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1.
Diseases ; 12(10)2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39452484

RESUMO

In systemic hyper-inflammation, as in severe COVID-19 disease, there are pronounced disorders of the hematological and lymphatic systems with prognostically relevant hemophagocytosis of the bone marrow. The current work aimed to address the importance of hemophagocytosis in the lymph nodes of patients with severe COVID-19 disease. From 28 patients who died of severe COVID-19 infection, samples of the vertebral bone marrow and lymph nodes from the cervical, hilar, para-aortic, mesenteric and inguinal locations were morphologically and immunohistologically (CD163, CD68, CD61, CD71, CD3, CD20, CD138) examined for the possible presence of hemophagocytosis. In the single-center study at the University Hospital Jena, a total of 191 hemophagocytes were found in the bone marrow and a total of 780 hemophagocytes in the lymph nodes in a standardized area of 21,924 mm2 per tissue sample. With 370 hemophagocytes, hilar lymph nodes were most frequently affected (370/780; 47.44%; 95%-CI: [43.94, 50.95]), followed by cervical lymph nodes (206/780; 26.41%; 95%-CI: [23.41, 29.59]), para-aortic lymph nodes (125/780; 16.03%; 95%-CI: [13.58, 18.73]) and inguinal/mesenteric lymph nodes (79/780; 10.13%; 95%-CI: [8.155, 12.4]). Based on the standard area (21,924 mm2), the difference in the number of hemophagocytes in the bone marrow and in the hilar lymph nodes was statistically significant (p < 0.05), while this did not apply to the lymph nodes from the other locations. In fatal COVID-19 disease, hemophagocytosis is particularly found in the hilar lymph nodes and is therefore a better indicator of the severity of the disease than hemophagocytosis in the bone marrow. The findings provide some evidence for the concept of compartmentalized human host responses to life-threatening infections.

2.
Int J Legal Med ; 138(1): 295-299, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36609734

RESUMO

In times of peace and except for terrorist attacks, fatalities by explosions are rare. Fireworks have deadly potential, especially self-made or illegally acquired devices. The use of professional pyrotechnics by untrained persons poses a life-threatening hazard. We present a case of devastating blunt force and blast injuries to the head and chest of a young man. After ignition of a display shell (syn. a real shell or mortar shell) without the use of a launching pipe, the device hit the man's face, nearly simultaneously followed by the explosion of the burst charge. The autopsy revealed injuries to the face and forehead as well as extensive tissue structure damage and a massive contusion with a bloody edema of the lungs. Autopsy results are supplemented with CT imaging and 3D reconstruction of the fractured mid face, as well as histological and toxicological examinations. This case of a misused display shell demonstrates both its devastating destructive potential and the corresponding and rarely observed injury pattern.


Assuntos
Traumatismos por Explosões , Terrorismo , Ferimentos não Penetrantes , Humanos , Traumatismos por Explosões/etiologia , Traumatismos por Explosões/patologia , Diagnóstico por Imagem , Ferimentos não Penetrantes/etiologia , Pulmão/patologia , Explosões
3.
Aging (Albany NY) ; 15(23): 13593-13607, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38095608

RESUMO

BACKGROUND: SARS-CoV-2 variants are constantly emerging with a variety of changes in the conformation of the spike protein, resulting in alterations of virus entry mechanisms. Solely omicron variants use the endosomal clathrin-mediated entry. Here, we investigate the influence of defined altered spike formations to study their impact on premature cellular senescence. METHODS: In our study, in vitro infections of SARS-CoV-2 variants delta (B.1.617.2) and omicron (B.1.1.529) were analyzed by using human primary small alveolar epithelial cells and human ex vivo lung slices. We confirmed cellular senescence in human lungs of COVID-19 patients. Hence, global gene expression patterns of infected human primary alveolar epithelial cells were identified via mRNA sequencing. RESULTS: Solely omicron variants of SARS-CoV-2 influenced the expression of cell cycle genes, highlighted by an increased p21 expression in human primary lung cells and human ex vivo lungs. Additionally, an upregulated senescence-associated secretory phenotype (SASP) was detected. Transcriptomic data indicate an increased gene expression of p16, and p38 in omicron-infected lung cells. CONCLUSIONS: Significant changes due to different SARS-CoV-2 infections in human primary alveolar epithelial cells with an overall impact on premature aging could be identified. A substantially different cellular response with an upregulation of cell cycle, inflammation- and integrin-associated pathways in omicron infected cells indicates premature cellular senescence.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/genética , Senescência Celular , Células Epiteliais Alveolares
4.
Int J Obes (Lond) ; 47(11): 1088-1099, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37587162

