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1.
Medicine (Baltimore) ; 100(15): e25255, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847623

RESUMO

RATIONALE: Fibrinolysis shutdown associated with severe thrombotic complications is a recently recognized syndrome that was previously seldom investigated in patients with severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It presents a unique therapeutic dilemma, as anticoagulation with heparin alone is insufficient to address the imbalance in fibrinolysis. And while the use of fibrinolytic agents could limit the disease severity, it is often associated with bleeding complications. There is a need for biomarkers that will guide the timely stratification of patients into those who may benefit from both anticoagulant and fibrinolytic therapies. PATIENT CONCERNS: All 3 patients presented with shortness of breath along with comorbidities predisposing them to severe SARS-CoV-2 infection. One patient (Patient 3) also suffered from bilateral deep venous thrombosis. DIAGNOSES: All 3 patients tested positive for SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) and were eventually diagnosed with respiratory failure necessitating intubation. INTERVENTIONS: All 3 patients required mechanical ventilation support, 2 of which also required renal replacement therapy. All 3 patients were also placed on anticoagulation therapy. OUTCOMES: In Patients 1 and 2, the initial D-dimer levels of 0.97 µg/ml fibrinogen equivalent units (FEU) and 0.83 µg/ml FEU were only slightly elevated (normal <0.50 µg/ml FEU). They developed rising D-dimer levels to a peak of 13.21 µg/ml FEU and >20.0 µg/ml FEU, respectively, which dropped to 1.34 µg/ml FEU 8 days later in Patient 1 and to 2.94 µg/ml on hospital day 13 in Patient 2. In Patient 3, the D-dimer level on admission was found to be elevated to >20.00 µg/ml FEU together with imaging evidence of thrombosis. And although he received therapeutic heparin infusion, he still developed pulmonary embolism (PE) and his D-dimer level declined to 5.91 µg/ml FEU. Despite "improvement" in their D-dimer levels, all 3 patients succumbed to multi-system organ failure. On postmortem examination, numerous arterial and venous thromboses of varying ages, many consisting primarily of fibrin, were identified in the lungs of all patients. LESSONS: High D-dimer levels, with subsequent downtrend correlating with clinical deterioration, seems to be an indicator of fibrinolysis suppression. These findings can help form a hypothesis, as larger cohorts are necessary to demonstrate their reproducibility.


Assuntos
Anticoagulantes/uso terapêutico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Insuficiência de Múltiplos Órgãos , Terapia Trombolítica/métodos , Autopsia/métodos , /complicações , /terapia , Deterioração Clínica , Feminino , Fibrinólise , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Valor Preditivo dos Testes , Prognóstico , Terapia de Substituição Renal/métodos , Respiração Artificial/métodos , Índice de Gravidade de Doença , Trombose Venosa/sangue , Trombose Venosa/complicações , Trombose Venosa/diagnóstico
2.
Curr Opin Pulm Med ; 27(3): 184-192, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399353

RESUMO

PURPOSE OF REVIEW: COVID-19 lung injury is a common manifestation of severe illness. Lung tissue examination has been largely derived from autopsy - a combination of case reports, small and moderately sized series with international scope. Common and uncommon histopathology provides insight into the progression of severe, fatal disease. RECENT FINDINGS: COVID-19 lung histology is most commonly diffuse alveolar damage as part of acute respiratory distress syndrome. Lung injury can be temporally heterogeneous, with patterns of healing alongside new injury. Viral studies, including immunohistochemistry, RNA in-situ hybridization, and tissue-based Polymerase chain reaction (PCR) assist in discerning complications of therapy (e.g. ventilator-associated pneumonia) from primary viral-induced injury. Response to viral infection produces systemic effects, and one major manifestation is thrombosis of micro-circulation and larger vessels. Less common patterns include neutrophil-rich inflammation, raising speculation that neutrophil extra-cellular traps may play a role in both viral control and exaggerated immune response. SUMMARY: The heterogeneity of fatal cases- persistence of viral infection in lung, clearance of virus but severe lung injury, thrombosis, and exaggerated immune response - suggest that antiviral, antithrombotic, anti-inflammatory, and supportive therapy play a role in treatment, but that the patient-specific cause and timing of the lung injury is important in choosing intervention.


