RESUMO
AIM: To evaluate the impact of a new, less-invasive micro-computed tomography (CT) service on autopsy service provision. We recorded parental consent, type of autopsy performed, autopsy reporting times and time taken for the body to be released from the mortuary. MATERIALS AND METHODS: A retrospective, single-centre case series was conducted for all perinatal deaths since the introduction of our micro-CT service in 2016, with a detailed review of records extracted from 2019 and 2021. Fetal demographics (gestational age, weight), type of autopsy conducted, and the time taken from receiving the body to releasing the body and issuing a final report were recorded. RESULTS: Micro-CT imaging uptake increased to over two hundred cases/year by 2021. Overall, invasive autopsies reduced from (45.8%, 196/428; 2019) to (32.1%, 125/390; 2021) with an equivalent rise in less-invasive autopsy from 54.2% (232/428;2019) to 67.9% (265/390;2019). Offering a micro-CT service resulted in an increase in consent to imaging-based autopsies from (76.9%, 329/428;2019) to (87.2%, 340/390;2021). Micro-CT has become the most common post-mortem imaging performed in our institution at 54.4% (212/251;2021), although the body preparation time from the tissue staining required has increased the time to provide an autopsy report to 17 days and release of the body to 18 days. CONCLUSION: Our study shows that introducing a micro-CT post-mortem imaging service was associated with reduced use of conventional invasive procedures, despite a slight increase in turnaround times. Understanding these factors and continued improvements in micro-CT service delivery will help make this accessible to a wider population in the future.
Assuntos
Autopsia , Microtomografia por Raio-X , Humanos , Autopsia/métodos , Estudos Retrospectivos , Microtomografia por Raio-X/métodos , Feminino , Feto/diagnóstico por imagem , GravidezRESUMO
OBJECTIVE: Prenatal diagnosis of a rare disease on ultrasound relies on a physician's ability to remember an intractable amount of knowledge. We developed a real-time decision support system (DSS) that suggests, at each step of the examination, the next phenotypic feature to assess, optimizing the diagnostic pathway to the smallest number of possible diagnoses. The objective of this study was to evaluate the performance of this real-time DSS using clinical data. METHODS: This validation study was conducted on a database of 549 perinatal phenotypes collected from two referral centers (one in France and one in the UK). Inclusion criteria were: at least one anomaly was visible on fetal ultrasound after 11 weeks' gestation; the anomaly was confirmed postnatally; an associated rare disease was confirmed or ruled out based on postnatal/postmortem investigation, including physical examination, genetic testing and imaging; and, when confirmed, the syndrome was known by the DSS software. The cases were assessed retrospectively by the software, using either the full phenotype as a single input, or a stepwise input of phenotypic features, as prompted by the software, mimicking its use in a real-life clinical setting. Adjudication of discordant cases, in which there was disagreement between the DSS output and the postnatally confirmed ('ascertained') diagnosis, was performed by a panel of external experts. The proportion of ascertained diagnoses within the software's top-10 differential diagnoses output was evaluated, as well as the sensitivity and specificity of the software to select correctly as its best guess a syndromic or isolated condition. RESULTS: The dataset covered 110/408 (27%) diagnoses within the software's database, yielding a cumulative prevalence of 83%. For syndromic cases, the ascertained diagnosis was within the top-10 list in 93% and 83% of cases using the full-phenotype and stepwise input, respectively, after adjudication. The full-phenotype and stepwise approaches were associated, respectively, with a specificity of 94% and 96% and a sensitivity of 99% and 84%. The stepwise approach required an average of 13 queries to reach the final set of diagnoses. CONCLUSIONS: The DSS showed high performance when applied to real-world data. This validation study suggests that such software can improve perinatal care, efficiently providing complex and otherwise overlooked knowledge to care-providers involved in ultrasound-based prenatal diagnosis. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Inteligência Artificial , Doenças Raras , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Ultrassonografia Pré-Natal , Diagnóstico Pré-Natal/métodosRESUMO
BACKGROUND: Pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, but little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. METHODS: We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT-qPCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. FINDINGS: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co-express the two proteins across the second trimester or at term. INTERPRETATION: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. TWEETABLE ABSTRACT: This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS-CoV-2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.
Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19 , Perfilação da Expressão Gênica , Placenta/metabolismo , Serina Endopeptidases/genética , Adulto , COVID-19/epidemiologia , COVID-19/genética , COVID-19/transmissão , Bases de Dados de Ácidos Nucleicos , Suscetibilidade a Doenças/metabolismo , Feminino , Pesquisa Fetal , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/estatística & dados numéricos , Testes Genéticos/métodos , Idade Gestacional , Humanos , Imuno-Histoquímica , Transmissão Vertical de Doenças Infecciosas , Gravidez , Fatores de Proteção , Ribonucleoproteínas Citoplasmáticas Pequenas/análise , SARS-CoV-2/fisiologiaRESUMO
AIM: To highlight the imaging findings in a case series of histologically confirmed infantile fibrosarcoma (IF) and identify any features specific to this entity. MATERIALS AND METHODS: Retrospective identification was undertaken of patients with histologically confirmed IF from the electronic patient databases of two institutions between 1 January 2010 and 1 May 2021. Available pre-treatment imaging, histopathological reports, and clinical records were reviewed. RESULTS: Eighteen patients with IF met the inclusion criteria. There were 10 male and eight female patients with a mean age at presentation of 3 weeks. All patients had the t (12; 15) chromosomal translocation. Eleven (61%) tumours were located in the extremities, three were in the craniofacial region, two were intrathoracic, one abdominal and one paraspinal. A single patient had extensive metastases. The tumours were generally isointense to skeletal muscle on T1-weighted sequences and hyperintense on T2 with heterogeneous enhancement and high cellularity seen as diffusion restriction. Fifteen of the 18 lesions were evaluated on ultrasound and appeared as heterogeneous, hypervascular solid or mixed solid/cystic masses, mimicking benign vascular lesions in two cases. CONCLUSION: The present two-centre, retrospective study of the largest case series described thus far demonstrates that IF is always highly cellular on magnetic resonance imaging but has no other specific imaging features. It should be considered in the differential diagnosis of any enlarging soft-tissue, solid mass arising in the limbs or neck at birth or in infancy.
Assuntos
Fibrossarcoma , Diagnóstico Diferencial , Feminino , Fibrossarcoma/diagnóstico por imagem , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Masculino , Pescoço , Estudos RetrospectivosRESUMO
Cinematic rendering (CR) is a novel post-processing technique similar to volume rendering (VR), which allows for a more photorealistic imaging reconstruction by using a complex light modelling algorithm, incorporating information from multiple light paths and predicted photon scattering patterns. Several recent publications relating to adult imaging have argued that CR gives a better "realism" and "expressiveness" experience over VR techniques. CR has also been shown to improve visualisation of musculoskeletal and vascular anatomy compared with conventional CT viewing, and may help non-radiologists to understand complex patient anatomy. In this review, we provide an overview of how CR could be used in paediatric musculoskeletal imaging, particularly in complex diagnoses, surgical planning, and patient consent processes. We present a direct comparison of VR and CR reconstructions across a range of congenital and acquired musculoskeletal pathologies, highlighting potential advantages and areas for further research.
Assuntos
Sistema Musculoesquelético , Adulto , Algoritmos , Criança , Humanos , Processamento de Imagem Assistida por Computador , Sistema Musculoesquelético/diagnóstico por imagem , Fótons , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: To determine the diagnostic accuracy of postmortem magnetic resonance imaging (PM-MRI) and postmortem ultrasound (PM-US) for perinatal autopsy in the same patient cohort, and to determine whether PM-US can provide the same anatomical information as PM-MRI. METHODS: In this prospective, 5-year (July 2014-July 2019) single-center study, we performed 1.5-T PM-MRI and PM-US in an unselected cohort of perinatal deaths. The diagnostic accuracies of both modalities were calculated, using autopsy as the reference standard. As a secondary objective, the concordance rates between the two imaging modalities for the overall main diagnosis and for five anatomical regions (brain, spine, thorax, heart and abdomen) were calculated. RESULTS: During the study period, 136 cases underwent both PM-US and PM-MRI, of which 88 (64.7%) also underwent autopsy. There was no significant difference in the rates of concordance with autopsy between the two modalities for overall diagnosis (PM-US, 86.4% (95% CI, 77.7-92.0%) vs PM-MRI, 88.6% (95% CI, 80.3-93.7%)) or in the sensitivities and specificities for individual anatomical regions. There were more non-diagnostic PM-US than PM-MRI examinations for the brain (22.8% vs 3.7%) and heart (14.7% vs 5.1%). If an 'imaging-only' autopsy had been performed, PM-US would have achieved the same diagnosis as 1.5-T PM-MRI in 86.8% (95% CI, 80.0-91.5%) of cases, with the highest rates of agreement being for spine (99.3% (95% CI, 95.9-99.9%)) and cardiac (97.3% (95% CI, 92.4-99.1%)) findings and the lowest being for brain diagnoses (85.2% (95% CI, 76.9-90.8%)). CONCLUSION: Although there were fewer non-diagnostic cases using PM-MRI than for PM-US, the high concordance rate for overall diagnosis suggests that PM-US could be used for triaging cases when PM-MRI access is limited or unavailable. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Autopsia/métodos , Feto/diagnóstico por imagem , Imageamento por Ressonância Magnética/estatística & dados numéricos , Morte Perinatal/etiologia , Ultrassonografia/estatística & dados numéricos , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia/métodosRESUMO