RESUMO

OBJECTIVE: Obesity is an independent risk factor for severe influenza virus and COVID-19 infections. There might be an interplay between adipose tissue and respiratory pathogens, although the mechanism is unknown. Proinflammatory factors secreted by the adipose tissue are often discussed to serve as indirect contributor to virus infection. However, the direct potential of adipose tissue to serve as a viral niche has not yet been investigated. METHODS: Two murine obesity models (DIO and ob/ob) were infected with influenza A virus (IAV) and monitored for 3 weeks. p.i. Lung and adipose tissue were harvested, and the viral load was analysed. Direct replication of IAV in vitro was investigated in human derived primary adipocytes and macrophages. The indirect impact of the secretory products of adipocytes during infection was analysed in a co-culture system with lung fibroblasts. Moreover, lung and adipose tissue was harvested from deceased patients infected with SARS-CoV-2 omicron variant. Additionally, replication of SARS-CoV-2 alpha, delta, and omicron variants was investigated in vitro in adipocytes and macrophages. RESULTS: Both murine obesity models presented high IAV titers compared to non-obese mice. Interestingly, adipose tissue adjacent to the lungs was a focal point for influenza virus replication in mice. We further detected IAV replication and antiviral response in human adipocytes. Co-cultivation of adipocytes and lung fibroblasts led to increased IL-8 concentration during infection. Though we observed SARS-CoV-2 in the thoracic adipose tissue of COVID-19 patients, no active replication was found in adipocytes in vitro. However, SARS-CoV-2 was detected in the macrophages and this finding was associated with increased inflammation. CONCLUSIONS: Our study revealed that thoracic adipose tissue contributes to respiratory virus infection. Besides indirect induction of proinflammatory factors during infection, adipocytes and macrophages within the tissue can directly support viral replication.


Assuntos
COVID-19 , Vírus da Influenza A , Influenza Humana , Humanos , Camundongos , Animais , Pulmão , Tecido Adiposo , Vírus da Influenza A/fisiologia , Obesidade
5.
Int J Legal Med ; 137(5): 1615-1627, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37395744

RESUMO

Temperature-based time of death estimation using simulation methods such as the finite element method promise higher accuracy and broader applicability in nonstandard cooling scenarios than established phenomenological methods. Their accuracy depends crucially on the simulation model to capture the actual situation, which in turn hinges on the representation of the corpse's anatomy in form of computational meshes as well as on the thermodynamic parameters. While inaccuracies in anatomy representation due to coarse mesh resolution are known to have a minor impact on the estimated time of death, the sensitivity with respect to larger differences in the anatomy has so far not been studied. We assess this sensitivity by comparing four independently generated and vastly different anatomical models in terms of the estimated time of death in an identical cooling scenario. In order to isolate the impact of shape variation, the models are scaled to a reference size, and the possible impact of measurement location variation is excluded explicitly by finding measurement locations leading to minimum deviations. The thus obtained lower bound on the impact of anatomy on the estimated time of death shows, that anatomy variations lead to deviations of at least 5-10%.


Assuntos
Temperatura Baixa , Humanos , Temperatura , Análise de Elementos Finitos , Simulação por Computador
6.
Biomolecules ; 13(3)2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36979408

RESUMO

In late 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the causative agent of coronavirus disease 2019 (COVID-19) emerged in China and spread rapidly around the world, causing an ongoing pandemic of global concern. COVID-19 proceeds with moderate symptoms in most patients, whereas others experience serious respiratory illness that requires intensive care treatment and may end in death. The severity of COVID-19 is linked to several risk factors including male sex, comorbidities, and advanced age. Apart from respiratory complications, further impairments by COVID-19 affecting other tissues of the human body are observed. In this respect, the human kidney is one of the most frequently affected extrapulmonary organs and acute kidney injury (AKI) is known as a direct or indirect complication of SARS-CoV-2 infection. The aim of this work was to investigate the importance of the protein angiotensin-converting enzyme 2 (ACE2) for a possible cell entry of SARS-CoV-2 into human kidney cells. First, the expression of the cellular receptor ACE2 was demonstrated to be decisive for viral SARS-CoV-2 cell entry in human AB8 podocytes, whereas the presence of the transmembrane protease serine 2 (TMPRSS2) was dispensable. Moreover, the ACE2 protein amount was well detectable by mass spectrometry analysis in human kidneys, while TMPRSS2 could be detected only in a few samples. Additionally, a negative correlation of the ACE2 protein abundance to male sex and elderly aged females in human kidney tissues was demonstrated in this work. Last, the possibility of a direct infection of kidney tubular renal structures by SARS-CoV-2 was demonstrated.


