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1.
Lancet Oncol ; 23(3): 374-381, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35157829

RESUMO

BACKGROUND: Genetically stratified therapy for malignant mesothelioma is unavailable. Mesotheliomas frequently harbour loss of the chromosome 9p21.3 locus (CDKN2A-MTAP), which is associated with shorter overall survival due to loss of the tumour suppressor p16ink4A, an endogenous suppressor of cyclin-dependent kinase (CDK)4 and CDK6. Genetic restoration of p16ink4A suppresses mesothelioma in preclinical models, underpinning the rationale for targeting CDK4 and CDK6 in p16ink4A-negative mesothelioma. We developed a multicentre, stratified, phase 2 trial to test this hypothesis. METHODS: The MiST2 study was a single-arm, open-label, phase 2 clinical trial done two UK centres. Patients older than 18 years with any histologically confirmed subtype of mesothelioma (pleural or peritoneal) with radiological progression after at least one course of platinum-based chemotherapy were molecularly screened by immunohistochemistry for p16ink4A. Patients with p16ink4A-negative mesothelioma were eligible for inclusion in the study. Patients were required to have measurable disease by modified Response Evaluation Criteria in Solid Tumours version 1.1 for malignant mesothelioma, a predicted life expectancy of at least 12 weeks, and an Eastern Cooperative Oncology Group performance status score of 0-1. Patients received oral abemaciclib 200 mg twice daily, administered in 28-day cycles for 24 weeks. The primary endpoint was the disease control rate (patients with complete responses, partial responses, or stable disease) at 12 weeks. The null hypothesis could be rejected if at least 11 patients had disease control. The efficacy and safety populations were defined as all patients who received at least one dose of the study drug. The study is registered with ClinicalTrials.gov, NCT03654833, and is ongoing (but MiST2 is now closed). FINDINGS: Between Sept 31, 2019, and March 2, 2020, 27 eligible patients consented to molecular screening. The median follow-up was 18·4 weeks (IQR 6·7-23·9). One patient was excluded before treatment because of a serious adverse event before study drug allocation. 26 (100%) of 26 treated patients were p16ink4A deficient and received at least one dose of abemaciclib. Disease control at 12 weeks was reported in 14 (54%) of 26 patients (95% CI 36-71). Grade 3 or worse treatment-related adverse events (of any cause) occurred in eight (27%) of 26 patients (diarrhoea, dyspnoea, thrombocytopenia, vomiting, urinary tract infection, increased alanine aminotransferase, ascites, chest infection or suspected chest infection, neutropenic sepsis, alopecia, blood clot left calf, fall [broken neck and collar bone], haemoptysis, lower respiratory tract infection, and pulmonary embolism). Grade 3 or worse treatment-related adverse events occurred in three (12%) of 26 patients (diarrhoea, thrombocytopenia, vomiting, increased alanine aminotransferase, and pulmonary embolism). Serious adverse events occurred in six (23%) of 26 patients, leading to treatment discontinuation in one (4%) patient (diarrhoea, urinary tract infection, chest infection, neutropenic sepsis, fall [broken neck and collar bone], haemoptysis, lower respiratory tract infection, and pulmonary embolism). One patient had a serious adverse event related to abemaciclib (diarrhoea). One (4%) of 26 patients died from an adverse event (neutropenic sepsis). INTERPRETATION: This study met its primary endpoint, showing promising clinical activity of abemaciclib in patients with p16ink4A-negative mesothelioma who were previously treated with chemotherapy, and warrants its further investigation in a randomised study as a targeted stratified therapy. FUNDING: University of Leicester, Asthma UK and British Lung Foundation Partnership, and the Victor Dahdaleh Foundation.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Embolia Pulmonar , Infecções Respiratórias , Sepse , Trombocitopenia , Alanina Transaminase , Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis , Diarreia/etiologia , Hemoptise/tratamento farmacológico , Hemoptise/etiologia , Humanos , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Neoplasias Pleurais/tratamento farmacológico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/etiologia , Vômito/tratamento farmacológico
2.
Br J Cancer ; 126(1): 34-41, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34671131

