heart activity was restored. Prolonged cardiac arrest led to hypoxic brain injury, which resulted in a persistent coma. Examinations carried out during hospitalization detected hypokinetic interventricular septum, frequent ventricular extrasystoles and ventricular fibrillation. The patient died within 35 hours of admission to the hospital. Gross findings of the heart included a noticeable increase of the adipose tissue in the right ventricular wall, where histologically focal myocardial atrophy with focal transmural lipomatosis reaching endocardium were detected. Death was attributed to arrhythmogenic ventricular cardiomyopathy. Pathogenic variants in JUP gene and KCNH2 gene confirmed the diagnosis. Other finding of note was fibromuscular dysplasia of ostial right main coronary artery causing a significant luminal narrowing.

[National and international aspects of the medico-legal examination of injured witnesses and defendants in criminal proceedings].

Depending on the type of offence, the medico-legal examination of victims of violence for the purpose of collecting evidence in criminal proceedings requires prompt physical examination of the victim, the exact description and, wherever possible, photographic documentation of the injuries and their forensically correct interpretation. Examination, documentation and assessment have to meet minimum standards. In addition it must be ensured that the examiner or expert has an independent organisational, administrative and financial status. An independent expert must not be an organisational part of the police force, the public prosecution and the court. Legal regulations have to make sure that the expert cannot be influenced "through official channels". His or her financial independence must make attempted bribery at least improbable. The independence of the expert is particularly important, if persons become victims of violence while they are under the custody of the state, especially the police, in prisons and after compulsory commitment to a psychiatric hospital.

Molecular identification of fungi found on decomposed human bodies in forensic autopsy cases.

To investigate which fungi can be found during forensic autopsies, a PubMed literature review was done in regard to fungal growth on decomposed human bodies. Unfortunately, the existing data is limited and not all fungi were identified to the species level. We, therefore, collected skin samples with macroscopically visible fungal growth from 23 autopsy cases in Germany and identified the fungi to the species level by molecular methods. The identified species included Aspergillus fumigatus and Candida albicans, which pose an allergenic risk, especially to persons with underlying lung diseases. Because safety standards are lacking, we recommend the use of respiratory protection during exhumations and forensic autopsies, when fungal growth is noted. With regard to the future, a database was set up which could possibly be used as a forensic tool to determine the time of death.

[Alleged suicide by insulin]. / Vermeintlicher Suizid durch Insulin.

A 26-year-old man, who was on probation, was found dead in his home by his mother. Insulin vials and 2 insulin pens, which the man's stepfather (an insulin-dependent diabetic) had been missing for over a week, were found next to the deceased. The circumstances suggested suicide by an injected insulin overdose. At the time of the autopsy, the corpse showed already marked signs of autolysis. Clinical chemical tests confirmed the injection of insulin, but indicated hyperglycemia at the time of death. Toxicological analyses revealed that the man had consumed amphetamine, cannabinoids, and tramadol in the recent past. Histological examination finally revealed extensive bronchopneumonia as the cause of death. The most plausible explanation for the results of the autopsy and the additional examinations was an injection of insulin as a failed attempt of self-treatment. It is conceivable that the man had discovered by a rapid test that he was a diabetic, but had decided not to go to a doctor to avoid disclosure of parole violation due to continued drug abuse. He may have misinterpreted the symptoms caused by his worsening bronchitis and the developing bronchopneumonia as symptoms of a diabetic metabolic status and may have felt compelled to treat himself with insulin.

[Cause and manner of death in the autopsy material of the Institute of Forensic Medicine, Justus Liebig University Giessen, from 2002-2006]. / Todesursachen und Todesarten im Obduktionsgut des Instituts für Rechtsmedizin der JLU Giessen in den Jahren 2002 bis 2006.

A retrospective analysis of the autopsy material of the Institute of Forensic Medicine, Justus Liebig University Giessen, in the years 2002 to 2006 showed that the Giessen material is similar to that of comparable studies but contains a relatively large share of lethal intoxications and cases with a concrete suspicion of poisoning in which the cause of death was not definitely clarified by further investigations. On the basis of our own results it is demonstrated that additional chemical, toxicological and histological examinations are helpful to determine initially unclear causes of death. In view of the already very low autopsy rates in Germany it is strange that more detailed diagnostic measures are often omitted.