Assuntos
COVID-19 , Idoso , Feminino , Humanos , Masculino , Enzima de Conversão de Angiotensina 2 , Rim/metabolismo , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , SARS-CoV-2/metabolismo
7.
Int J Legal Med ; 137(2): 427-435, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36565316

RESUMO

The age of majority, which corresponds to the age of 18 years in most European countries, plays a crucial role for a large number of legal decisions. Accordingly, an increasing number of requests by authorities to forensic age estimation experts comprise the question of whether the age of 18 years has been reached by an individual. In recent years, novel study data suggested that magnetic resonance imaging (MRI) of the knee might likewise allow for the determination of majority beyond reasonable doubt. However, the data basis, especially concerning the distal femoral epiphysis (DFE), is still poor. For this reason, 392 routine MRI cases of the knee (204 males and 188 females of a Western Caucasian population, aged between 12 and 25 years) were retrospectively analyzed. T1-weighted and water-selective fat-saturated PD/T2-weighted sequences, generated at 1.5 and 3.0 T clinical MR scanners, were available. Ossification stages of the DFE were determined by means of the classification system by Vieth et al. (Eur Radiol 2018; 28:3255-3262). Both the intra-observer agreement and inter-observer agreement were found to be "very good" (κ = 0.899 and κ = 0.830). The present study confirmed that MRI of the DFE is suitable to determine majority in both sexes when stage 6 is present as the study revealed minimum ages above the age of 18 years for this stage (20.40 years in males and 20.60 years in females). Accordingly, the data represent a strong support for the so far existing database. Hence, the investigation of the knee using routine MRI appears to become a realistic alternative for forensic age estimation practice in the near future.


Assuntos
Determinação da Idade pelo Esqueleto , Osteogênese , Masculino , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Estudos Retrospectivos , Determinação da Idade pelo Esqueleto/métodos , Imageamento por Ressonância Magnética/métodos , Epífises/diagnóstico por imagem , Antropologia Forense
8.
Int J Legal Med ; 137(2): 601-607, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36547700

RESUMO

The reconstruction of traffic accidents involving powered two-wheelers (PTWs) frequently proves to be a challenging task. A case in which a fatal head-on crash of a PTW with a small truck where only minor vehicles damage was observed but resulted in isolated fatal chest trauma is discussed here. External examination of the corpse revealed two lacerations on the back, at the first glance implying sharp trauma. Based on the accident traces, the technical expert assumed an emergency break of the PTW rider resulting in a rotation of the PTW in terms of a wheelie on the front wheel. The first contact between the PTW rider and the tail end of the small truck probably occurred with the upper side of the helmet, and then, the back handle of the PTW caused the stab-like injuries followed by compression of the rider between the small truck or asphalt and the PTW. Based on the few accident traces available, neither a reconstruction of the pre-impact velocity nor a detailed reconstruction of the PTW rider kinematics was possible. However, using an interdisciplinary approach, the principal collision position as well as the injury mechanisms could be reconstructed.


Assuntos
Lacerações , Traumatismos Torácicos , Humanos , Acidentes de Trânsito , Motocicletas , Veículos Automotores
9.
Sci Rep ; 12(1): 20147, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36418341

RESUMO

In a previous article a new algorithm for fully automatic 'CT histogram based Fat Estimation and quasi-Segmentation' (CFES) was validated on synthetic data, on a special CT phantom, and tested on one corpse. Usage of said data in FE-modelling for temperature-based death time estimation is the investigation's number one long-term goal. The article presents CFES's results on a human corpse sample of size R = 32, evaluating three different performance measures: the τ-value, measuring the ability to differentiate fat from muscle, the anatomical fat-muscle misclassification rate D, and the weighted distance S between the empirical and the theoretical grey-scale value histogram. CFES-performance on the sample was: D = 3.6% for weight exponent α = 1, slightly higher for α ≥ 2 and much higher for α ≤ 0. Investigating τ, S and D on the sample revealed some unexpected results: While large values of τ imply small D-values, rising S implies falling D and there is a positive linear relationship between τ and S. The latter two findings seem to be counter-intuitive. Our Monte Carlo analysis detected a general umbrella type relation between τ and S, which seems to stem from a pivotal problem in fitting Normal mixture distributions.