RESUMO

BACKGROUND: We investigated the first-line activity of vinflunine in patients with penis cancer. Cisplatin-based combinations are commonly used, but survival is not prolonged; many patients are unfit for such treatment or experience toxicity that outweighs clinical benefit. METHODS: Twenty-five patients with inoperable squamous carcinoma of the penis were recruited to a single-arm, Fleming-A'Hern exact phase II trial. Treatment comprised 4 cycles of vinflunine 320 mg/m2, given every 21 days. Primary endpoint was clinical benefit rate (CBR: objective responses plus stable disease) assessed after 4 cycles. Seven or more objective responses or disease stabilisations observed in 22 evaluable participants would exclude a CBR of <15%, with a true CBR of >40% being probable. RESULTS: Twenty-two participants were evaluable. Ten objective responses or disease stabilisations were confirmed. CBR was 45.5%, meeting the primary endpoint; partial response rate was 27.3%. Seven patients received >4 cycles of vinflunine. Dose reduction or treatment delay was required for 20% of cycles. In all, 68% of patients experienced at least one grade 3 adverse event. Two deaths on treatment were not caused by disease progression. CONCLUSIONS: Pre-specified clinical activity threshold was exceeded. Toxicity was in keeping with experience in other tumours. Vinflunine merits further study in this disease. TRIAL REGISTRATION: NCT02057913.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Penianas/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Segurança do Paciente , Neoplasias Penianas/patologia , Taxa de Sobrevida , Resultado do Tratamento , Moduladores de Tubulina/uso terapêutico , Vimblastina/uso terapêutico
3.
Int J Legal Med ; 134(2): 637-643, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31250083

RESUMO

On 14 June 2017 at 00:54 h, the worst residential fire since the conclusion of the Second World War broke out in Flat 16, 4th floor of the 24-storey residential Grenfell Tower Block of flats, North Kensington, West London, UK. Seventy-one adults and children died, including one stillbirth. All victims of the Grenfell Tower disaster who died at the scene underwent post-mortem computed tomography (PMCT) imaging using a mortuary-sited mobile computed tomography scanner. For the first time, to the authors' knowledge, the disaster victim identification (DVI) radiology reporting was undertaken remote to the mortuary scanning. Over an 11-week period, 119 scans were undertaken on 16 days, with up to 18 scans a day. These were delivered to a remote reporting centre at Leicester on 13 days with between 2 and 20 scans arriving each day. Using a disaster-specific process pathway, a team of 4 reporters, with 3 support staff members, trialled a prototype INTERPOL DVI radiology reporting form and produced full radiology reports and supporting image datasets such that they were able to provide 96% of prototype DVI forms, 99% of image datasets and 86% of preliminary reports to the DVI teams in London within one working day of image receipt. This paper describes the first use of remote radiology reporting for DVI and exemplifies how remote PMCT reporting can be used to support a DVI process of this scale.


Assuntos
Restos Mortais/diagnóstico por imagem , Vítimas de Desastres , Documentação , Antropologia Forense/instrumentação , Tomógrafos Computadorizados , Tomografia Computadorizada por Raios X/métodos , Incêndios , Humanos , Reino Unido
4.
Forensic Sci Med Pathol ; 16(1): 113-118, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31797213

RESUMO

Use of post-mortem computed tomography (PMCT) scanning to investigate natural and unnatural death has increased dramatically in recent years. Powerful software exists to allow detailed analysis of the scanned anatomy and pathology, and users of PMCT and other medical imaging will already be familiar with both two-dimensional and three-dimensional (3D) representations of this data. However, standard medical image viewing programs do not allow direct manipulation of the visible anatomy. By extracting anatomical features from medical images, this data can be exported into 3D manipulation software to enhance pathological examination and anatomical demonstration. Here we illustrate, using an example of lower limb fractures from a pedestrian road traffic fatality, that open source software (Blender) can be used not only to manipulate the anatomical data, but to produce high-quality images and animations that are superior to what is achievable using the available output of standard medical image viewers. The described software provides practitioners from many different disciplines an ability to manipulate medical imaging data that may previously have seemed too expensive or otherwise inaccessible. The potential applications for this technique are not limited to trauma analysis, and the purpose of this document is to encourage others to explore this powerful software and its abilities. The article contains many specific terms, and targeted online searches using this vocabulary will reveal an abundance of guidance and video tutorials that will help even the complete novice begin to undertake apparently sophisticated 3D software tasks with relative ease and at no additional cost.