BACKGROUND: Genotype-phenotype studies can identify subgroups of patients with specific clinical features or differing outcomes, which can help shape management. OBJECTIVES: To characterize the frequency of different causative genotypes in congenital melanocytic naevi (CMN), and to investigate genotype-phenotype and genotype-outcome associations. METHODS: We conducted a large cohort study in which we undertook MC1R genotyping from blood, and high-sensitivity genotyping of NRAS and BRAF hotspots in 156 naevus biopsies from 134 patients with CMN [male 40%; multiple CMN 76%; projected adult size (PAS) > 20 cm, 59%]. RESULTS: Mosaic NRAS mutations were detected in 68%, mutually exclusive with BRAF mutations in 7%, with double wild-type in 25%. Two separate naevi were sequenced in five of seven patients with BRAF mutations, confirming clonality. Five of seven patients with BRAF mutations had a dramatic multinodular phenotype, with characteristic histology distinct from classical proliferative nodules. NRAS mutation was the commonest in all sizes of CMN, but was particularly common in naevi with PAS > 60 cm, implying more tolerance to that mutation early in embryogenesis. Facial features were less common in double wild-type patients. Importantly, the incidence of congenital neurological disease, and apparently of melanoma, was not altered by genotype; no cases of melanoma were seen in BRAF-mutant multiple CMN, however, this genotype is rare. CONCLUSIONS: CMN of all sizes are most commonly caused by mutations in NRAS. BRAF is confirmed as a much rarer cause of multiple CMN, and appears to be commonly associated with a multinodular phenotype. Genotype in this cohort was not associated with differences in incidence of neurological disease in childhood. However, genotyping should be undertaken in suspected melanoma, for guidance of treatment. What's already known about this topic? Multiple congenital melanocytic naevi (CMN) have been shown to be caused by NRAS mosaic mutations in 70-80% of cases, by BRAF mosaicism in one case report and by inference in some previous cases. There has been debate about genotypic association with different sizes of CMN, and no data on genotype-outcome. What does this study add? NRAS mosaicism was found in 68%, BRAF in 7% and double wild-type in 25% of cases of CMN. NRAS was the commonest mutation in all sizes of CMN, but was nearly universal in projected adult size > 60 cm. BRAF is often associated with a distinct multinodular clinical/histological phenotype. Adverse outcomes did not differ between genotypes on current numbers.
Assuntos
Nevo Pigmentado , Neoplasias Cutâneas , Adulto , Estudos de Coortes , Genótipo , Humanos , Masculino , Mutação/genética , Nevo Pigmentado/genética , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genéticaRESUMO
OBJECTIVE: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country. DESIGN: Historical cohort study. SETTING: Charing Cross Hospital, United Kingdom. POPULATION: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2). METHODS: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups. MAIN OUTCOME MEASURES: MTX resistance, recurrence rate and survival. RESULTS: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups. CONCLUSIONS: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered. TWEETABLE ABSTRACT: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival.
Assuntos
Coriocarcinoma , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Doença Trofoblástica Gestacional , Neoplasias Pulmonares , Metotrexato , Adulto , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Estudos de Coortes , Feminino , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/patologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Países Baixos/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Recidiva , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: To determine the feasibility and tissue yield of a perinatal incisionless ultrasound-guided biopsy procedure, the INcisionless Targeted Core Tissue (INTACT) technique, in the context of minimally invasive autopsy. METHODS: Cases of perinatal death in which the parents consented for minimally invasive autopsy underwent postmortem magnetic resonance imaging and an INTACT biopsy procedure, defined as needle biopsy of organs via the umbilical cord, performed under ultrasound guidance. In each case, three cores of tissue