Assuntos
Adiposidade , Humanos , Algoritmos , Cadáver , Tomografia Computadorizada por Raios X
10.
Virchows Arch ; 481(2): 139-159, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35364700

RESUMO

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.


Assuntos
COVID-19 , Autopsia , Humanos , Pulmão/patologia , Pandemias , SARS-CoV-2
11.
Int J Legal Med ; 136(3): 777-784, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34962588

RESUMO

Determining majority plays a key role for forensic age diagnostics in living individuals. Recent data suggest that magnetic resonance imaging (MRI) of the proximal tibial epiphysis (PTE) may be a suitable alternative or at least an additional tool to clarify whether an individual has reached majority. However, the reference data situation is still sparse. Hence, the present dual center study retrospectively analyzed routine MRI of the knee in 413 cases (214 males and 199 females) of a Western Caucasian population aged between 12 and 25 years. MRI was performed at 1.5 and 3.0 T clinical scanners using T1- and T2-weighted sequences. The classification system by Vieth et al. (Eur Radiol 2018; 28:3255-3262) was applied for determining the ossification stages of the PTE. Intra-observer agreement was "very good" (κ = 0.931), and inter-observer agreement was "good" (κ = 0.798). Minimum ages above the age of 18 years were observed with the final stage (stage 6) in either sex (20.27 years in males and 18.55 years in females). The results are not in contradiction with the previous data and can be considered a strong and valuable support of the so far existing database. Therefore, the investigation of the PTE using routine MRI (either at 1.5 or 3.0 T) could be taken into consideration for application in forensic age estimation practice in near future.


Assuntos
Determinação da Idade pelo Esqueleto , Epífises , Adolescente , Adulto , Determinação da Idade pelo Esqueleto/métodos , Criança , Epífises/anatomia & histologia , Epífises/diagnóstico por imagem , Feminino , Antropologia Forense , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Osteogênese , Estudos Retrospectivos , Tíbia/anatomia & histologia , Tíbia/diagnóstico por imagem , Adulto Jovem
12.
Insects ; 12(4)2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33800533

RESUMO

Skeletonization is often perceived as an indicator of long post-mortem intervals. The finding of feeding larvae of first colonizers, on the other hand, indicates days. We present a case in which both findings were present. Larvae of Phormia regina, aged 9 days, and skeletonization of the head and part of the thorax were both found on an unidentified female body. Identification of dentures eventually led to resolution of the case and a confession, which settled the seeming contradiction in favor of forensic entomology.

13.
Elife ; 102021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781385

RESUMO

Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body and its correlation with tissue damage can aid in understanding the pathophysiology of SARS-CoV-2 infection. We present a detailed mapping of the viral RNA in 61 tissues and organs of 11 deceased patients with COVID-19. The autopsies were performed within the early postmortem interval (between 1.5 and 15 hr, mean: 5.6 hr) to minimize the bias due to viral RNA and tissue degradation. Very high viral loads (>104copies/ml) were detected in most patients' lungs, and the presence of intact viral particles in the lung tissue could be verified by transmission electron microscopy. Interestingly, viral RNA was detected throughout various extrapulmonary tissues and organs without visible tissue damage. The dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis that there is a maladaptive host response with viremia and multiorgan dysfunction.