Assuntos
Fraturas Ósseas/diagnóstico por imagem , Imageamento Tridimensional , Software , Tomografia Computadorizada por Raios X , Autopsia/métodos , Medicina Legal/métodos , Humanos , Extremidade Inferior/diagnóstico por imagem , Extremidade Inferior/lesões , Masculino , Pessoa de Meia-Idade , Interface Usuário-Computador
5.
J Nutr ; 149(7): 1133-1139, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132111

RESUMO

BACKGROUND: Curcumin is the main active ingredient of the spice turmeric, investigated extensively for putative anticancer properties. OBJECTIVES: This phase IIa open-labelled randomized controlled trial aimed to assess safety, efficacy, quality of life, neurotoxicity, curcuminoids, and C-X-C-motif chemokine ligand 1 (CXCL1) in patients receiving folinic acid/5-fluorouracil/oxaliplatin chemotherapy (FOLFOX) compared with FOLFOX + 2 g oral curcumin/d (CUFOX). METHODS: Twenty-eight patients aged >18 y with a histological diagnosis of metastatic colorectal cancer were randomly assigned (1:2) to receive either FOLFOX or CUFOX. Safety was assessed by Common Toxicity Criteria-Adverse Event reporting, and efficacy via progression-free survival (PFS) and overall survival (OS). Quality of life and neurotoxicity were assessed using questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and Functional Assessment of Cancer Treatment-Gynecologic Oncology Group-Neurotoxicity). Plasma curcuminoids were determined with liquid chromatography (LC) electrospray ionization tandem mass spectrometry and CXCL1 by ELISA. RESULTS: Addition of daily oral curcumin to FOLFOX chemotherapy was safe and tolerable (primary outcome). Similar adverse event profiles were observed for both arms. In the intention-to-treat population, the HR for PFS was 0.57 (95% CI: 0.24, 1.36; P = 0.2) (median of 171 and 291 d for FOLFOX and CUFOX, respectively) and for OS was 0.34 (95% CI: 0.14, 0.82; P = 0.02) (median of 200 and 502 d for FOLFOX and CUFOX, respectively). There was no significant difference between arms for quality of life (P = 0.248) or neurotoxicity (P = 0.223). Curcumin glucuronide was detectable at concentrations >1.00 pmol/mL in 15 of 18 patients receiving CUFOX. Curcumin did not significantly alter CXCL1 over time (P = 0.712). CONCLUSION: Curcumin is a safe and tolerable adjunct to FOLFOX chemotherapy in patients with metastatic colorectal cancer. This trial was registered at clinicaltrials.gov as NCT01490996 and at www.clinicaltrialsregister.eu as EudraCT 2011-002289-19.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Curcumina/uso terapêutico , Administração Oral , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/patologia , Curcumina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Resultado do Tratamento
6.
Lancet ; 390(10090): 145-154, 2017 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-28551075

RESUMO

BACKGROUND: England and Wales have one of the highest frequencies of autopsy in the world. Implementation of post-mortem CT (PMCT), enhanced with targeted coronary angiography (PMCTA), in adults to avoid invasive autopsy would have cultural, religious, and potential economic benefits. We aimed to assess the diagnostic accuracy of PMCTA as a first-line technique in post-mortem investigations. METHODS: In this single-centre (Leicester, UK), prospective, controlled study, we selected cases of natural and non-suspicious unnatural death referred to Her Majesty's (HM) Coroners. We excluded cases younger than 18 years, known to have had a transmittable disease, or who weighed more than 125 kg. Each case was assessed by PMCTA, followed by autopsy. Pathologists were masked to the PMCTA findings, unless a potential risk was shown. The primary endpoint was the accuracy of the cause of death diagnosis from PMCTA against a gold standard of autopsy findings, modified by PMCTA findings only if additional substantially incontrovertible findings were identified. FINDINGS: Between Jan 20, 2010, and Sept 13, 2012, we selected 241 cases, for which PMCTA was successful in 204 (85%). Seven cases were excluded from the analysis because of procedural unmasking or no autopsy data, as were 24 cases with a clear diagnosis of traumatic death before investigation; 210 cases were included. In 40 (19%) cases, predictable toxicology or histology testing accessible by PMCT informed the result. PMCTA provided a cause of death in 193 (92%) cases. A major discrepancy with the gold standard was noted in 12 (6%) cases identified by PMCTA, and in nine (5%) cases identified by autopsy (because of specific findings on PMCTA). The frequency of autopsy and PMCTA discrepancies were not significantly different (p=0·65 for major discrepancies and p=0·21 for minor discrepancies). Cause of death given by PMCTA did not overlook clinically significant trauma, occupational lung disease, or reportable disease, and did not significantly affect the overall population data for cause of death (p≥0·31). PMCTA was better at identifying trauma and haemorrhage (p=0·008), whereas autopsy was better at identifying pulmonary thromboembolism (p=0·004). INTERPRETATION: For most sudden natural adult deaths investigated by HM Coroners, PMCTA could be used to avoid invasive autopsy. The gold standard of post-mortem investigations should include both PMCT and invasive autopsy. FUNDING: National Institute for Health Research.