[Intentional poisoning of two wives by their husband?]. / Vorsätzliche Vergiftung zweier Frauen durch ihren Ehemann?

The authors report on the death of two women who were married to the same man one after the other. Exhumation and toxicological investigation of the first wife, who had died 7 years before, did not produce any conclusive evidence of homicide. With regard to the circumstances of death of the second wife the husband made different statements. According to the result of the chemical and toxicological investigations death was caused by acute intoxication with the beta-blocker metoprolol. The man was found guilty of killing on request (which is a criminal offence in Germany) by administering the beta-blocker metoprolol through a transnasal gastric tube.

[Forensic assessment of suspected medical malpractice and outcome of preliminary proceedings against medical practitioners]. / Rechtsmedizinische Begutachtung bei Behandlungsfehlerverdacht und Ausgang arztstrafrechtlicher Ermittlungsverfahren.

In a retrospective study, all autopsies performed at the Institute of Forensic Medicine of the Justus Liebig University of Giessen between 1968 and 2007 for suspected medical malpractice with fatal outcome were evaluated and analysed with regard to the reason for initiating preliminary investigations and the medical specialties involved. In 109 cases, the prosecution files could be inspected as to the outcome of the proceedings. As there are hardly any comparable studies in the German-speaking countries, the data were compared with the results of two older studies. In many cases, medical malpractice could be excluded directly at the end of the post-mortem examination. Most of the charges were dropped according to Section 170 subs. 2 Code of Criminal Procedure.

Serial Killings and Attempted Serial Killings in Hospitals, Nursing Homes, and Nursing Care.

BACKGROUND: Serial killing by doctors or nurses is rare. When it occurs, it is generally only detected after multiple homicides by the same perpetrator have escaped detection in the past. The persons at greatest risk are multimorbid elderly patients whose sudden death for natural reasons would not come as a surprise. However, patients' risk of falling victim to homicide is increased only if such vulnerable patients are exposed to perpetrators with certain personality traits. In this situation, homicides can be committed in which little or no evidence of the crime is left behind. In this review, we address the frequency, nature, and circumstances of serial killings and attempted serial killings in hospitals, nursing homes, and nursing care. METHODS: This review is based on publications retrieved by a selective review of the literature in monographs, medical databases, specialty journals, general-interest media, and the Internet. RESULTS: An evaluation of searchable, published case descriptions of serial killings and attempted serial killings in hospitals, nursing homes, and nursing care, mainly from Europe and the English-speaking countries, enables identification of the type of patients at risk, the modes of homicide, and the personality traits of the perpetrators. Multimorbid, care-dependent and nursing-dependent persons are the main victims. The perpetrators (men and women) generally act alone and have often been working in patient care for many years. The most common method of homicide is by drug injection; violent physical homicide is rarer. In many cases, irregularities in drug stocks, erratic behavior of a staff member, and/or a cluster of sudden deaths are indeed noticed, but are too slowly acted upon. CONCLUSION: Irregularities in drug stocks, inexplicably empty drug packages and used syringes, erratic behavior of a staff member before and after a patient's death, or a cluster of unexpected deaths mainly involving elderly, multimorbid patients (detectable from internal mortality statistics) should always lead to further questioning and investigation.

[Reform of forensic autopsy in the German Code of Criminal Procedure]. / Die dritte Anfrage: Zur Reform der gerichtlichen Leichenöffnung in der Strafprozessordnung.

The Federal Ministry of Justice has presented another proposal to rephrase the wording of Section 87 of the German Code of Criminal Procedure (StPO). The new version of Section 87 StPO is to be rejected as it would lead to a loss of institutional and professional standards. The bill is clearly influenced by a tendency towards privatisation for the benefit of a small group of specialists in forensic medicine mostly organised in limited liability companies and thus at the expense of institutes of legal medicine affiliated to universities or physicians working in the forensic service of regional courts. In the long run, this reform would not only jeopardize medicolegal research and teaching but also medical education and specialist medical training. For future severe negative consequences would have to be expected on the rule of law and legal certainty.

