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1.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34493667

RESUMO

The Santa Rosa fossil locality in eastern Perú produced the first Paleogene vertebrate fauna from the Amazon Basin, including the oldest known monkeys from South America. This diverse paleofauna was originally assigned an Eocene age based largely on the stage of evolution of the site's caviomorph rodents and marsupials. Here, we present detrital zircon dates that indicate that the maximum composite age of Santa Rosa is 29.6 ± 0.08 Ma (Lower Oligocene), although several zircons from Santa Rosa date to the Upper Oligocene. The first appearance datum for Caviomorpha in South America is purported to be the CTA-27 site in the Contamana region of Perú, which is hypothesized to be ∼41 Ma (Middle Eocene) in age. However, the presence of the same caviomorph species and/or genera at both CTA-27 and at Santa Rosa is now difficult to reconcile with a >11-My age difference. To further test the Middle Eocene age estimate for CTA-27, we ran multiple Bayesian tip-dating analyses of Caviomorpha, treating the ages of all Paleogene species from Perú as unknown. These analyses produced mean age estimates for Santa Rosa that closely approximate the maximum 29.6 ± 0.08 Ma composite date provided by detrital zircons, but predict that CTA-27 is much younger than currently thought (∼30 Ma). We conclude that the ∼41 Ma age proposed for CTA-27 is incorrect, and that there are currently no compelling Eocene records of either rodents or primates in the known fossil record of South America.


Assuntos
Migração Animal/fisiologia , Teorema de Bayes , Evolução Biológica , Fósseis , Haplorrinos/classificação , Filogenia , Roedores/classificação , Animais , Geografia , América do Sul
2.
BMC Urol ; 18(1): 18, 2018 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-29523118

RESUMO

BACKGROUND: The non-invasive Cxbladder urine test system has demonstrated clinical utility in ruling out urothelial carcinoma (UC) in patients with asymptomatic microscopic hematuria (AMH), suggesting that the number of invasive diagnostic tests, including cystoscopy, used in this patient population may be reduced by Cxbladder testing prior to conducting a full urological work-up. The aim of this study was to demonstrate the enhanced clinical utility of communicating objective information on diagnostic decisions made by individual physicians on individual patients with AMH. METHODS: Three hundred ninety-six physician-patient decisions were generated from twelve participant physicians evaluating real world case notes from the same 33 patients presenting with AMH. Each physician reviewed and recommended diagnostic tests and procedures based on each patient's referral data and then re-evaluated their clinical recommendation following disclosure of the non-invasive Cxbladder urine test result. Changes assessed were the total number of requested diagnostic procedures and the number of invasive procedures, including cystoscopy, following addition of information from Cxbladder in the Triage and Triage and Detect modalities. RESULTS: Physicians made significant changes to their diagnostic behavior for patients with AMH when presented with Cxbladder test results, including a reduction in the number of total and invasive procedures including cystoscopy for individuals identified as having a low probability of UC. The intensity of investigation was targeted and increased, including use of total procedures and cystoscopy, for patients identified by Cxbladder tests as having a high probability of UC: urologists increased the level of investigation for both total procedures and invasive procedures. The outcome resulted in patients with a high risk of UC receiving appropriate guideline-recommended invasive diagnostic tests. Patients who tested negative were offered fewer and significantly less invasive procedures. This change in physician behavior results in an increased clinical and patient utility, lower risk of missed UC and invasive test-related harm incidents. CONCLUSIONS: This study demonstrated the potential for increased clinical resolution and significantly enhanced patient management, when physicians consider Cxbladder test results in their clinical evaluation. The change in physician behavior led to more appropriate diagnostic procedure selection and resource allocation to the benefit of both patients and healthcare systems.