Assuntos
Autopsia/métodos , Morte Súbita/etiologia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Hemorragia Cerebral/diagnóstico por imagem , Angiografia Coronária , Médicos Legistas , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Estudos Prospectivos , Adulto Jovem
7.
Radiology ; 288(1): 270-276, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29714682

RESUMO

Purpose To determine if postmortem computed tomography (CT) and postmortem CT angiography help to detect more lesions than autopsy in postmortem examinations, to evaluate the strengths and weaknesses of each method, and to define their indications. Materials and Methods Postmortem CT angiography was performed on 500 human corpses and followed by conventional autopsy. Nine centers were involved. All CT images were read by an experienced team including one forensic pathologist and one radiologist, blinded to the autopsy results. All findings were recorded for each method and categorized by anatomic structure (bone, organ parenchyma, soft tissue, and vascular) and relative importance in the forensic case (essential, useful, and unimportant). Results Among 18 654 findings, autopsies helped to identify 61.3% (11 433 of 18 654), postmortem CT helped to identify 76.0% (14 179 of 18 654), and postmortem CT angiography helped to identify 89.9% (16 780 of 18 654; P < .001). Postmortem CT angiography was superior to autopsy, especially at helping to identify essential skeletal lesions (96.1% [625 of 650] vs 65.4% [425 of 650], respectively; P < .001) and vascular lesions (93.5% [938 of 1003] vs 65.3% [655 of 1003], respectively; P < .001). Among the forensically essential findings, 23.4% (1029 of 4393) were not detected at autopsy, while only 9.7% (428 of 4393) were missed at postmortem CT angiography (P < .001). The best results were obtained when postmortem CT angiography was combined with autopsy. Conclusion Postmortem CT and postmortem CT angiography and autopsy each detect important lesions not detected by the other method. More lesions were identified by combining postmortem CT angiography and autopsy, which may increase the quality of postmortem diagnosis. Online supplemental material is available for this article.


Assuntos
Autopsia/métodos , Causas de Morte , Angiografia por Tomografia Computadorizada/métodos , Patologia Legal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia/estatística & dados numéricos , Angiografia por Tomografia Computadorizada/estatística & dados numéricos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
8.
Int J Legal Med ; 131(1): 211-216, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27817167

RESUMO

We report for the first time the use of coaxial cutting needle biopsy, guided by post-mortem computed tomography (PMCT), to sample internal body tissues for bacterioplankton PCR analysis to investigate drowning. This technical report describes the biopsy technique, the comparison of the needle biopsy and the invasive autopsy sampling results, as well as the PMCT and autopsy findings. By using this new biopsy sampling approach for bacterioplankton PCR, we have developed on previous papers describing the minimally invasive PMCT approach for the diagnosis of drowning. When such a system is used, the operator must take all precautions to avoid contamination of the core biopsy samples due to the sensitivity of PCR-based analytic systems.