Extremely Preterm Babies-Legal Aspects and Palliative Care at the Border of Viability.

There are various legal considerations and rare decisions of courts in western countries concerning palliative care and the border of viability in cases of extremely preterm babies. Nevertheless, on the one hand, regulations and decisions of courts describe the conditions physicians have to accept. On the other hand, courts are also able to accept that every case can be special, and needs a unique answer. Therefore, the framework can be described as well as the medical disciplines, which should be involved in a particular case.

Organ manifestations of COVID-19: what have we learned so far (not only) from autopsies?

The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.

[From alcohol to liquid ecstasy (GHB)--a survey of old and modern knockout agents. Part 1: historic and classic knockout agents]. / Vom Alkohol zum Liquid Ecstasy (GHB)--ein Uberblick über alte und moderne K.-o.-Mittel. Teil 1: Historische und klassische K.-o.-Mittel.

Alcohol has been the most important knockout drug in history and literature and continues to play an essential role up to now. Blunt force to the head in the form of a knockout punch is another mechanism leading to a transient loss of consciousness. Diethyl ether and chloroform are among the classical knockout substances. Although they have meanwhile been replaced by modern sedatives and hypnotics, their use is still observed in isolated cases.

[Medical and legal aspects of genital mutilation and circumcision. Part II: Male circumcision]. / Medizinische und rechtliche Aspekte der Genitalverstümmelung bzw. Beschneidung. Tell II: Die rituelle Zirkumzision.

In the last few years, male circumcision has become the subject of controversial discussion. On the one hand, medical and hygienic arguments, ideology, freedom of religion, cultural identity and social adequacy are claimed by those supporting male circumcision. On the other hand, the justification of this practice also has to be critically scrutinized just as the question whether the parents have the right to consent to the operation. Today, opinions range from those who claim that religion and culture alone justify the practice to those who consider circumcision of minors unable to give their consent as bodily injury subject to punishment. In contrast to female genital mutilation, most positions do not postulate that circumcision violates morality. If the person concerned is able to give his consent, freedom of religion may also justify circumcision after weighing its pros and cons as well as its risks and potential side effects.

[Medical and legal aspects of genital mutilation and circumcision part I: female genital mutilation (FGM)]. / Medizinische und Rechtliche Aspekte der Genitalverstiimmelung bzw. Beschneidung Teil I: Weibliche Genitalversttimmelung.

Female genital mutilation (FGM) is considered to be against the law and against morality not only in Western countries, although a woman of age and able to consent may sometimes think differently. The procedure may have serious physical and emotional consequences for the girl or woman. Nevertheless there are attempts to justify the procedure with medical and hygienic pseudoarguments, ideology, freedom of religion, cultural identity and social adequacy. Outside the Western world, some people claim that religion and culture alone justify the practice. In Germany, parents can lose the right to determine the residence of their daughter, if she is faced with the risk of genital mutilation in order to prevent that the child or girl is taken to her home country. Genital mutilation as a gender-specific threat is recognized as a reason to grant asylum or prevent deportation. Proposals to make genital mutilation a separate punishable offence are presently discussed by the legislator.

Liquid silicone embolism syndrome (SES) in lungs and liver - A case report.

Silicone embolism syndrome (SES) is a well known complication after injection of silicone gel as well as liquid silicone. Rarely, men use physiologic salt solution or liquid silicone injected into the subcutaneous tissue of the scrotum, the penis, the upper genital or the inguinal region. Those men, who call themselves "siliconers", want to get a larger penis and scrotum, also visible when wearing clothes. Injections of liquid silicone in the mentioned regions can lead to liquid silicone embolism in the lungs and also the liver, sometimes eventually leading to death via right heart failure as in the present case. Autopsy revealed "frog spawn"-like vacuoles in the subcutaneous tissue of the genital region and liquid silicone embolism in lungs and liver. Additionally, toxicological analyses revealed different liquid silicones. Smaller oligomers were transported into lung and liver, larger ones showed local enrichment at the injection site. The seized Polydimethylsiloxane (PDMS) could not be detected in abdominal fat, blood or urine, potentially due to low perfusion of fat tissue, the aqueous character of blood and urine or the time span between last injection and death.