Assuntos
Tomada de Decisão Clínica/métodos , Hematúria/diagnóstico por imagem , Hematúria/urina , Relações Médico-Paciente , Estatística como Assunto/métodos , Testes Diagnósticos de Rotina/métodos , Hematúria/epidemiologia , Humanos , Estudos Prospectivos , Medição de Risco , Urinálise/métodos
3.
J Urol ; 197(6): 1419-1426, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27986532

RESUMO

PURPOSE: Urothelial carcinoma is associated with a high rate of recurrence. Guidelines recommend rigorous, regular surveillance programs that are invasive and expensive. This study describes a noninvasive urine test with sufficient sensitivity to rule out recurrent urothelial carcinoma, thereby reducing invasive diagnostic evaluations without compromising patient care. METHODS AND MATERIALS: A total of 1,036 urine samples were prospectively collected from 763 patients undergoing routine surveillance for recurrent urothelial carcinoma of the bladder. The purpose was to develop and validate a test with combined high sensitivity and high negative predictive value. Cxbladder Monitor combines gene expression, clinical and patient data, and it is designed to rule out the presence of recurrent urothelial carcinoma. RESULTS: Cxbladder Monitor showed an internally validated sensitivity of 0.93 with a negative predictive value of 0.97 and a test negative rate of 0.34. Sensitivity was 0.95 for recurrent disease with a high risk of progression (all high grade disease and low grade, stage T1 or greater disease) compared with 0.86 for low grade Ta disease. Subgroup analyses indicated that diagnostic performance was not significantly different in different age groups, or by gender or tumor stage. Sensitivity was not affected by adjuvant bacillus Calmette-Guérin treatment within the last 6 months. False-negative findings were reported in fewer than 1.5% of all samples collected. CONCLUSIONS: The Cxbladder Monitor test offers combined high sensitivity and high negative predictive value to rule out urothelial carcinoma. This test has clinical utility as a confirmatory negative adjunct to cystoscopy, potentially justifying the postponement/avoidance of cystoscopic investigations to monitor recurrence in patients.


Assuntos
Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/urina , Recidiva Local de Neoplasia/urina , Neoplasias da Bexiga Urinária/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Vigilância da População , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias da Bexiga Urinária/genética
4.
Biochem J ; 473(12): 1759-68, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27071417

RESUMO

Inherited and de novo mutations in the CARD14 gene promote the development of psoriasis, an inflammatory disease of the skin. Caspase recruitment domain-containing protein 14 (CARD14) is a member of the CARMA protein family that includes the structurally related CARD11 adaptor that mediates NF-κB activation by antigen receptors. We investigated the mechanism by which CARD14 mutation in psoriasis activates NF-κB. In contrast with wild-type CARD14, CARD14(E138A) and CARD14(G117S) psoriasis mutants interacted constitutively with BCL10 and MALT1, and triggered BCL10- and MALT1-dependent activation of NF-κB in keratinocytes. These alterations disrupted the inhibitory effect of the CARD14 linker region (LR) on NF-κB activation by facilitating BCL10 binding. Therefore, psoriasis mutations activated CARD14 by a mechanism analogous to oncogenic CARD11 mutations in non-Hodgkin B cell lymphomas. CARD14(E138A) also stimulated MALT1 paracaspase activity and activated both ERK1/2 and p38α MAP kinases. Inhibition of MALT1 with mepazine reduced CARD14(E138A)-induced expression of specific psoriasis-associated transcripts in keratinocytes. Our results establish the mechanism whereby gain-of-function CARD14 variants, which induce psoriatic disease in affected individuals, activate pro-inflammatory signalling.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Caspases/metabolismo , Guanilato Ciclase/metabolismo , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Psoríase/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteína 10 de Linfoma CCL de Células B , Proteínas Adaptadoras de Sinalização CARD/genética , Caspases/genética , Linhagem Celular , Guanilato Ciclase/genética , Humanos , Imunoprecipitação , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas de Membrana/genética , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , Mutação/genética , Proteínas de Neoplasias/genética , Ligação Proteica/genética , Ligação Proteica/fisiologia , Psoríase/genética , RNA Interferente Pequeno , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
5.
BMC Med Res Methodol ; 15: 45, 2015 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-25962444