Assuntos
Aeromonas/genética , Biópsia por Agulha/métodos , DNA Bacteriano/isolamento & purificação , Afogamento/diagnóstico , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/microbiologia , Encéfalo/patologia , Humanos , Rim/diagnóstico por imagem , Rim/microbiologia , Rim/patologia , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Pulmão/patologia , Masculino , Reação em Cadeia da Polimerase , Radiografia Intervencionista , Baço/diagnóstico por imagem , Baço/microbiologia , Baço/patologia , Tomografia Computadorizada por Raios X , Imagem Corporal Total
9.
Lancet ; 385(9964): 253-9, 2015 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-25238931

RESUMO

BACKGROUND: Richard III was the last king of England to die in battle, but how he died is unknown. On Sept 4, 2012, a skeleton was excavated in Leicester that was identified as Richard. We investigated the trauma to the skeleton with modern forensic techniques, such as conventional CT and micro-CT scanning, to characterise the injuries and establish the probable cause of death. METHODS: We assessed age and sex through direct analysis of the skeleton and from CT images. All bones were examined under direct light and multi-spectral illumination. We then scanned the skeleton with whole-body post-mortem CT. We subsequently examined bones with identified injuries with micro-CT. We deemed that trauma was perimortem when we recorded no evidence of healing and when breakage characteristics were typical of fresh bone. We used previous data to identify the weapons responsible for the recorded injuries. FINDINGS: The skeleton was that of an adult man with a gracile build and severe scoliosis of the thoracic spine. Standard anthropological age estimation techniques based on dry bone analysis gave an age range between 20s and 30s. Standard post-mortem CT methods were used to assess rib end morphology, auricular surfaces, pubic symphyseal face, and cranial sutures, to produce a multifactorial narrower age range estimation of 30-34 years. We identified nine perimortem injuries to the skull and two to the postcranial skeleton. We identified no healed injuries. The injuries were consistent with those created by weapons from the later medieval period. We could not identify the specific order of the injuries, because they were all distinct, with no overlapping wounds. Three of the injuries-two to the inferior cranium and one to the pelvis-could have been fatal. INTERPRETATION: The wounds to the skull suggest that Richard was not wearing a helmet, although the absence of defensive wounds on his arms and hands suggests he was still otherwise armoured. Therefore, the potentially fatal pelvis injury was probably received post mortem, meaning that the most likely injuries to have caused his death are the two to the inferior cranium. FUNDING: The University of Leicester.


Assuntos
Traumatismos Faciais/patologia , Traumatismos Cranianos Penetrantes/patologia , Ossos Pélvicos/lesões , Costelas/lesões , Fraturas Cranianas/patologia , Armas , Adulto , Autopsia , Inglaterra , Traumatismos Cranianos Penetrantes/diagnóstico por imagem , História Medieval , Humanos , Masculino , Roupa de Proteção/história , Fraturas Cranianas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ferimentos Penetrantes/diagnóstico por imagem , Ferimentos Penetrantes/patologia
10.
Int J Legal Med ; 129(2): 325-34, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25524761

RESUMO

Ventilated post-mortem computed tomography (VPMCT) has been shown to achieve lung expansion in cadavers and has been proposed to enhance the diagnosis of lung pathology. Two key problems of the method of ventilation have been identified: firstly, the presence of head and neck rigor making airway insertion challenging and, secondly, air leak, if there is not a good seal around the airway, which diminishes lung expansion and causes inflation of the stomach. Simple procedures to insert a 'definitive' cuffed airway, which has a balloon inflated within the trachea, are therefore desirable. This study aims to test different procedures for inserting cuffed airways in cadavers and compare their ventilation efficacy and to propose a decision algorithm to select the most appropriate method. We prospectively tested variations on two ways of inserting a cuffed airway into the trachea: firstly, using an endotracheal tube (ET) approach, either blind or by direct visualisation, and, secondly, using a tracheostomy incision, either using a standard tracheostomy tube or shortened ET tube. We compare these approaches with a retrospective analysis of a previously reported series using supraglottic airways. All techniques, except 'blind' insertion of ET tubes, were possible with adequate placement of the airway in most cases. However, achieving both adequate insertion and a complete tracheal seal was better for definitive airways with 56 successful cases from 59 (95 %), compared with 9 cases from 18 (50 %) using supraglottic airways (p < 0.0001). Good lung expansion was achieved using all techniques if the airway was adequately positioned and achieved a good seal, and there was no significant chest pathology. We prefer inserting a shortened ET tube via a tracheostomy incision, as we find this the easiest technique to perform and train. Based on our experience, we have developed a decision algorithm to select the most appropriate method for VPMCT.


