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BACKGROUND: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life. RESULTS: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups. CONCLUSIONS: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).
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Antineoplásicos , Niacinamida , Neoplasias Cutâneas , Transplantados , Humanos , Austrália , Carcinoma Basocelular/etiologia , Carcinoma Basocelular/prevenção & controle , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/prevenção & controle , Quimioprevenção , Ceratose Actínica/etiologia , Ceratose Actínica/prevenção & controle , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Qualidade de Vida , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Hospedeiro Imunocomprometido , Transplante de Órgãos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Raios Ultravioleta/efeitos adversosRESUMO
Background Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation. ClinicalTrials.gov Identifier: NCT04012242 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Yin in this issue.
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Fígado Gorduroso , Cirrose Hepática , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Cirrose Hepática/diagnóstico por imagem , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/complicações , Ultrassonografia/métodos , Adulto , Fígado/diagnóstico por imagem , Fígado/patologia , Idoso , Inflamação/diagnóstico por imagem , Biomarcadores/sangueRESUMO
Prostate cancer (PC), particularly its metastatic castration-resistant form (mCRPC), is a leading cause of cancer-related deaths among men in the Western world. Traditional systemic treatments, including hormonal therapy and chemotherapy, offer limited effectiveness due to tumors' inherent resistance to these therapies. Moreover, they often come with significant side effects. We have developed a delivery method using a tumor-cell-specific heptamethine carbocyanine dye (DZ) designed to transport therapeutic agents directly to tumor cells. This research evaluated simvastatin (SIM) as the antitumor payload because of its demonstrated chemopreventive effects on human cancers and its well-documented safety profile. We designed and synthesized a DZ-SIM conjugate for tumor cell targeting. PC cell lines and xenograft tumor models were used to assess tumor-cell targeting specificity and killing activity and to investigate the corresponding mechanisms. DZ-SIM treatment effectively killed PC cells regardless of their androgen receptor status or inherent therapeutic resistance. The conjugate targeted and suppressed xenograft tumor formation without harming normal cells of the host. In cancer cells, DZ-SIM was enriched in subcellular organelles, including mitochondria, where the conjugate formed adducts with multiple proteins and caused the loss of transmembrane potential, promoting cell death. The DZ-SIM specifically targets PC cells and their mitochondria, resulting in a loss of mitochondrial function and cell death. With a unique subcellular targeting strategy, the conjugate holds the potential to outperform existing chemotherapeutic drugs. It presents a novel strategy to circumvent therapeutic resistance, offering a more potent treatment for mCRPC.
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Neoplasias de Próstata Resistentes à Castração , Sinvastatina , Masculino , Humanos , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Próstata/metabolismo , Carbocianinas , Linhagem Celular TumoralRESUMO
Objective - Addressing the challenges that come with identifying and delineating brain tumours in intraoperative ultrasound. Our goal is to both qualitatively and quantitatively assess the interobserver variation, amongst experienced neuro-oncological intraoperative ultrasound users (neurosurgeons and neuroradiologists), in detecting and segmenting brain tumours on ultrasound. We then propose that, due to the inherent challenges of this task, annotation by localisation of the entire tumour mass with a bounding box could serve as an ancillary solution to segmentation for clinical training, encompassing margin uncertainty and the curation of large datasets. Methods - 30 ultrasound images of brain lesions in 30 patients were annotated by 4 annotators - 1 neuroradiologist and 3 neurosurgeons. The annotation variation of the 3 neurosurgeons was first measured, and then the annotations of each neurosurgeon were individually compared to the neuroradiologist's, which served as a reference standard as their segmentations were further refined by cross-reference to the preoperative magnetic resonance imaging (MRI). The following statistical metrics were used: Intersection Over Union (IoU), Sørensen-Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD). These annotations were then converted into bounding boxes for the same evaluation. Results - There was a moderate level of interobserver variance between the neurosurgeons [ I o U : 0.789 , D S C : 0.876 , H D : 103.227 ] and a larger level of variance when compared against the MRI-informed reference standard annotations by the neuroradiologist, mean across annotators [ I o U : 0.723 , D S C : 0.813 , H D : 115.675 ] . After converting the segments to bounding boxes, all metrics improve, most significantly, the interquartile range drops by [ I o U : 37 % , D S C : 41 % , H D : 54 % ] . Conclusion - This study highlights the current challenges with detecting and defining tumour boundaries in neuro-oncological intraoperative brain ultrasound. We then show that bounding box annotation could serve as a useful complementary approach for both clinical and technical reasons.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Ultrassonografia/métodos , Neurocirurgiões , Variações Dependentes do Observador , Imageamento por Ressonância Magnética/métodos , Procedimentos Neurocirúrgicos/métodosRESUMO
Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US.