RESUMO

BACKGROUND: Comparing the relative utility of diagnostic tests is challenging when available datasets are small, partial or incomplete. The analytical leverage associated with a large sample size can be gained by integrating several small datasets to enable effective and accurate across-dataset comparisons. Accordingly, we propose a methodology for a holistic comparative analysis and ranking of cancer diagnostic tests through dataset integration and imputation of missing values, using urothelial carcinoma (UC) as a case study. METHODS: Five datasets comprising samples from 939 subjects, including 89 with UC, where up to four diagnostic tests (cytology, NMP22®, UroVysion® Fluorescence In-Situ Hybridization (FISH) and Cxbladder Detect) were integrated into a single dataset containing all measured records and missing values. The tests were firstly ranked using three criteria: sensitivity, specificity and a standard variable (feature) ranking method popularly known as signal-to-noise ratio (SNR) index derived from the mean values for all subjects clinically known to have UC versus healthy subjects. Secondly, step-wise unsupervised and supervised imputation (the latter accounting for the 'clinical truth' as determined by cystoscopy) was performed using personalized modelling, k-nearest-neighbour methods, multiple logistic regression and multilayer perceptron neural networks. All imputation models were cross-validated by comparing their post-imputation predictive accuracy for UC with their pre-imputation accuracy. Finally, the post-imputation tests were re-ranked using the same three criteria. RESULTS: In both measured and imputed data sets, Cxbladder Detect ranked higher for sensitivity, and urine cytology a higher specificity, when compared with other UC tests. Cxbladder Detect consistently ranked higher than FISH and all other tests when SNR analyses were performed on measured, unsupervised and supervised imputed datasets. Supervised imputation resulted in a smaller cross-validation error. Cxbladder Detect was robust to imputation showing a 2% difference in its predictive versus clinical accuracy, outperforming FISH, NMP22 and cytology. CONCLUSION: All data analysed, pre- and post-imputation showed that Cxbladder Detect had higher SNR and outperformed all other comparator tests, including FISH. The methodology developed and validated for comparative ranking of the diagnostic tests for detecting UC, may be further applied to other cancer diagnostic datasets across population groups and multiple datasets.


Assuntos
Algoritmos , Carcinoma de Células de Transição/diagnóstico , Testes Diagnósticos de Rotina/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Carcinoma de Células de Transição/genética , Citodiagnóstico , Bases de Dados Factuais/estatística & dados numéricos , Testes Diagnósticos de Rotina/normas , Testes Diagnósticos de Rotina/estatística & dados numéricos , Humanos , Hibridização in Situ Fluorescente , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/genética
6.
BMC Urol ; 15: 23, 2015 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-25888331

RESUMO

BACKGROUND: Hematuria can be symptomatic of urothelial carcinoma (UC) and ruling out patients with benign causes during primary evaluation is challenging. Patients with hematuria undergoing urological work-ups place significant clinical and financial burdens on healthcare systems. Current clinical evaluation involves processes that individually lack the sensitivity for accurate determination of UC. Algorithms and nomograms combining genotypic and phenotypic variables have largely focused on cancer detection and failed to improve performance. This study aimed to develop and validate a model incorporating both genotypic and phenotypic variables with high sensitivity and a high negative predictive value (NPV) combined to triage out patients with hematuria who have a low probability of having UC and may not require urological work-up. METHODS: Expression of IGFBP5, HOXA13, MDK, CDK1 and CXCR2 genes in a voided urine sample (genotypic) and age, gender, frequency of macrohematuria and smoking history (phenotypic) data were collected from 587 patients with macrohematuria. Logistic regression was used to develop predictive models for UC. A combined genotypic-phenotypic model (G + P INDEX) was compared with genotypic (G INDEX) and phenotypic (P INDEX) models. Area under receiver operating characteristic curves (AUC) defined the performance of each INDEX: high sensitivity, NPV >0.97 and a high test-negative rate was considered optimal for triaging out patients. The robustness of the G + P INDEX was tested in 40 microhematuria patients without UC. RESULTS: The G + P INDEX offered a bias-corrected AUC of 0.86 compared with 0.61 and 0.83, for the P and G INDEXs respectively. When the test-negative rate was 0.4, the G + P INDEX (sensitivity = 0.95; NPV = 0.98) offered improved performance compared with the G INDEX (sensitivity = 0.86; NPV = 0.96). 80% of patients with microhematuria who did not have UC were correctly triaged out using the G + P INDEX, therefore not requiring a full urological work-up. CONCLUSION: The adoption of G + P INDEX enables a significant change in clinical utility. G + P INDEX can be used to segregate hematuria patients with a low probability of UC with a high degree of confidence in the primary evaluation. Triaging out low-probability patients early significantly reduces the need for expensive and invasive work-ups, thereby lowering diagnosis-related adverse events and costs.