Since the discovery of the new coronavirus that causes COVID-19, scientists have been scrambling to understand the different features of the virus. While a lot more is now known about SARS-CoV-2, several key questions have proved more difficult to answer. For example, it remained unclear where the virus travels to in the body and causes the most harm. To help answer this question, Deinhardt-Emmer, Wittschieber et al. performed postmortem examinations on 11 patients who had recently died of COVID-19. After sampling 61 different organs and tissues from each patient, several tests were used to detect traces of SARS-CoV-2. The experiments showed that the largest pool of SARS-CoV-2 was present in the lungs, where it had caused severe damage to the alveolae, the delicate air sacs at the end of the lungs' main air tubes. Small amounts of the virus were also detected in other organs and tissues, but no severe tissue damage was seen. In addition, Deinhardt-Emmer, Wittschieber et al. found that each patient had increased levels of some of the proteins involved in inflammation and blood clotting circulating their bloodstream. This suggests that the inflammation caused by SARS-CoV-2 leads to an excessive immune reaction throughout the entire body. This research provides important new insights into which areas of the body are most impacted by SARS-CoV-2. These findings may help to design more effective drug treatments that target the places SARS-CoV-2 is most likely to accumulate and help patients fight off the infection at these regions.


Assuntos
Autopsia , COVID-19/patologia , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/imunologia , COVID-19/terapia , Causas de Morte , Comorbidade , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , RNA Viral/sangue , Carga Viral
14.
Cancer Rep (Hoboken) ; 4(4): e1366, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33719186

RESUMO

BACKGROUND: In patients diagnosed with cervical cancer, the purpose of lymphadenectomy is the removal of lymph nodes for diagnosis and potential treatment of metastasized tumor cells. It is unclear if afferent lymphatic vessels harbor tumor cells and, thus, may pose additional risk for recurrence or progression if not removed. AIM: In this feasibility study, we analyzed the lymphatic vessels afferent to sentinel lymph node (SLN) using a highly sensitive and specific molecular marker for cervical cancer cells. METHODS AND RESULTS: Twenty patients diagnosed with cervical cancer of FIGO stage IA1 to IIB2 underwent laparoscopic SLN removal. Labeling was done using patent blue and the afferent lymphatic vessels were harvested from the parametric tissue and frozen at -80°C. HPV DNA type was evaluated in the primary tumor. Lymphatic vessels afferent to the sentinel lymph nodes were analyzed for the presence of viral oncogene transcripts of the respective HPV type. In one of 18 patients, all with tumor stage ≤IBI and pN0 by conventional histopathology, HPV mRNA could be detected in two of four lymphatic vessels, whereas at least one of the lymphatic vessel biopsies of both patients with tumors ˃4 cm and pN1 status was HPV mRNA positive. No clinical correlation with recurrence after a median follow-up of 9 years was noticed. CONCLUSION: HPV mRNA indicative of disseminated tumor cells could be detected in lymphatic vessels. The relevance of harvesting lymphatic vessels afferent to SLN in order to increase oncologic safety will have to be investigated in a future prospective study.


Assuntos
Excisão de Linfonodo/métodos , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Linfonodo Sentinela/cirurgia , Neoplasias do Colo do Útero/diagnóstico , Adulto , Estudos de Viabilidade , Feminino , Humanos , Vasos Linfáticos/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
15.
Histopathology ; 78(5): 727-737, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33067892

RESUMO

AIMS: Haemophagocytosis in the bone marrow of patients who have succumbed to coronavirus disease 19 (COVID-19) has not been widely studied. The aims of the present study were to perform morphological analyses and morphometry of haemophagocytosis in the bone marrow of patients with severe COVID-19, and to correlate the findings with the clinical course of the disease. METHODS AND RESULTS: In this single-centre study performed at the University Hospital Jena, bone marrow specimens of 15 deceased patients who had experienced a severe course of COVID-19 were sampled from the vertebral column during autopsy. Slides of the bone marrow were stained with routine stains or immunohistochemically, and further examined for haemophagocytosis by the use of light microscopy. To substantiate the morphological findings, additional slides were stained for CD163 and morphometry was performed. In all bone marrow samples, an increase in cellularity was found. Haemophagocytes with erythrophagocytosis were detected in 67% of the deceased patients. In tissues with low numbers of haemophagocytes or ill-defined haemophagocytes, an increase in iron deposits was frequently seen. Morphological findings were then correlated with several important clinical data, and the HScore (probability of having a reactive hemophagocytic syndrome) was calculated to posthumously confirm the diagnosis of secondary haemophagocytic lymphohistiocytosis. The median duration of disease and the hospitalisation time were lower in patients with haemophagocytosis (n = 10) than in patients without haemophagocytosis (n = 5). In addition, patients with haemophagocytes showed increased inflammatory parameters 2-5 days prior to death, in contrast to patients without haemophagocytes. CONCLUSIONS: Haemophagocytosis is a common finding in the bone marrow of deceased individuals with severe COVID-19, and may indicate fatal severe acute respiratory syndrome coronavirus 2 infections.