Gastrointestinal Symptoms in Children With Life-Limiting Conditions Receiving Palliative Home Care.

Context: Children with life-limiting diseases suffer from gastrointestinal (GI) symptoms. Since the introduction of specialized palliative home care (SPHC) in Germany, it is possible to care for these children at home. In phase 1 of care the aim is to stabilize the patient. In phase 2, terminal support is provided. Objectives: Analysis were performed of the differences between these phases. The causes and modalities/outcome of treatment were evaluated. Methods: A retrospective study was performed from 2014 to 2020. All home visits were analyzed with regard to the abovementioned symptoms, their causes, treatment and results. Results: In total, 149 children were included (45.9% female, mean age 8.17 ± 7.67 years), and 126 patients were evaluated. GI symptoms were common in both phases. Vomiting was more common in phase 2 (59.3 vs. 27.1%; p < 0.001). After therapy, the proportion of asymptomatic children in phase 1 increased from 40.1 to 75.7%; (p < 0.001). Constipation was present in 52.3% (phase 1) and 54.1% (phase 2). After treatment, the proportion of asymptomatic patients increased from 47.3 to 75.7% in phase 1 (p < 0.001), and grade 3 constipation was reduced from 33.9 to 15% in phase 2 (p < 0.05). Conclusion: Painful GI symptoms occur in both palliative care phases but are more common in phase 2. The severity and frequency can usually be controlled at home. The study limitations were the retrospective design and small number of patients, but the study had a representative population, good data quality and a unique perspective on the reality of outpatient pediatric palliative care in Germany.

[Reform of forensic autopsy in the German Code of Criminal Procedure]. / Zur Reform der gerichtlichen Leichenöffnung in der Strafprozessordnung.

The German Federal Ministry of Justice has presented a proposal to amend Section 87 subs. 2 of the German Code of Criminal Procedure (StPO). In the reasons for the bill, the priority of the institutional forensic medicine is emphasized. While parts of the revised version are appreciated, some changes are considered necessary in order to take the special features of the German states into account.

Estimates of Non-Alcoholic Food-Derived Ethanol and Methanol Exposure in Human.

Food-derived alcohol is almost not in question due to its low concentration. Nevertheless, could it pose a problem for some risk groups and forensic cases? To answer this, we aimed to simultaneously evaluate ethanol and methanol ingredients of a variety of non-alcoholic foods in two different countries and estimate their possible health and forensic consequences. Alcohols in foods were analysed by headspace gas chromatography (HS-GC). Human average acute daily food consumptions and food-derived blood alcohol concentrations (BAC) were determined by using the data of the EFSA Nutrition Survey. Methanol and ethanol ingredients of similar foods varied between the two cities. Most foods produce higher methanol concentrations than the Maximum Allowable Dose Level (23 mg). Especially fruit juices lead to the critical level of ethanol for children (6.0 mg/kg bw). Based on the results, adult daily intake of selected food groups does not bear ethanol that exceeds the legal limit of BAC or the limit not allowed by the religious and does not lead to acute alcohol toxicity. But these low levels of ethanol and methanol consumed via non-alcoholic foods for life can raise the vulnerability to chronic health problems (cancer, liver cirrhosis, Alzheimer's disease, autism, ocular toxicity, alterations in fetal development), and may lead to positive ethanol metabolite results (e. g. Ethyl glucuronide) when a low cut-off level is used. Therefore, studies on the alcohol contents of various natural and processed non-alcoholic foods along with their effects on humans, and new regulations on labeling the food products and conscious food consumption are in particular importance. It would also be important to consider unintentional alcohol consumption via non-alcoholic foods in the evaluation of clinical and forensic cases.