Assuntos
Autopsia/métodos , Pulmão/patologia , Trombose/patologia , /imunologia , /terapia , Gerenciamento Clínico , Humanos , Imunidade , Trombose/tratamento farmacológico , Trombose/etiologia
3.
PLoS One ; 16(1): e0244552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33507902

RESUMO

In low-and middle-income countries, determining the cause of death of any given individual is impaired by poor access to healthcare systems, resource-poor diagnostic facilities, and limited acceptance of complete diagnostic autopsies. Minimally invasive tissue sampling (MITS), an innovative post-mortem procedure based on obtaining tissue specimens using fine needle biopsies suitable for laboratory analysis, is an acceptable proxy of the complete diagnostic autopsy, and thus could reduce the uncertainty of cause of death. This study describes rumor surveillance activities developed and implemented in Bangladesh, Mali, and Mozambique to identify, track and understand rumors about the MITS procedure. Our surveillance activities included observations and interviews with stakeholders to understand how rumors are developed and spread and to anticipate rumors in the program areas. We also engaged young volunteers, local stakeholders, community leaders, and study staff to report rumors being spread in the community after MITS launch. Through community meetings, we also managed and responded to rumors. When a rumor was reported, the field team purposively conducted interviews and group discussions to track, verify and understand the rumor. From July 2016 through April 2018, the surveillance identified several rumors including suspicions of organs being harvested or transplanted; MITS having been performed on a living child, and concerns related to disrespecting the body and mistrust related to the study purpose. These rumors, concerns, and cues of mistrust were passed by word of mouth. We managed the rumors by modifying the consent protocol and giving additional information and support to the bereaved family and to the community members. Rumor surveillance was critical for anticipating and readily identifying rumors and managing them. Setting up rumor surveillance by engaging community residents, stakeholders, and volunteers could be an essential part of any public health program where there is a need to identify and react in real-time to public concern.


Assuntos
Mortalidade da Criança , Adolescente , Adulto , Autopsia/métodos , Bangladesh/epidemiologia , Causas de Morte , Criança , Feminino , Humanos , Masculino , Mali/epidemiologia , Pessoa de Meia-Idade , Moçambique/epidemiologia , Pobreza , Pesquisa Qualitativa , Características de Residência , Adulto Jovem
4.
Ann Diagn Pathol ; 51: 151682, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33360731

RESUMO

Neurologic complications of symptomatic COVID-19 are common. Brain tissues from 13 autopsies of people who died of COVID-19 were examined. Cultured endothelial and neuronal cells were incubated with and wild type mice were injected IV with different spike subunits. In situ analyses were used to detect SARS-CoV-2 proteins and the host response. In 13/13 brains from fatal COVID-19, pseudovirions (spike, envelope, and membrane proteins without viral RNA) were present in the endothelia of microvessels ranging from 0 to 14 positive cells/200× field (mean 4.3). The pseudovirions strongly co-localized with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons demonstrated increased NMDAR2 and neuronal NOS plus decreased MFSD2a and SHIP1 proteins. Tail vein injection of the full length S1 spike subunit in mice led to neurologic signs (increased thirst, stressed behavior) not evident in those injected with the S2 subunit. The S1 subunit localized to the endothelia of microvessels in the mice brain and showed co-localization with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons showed increased neuronal NOS and decreased MFSD2a. It is concluded that ACE2+ endothelial damage is a central part of SARS-CoV2 pathology and may be induced by the spike protein alone. Thus, the diagnostic pathologist can use either hematoxylin and eosin stain or immunohistochemistry for caspase 3 and ACE2 to document the endothelial cell damage of COVID-19.