were obtained from seven target organs (both lungs, both kidneys, heart, spleen and liver). Biopsy success was predefined as an adequate volume of the intended target organ for pathological analysis, as judged by a pathologist blinded to the case and biopsy procedure. RESULTS: Thirty fetuses underwent organ sampling. Mean gestational age was 30 weeks (range, 18-40 weeks) and mean delivery-to-biopsy interval was 12 days (range, 6-22 days). The overall biopsy success rate was 153/201 (76.1%) samples, with the success rates in individual organs being highest for the heart and lungs (93% and 91%, respectively) and lowest for the spleen (11%). Excluding splenic samples, the biopsy success rate was 150/173 (86.7%). Histological abnormalities were found in 4/201 (2%) samples, all of which occurred in the lungs and kidneys of a fetus with pulmonary hypoplasia and multicystic kidney disease. CONCLUSIONS: Incisionless ultrasound-guided organ biopsy using the INTACT procedure is feasible, with an overall biopsy success rate of over 75%. This novel technique offers the ideal combination of an imaging-led autopsy with organ sampling for parents who decline the conventional invasive approach. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Autopsia/métodos , Feto/diagnóstico por imagem , Biópsia Guiada por Imagem/métodos , Ultrassonografia Pré-Natal/métodos , Estudos de Viabilidade , Feminino , Feto/patologia , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Morte Perinatal/etiologia , GravidezRESUMO
AIM: To determine whether the presence of internal calcifications on perinatal post-mortem skeletal surveys (PMSS) are associated with certain diagnoses of fetal loss. METHODS AND MATERIALS: A 6-month retrospective, single-centre, cohort study was conducted on PMSS performed for perinatal death assessment. One reader re-reviewed all PMSS images for the presence and location of internal calcifications, and noted whether these were included within the original radiology report. Findings at autopsy were then reviewed independently by a second researcher and cause of fetal loss or main diagnosis recorded. Chi-squared tests were conducted to identify differences between those with and without internal calcifications at PMSS. RESULTS: Two hundred and thirty perinatal deaths (mean gestational age 18 weeks; average 12-35 weeks) were included in the study, of which 42 (18.3%) demonstrated intra-abdominal calcifications, and 16/42 (38.1%) were mentioned in the radiology reports. Most calcifications were found to be within the lumen of the gastrointestinal tract, and in the left upper quadrant of the abdomen. There was no statistical difference between identifiable causes for fetal loss at autopsy in cases with and without calcification at PMSS (59.5% versus 58.5% respectively, p=0.904). Nevertheless, where calcification and a cause for fetal loss were found, the aetiology was more likely to be due a fetal rather than placental issue. CONCLUSION: The presence of internal calcifications on PMSS was not associated with an increased likelihood of explainable fetal loss or particular diagnosis at autopsy.
Assuntos
Calcinose/diagnóstico por imagem , Morte Fetal , Autopsia , Calcinose/embriologia , Diagnóstico , Feminino , Morte Fetal/etiologia , Idade Gestacional , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Estudos Retrospectivos , Microtomografia por Raio-XRESUMO
BACKGROUND: Linear morphoea (LM) is a rare connective tissue disorder characterized by a line of thickened skin and subcutaneous tissue and can also affect the underlying muscle and bone. Little is known about the disease aetiology, with treatment currently limited to immune suppression, and disease recurrence post-treatment is common. OBJECTIVES: In order to uncover new therapeutic avenues, the cell-intrinsic changes in LM fibroblasts compared with site-matched controls were characterized. METHODS: We grew fibroblasts from site-matched affected and unaffected regions from five patients with LM, we subjected them to gene expression analysis and investigation of SMAD signalling. RESULTS: Fibroblasts from LM lesions showed increased migration, proliferation, altered collagen processing, and abnormally high basal levels of phosphorylated SMAD2, thereby rendering them less responsive to transforming growth factor (TGF)-ß1 and reducing the degree of myofibroblast differentiation, which is a key component of the wound-healing and scarring process in normal skin. Conditioned media from normal fibroblasts could reverse LM-affected fibroblast migration and proliferation, suggesting that the LM phenotype is driven by an altered secretome. Gene array analysis and RNA-Seq indicated upregulation of ADAMTS8 and downregulation of FRAS1 and SOSTDC1. SOSTDC1 knock-down recapitulated the reduced TGF-ß1 responsiveness and LM fibroblast migration, while overexpression of ADAMTS8 induced myofibroblast markers. CONCLUSIONS: We demonstrate that cell-intrinsic changes in the LM fibroblast secretome lead to changes observed in the disease, and that secretome modulation could be a viable therapeutic approach in the treatment of LM.