Assuntos
Autopsia/métodos , Insuflação/métodos , Intubação Intratraqueal/instrumentação , Pulmão/diagnóstico por imagem , Respiração Artificial , Traqueostomia/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Cadáver , Feminino , Patologia Legal , Humanos , Insuflação/instrumentação , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Estudos Prospectivos , Estudos Retrospectivos , Imagem Corporal Total , Adulto Jovem
11.
Int J Legal Med ; 128(4): 653-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24425671

RESUMO

Age estimation is one of the primary demographic features used in the identification of juvenile remains. Determining the accuracy and repeatability of age estimations based on postmortem computed tomography (PMCT) data compared with those using conventional orthopantomography (OPT) images is important to validate the use of PMCT as a single imaging technique in forensic and disaster victim identification (DVI). In this study, 19 juvenile mandibles and maxilla of known age underwent both OPT and PMCT. Three raters then estimated dental age using the resulting images and 3D reconstructions. This assessment showed excellent agreement between the age estimations using the two techniques for all three observers. PMCT also offers a greater range of measurements for both the dentition and the whole human skeleton using a single image acquisition and therefore has the potential to improve both the speed and accuracy of age estimation.


Assuntos
Determinação da Idade pelos Dentes/métodos , Tomografia Computadorizada Multidetectores , Radiografia Panorâmica , Adolescente , Criança , Pré-Escolar , Dentição , Odontologia Legal , Humanos , Imageamento Tridimensional , Lactente , Variações Dependentes do Observador , Dente/diagnóstico por imagem , Adulto Jovem
12.
Future Oncol ; 10(5): 823-33, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24799063

RESUMO

AIMS: To assess the utility of dynamic contrast-enhanced MRI parameters in the demonstration of early antiangiogenic effects and as prognostic biomarkers in second-line treatment of advanced-stage non-small-cell lung cancer with vatalanib. PATIENTS & METHODS: The transfer constant (K(trans)) and the initial area under the contrast concentration-time curve at 60 s (AUC60) were assessed in 46 patients. Changes were compared with response evaluation from computed tomography imaging and Response Evaluation Criteria In Solid Tumors guidelines. RESULTS: Statistically significant mean reductions in K(trans) (38.4%; p < 0.0001) and AUC60 (24.9%; p < 0.0001) were found at day 2. After 12 weeks, 16 patients (35%) demonstrated stable disease and 30 (65%) demonstrated progressive disease. No statistically significant differences in day 2 K(trans) and AUC60 reductions between stable disease and progressive disease patients were found. CONCLUSION: Dynamic contrast-enhanced MRI can demonstrate a statistically significant reduction in vascular parameters of non-small-cell lung cancer, but does not predict patient outcome.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imageamento por Ressonância Magnética , Ftalazinas/administração & dosagem , Piridinas/administração & dosagem , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos como Assunto , Meios de Contraste/administração & dosagem , Meios de Contraste/uso terapêutico , Avaliação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ftalazinas/efeitos adversos , Piridinas/efeitos adversos , Radiografia
13.
Forensic Sci Med Pathol ; 10(4): 504-12, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25037236

RESUMO

Anthropological examination of bones is routinely undertaken in medico-legal investigations to establish an individual's biological profile, particularly their age. This often requires the removal of soft tissue from bone (de-fleshing), which, especially when dealing with the recently deceased, is a time consuming and invasive procedure. Recent advances in multi-detector computed tomography have made it practical to rapidly acquire high-resolution morphological skeletal information from images of "fleshed" remains. The aim of this study was to develop a short standard form, created from post-mortem computed tomography images, that contains the minimum image-set required to anthropologically assess an individual. The proposed standard forms were created for 31 juvenile forensic cases with known age-at-death, spanning the full age range of the developing human. Five observers independently used this form to estimate age-at-death. All observers estimated age in all cases, and all estimations were within the accepted ranges for traditional anthropological and odontological assessment. This study supports the implementation of this approach in forensic radiological practice.