Assuntos
/virologia , Células Endoteliais/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Autopsia/métodos , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Feminino , Humanos , Masculino , Camundongos , Microvasos/metabolismo , Microvasos/virologia , Pessoa de Meia-Idade , Subunidades Proteicas/metabolismo , RNA Viral/genética , Glicoproteína da Espícula de Coronavírus/genética
5.
PLoS One ; 15(12): e0242574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315918

RESUMO

Establishing the cause of death (CoD) is critical to better understanding health and prioritizing health investments, however the use of full post-mortem examination is rare in most low and middle-income counties for multiple reasons. The use of minimally invasive autopsy (MIA) approaches, such as needle biopsies, presents an alternate means to assess CoD. In order to understand the feasibility and acceptability of MIA among communities in western Kenya, we conducted focus groups and in-depth interviews with next-of-kin of recently deceased persons, community leaders and health care workers in Siaya and Kisumu counties. Results suggest two conceptual framework can be drawn, one with facilitating factors for acceptance of MIA due to the ability to satisfy immediate needs related to interest in learning CoD or protecting social status and honoring the deceased), and one framework covering barriers to acceptance of MIA, for reasons relating to the failure to serve an existing need, and/or the exacerbation of an already difficult time.


Assuntos
Autopsia/ética , Biópsia por Agulha/psicologia , Causas de Morte , Adulto , Autopsia/métodos , Biópsia por Agulha/ética , Estudos de Viabilidade , Feminino , Grupos Focais , Pessoal de Saúde/psicologia , Humanos , Quênia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
7.
Lancet Neurol ; 19(11): 919-929, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33031735

RESUMO

BACKGROUND: Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. METHODS: In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. FINDINGS: 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70-86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. INTERPRETATION: In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. FUNDING: German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).


Assuntos
Betacoronavirus/isolamento & purificação , Encéfalo/patologia , Encéfalo/virologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuropatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Transcriptoma/genética
10.
Pathol Res Pract ; 216(11): 153195, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32890939

RESUMO

During the COVID-19 pandemic, many deaths occurred especially among the old patients with cardiovascular comorbidities. Many questions have been asked and few simple answers have been given. The autopsy data are few and the aspects often observed are pulmonary diffuse alveolar damage (DAD), myocarditis, acute myocardial infarction (AMI), and disseminated intravascular coagulation (DIC); these aspects are not only in COVID-19 but also in other viral infections and in sepsis. It should be considered that coronavirus with its pathological organ changes have already been described in the years preceding the pandemic.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Pulmão/patologia , Patologistas , Pneumonia Viral/patologia , Autopsia/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Humanos , Pulmão/virologia , Miocardite/patologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia
13.
Am J Trop Med Hyg ; 103(4): 1604-1607, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32876012

RESUMO

Although high mortality has been reported in many COVID-19 studies, very limited postmortem information from complete autopsies is available. We report the findings in the adrenal glands in 28 autopsies with confirmed SARS-CoV-2 infection. Microscopic lesions were identified in the adrenal glands in 12/28 patients (46%). Seven cases showed necrosis, generally ischemic; four showed cortical lipid degeneration; two showed hemorrhage; and one unspecific focal adrenalitis. Vascular thrombosis in one patient and focal inflammation in association with other findings in three patients were observed. No case presented adrenal insufficiency. In conclusion, adrenal lesions are frequent in patients with severe COVID-19. The lesions are mild but could contribute to the lethal outcome.


Assuntos
Glândulas Suprarrenais/patologia , Autopsia/normas , Betacoronavirus , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Adulto , Idoso , Autopsia/métodos , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Pandemias
14.
Rev. esp. patol ; 53(3): 188-192, jul.-sept. 2020. ilus
Artigo em Inglês | IBECS | ID: ibc-192406

RESUMO

The new coronavirus SARS-CoV-2, first identified in Wuhan, China in December, 2019, can cause Severe Acute Respiratory Syndrome (SARS) with massive alveolar damage and progressive respiratory failure. We present the relevant autopsy findings of the first patient known to have died from COVID19 pneumonia in Spain, carried out on the 14th of February, 2020, in our hospital (Hospital Arnau de Vilanova-Lliria, Valencia). Histological examination revealed changes typical of diffuse alveolar damage (DAD) in both the exudative and proliferative phase of acute lung injury. Intra-alveolar multinucleated giant cells, smudge cells and vascular thrombosis were present. The diagnosis was confirmed by reverse real-time PCR assay on a throat swab sample taken during the patient's admission. The positive result was reported fifteen days subsequent to autopsy