Assuntos
Proteínas ADAMTS/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fibroblastos/metabolismo , Esclerodermia Localizada/patologia , Pele/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Animais , Biópsia , Movimento Celular/genética , Proliferação de Células/genética , Criança , Proteínas da Matriz Extracelular/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Células NIH 3T3 , Cultura Primária de Células , RNA-Seq , Transdução de Sinais/genética , Pele/citologia , Fator de Crescimento Transformador beta1/metabolismo , Regulação para CimaRESUMO
OBJECTIVE: To investigate whether less invasive methods of autopsy would be acceptable to bereaved parents and likely to increase uptake. DESIGN: Mixed methods study. SETTING: Bereaved parents recruited prospectively across seven hospitals in England and retrospectively through four parent support organisations. SAMPLE: Eight hundred and fifty-nine surveys and 20 interviews with bereaved parents. METHODS: Cross-sectional survey and qualitative semi-structured telephone interviews. MAIN OUTCOME MEASURES: Likely uptake, preferences, factors impacting decision-making, views on different autopsy methods. RESULTS: Overall, 90.5% of participants indicated that they would consent to some form of less invasive autopsy [either minimally invasive autopsy (MIA), non-invasive autopsy (NIA) or both]; 53.8% would consent to standard autopsy, 74.3% to MIA and 77.3% to NIA. Regarding parental preferences, 45.5% preferred MIA, 30.8% preferred NIA and 14.3% preferred standard autopsy. Participants who indicated they would decline standard autopsy but would consent to a less invasive option were significantly more likely to have a lower educational level (odds ratio 0.49; 95% CI 0.35-0.70; P = 0.000062). Qualitative findings suggest that parents value NIA because of the lack of any incision and MIA is considered a good compromise as it enables tissue sampling while easing the parental burden associated with consenting to standard autopsy. CONCLUSION: Less invasive methods of autopsy are acceptable alternatives for bereaved parents, and if offered, are likely to increase uptake and improve parental experience. Further health economic, validation and implementation studies are now required to assess the viability of offering these in routine widespread clinical care. TWEETABLE ABSTRACT: Mixed methods UK study finds less invasive methods of autopsy are acceptable alternatives for bereaved parents, and if offered, are likely to increase uptake and improve parental experience.
Assuntos
Feto Abortado/patologia , Autopsia/métodos , Anormalidades Congênitas , Morte Fetal/etiologia , Pais/psicologia , Morte Perinatal/etiologia , Natimorto , Luto , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/patologia , Aconselhamento/métodos , Estudos Transversais , Tomada de Decisões , Inglaterra , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Gravidez , Complicações na Gravidez/psicologia , Pesquisa Qualitativa , Natimorto/psicologiaRESUMO
OBJECTIVE: To compare the diagnostic rate and accuracy of 3-Tesla (T) postmortem magnetic resonance imaging (PM-MRI) and postmortem ultrasound (PM-US) in an unselected fetal population. METHODS: We performed prospectively, in a blinded manner, 3-T PM-MRI and PM-US on 160 unselected fetuses at 13-41 weeks of gestation. All imaging was reported according to a prespecified template, for five anatomical regions: brain, thorax, heart, abdomen and spine. The rates of non-diagnostic results for PM-US and PM-MRI were compared and, for results that were diagnostic, we calculated sensitivity, specificity and concordance rates for each anatomical region, using conventional autopsy as the reference standard. RESULTS: 3-T PM-MRI performed significantly better than did PM-US overall and in particular for fetuses ≥ 20 weeks' gestation. Specifically, the non-diagnostic rates for PM-MRI vs PM-US were 4.4% vs 26.9% (7/160 vs 43/160; P < 0.001) for the brain, 5.2% vs 17.4% (8/155 vs 27/155; P < 0.001) for the thorax, 3.8% vs 30.6% (6/157 vs 48/157; P < 0.001) for the heart and 3.2% vs 23.6% (5/157 vs 37/157; P < 0.001) for the abdomen. For the spine, both techniques showed an equally low non-diagnostic rate. When both postmortem imaging techniques were diagnostic, they had similar accuracy, with no difference in sensitivity or specificity, and similar concordance with autopsy (PM-US, 79.5-96.5%; PM-MRI, 81.6-99.1%). CONCLUSIONS: PM-MRI performed significantly better than PM-US in this unselected population, due mainly to a lower non-diagnostic rate. PM-MRI should remain the first-line imaging investigation for perinatal autopsy, but PM-US could be considered if MRI is not available, albeit with a higher non-diagnostic rate. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
Autopsia/métodos , Morte Fetal/etiologia , Feto/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Ultrassonografia/métodos , Abdome/diagnóstico por imagem , Aborto Induzido/estatística & dados numéricos , Autopsia/estatística & dados numéricos , Autopsia/tendências , Bélgica/epidemiologia , Encéfalo/diagnóstico por imagem , Causas de Morte , Feminino , Feto/patologia , Idade Gestacional , Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Gravidez , Estudos Prospectivos , Sensibilidade e Especificidade , Coluna Vertebral/diagnóstico por imagem , Tórax/diagnóstico por imagem , Ultrassonografia/estatística & dados numéricosRESUMO