Assuntos
Biomarcadores Tumorais/urina , Hematúria/diagnóstico , Hematúria/epidemiologia , Triagem/métodos , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Causalidade , Comorbidade , Feminino , Hematúria/urina , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/urina , Nova Zelândia/epidemiologia , Reprodutibilidade dos Testes , Medição de Risco/métodos , Sensibilidade e Especificidade , Triagem/estatística & dados numéricos
7.
J Urol ; 188(3): 741-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22818138

RESUMO

PURPOSE: We investigated whether the RNA assay uRNA® and its derivative Cxbladder® have greater sensitivity for the detection of bladder cancer than cytology, NMP22™ BladderChek™ and NMP22™ ELISA, and whether they are useful in risk stratification. MATERIALS AND METHODS: A total of 485 patients presenting with gross hematuria but without a history of urothelial cancer were recruited prospectively from 11 urology clinics in Australasia. Voided urine samples were obtained before cystoscopy. The sensitivity and specificity of the RNA tests were compared to cytology and the NMP22 assays using cystoscopy as the reference. The ability of Cxbladder to distinguish between low grade, stage Ta urothelial carcinoma and more advanced urothelial carcinoma was also determined. RESULTS: uRNA detected 41 of 66 urothelial carcinoma cases (62.1% sensitivity, 95% CI 49.3-73.8) compared with NMP22 ELISA (50.0%, 95% CI 37.4-62.6), BladderChek (37.9%, 95% CI 26.2-50.7) and cytology (56.1%, 95% CI 43.8-68.3). Cxbladder, which was developed on the study data, detected 82%, including 97% of the high grade tumors and 100% of tumors stage 1 or greater. The cutoffs for uRNA and Cxbladder were prespecified to give a specificity of 85%. The specificity of cytology was 94.5% (95% CI 91.9-96.5), NMP22 ELISA 88.0%, (95% CI 84.6-91.0) and BladderChek 96.4% (95% CI 94.2-98.0). Cxbladder distinguished between low grade Ta tumors and other detected urothelial carcinoma with a sensitivity of 91% and a specificity of 90%. CONCLUSIONS: uRNA and Cxbladder showed improved sensitivity for the detection of urothelial carcinoma compared to the NMP22 assays. Stratification with Cxbladder provides a potential method to prioritize patients for the management of waiting lists.


Assuntos
Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/urina , Hematúria/urina , RNA/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Idoso , Carcinoma de Células de Transição/complicações , Carcinoma de Células de Transição/genética , Feminino , Hematúria/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Estudos Prospectivos , Medição de Risco/métodos , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/genética , Urina/citologia
8.
AJR Am J Roentgenol ; 197(6): W985-91, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22109344

RESUMO

OBJECTIVE: It is assumed that memory has a role to play in repeated radiologic observation studies. The main objective of this study was to examine this assumption and evaluate the effect that memory may have on receiver operating characteristic (ROC) methods. MATERIALS AND METHODS: A two-center observer study was performed with a total of 24 experienced radiologists. Over two viewings, chest radiographs showing the tip of a central line in either the superior vena cava or the azygos vein were presented. Half of the images were changed between the two viewings. The participants' attention was directed on the first reading to the position of the central line. At the second reading, the participants were asked to assign a confidence score on a 6-point scale about whether each image had been included in the first reading. RESULTS: For the images that were scored as "definitely included" in the first viewing, readers at our two centers recalled only an average of 2.5 and 4.9 of the 20 repeated images, which is close to a random allocation of images to each score. As the confidence levels diminished for positive identification of repeated images, the numbers of correct answers increased. For images scored as not having been previously included, the numbers of correct answers remained low suggesting that identification of nonrepeated images is poor. Images with a greater number of incidental abnormalities and with more striking abnormalities were recognized more accurately than those with fewer and less striking abnormalities. CONCLUSION: This study shows a "memory effect" when the same images are presented at a second viewing within a small interval period. This effect appears to occur mainly at low confidence levels. These results suggest that including images with obvious incidental abnormalities in reader performance studies should be avoided.