Assuntos
COVID-19/virologia , Linfo-Histiocitose Hemofagocítica/virologia , SARS-CoV-2/fisiologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Medula Óssea/patologia , Medula Óssea/virologia , COVID-19/complicações , COVID-19/patologia , Feminino , Hospitalização , Humanos , Imuno-Histoquímica , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Pessoa de Meia-Idade
16.
ESC Heart Fail ; 7(5): 2305-2317, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32619089

RESUMO

AIMS: Dendritic cells (DCs) are central mediators of adaptive immunity, and there is growing evidence of their role in myocardial inflammatory disease. We hypothesized that plasmacytoid and myeloid DCs are involved in the mechanisms of myocarditis and analysed these two main subtypes in human myocarditis subjects, as well as in a murine model of experimental autoimmune myocarditis (EAM). METHODS AND RESULTS: Circulating DCs were analysed by flow cytometry in patients with acute myocarditis, dilated cardiomyopathy, and controls. Myocardial biopsies were immunostained for the presence of DCs and compared with non-diseased controls. In a mouse model of acute myocarditis induced through synthetic cardiac myosine peptide injection, effects of immunomodulation including DC inhibition through MCS-18 versus placebo treatment were tested at the peak of inflammation (Day 21), as well as 1 week later (partial recovery). Circulatory pDCs and mDCs were significantly reduced in myocarditis patients compared with controls (P < 0.01 for both) and remained so even after 6 months of follow-up. Human myocarditis biopsies showed accumulation of pDCs (two-fold CD304+/three-fold CD123+, all P < 0.05) compared with controls. Myocardial pDCs and mDCs accumulated in EAM (P for both <0.0001). MCS-18 treatment reduced pDC levels (P = 0.009), reduced myocardial inflammation (myocarditis score reduction from 2.6 to 1.8, P = 0.026), and improved ejection fraction (P = 0.03) in EAM at Day 21 (peak of inflammation). This effect was not observed during the partial recovery of inflammation on Day 28. CONCLUSIONS: Circulating DCs are reduced in human myocarditis and accumulate in the inflamed myocardium. MCS-18 treatment reduces DCs in EAM, leading to amelioration of inflammation and left ventricular remodelling during the acute phase of myocarditis. Our data further elucidate the role of DCs and their specific subsets in acute inflammatory cardiomyopathies.


Assuntos
Cardiomiopatia Dilatada , Miocardite , Animais , Células Dendríticas , Humanos , Inflamação , Camundongos , Miocárdio
17.
Leukemia ; 34(3): 771-786, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31690822

RESUMO

The proximal DNA damage response kinase ATM is frequently inactivated in human malignancies. Germline mutations in the ATM gene cause Ataxia-telangiectasia (A-T), characterized by cerebellar ataxia and cancer predisposition. Whether ATM deficiency impacts on tumor initiation or also on the maintenance of the malignant state is unclear. Here, we show that Atm reactivation in initially Atm-deficient B- and T cell lymphomas induces tumor regression. We further find a reduced T cell abundance in B cell lymphomas from Atm-defective mice and A-T patients. Using T cell-specific Atm-knockout models, as well as allogeneic transplantation experiments, we pinpoint impaired immune surveillance as a contributor to cancer predisposition and development. Moreover, we demonstrate that Atm-deficient T cells display impaired proliferation capacity upon stimulation, due to replication stress. Altogether, our data indicate that T cell-specific restoration of ATM activity or allogeneic hematopoietic stem cell transplantation may prevent lymphomagenesis in A-T patients.


Assuntos
Linfoma/imunologia , Linfócitos T/imunologia , Alelos , Animais , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proliferação de Células , Etoposídeo/farmacologia , Transplante de Células-Tronco Hematopoéticas , Linfoma/metabolismo , Camundongos , Camundongos Knockout , Linfócitos T/metabolismo , Transplante Homólogo , Resultado do Tratamento
18.
Forensic Sci Int ; 290: 189-195, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30081326