El nuevo coronavirus SARS-CoV-2, identificado inicialmente en China en diciembre de 2019 puede cursar con un Síndrome Respiratorio Agudo Severo (SARS) con daño alveolar masivo y fracaso respiratorio progresivo. Presentamos los hallazgos más relevantes encontrados en la autopsia clínica efectuada en nuestro hospital (Hospital Arnau de Vilanova-Lliria de Valencia) a fecha de 14 de febrero de 2020, al primer paciente fallecido conocido en España por neumonía COVID-19. A nivel pulmonar, la autopsia revela cambios típicos de daño alveolar difuso (DAD) en fase exudativa y fase proliferativa. Se observan células multinucleadas gigantes, células tipo smudge intraalveolares y trombosis vasculares. El diagnóstico microbiológico confirmativo mediante PCR se realizó 15 días después de la autopsia sobre la muestra faríngea del enfermo tomada durante su ingreso


Assuntos
Humanos , Masculino , Idoso , Autopsia/métodos , Infecções por Coronavirus/mortalidade , Síndrome Respiratória Aguda Grave/mortalidade , Vírus da SARS/isolamento & purificação , Técnicas Histológicas/métodos , Alvéolos Pulmonares/patologia , Espanha/epidemiologia , Causas de Morte , Pandemias
15.
Med Sci Law ; 60(4): 287-293, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32799740

RESUMO

Wuhan Municipal Health Commission, China, reported a cluster of cases of 'pneumonia of unknown aetiology' in Wuhan, Hubei province in late 2019. The causative organism was eventually identified as a novel coronavirus. Subsequently, the disease spread to more provinces in China, then the rest of the world, and the World Health Organization declared it a pandemic. The virus was named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the disease was termed COVID-19 (Coronavirus disease). Since then, an increasing number of people have succumbed to this infectious disease. High contagiousness and rapid spread of the disease has been a matter of concern, as it may overburden healthcare systems. Hence, it is vital to implement strict infection prevention and control measures to curb the spread of the disease. This article reviews the guidelines available for the handling of bodies of deceased persons with suspected or confirmed COVID-19, and for their safe disposal. It also provides a summary of recommendations for conducting autopsies in cases where COVID-19 is suspected.


Assuntos
Infecções por Coronavirus/patologia , Práticas Mortuárias/organização & administração , Pneumonia Viral/patologia , Autopsia/métodos , Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Humanos , Pandemias , Guias de Prática Clínica como Assunto
16.
Leg Med (Tokyo) ; 47: 101776, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32795931

RESUMO

The RapidHIT™ ID system produces GlobalFiler™ analysis results after a short operating time. This device is effective because it automatically extracts DNA from oral mucosal cells or from blood stains and saliva collected at a crime scene, with subsequent polymerase chain reaction performed to produce a DNA profile. Two types of dedicated cartridges are available for RapidHIT™ ID: the RapidHIT™ ID ACE GlobalFiler Express sample cartridge for oral cells and other samples and the RapidINTEL™ sample cartridge for minute samples, such as blood stains. Previously validated specimens include oral mucosa cells and blood stains left at crime scenes. There have been no reports of blood and nail clipping samples collected from the postmortem bodies at the time of death. This report summarizes the results of using the RapidHIT™ ID system by collecting a variety of actual forensic samples from postmortem bodies at different stages of decomposition, which were subsequently analyzed using these cartridges.