Assuntos
Memória , Radiografia Torácica , Competência Clínica , Erros de Diagnóstico , Humanos , Variações Dependentes do Observador , Curva ROC
9.
AJR Am J Roentgenol ; 196(4): 783-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21427325

RESUMO

OBJECTIVE: The purpose of this study was to determine, first, the accuracy with which radiologists reading posteroanterior chest radiographs differentiate whether a central venous line is in the superior vena cava or the azygos vein and, second, the circumstances in which radiologists may omit the lateral view to determine the position of a central venous line. MATERIALS AND METHODS: Twenty-four radiologists evaluated 60 posteroanterior chest radiographs to determine the position of a central venous line in the superior vena cava or azygos vein. Investigators evaluated the appearance of the central venous lines to refine rules for determining central venous line position on a frontal radiograph and omitting the lateral view. RESULTS: The accuracy of posteroanterior radiography for determining central venous line position was 90% at one study location and 85.5% at the other. No central venous line in the azygos vein extended more than 10.9 mm caudal to the cephalic edge of the right main bronchus. No central venous line in the superior vena cava had a down-the-barrel or curved appearance at the caudal edge. CONCLUSION: For central venous lines extending at least 15 mm caudal to the cephalic edge of the right main bronchus and having no down-the-barrel or curved caudal appearance, categorization was nearly 100% accurate. Therefore, if desired to save radiation exposure and cost, it may be feasible to omit lateral views in radiography of patients with central venous lines extending at least 15 mm caudal to the cephalic edge of the right main bronchus in whom the caudal edge does not have a down-the-barrel or curved appearance.


Assuntos
Veia Ázigos/diagnóstico por imagem , Cateterismo Venoso Central , Radiografia Torácica , Veia Cava Superior/diagnóstico por imagem , Humanos , Irlanda , Curva ROC , Sistemas de Informação em Radiologia , Estados Unidos
10.
Clin Cancer Res ; 14(3): 742-9, 2008 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-18245534

RESUMO

PURPOSE: New markers that enable the percentage of transitional cell carcinomas (TCC) of the bladder that are diagnosed before invasion of the bladder muscle layers to be increased would reduce the morbidity and mortality associated with this disease. The purpose of this study was to develop a simple, accurate urine test based on mRNA markers and simple gene signatures that (a) could detect TCC before muscle invasion while maintaining high specificity in patients with hematuria or urinary tract infections and (b) identify patients most likely to have grade 3 or stage > or =T1 disease. EXPERIMENTAL DESIGN: RNA markers with high overexpression in stage Ta tumors and/or T1 to T4 tumors but low expression in blood or inflammatory cells were characterized by quantitative reverse transcription-PCR using 2 mL of voided urine from 75 TCC patients and 77 control patients with other urological diseases. RESULTS: A combination of the RNAs CDC2, MDK, IGFBP5, and HOXA13 detected 48%, 90%, and 100% of stage Ta, T1, and >T1 TCCs, respectively, at a specificity of 85%. Detection of Ta tumors increased to 60% for primary (non-recurrent) Ta tumors and 76% for Ta tumors > or =1 cm in diameter. Test specificity was 80% for the 20 control patients with urinary tract infections. The combination of CDC2 and HOXA13 distinguished between grade 1 to 2 TCCs and grade 3 or stage > or =T1 TCCs with approximately 80% specificity and sensitivity. CONCLUSIONS: Simple gene expression signatures can be used as urine markers for the accurate detection and characterization of bladder cancer.