OBJECTIVE: Less invasive autopsy techniques in cases of fetal or infant death have good acceptability among parents, but the published sampling adequacy in needle biopsy studies is generally poor. Minimally Invasive Autopsy with Laparoscopically assisted sampling (MinImAL) has the potential to increase the diagnostic yield of less invasive autopsy by improving the quality and quantity of tissue samples obtained, whilst permitting visualization, extraction and examination of internal organs through a small incision. The aim of this study was to present the findings of our experience with the MinImAL procedure in cases of fetal, neonatal and pediatric death. METHODS: This was a retrospective analysis of 103 prospectively recruited unselected cases of fetal, neonatal or pediatric death that underwent the MinImAL procedure at a tertiary referral center over a 5-year period. Following preprocedure 1.5-T whole-body postmortem magnetic resonance imaging, MinImAL autopsy was performed. Procedure duration, sampling adequacy and cause of death were assessed. Chi-square analysis was used to compare the 'unexplained' rate of intrauterine deaths in the cohort with that in a previously published cohort of > 1000 cases of intrauterine death examined by standard autopsy. RESULTS: MinImAL autopsy was performed successfully in 97.8% (91/93) of the cases undergoing a complete procedure. There was a satisfactory rate of adequate histological sampling in most major organs; heart (100%, 91 cases), lung (100%, 91 cases), kidney (100%, 91 cases), liver (96.7%, 88 cases), spleen (94.5%, 86 cases), adrenal glands (89.0%, 81 cases), pancreas (82.4%, 75 cases) and thymus (56.0%, 51 cases). Procedure duration was similar to that of standard autopsy in a previously published cohort of intrauterine deaths. The unexplained rate in stillbirths and intrauterine fetal deaths that underwent MinImAL autopsy was not significantly different from that following standard autopsy. CONCLUSIONS: The MinImAL procedure provides good histological yield from major organs with minimal cosmetic damage and can be learned by an autopsy practitioner. The MinImAL procedure is an appropriate minimally invasive alternative for the investigation of perinatal and pediatric deaths in which consent to full autopsy is withheld, and may have applications in both high- and low/middle-income settings. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
Autopsia/métodos , Laparoscopia/métodos , Adolescente , Causas de Morte , Criança , Pré-Escolar , Estudos de Viabilidade , Morte Fetal/etiologia , Humanos , Lactente , Morte do Lactente/etiologia , Recém-Nascido , Estudos Retrospectivos , Imagem Corporal TotalRESUMO
OBJECTIVE: To determine, by expert consensus using a Delphi procedure, a minimum reporting set of study variables for fetal growth restriction (FGR) research studies. METHODS: A panel of experts, identified based on their publication record as lead or senior author of studies on FGR, was asked to select a set of essential reporting study parameters from a literature-based list of variables, utilizing the Delphi consensus methodology. Responses were collected in four consecutive rounds by online questionnaires presented to the panelists through a unique token-secured link for each round. The experts were asked to rate the importance of each parameter on a five-point Likert scale. Variables were selected in the three first rounds based on a 70% threshold for agreement on the Likert-scale scoring. In the final round, retained parameters were categorized as essential (to be reported in all FGR studies) or recommended (important but not mandatory). RESULTS: Of the 100 invited experts, 87 agreed to participate and of these 62 (71%) completed all four rounds. Agreement was reached for 16 essential and 30 recommended parameters including maternal characteristics, prenatal investigations, prenatal management and pregnancy/neonatal outcomes. Essential parameters included hypertensive complication in the current pregnancy, smoking, parity, maternal age, fetal abdominal circumference, estimated fetal weight, umbilical artery Doppler (pulsatility index and end-diastolic flow), fetal middle cerebral artery Doppler, indications for intervention, pregnancy outcome (live birth, stillbirth or neonatal death), gestational age at delivery, birth weight, birth-weight centile, mode of delivery and 5-min Apgar score. CONCLUSIONS: We present a list of essential and recommended parameters that characterize FGR independent of study hypotheses. Uniform reporting of these variables in prospective clinical research is expected to improve data quality, study consistency and ultimately our understanding of FGR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
Confiabilidade dos Dados , Retardo do Crescimento Fetal , Projetos de Pesquisa/normas , Consenso , Técnica Delphi , Feminino , Humanos , GravidezRESUMO
OBJECTIVE: To assess the diagnostic accuracy of postmortem ultrasound performed by operators blinded to prenatal findings and to invasive autopsy results in fetuses at different gestational ages and to investigate the effect of various parameters on its diagnostic success. METHODS: We performed postmortem two-dimensional ultrasound examination, blinded to clinical details, on 163 fetuses at 13-42 weeks' gestation. Logistic regression analysis was used to investigate the effect of: (i) gestational age at postmortem ultrasound, (ii) presence of maceration and (iii) mode of death, on whether the exam succeeded or failed to reach a diagnosis. In 123 cases in which invasive autopsy was available, the diagnostic accuracy of ultrasound in detecting major organ abnormalities was evaluated, using invasive autopsy as the gold standard. RESULTS: For the fetal brain, postmortem ultrasound