Assuntos
Determinação da Idade pelo Esqueleto/métodos , Determinação da Idade pelos Dentes/métodos , Osso e Ossos/diagnóstico por imagem , Antropologia Forense/métodos , Tomografia Computadorizada Multidetectores , Sistemas de Informação em Radiologia , Registros , Adolescente , Adulto , Fatores Etários , Autopsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores Sexuais , Adulto Jovem
14.
Int J Legal Med ; 127(3): 661-6, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23232542

RESUMO

Targeted post-mortem computed tomography angiography (PMCTA) is one of several methods described that can be used to investigate the coronary arteries after death. Previously, this particular method has involved the manual injection of contrast media. However, manual systems do not mimic physiological conditions (arterial pressure) and may not provide optimal contrast, as iodinated contrast medium dissipates rapidly from the intra- to the extra-vascular space. To try and overcome these problems, we now report the use of a clinical automatic pump injector for targeted PMCTA. We present our final protocol for this pump system developed from experience of 74 cases, showing how these clinical pumps can be translated from clinical into autopsy practice for the injection of air and positive contrast media to visualise the coronary arteries of cadavers.


Assuntos
Autopsia/métodos , Meios de Contraste/administração & dosagem , Angiografia Coronária/métodos , Tomografia Computadorizada por Raios X/métodos , Angiografia Coronária/instrumentação , Humanos , Mudanças Depois da Morte , Tomografia Computadorizada por Raios X/instrumentação
15.
Int J Legal Med ; 127(5): 991-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23455719

RESUMO

Social, cultural and practical barriers to conventional invasive autopsy have led to considerable interest in the development of minimally invasive radiological techniques as an alternative to the invasive autopsy for determining the cause of death. Critical to accurate diagnosis in this context is detailed examination of coronary anatomy and pathology. Current computed tomography and magnetic resonance imaging approaches have significantly advanced minimally invasive autopsy practice but have limited spatial resolution. This prohibits assessment at a microscopic level, meaning that histological assessment is still required for detailed analysis of, for example, coronary plaque rupture or dissection. Coronary optical coherence tomography (OCT) is used in the living during percutaneous coronary interventions to provide high-resolution coronary imaging, but this technique for obtaining virtual histology has not, to date, been translated into minimally invasive autopsy practice. We present a first description of minimally invasive post-mortem coronary OCT and discuss the potential for this technique to advance current practice.


Assuntos
Vasos Coronários/patologia , Tomografia de Coerência Óptica , Cateterismo Cardíaco , Angiografia Coronária , Endotélio Vascular/patologia , Fluoroscopia , Patologia Legal/métodos , Humanos , Imageamento Tridimensional , Tomografia Computadorizada Multidetectores
16.
Hepatol Res ; 43(8): 809-19, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23745715

RESUMO

The use of contrast agents (CA) with liver ultrasound (US) has gained recently an established role for the diagnosis of various hepatic diseases due to their safety, high versatility and low costs (contrast-enhanced ultrasound: CEUS). The purpose of this review is to provide a state-of-the-art summary of the available evidence for their use in the characterization of focal liver lesions. A published work search was conducted for all preclinical and clinical studies involving CA on hepatic US imaging. CEUS increases the sensitivity for lesion detection and the specificity to differentiate between benign and malignant diseases due to the enhanced visualization of the tumor microcirculation. Results achieved seem at least equivalent to those of spiral computed tomography or magnetic resonance imaging. The association of CA with intraoperative ultrasound has changed the surgical approach in 25% of patients and guarantees complete ablations by a single session in most of them. CEUS provides detailed information about tumor vasculature, improves the preoperative characterization and therefore the therapeutic strategy, and can evaluate the intraoperative completeness of the ablation.

17.
Forensic Sci Med Pathol ; 9(4): 489-95, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23832424

RESUMO

Post-mortem computed tomography angiography (PMCTA) involves the injection of contrast agents. This could have both a dilution effect on biological fluid samples and could affect subsequent post-contrast analytical laboratory processes. We undertook a small sample study of 10 targeted and 10 whole body PMCTA cases to consider whether or not these two methods of PMCTA could affect post-PMCTA cadaver blood based DNA identification. We used standard methodology to examine DNA from blood samples obtained before and after the PMCTA procedure. We illustrate that neither of these PMCTA methods had an effect on the alleles called following short tandem repeat based DNA profiling, and therefore the ability to undertake post-PMCTA blood based DNA identification.