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Meios de Contraste , Neoplasias , Humanos , Ultrassonografia/métodos , PerfusãoRESUMO
BACKGROUND: The pathogenesis of delayed-onset tissue nodules (DTNs) due to hyaluronic acid (HA) injections is uncertain. OBJECTIVES: To formulate a rational theory for DTN development and their avoidance and treatment. METHODS: A multidisciplinary and multicountry DTN consensus panel was established, with 20 questions posed and consensus sought. Consensus was set at 75% agreement. RESULTS: Consensus was reached in 16 of 20 questions regarding the pathogenesis of DTNs, forming the basis for a classification and treatment guide. CONCLUSIONS: The group believes that filler, pathogens, and inflammation are all involved in DTNs and that DTNs most likely are infection initiated with a variable immune response. Injected filler may incorporate surface bacteria, either a commensal or a true pathogen, if the skin barrier is altered. The initially high molecular weight HA filler is degraded to low molecular weight HA (LMWHA) at the edge of the filler. Commensals positioned within the filler bolus may be well tolerated until the filler is degraded and the commensal becomes visible to the immune system. LMWHA is particularly inflammatory in the presence of any local bacteria. Commensals may still be tolerated unless the immune system is generally heightened by viremia or vaccination. Systemic pathogenic bacteremia may also interact with the filler peripheral LMWHA, activating Toll-like receptors that induce DTN formation. Given this scenario, attention to practitioner and patient hygiene and early systemic infection treatment deserve attention. Classification and treatment systems were devised by considering each of the 3 factors-filler, inflammation, and infection-separately.
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Técnicas Cosméticas , Preenchedores Dérmicos , Humanos , Ácido Hialurônico/efeitos adversos , Injeções , Técnicas Cosméticas/efeitos adversos , Inflamação/etiologia , Preenchedores Dérmicos/efeitos adversosRESUMO
Accurate and reliable intraoperative neuronavigation is crucial for achieving maximal safe resection of brain tumors. Intraoperative MRI (iMRI) has received significant attention as the next step in improving navigation. However, the immense cost and logistical challenge of iMRI precludes implementation in most centers worldwide. In comparison, intraoperative ultrasound (ioUS) is an affordable tool, easily incorporated into existing theatre infrastructure, and operative workflow. Historically, ultrasound has been perceived as difficult to learn and standardize, with poor, artifact-prone image quality. However, ioUS has dramatically evolved over the last decade, with vast improvements in image quality and well-integrated navigation tools. Advanced techniques, such as contrast-enhanced ultrasound (CEUS), have also matured and moved from the research field into actual clinical use. In this review, we provide a comprehensive and pragmatic guide to ioUS. A suggested protocol to facilitate learning ioUS and improve standardization is provided, and an outline of common artifacts and methods to minimize them given. The review also includes an update of advanced techniques and how they can be incorporated into clinical practice.
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Neoplasias Encefálicas , Neuronavegação , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Humanos , Imageamento por Ressonância Magnética , Neuronavegação/métodos , Ultrassonografia/métodosRESUMO
This first position paper of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) on professional standards presents a common position across the different medical professions within EFSUMB regarding optimal standards for the performing and reporting of ultrasound examinations by any professional ultrasound operator. It describes general aspects of professionality that ensure procedure quality, effectiveness, efficiency, and sustainability in virtually all application fields of medical ultrasound. Recommendations are given related to safety and indication of ultrasound examinations, requirements for examination rooms, structured examination, systematic reporting of results, and management, communication and archiving of ultrasound data. The print version of this article is a short version. The long version is published online.
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Sociedades Médicas , Humanos , Ultrassonografia/métodosRESUMO
This first position paper of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) on professional standards presents a common position across the different medical professions within EFSUMB regarding optimal standards for the performing and reporting of ultrasound examinations by any professional ultrasound operator. It describes general aspects of professionality that ensure procedure quality, effectiveness, efficiency, and sustainability in virtually all application fields of medical ultrasound. Recommendations are given related to safety and indication of ultrasound examinations, requirements for examination rooms, structured examination, systematic reporting of results, and management, communication and archiving of ultrasound data. The print version of this article is a short version. The long version is published online.