Assuntos
Carcinoma de Células de Transição/genética , RNA Mensageiro/urina , RNA Neoplásico/urina , Neoplasias da Bexiga Urinária/genética , Carcinoma de Células de Transição/classificação , Carcinoma de Células de Transição/patologia , Humanos , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Neoplásico/genética , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/patologia
11.
Radiol Clin North Am ; 46(3): 475-86, v, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18707958

RESUMO

Positron emission tomography (PET)-computed tomography (CT) is a useful device in identifying musculoskeletal lesions that require biopsy. It can be used to localize the primary lesion, identify a site to biopsy, and evaluate metastatic lesions that require follow-up biopsies. Not all malignant tumors have hypermetabolic activity, and there are many benign lesions and physiologic processes that do have increased F-18 fluorodeoxyglucose uptake. Knowledge of these issues is important when reviewing PET-CT and directing subsequent musculoskeletal biopsies.


Assuntos
Biópsia por Agulha/métodos , Neoplasias Ósseas/patologia , Neoplasias Musculares/patologia , Sistema Musculoesquelético/patologia , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/diagnóstico por imagem , Necrose , Compostos Radiofarmacêuticos
12.
AJR Am J Roentgenol ; 190(6): 1605-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18492913

RESUMO

OBJECTIVE: The purpose of this study was to assess the radiographic features of pulmonary fusariosis, an increasingly encountered cause of severe opportunistic mold pneumonia. CONCLUSION: Pulmonary fusariosis has radiographic manifestations that are suggestive of an angioinvasive mold. Nodules or masses were the most common findings at CT, seen in 82% of patients compared with only 45% on chest radiography. The halo sign was not seen. Chest radiographs showed nonspecific findings in 30% of patients, and findings were normal at presentation in 25%. All of the patients had underlying hematologic malignancies. Thirteen of the 20 patients studied (65%) died within 1 month of diagnosis of pulmonary fusariosis. Because early initiation of intense antifungal therapy offers the best chance for survival in pulmonary fusariosis, early CT and appropriate microbiologic investigation should be obtained in severely immunocompromised patients.


Assuntos
Fusarium , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/diagnóstico por imagem , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Oncol Ther ; 6(1): 73-85, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32700139

RESUMO

INTRODUCTION: International guidelines advocate regular surveillance of patients following urothelial carcinoma (UC). A validated molecular diagnostic non-invasive urine test, Cxbladder Monitor, correctly identifies patients with a UC history who have low-probability of recurrence. The present study assesses the clinical utility of Cxbladder Monitor in reducing the number and frequency of urologic procedures ordered without missing detection of recurrent UC. METHODS: Data from 828 physician-patient assessments were generated from 18 participant physicians who each evaluated the same real-world clinical case data for 30 patients undergoing surveillance for recurrent UC. Each physician ordered tests and procedures and their timing, following review of the patient's demographic data, pre-existing conditions, risk factors and clinical history before and after disclosure of Cxbladder Monitor results. Changes in the number, type and timing of procedures ordered were assessed. RESULTS: The addition of Cxbladder Monitor significantly reduced the overall number of tests ordered by 38.7%, including flexible cystoscopy by 43%, for patients whose Cxbladder Monitor result was low-probability. When the result was elevated-probability, the number of procedures ordered, including cystoscopy, was increased consistent with the increased risk of recurrent UC. Importantly, based on the tests ordered by each physician for each of the patients, all cases of recurrent UC would have been detected. CONCLUSION: The increase in clinical utility of Cxbladder Monitor for the management of patients undergoing surveillance for recurrent UC was shown to be driven by the reduction in procedures ordered for low-probability patients and for the more invasive procedures ordered for elevated-probability patients. In this study, the total number of procedures ordered, including the number of cystoscopies, was reduced especially in patients with low-probability of UC. The invasive procedures were ordered in a more targeted fashion for elevated-probability patients, without compromising the detection of recurrent UC. CLINICALTRIALS. GOV IDENTIFIER: NCT02700659. FUNDING: Pacific Edge Limited.