Assuntos
Angiografia/métodos , Impressões Digitais de DNA , DNA/sangue , Tomografia Computadorizada por Raios X , Imagem Corporal Total/métodos , Autopsia , Cadáver , Meios de Contraste/administração & dosagem , Diatrizoato de Meglumina/administração & dosagem , Humanos , Injeções , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
18.
J Plast Reconstr Aesthet Surg ; 85: 401-413, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37572388

RESUMO

AIMS: In July 2022, NICE updated the guidelines on the management of melanoma by lowering the number of follow-up appointments and sentinel lymph node biopsy (SLNB) but increasing the number of scans. This study aims to evaluate the implications of executing the new guidelines in terms of cost-effectiveness and personnel. METHODS: All patients newly diagnosed with melanoma in 2019 at a regional skin cancer specialist center were reviewed. Data were analyzed for their journey on an idealized pathway modeled over a 5-year follow-up period when adhering to both the previous and new guidelines. Differences in the management of melanoma were elucidated by comparing these changes. The cost was quantified on a perpatient basis and the financial implication on each department was considered. RESULTS: One hundred and ten patients were diagnosed with melanoma in 2019, stages I-III. The changes ease the burden on plastic surgery and dermatology; however, increased pressure is faced by radiologists and histopathologists. An overall cost benefit of £141.85 perpatient was calculated, resulting in a decrease of 1.22 hospital visits on average and an increase in the time spent there (19.55 min). The additional expenses of implementing the new guidelines due to the added BRAF tests, CT, and ultrasound scans are outweighed by savings from the reduction in follow-up appointments and SLNB. CONCLUSION: The focus has shifted to less invasive procedures for lower melanoma stages and fewer follow-up appointments, at the expense of more genetic testing and imaging. This paper serves as a useful baseline for other centers to plan their service provision and resource allocation to adhere to the updated guidelines.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/cirurgia , Melanoma/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Biópsia de Linfonodo Sentinela/métodos , Estudos Retrospectivos
19.
Forensic Sci Med Pathol ; 8(1): 40-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21811877

RESUMO

With the introduction of targeted coronary artery angiography to post-mortem computed tomography (PMCT) it is now possible to assess the coronary arteries and left ventricle after death without, case dependent, the necessity to undertake an invasive autopsy. The purpose of this pictorial review is to act as a walk through aid memoire and educational learning document for radiologists and pathologists alike who may be new to the use and interpretation of targeted PMCT angiography. By using an example scanning protocol, which uses both positive and negative (air) contrast mediums, this pictorial review provides a systematic approach to vessel and ventricular assessment that is based upon clinical cardiac angiography but adapted to PMCT.


Assuntos
Autopsia/métodos , Angiografia Coronária/métodos , Tomografia Computadorizada por Raios X , Ar , Cardiomiopatias/diagnóstico por imagem , Cateterismo , Catéteres , Meios de Contraste , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Patologia Legal , Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Mudanças Depois da Morte , Artéria Pulmonar/diagnóstico por imagem , Stents , Grau de Desobstrução Vascular
20.
Forensic Sci Med Pathol ; 8(3): 270-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22581318

RESUMO

Anthropological examination of defleshed bones is routinely used in medico-legal investigations to establish an individual's biological profile. However, when dealing with the recently deceased, the removal of soft tissue from bone can be an extremely time consuming procedure that requires the presence of a trained anthropologist. In addition, due to its invasive nature, in some disaster victim identification scenarios the maceration of bones is discouraged by religious practices and beliefs, or even prohibited by national laws and regulations. Currently, three different radiological techniques may be used in the investigative process; plain X-ray, dental X-ray and fluoroscopy. However, recent advances in multi-detector computed tomography (MDCT) mean that it is now possible to acquire morphological skeletal information from high resolution images, reducing the necessity for invasive procedures. This review paper considers the possible applications of a virtual anthropological examination by reviewing the main juvenile age determination methods used by anthropologists at present and their possible adaption to MDCT.


Assuntos
Determinação da Idade pelo Esqueleto/métodos , Determinação da Idade pelos Dentes/métodos , Osso e Ossos/diagnóstico por imagem , Antropologia Forense/métodos , Imageamento Tridimensional , Tomografia Computadorizada Multidetectores , Interpretação de Imagem Radiográfica Assistida por Computador , Dente/diagnóstico por imagem , Fatores Etários , Autopsia , Humanos , Dente/crescimento & desenvolvimento
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