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Sociedades Médicas , Humanos , Ultrassonografia/métodosRESUMO
OBJECTIVES: To compare liver stiffness measurement (LSM) provided by Canon 2D-shear wave elastography (2D-SWE) and transient elastography (TE), the latter being the reference method. METHODS: Prospective study conducted in four European centres from 2015 to 2016 including patients with various chronic liver diseases who had LSMs with both 2D-SWE and TE on the same day. Median of 10 valid measurements (in kPa) was used for comparison using paired t test, Pearson correlation, intraclass correlation coefficient (ICC) and Bland-Altman plot. The ability of 2D-SWE to stratify patient according to recognised LSM-TE thresholds was assessed by ROC curve analysis. RESULTS: Six hundred forty patients were scanned, where 593 (92.7%), 572 (89.4%) and 537 (83.9%) had reliable LSMs by TE, 2D-SWE and both combined, respectively. In the latter (n = 537, 310 [57.7%] male, mean 55.3 ± 14.8 years), median LSM-TE and LSM-2D-SWE had a mean of 10.1 ± 9.4 kPa (range 2.4-75) and 9.1 ± 6.1 kPa (range 3.6-55.7) (paired t test: p < 0.001), respectively. These were significantly correlated (Pearson r = 0.932, p < 0.001, ICC 0.850 (0.825-0.872), bias 0.99 ± 4.33 kPa [95% limits of agreement - 9.48 to + 7.49] with proportional error towards higher LSM values). LSM-2D-SWE values significantly increased with TE categories (ANOVA: p < 0.001). AUROCs ranged from 0.935 ± 0.010 (95% CI 0.910-0.954) to 0.973 ± 0.009 (95% CI 0.955-0.985), resulting in correct classification of 390/537 (73%) patients. Three 2D-SWE measurements were sufficient for reliable LSMs. CONCLUSION: LSM using 2D-SWE correlates well with TE. It tends to underestimate higher stages of liver fibrosis but correctly classifies the majority of patients. It may be used in TE-derived algorithms to manage patients. KEY POINTS: ⢠Liver stiffness measurement (LSM) by 2D-shear wave elastography (2D-SWE) and transient elastography (TE) are strongly correlated. ⢠2D-SWE shows proportionately lower LSM values compared to TE, particularly with the higher LSM range. ⢠Three individual measurements by 2D-SWE are sufficient to assess LSM reliably.
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Técnicas de Imagem por Elasticidade , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Masculino , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Lumbar disc degeneration (LDD) is a condition associated with recurrent low back pain (LBP). Knowledge regarding effective management is limited. As a step towards the identification of risk, prognostic or potentially modifiable factors in LDD patients, the aim of this study was to explore the hypothesis that intrinsic lumbar spine shape is associated with LDD and clinical outcomes in symptomatic adults. METHODS: 3 T MRI was used to acquire T2-weighted sagittal images (L1-S1) from 70 healthy controls and LDD patients (mean age 49 years, SD 11, range 31-71 years). Statistical Shape Modelling (SSM) was used to describe lumbar spine shape. SSM identified variations in lumbar shape as 'modes' of variation and quantified deviation from the mean. Intrinsic shape differences were determined between LDD groups using analysis of variance with post-hoc comparisons. The relationship between intrinsic shape and self-reported function, mental health and quality of life were also examined. RESULTS: The first 7 modes of variation explained 91% of variance in lumbar shape. Higher LDD sum scores correlated with a larger lumbar lordosis (Mode 1 (55% variance), P = 0.02), even lumbar curve distribution (Mode 2 (12% variance), P = 0.05), larger anterior-posterior (A-P) vertebral diameter (Mode 3 (10% variance), P = 0.007) and smaller L4-S1 disc spaces (Mode 7 (2% variance), P ≤ 0.001). In the presence of recurrent LBP, LDD was associated with a larger A-P vertebral diameter (Mode 3) and a more even lumbar curvature with smaller L5/S1 disc spaces (Mode 4), which was significantly associated with patient quality of life (P = 0.002-0.04, rp = 0.43-0.61)). CONCLUSIONS: This exploratory study provides new evidence that intrinsic shape phenotypes are associated with LDD and quality of life in patients. Longitudinal studies are required to establish the potential role of these risk or prognostic shape phenotypes.
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Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/patologia , Lordose/patologia , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Feminino , Humanos , Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/complicações , Lordose/diagnóstico por imagem , Dor Lombar/etiologia , Dor Lombar/patologia , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Qualidade de VidaRESUMO
The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients.