Assuntos
Autopsia/métodos , Impressões Digitais de DNA/instrumentação , DNA/genética , DNA/isolamento & purificação , Genética Forense , Manchas de Sangue , Crime , Impressões Digitais de DNA/métodos , Humanos , Mucosa Bucal , Reação em Cadeia da Polimerase , Saliva
18.
Am J Pathol ; 190(11): 2180-2184, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32827462

RESUMO

The current coronavirus disease 2019 (COVID-19) pandemic has raised concerns about the safety of laboratory personnel who handle tissue samples that harbor pathogens, including those performing autopsies. While pathologists have performed autopsies on infected decedents for centuries, universal precaution protocols for limiting exposure to pathogens were not developed until the 20th century. This article reviews the history and effectiveness of universal precautions, with an emphasis on performing autopsies on COVID-19 decedents.


Assuntos
Betacoronavirus/patogenicidade , Doenças Transmissíveis/patologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Precauções Universais , Autopsia/métodos , Doenças Transmissíveis/diagnóstico , Infecções por Coronavirus/diagnóstico , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Precauções Universais/métodos
19.
J Korean Med Sci ; 35(33): e310, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32830471

RESUMO

With the rapidly spreading coronavirus disease 2019 (COVID-19) pandemic over the past few months, the world is facing an unprecedented crisis. Innumerable lives have been lost to this novel infectious disease, the nature of which supersedes conventional medical understanding. The COVID-19 pandemic is not just a global health crisis, several aspects of life in the post-COVID-19 era are also being contemplated. Experts in unison are warning that the upcoming changes in all areas of life could potentially be far more drastic than ever experienced in the entire human civilization. The medical community is no exception, and therefore, personnel involved in forensic medicine also need to be adequately prepared for the future. Forensic medicine is a branch of medicine dedicated to one of the most important stages of the human lifecycle and has always been at the forefront in times of unprecedented social change. The autopsy, one of the most important tools of forensic medicine, is also useful to infectious diseases because it identifies the causal relationship between death and infection, reveals medical and epidemiological knowledge, and provides objective evidence for legal disputes. We present new autopsy guidelines in forensic medicine, formulated based on the various infectious diseases that we presently live with and may encounter in the future. In formulation of these guidelines several considerations have been taken into account, namely, the role forensic pathologists should play in the post-COVID-19 era and the necessary preparations as well as the support needed from society to fulfill that role. The present COVID-19 outbreak should be a starting point for formulating improvements in current practices in forensic science, including autopsy biosafety practices and the medicolegal death investigation system.


Assuntos
Autopsia/métodos , Betacoronavirus , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Guias de Prática Clínica como Assunto , Contenção de Riscos Biológicos , Infecções por Coronavirus/prevenção & controle , Medicina Legal , Recursos em Saúde , Humanos , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Pneumonia Viral/prevenção & controle , República da Coreia
20.
Ann Diagn Pathol ; 48: 151562, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32653819

RESUMO

A new viral disease named COVID-19 has recently turned into a pandemic. Compared to a common viral pneumonia it may evolve in an atypical way, causing the rapid death of the patient. For over two centuries, autopsy has been recognized as a fundamental diagnostic technique, particularly for new or little-known diseases. To date, it is often considered obsolete giving the inadequacy to provide samples of a quality appropriate to the sophisticated diagnostic techniques available today. This is probably one of the reasons why during this pandemic autopsies were often requested only in few cases, late and discouraged, if not prohibited, by more than one nation. This is in contrast with our firm conviction: to understand the unknown we must look at it directly and with our own eyes. This has led us to implement an autopsy procedure that allows the beginning of the autopsy shortly after death (within 1-2 h) and its rapid execution, also including sampling for ultrastructural and molecular investigations. In our experience, the tissue sample collected for diagnosis and research were of quality similar to biopsy or surgical resections. This procedure was performed ensuring staff and environmental safety. We want to propose our experience, our main qualitative results and a few general considerations, hoping that they can be an incentive to use autopsy with a new procedure adjusted to match the diagnostic challenges of the third millennium.


Assuntos
Autopsia/métodos , Infecções por Coronavirus/patologia , Controle de Infecções/métodos , Pneumonia Viral/patologia , Manejo de Espécimes/métodos , Betacoronavirus , Humanos , Pandemias , Fatores de Tempo
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