14.
Adv Ther ; 34(5): 1087-1096, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28341930

RESUMO

INTRODUCTION: This study aimed to demonstrate the clinical utility of non-invasive multigene Cxbladder urine tests in reducing the overall number of diagnostic tests and invasive procedures used in the clinical evaluation of patients presenting with microhematuria, a key symptom of urothelial carcinoma (UC). There is a belief that using non-invasive molecular diagnostic tests in patients with hematuria may lead to patients undergoing unnecessary and costly invasive procedures that can cause adverse events and decrease patient quality of life. The objective of this study was to determine whether or not this was the case, using Cxbladder. METHODS: Data from 396 patient-by-urologist interactions generated 792 decision points from a standardized cohort of 33 patients evaluated by 12 urologists. Participant physicians recommended a selection of tests and procedures based on referral data, then reviewed and amended their recommendations in the context of diagnostic information from Cxbladder used in the Triage and Triage and Detect clinical modalities. RESULTS: All urologists changed their diagnostic behavior in at least one patient case with the addition of Cxbladder results. The total number of diagnostic procedures was reduced by 5% and 25% following disclosure of results from Cxbladder in the Triage and the Triage and Detect modalities, respectively. The total number of requested invasive procedures was reduced from 425 at referral to 379 (-11%) and 292 (-31%) following disclosure of Cxbladder information in the Triage and Triage and Detect modalities, respectively. CONCLUSIONS: Urologists made compelling changes to their clinical decision-making when they were provided with Cxbladder results for patients presenting with hematuria. Cxbladder provides an increase in clinical utility by focusing the use of invasive diagnostic procedures to appropriate patients, reducing both the total number and number of invasive procedures used in the clinical management of patients with hematuria, thereby improving the diagnostic experience and outcomes for patients. FUNDING: Pacific Edge Ltd.


Assuntos
Biomarcadores Tumorais/urina , Carcinoma/diagnóstico , Carcinoma/genética , Hematúria/diagnóstico , RNA/urina , Neoplasias Uretrais/diagnóstico , Neoplasias Uretrais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Int J Surg Pathol ; 25(3): 281-286, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27829209

RESUMO

Composite lymphoma (CL) describes the rare occurrence of 2 or more distinct types of lymphoma in a single anatomical location. We present the case of a 78-year-old man presenting with a 3-month history of weakness, malaise, and increasing dyspnea. A lymph node excised from the posterior triangle of the neck revealed the coexistence of 2 morphologically and phenotypically distinct lymphoid neoplasms consistent with a blastoid variant of mantle cell lymphoma (MCL) occurring in composite with classical Hodgkin lymphoma (cHL), mixed cellularity subtype. A t(11;14)(q13;q32) translocation was demonstrated by fluorescence in situ hybridization in the MCL and Hodgkin Reed-Sternberg cells of the cHL. Multiplex polymerase chain reaction detected clonal Immunoglobulin heavy chain (VFR1-J, VFR2-J, and VFR3-J), clonal immunoglobulin light chain kappa (V-J and V/JC intron-kde) and clonal immunoglobulin light chain lambda (V-J) gene rearrangements in the MCL. This report represents the first case of a blastoid variant of MCL occurring in composite with cHL.


Assuntos
Linfoma Composto/patologia , Doença de Hodgkin/patologia , Linfoma de Célula do Manto/patologia , Idoso , Linfoma Composto/genética , Doença de Hodgkin/genética , Humanos , Hibridização in Situ Fluorescente , Linfonodos/patologia , Linfoma de Célula do Manto/genética , Masculino , Reação em Cadeia da Polimerase Multiplex
16.
Nucleic Acids Res ; 30(21): e114, 2002 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-12409473