RESUMO

Temperature based death time estimation (TDE) is severely limited in situations where body core temperature has almost decreased to ambient temperature. The TDE method of Marshall/Hoare and Henßge (MHH) defines a lower bound TK for body core temperature below which the time p.m. should be stated to be >10h only. A recent study (Potente et al., 2017 [10]) established a new method, called variance-bias-tradeoff (VBT) complementing MHH in constructing a right-side-half-infinite 97.5%-confidence interval for such 'near equilibrium'-situations. It seemingly proved the validity for all body core temperatures T

Assuntos
Intervalos de Confiança , Modelos Estatísticos , Mudanças Depois da Morte , Temperatura Corporal , Medicina Legal/métodos , Humanos , Temperatura
19.
Rofo ; 190(12): 1152-1158, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29913524

RESUMO

PURPOSE: In forensic odontology the comparison between antemortem and postmortem panoramic radiographs (PRs) is a reliable method for person identification. The purpose of this study was to improve and automate identification of unknown people by comparison between antemortem and postmortem PR using computer vision. MATERIALS AND METHODS: The study includes 43 467 PRs from 24 545 patients (46 % females/54 % males). All PRs were filtered and evaluated with Matlab R2014b including the toolboxes image processing and computer vision system. The matching process used the SURF feature to find the corresponding points between two PRs (unknown person and database entry) out of the whole database. RESULTS: From 40 randomly selected persons, 34 persons (85 %) could be reliably identified by corresponding PR matching points between an already existing scan in the database and the most recent PR. The systematic matching yielded a maximum of 259 points for a successful identification between two different PRs of the same person and a maximum of 12 corresponding matching points for other non-identical persons in the database. Hence 12 matching points are the threshold for reliable assignment. CONCLUSION: Operating with an automatic PR system and computer vision could be a successful and reliable tool for identification purposes. The applied method distinguishes itself by virtue of its fast and reliable identification of persons by PR. This Identification method is suitable even if dental characteristics were removed or added in the past. The system seems to be robust for large amounts of data. KEY POINTS: · Computer vision allows an automated antemortem and postmortem comparison of panoramic radiographs (PRs) for person identification.. · The present method is able to find identical matching partners among huge datasets (big data) in a short computing time.. · The identification method is suitable even if dental characteristics were removed or added.. CITATION FORMAT: · Heinrich A, Güttler F, Wendt S et al. Forensic Odontology: Automatic Identification of Persons Comparing Antemortem and Postmortem Panoramic Radiographs Using Computer Vision. Fortschr Röntgenstr 2018; 190: 1152 - 1158.


Assuntos
Inteligência Artificial , Odontologia Legal/métodos , Processamento de Imagem Assistida por Computador/métodos , Radiografia Panorâmica/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Criança , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Int J Legal Med ; 132(2): 563-577, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29335777

RESUMO

Post-mortem body cooling is the foundation of temperature-based death time estimations (TDE) in homicide cases. Forensic science generally provides two types of p.m. body cooling models, the phenomenological and the physical models. Since both of them have to implement important individual parameters like the quantity of abdominal fat explicitly or implicitly, a more exact quantification and localization of abdominal fat is a desideratum in TDE. Particularly for the physical models, a better knowledge of the abdominal fat distribution could lead to relevant improvements in TDEs. Modern imaging methods in medicine like computed tomography (CT) are opening up the possibility to register the quantity and spatial distribution of body fat in individual cases with unprecedented precision. Since a CT-scan of an individual's abdominal region can comprise 1000 slices as an order of magnitude, it is evident that their evaluation for body fat quantification and localization needs fully automated algorithms. The paper at hand describes the development and validation of such an algorithm called "CT-histogram-based fat estimation and quasi-segmentation" (CFES). The approach can be characterized as a weighted least squares method dealing with the gray value histogram of single CT-slices only. It does not require any anatomical a priori information nor does it perform time-consuming feature detection on the CT-images. The processing result consists in numbers quantifying the amount of abdominal body fat and of muscle-, organ-, and connective tissue. As a by-product, CFES generates a quasi-segmentation of the slices processed differentiating fat from muscle-, organ-, and connective tissue. The tool is validated on synthetic data and on CT-data of a special phantom. It was also applied on a CT-scan of a dead body, where it produced anatomically plausible results.


Assuntos
Gordura Abdominal/diagnóstico por imagem , Algoritmos , Imagens de Fantasmas , Tomografia Computadorizada por Raios X , Adulto , Temperatura Corporal , Patologia Legal , Humanos , Análise dos Mínimos Quadrados , Masculino , Mudanças Depois da Morte
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