exam was non-diagnostic in significantly more fetuses with maceration (39.5%; 17/43) vs those without maceration (20.0%; 24/120) (P = 0.013). For the fetal thorax, the exam was non-diagnostic in 34.1% (15/44) of fetuses < 20 weeks of gestation and in 10.9% (13/119) of fetuses ≥ 20 weeks (P < 0.001). For the heart and abdominal organs, there was no association between non-diagnostic postmortem ultrasound and the variables tested. For fetuses < 20 weeks, specificity of postmortem ultrasound examination was 83.3% for detection of anomalies of the brain, 68.6% for the thorax and 77.4% for the heart. For fetuses ≥ 20 weeks, sensitivity and specificity were, respectively, 61.9% and 74.2% for detection of anomalies of the brain, 29.5% and 87.0% for the thorax and 65.0% and 83.1% for the heart. For the fetal abdominal organs, sensitivity was 60.7% and specificity 75.8%, and postmortem ultrasound was particularly useful for detection of abnormalities of the kidneys, irrespective of gestational age. CONCLUSION: Although maceration may lead to failure of postmortem ultrasound examination in some cases, this technique achieves diagnostically acceptable levels of accuracy for fetal brain and abdominal organs, compared with conventional autopsy. It may therefore play a role as a first-line examination before other virtual autopsy techniques are indicated. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
Autopsia/métodos , Morte Fetal/etiologia , Feto/diagnóstico por imagem , Ultrassonografia/métodos , Aborto Espontâneo/etiologia , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Prospectivos , Análise de Regressão , Sensibilidade e Especificidade , Método Simples-CegoRESUMO
AIM: To determine local departmental adherence to the paediatric post-mortem magnetic resonance imaging (MRI) protocols, using a customised automated computational approach. MATERIALS AND METHODS: A retrospective review of 460 whole-body post-mortem MRI examinations performed at Great Ormond Street Hospital for Children over a 5.5-year period was assessed for adherence to a full or abbreviated imaging sequence protocol. A simple computer program was developed to batch process DICOM (digital imaging and communications in medicine) files, extracting imaging sequence details, followed by natural language processing (NLP) of authorised reports to automate information extraction of diagnostic image quality. RESULTS: The program was able to extract study parameters from the entire dataset (approximately 80 GB of data) in a few hours, and retrieve information on diagnostic image quality using NLP with an overall diagnostic accuracy for data extraction of 96.7% (445/460, 95% confidence interval [CI]: 94.7-98%). The full imaging protocol was adhered to in 305/460 (66.3%) cases, and an abbreviated protocol in 140/460 (30.4%) cases. Overall, 423/460 (91.9%) of studies were of diagnostic quality. These included 298/305 (97.7%) of the full protocol, 111/140 (79.3%) of the abbreviated protocol. In only five cases were the examinations non-diagnostic for all body systems, all of whom weighed <100 g (24.7-72 g) and imaged using the abbreviated protocol. CONCLUSION: The present study demonstrated a successful application of an automated approach for data collection for audit and quality assessment purposes using paediatric post-mortem imaging as a specific example. Re-audit of these data following change implementation will be straightforward now that the automated workflow is clearly established.
Assuntos
Autopsia/métodos , Armazenamento e Recuperação da Informação , Imageamento por Ressonância Magnética , Automação , Criança , Pré-Escolar , Auditoria Clínica , Inglaterra , Feto , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Imagem Corporal Total , Fluxo de TrabalhoRESUMO
Uterine artery application of adenoviral vascular endothelial growth factor A165 (Ad.VEGF-A165) gene therapy increases uterine blood flow and fetal growth in experimental animals with fetal growth restriction (FGR). Whether Ad.VEGF-A165 reduces lifelong cardiovascular disease risk imposed by FGR remains unknown. Here, pregnant guinea pigs fed 70% normal food intake to induce FGR received Ad.VEGF-A165 (1×1010 viral particles, n = 15) or vehicle ( n = 10), delivered to the external surface of the uterine arteries, in midpregnancy. Ad libitum-fed controls received vehicle only ( n = 14). Litter size, gestation length, and perinatal mortality were similar in control, untreated FGR, and FGR+Ad.VEGF-A165 animals. When compared with controls, birth weight was lower in male but higher in female pups following maternal nutrient restriction, whereas both male and female FGR+Ad.VEGF-A165 pups were heavier than untreated FGR pups ( P < 0.05, ANOVA). Postnatal weight gain was 10-20% greater in female FGR+Ad.VEGF-A165 than in untreated FGR pups, depending on age, although neither group differed from controls. Maternal nutrient restriction reduced heart weight in adult female offspring irrespective of Ad.VEGF-A165 treatment but did not alter ventricular wall thickness. In males, postnatal weight gain and heart morphology were not affected by maternal treatment. Neither systolic, diastolic, mean arterial pressure, adrenal weight, nor basal or challenged plasma cortisol were affected by maternal undernutrition or Ad.VEGF-A165 in either sex. Therefore, increased fetal growth conferred by maternal uterine artery Ad.VEGF-A165 is sustained postnatally in FGR female guinea pigs. In this study, we did not find evidence for an effect of maternal nutrient restriction or Ad.VEGF-A165 therapy on adult offspring blood pressure.