RESUMO

Monofunctional, p-isothiocyanatophenyl-derivatives of platinum (II)-coproporphyrin-I (PtCP-NCS) were evaluated as phosphorescent labelling reagents for synthetic oligonucleotides containing a 3'- or 5'-amino modification. Synthesis and purification conditions were optimised to generate high yields and purity of PtCP-labelled oligonucleotide probes. Phosphorescent properties of the PtCP label have been shown to be largely unaffected by conjugation to oligonucleotides of various length, GC composition and label attachment site. 5'-PtCP-labelled oligonucleotides were shown to work efficiently as primers in a standard PCR. A dedicated 532 nm laser-based time-resolved fluorescence plate reader enabled highly sensitive detection of PtCP-labelled oligonucleotides and PCR products, both in solution and in agarose gels, with limits of detection in the order of 0.3 pM. A model system employing two complementary oligonucleotides labelled with PtCP and QSY 7 dye (dark quencher) showed strong (approximately 20-fold) and specific proximity quenching of PtCP label upon hybridisation in solution. The potential applications of PtCP-labelled probes in hybridisation assays were discussed.


Assuntos
Medições Luminescentes , Hibridização de Ácido Nucleico/métodos , Sondas de Oligonucleotídeos/química , Sondas de Oligonucleotídeos/síntese química , Sondas de Oligonucleotídeos/genética , Sondas de Oligonucleotídeos/isolamento & purificação , Reação em Cadeia da Polimerase , Soluções
17.
Clin Imaging ; 39(2): 247-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25467424

RESUMO

PURPOSE: Understanding the radiographic appearance and normal rate of fluid accumulation after pneumonectomy is important in order to detect postoperative complications. METHODS: Upright posterior-anterior chest radiographs of 94 postpneumonectomy patients were assessed for the rate of pleural fluid accumulation as a percentage of hemithorax volume. RESULTS: Overall median time to 70% hemithoracic opacification was 3 days and mean time was 27 days. The median time to 100% opacification was 66 days and mean time was 96 days. CONCLUSION: The median time to 70% hemithoracic opacification postpneumonectomy is 3 days, while median time to 100% opacification was 66 days.


Assuntos
Cavidade Pleural/diagnóstico por imagem , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Estudos Retrospectivos , Adulto Jovem
19.
Semin Ultrasound CT MR ; 32(5): 365-76, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21963160

RESUMO

Primary sarcomas of the thorax are uncommon. The purpose of this review is to describe the radiologic findings of sarcomas affecting the thorax, in particular the chest wall, pleura, and lungs. Most primary sarcomas affecting the thorax arise in the chest wall, and the most common sarcomas of the chest wall are chondrosarcoma, osteosarcoma, Ewing's sarcoma/primitive neuroectodermal tumor, malignant fibrous histiocytoma, and fibrosarcoma. Primary pleural and pulmonary sarcomas are rare. Although histologic analysis is almost always required for accurate diagnosis, imaging is important for staging of these tumors, and several of these tumors have distinctive radiologic features, allowing the radiologist to narrow the differential diagnosis.


Assuntos
Diagnóstico por Imagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pleurais/diagnóstico , Sarcoma/diagnóstico , Neoplasias Torácicas/diagnóstico , Meios de Contraste , Diagnóstico Diferencial , Humanos , Compostos Radiofarmacêuticos
20.
Semin Ultrasound CT MR ; 32(5): 442-55, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21963165

RESUMO

Soft tissue and osseous sarcomas of the extremities are uncommon malignancies that represent very important diagnostic entities because of their aggressive nature. Radiologic investigations, including plain film, computed tomography, contrast-enhanced magnetic resonance imaging; scintigraphy, ultrasound, and positron emission tomography-computed tomography, play critical roles in providing a differential, establishing the diagnosis, demonstrating prognostic characteristics, and tailoring tumor treatment. The purpose of this review is to describe the most common soft tissue and osseous sarcomas of the extremities, with emphasis on their plain film and magnetic resonance imaging characteristics with the aim of aiding the reader to accurately describe the important imaging features and generate an appropriate differential diagnosis to aid the referring clinician with prompt appropriate management and treatment.


Assuntos
Neoplasias Ósseas/diagnóstico , Diagnóstico por Imagem , Extremidades , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Meios de Contraste , Diagnóstico Diferencial , Humanos , Prognóstico , Compostos Radiofarmacêuticos
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