Assuntos
Adenoviridae/genética , Retardo do Crescimento Fetal/terapia , Técnicas de Transferência de Genes , Terapia Genética/métodos , Vetores Genéticos , Artéria Uterina/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/genética , Fatores Etários , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Peso ao Nascer , Pressão Sanguínea , Restrição Calórica , Modelos Animais de Doenças , Feminino , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/metabolismo , Idade Gestacional , Cobaias , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Gravidez , Fluxo Sanguíneo Regional , Fatores Sexuais , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Aumento de PesoRESUMO
BACKGROUND: Postmortem examination is the single most useful investigation in providing information to parents about why their baby or child died. Despite this, uptake remains well below the recommended 75%. OBJECTIVE: To address the question 'what are the barriers and motivators to perinatal, prenatal and paediatric PM examination?' SEARCH STRATEGY: Key databases including Pubmed and CINAHL; Cochrane library, websites of relevant patient organisations, hand search of key journals, first and last authors and references. SELECTION CRITERIA: Peer-reviewed qualitative, quantitative or mixed methods research examining factors affecting uptake or decline of perinatal or paediatric postmortem examination. DATA COLLECTION AND ANALYSIS: Narrative synthesis; findings were compared across studies to examine interrelations. MAIN RESULTS: Seven major themes describing barriers to postmortem uptake were identified: dislike of invasiveness, practicalities of the procedure, organ retention issues, protective parenting, communication and understanding, religion and culture and professional or organisational barriers. Six major themes related to factors which facilitated parental consent were identified: desire for information, contributing to research, coping and well-being, respectful care, minimally invasive options, and policy and practice. There were a number of themes in the literature that reflected best practice. CONCLUSION: Findings highlight the need for better health professional education and the fact some concerns may be mitigated if less invasive methods of postmortem were routinely available. New consent packages and codes of practice may have a positive impact on perception of examination after death. The landscape is changing; further research is necessary to assess the impact on postmortem uptake rates. TWEETABLE ABSTRACT: Systematic review to explore the barriers and motivators to perinatal, prenatal and paediatric postmortem examination.
Assuntos
Autopsia/estatística & dados numéricos , Causas de Morte , Acessibilidade aos Serviços de Saúde , Natimorto , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Worldwide introduction of the International Fedaration of Gynaecology and Obstetrics (FIGO) 2000 scoring system has provided an effective means to stratify patients with gestational trophoblastic neoplasia to single- or multi-agent chemotherapy. However, the system is quite elaborate with an extensive set of risk factors. In this study, we re-evaluate all prognostic risk factors involved in the FIGO 2000 scoring system and examine if simplification is feasible. PATIENTS AND METHODS: Between January 2003 and December 2012, 813 patients diagnosed with gestational trophoblastic neoplasia were identified at the Trophoblastic Disease Centre in London and scored using the FIGO 2000. Multivariable analysis and stepwise logistic regression were carried out to evaluate whether the FIGO 2000 scoring system could be simplified. RESULTS: Of the eight FIGO risk factors only pre-treatment serum human chorionic gonadotropin (hCG) levels exceeding 10 000 IU/l (OR = 5.0; 95% CI 2.5-10.4) and 100 000 IU/l (OR = 14.3; 95% CI 4.7-44.1), interval exceeding 7 months since antecedent pregnancy (OR = 4.1; 95% CI 1.0-16.2), and tumor size of over 5 cm (OR = 2.2; 95% CI 1.3-3.6) were identified as independently predictive for single-agent resistance. In addition, increased risk was apparent for antecedent term pregnancy (OR = 3.4; 95% CI 0.9-12.7) and the presence of five or more metastases (OR = 3.5; 95% CI 0.4-30.4), but patient numbers in these categories were relatively small. Stepwise logistic regression identified a simplified risk scoring model comprising age, pretreatment serum hCG, number of metastases, antecedent pregnancy, and interval but omitting tumor size, previous failed chemotherapy, and site of metastases. With this model only 1 out 725 patients was classified different from the FIGO 2000 system. CONCLUSION: Our simplified alternative using only five of the FIGO prognostic factors appears to be an accurate system for discriminating patients requiring single as opposed to multi-agent chemotherapy. Further work is urgently needed to validate these findings.