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Meios de Contraste , Ultrassonografia , Meios de Contraste/normas , Humanos , Ultrassonografia/normasRESUMO
BACKGROUND: Breast cancer (BC) is the most common cancer in women, and despite the introduction of new screening programmes, therapies and monitoring technologies, there is still a need to develop more useful tests for monitoring treatment response and to inform clinical decision making. The purpose of this study was to compare circulating cell-free DNA (cfDNA) and circulating tumour cells (CTCs) with conventional breast cancer blood biomarkers (CA15-3 and alkaline phosphatase (AP)) as predictors of response to treatment and prognosis in patients with metastatic breast cancer (MBC). METHODS: One hundred ninety-four female patients with radiologically confirmed MBC were recruited to the study. Total cfDNA levels were determined by qPCR and compared with CELLSEARCH® CTC counts and CA15-3 and alkaline phosphatase (AP) values. Blood biomarker data were compared with conventional tumour markers, treatment(s) and response as assessed by RECIST and survival. Non-parametric statistical hypothesis tests were used to examine differences, correlation analysis and linear regression to determine correlation and to describe its effects, logistic regression and receiver operating characteristic curve (ROC curve) to estimate the strength of the relationship between biomarkers and clinical outcomes and value normalization against standard deviation to make biomarker values comparable. Kaplan-Meier estimator and Cox regression models were used to assess survival. Univariate and multivariate models were performed where appropriate. RESULTS: Multivariate analysis showed that both the amount of total cfDNA (p value = 0.024, HR = 1.199, CI = 1.024-1.405) and the number of CTCs (p value = 0.001, HR = 1.243, CI = 1.088-1.421) are predictors of overall survival (OS), whereas total cfDNA levels is the sole predictor for progression-free survival (PFS) (p value = 0.042, HR = 1.193, CI = 1.007-1.415) and disease response when comparing response to non-response to treatment (HR = 15.917, HR = 12.481 for univariate and multivariate analysis, respectively). Lastly, combined analysis of CTCs and cfDNA is more informative than the combination of two conventional biomarkers (CA15-3 and AP) for prediction of OS. CONCLUSION: Measurement of total cfDNA levels, which is a simpler and less expensive biomarker than CTC counts, is associated with PFS, OS and response in MBC, suggesting potential clinical application of a cheap and simple blood-based test.
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Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , DNA Tumoral Circulante , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Tomada de Decisão Clínica , Gerenciamento Clínico , Feminino , Humanos , Estimativa de Kaplan-Meier , Biópsia Líquida , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Razão de Chances , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
Background Variations in lymph node (LN) microcirculation can be indicative of metastasis. The identification and quantification of metastatic LNs remains essential for prognosis and treatment planning, but a reliable noninvasive imaging technique is lacking. Three-dimensional super-resolution (SR) US has shown potential to noninvasively visualize microvascular networks in vivo. Purpose To study the feasibility of three-dimensional SR US imaging of rabbit LN microvascular structure and blood flow by using microbubbles. Materials and Methods In vivo studies were carried out to image popliteal LNs of two healthy male New Zealand white rabbits aged 6-8 weeks. Three-dimensional, high-frame-rate, contrast material-enhanced US was achieved by mechanically scanning with a linear imaging probe. Individual microbubbles were identified, localized, and tracked to form three-dimensional SR images and super-resolved velocity maps. Acoustic subaperture processing was used to improve image contrast and to generate enhanced power Doppler and color Doppler images. Vessel size and blood flow velocity distributions were evaluated and assessed by using Student paired t test. Results SR images revealed microvessels in the rabbit LN, with branches clearly resolved when separated by 30 µm, which is less than half of the acoustic wavelength and not resolvable by using power or color Doppler. The apparent size distribution of most vessels in the SR images was below 80 µm and agrees with micro-CT data, whereas most of those detected with Doppler techniques were larger than 80 µm in the images. The blood flow velocity distribution indicated that most of the blood flow in rabbit popliteal LN was at velocities lower than 5 mm/sec. Conclusion Three-dimensional super-resolution US imaging using microbubbles allows noninvasive nonionizing visualization and quantification of lymph node microvascular structures and blood flow dynamics with resolution below the wave diffraction limit. This technology has potential for studying the physiologic functions of the lymph system and for clinical detection of lymph node metastasis. Published under a CC BY 4.0 license. Online supplemental material is available for this article.
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Imageamento Tridimensional/métodos , Linfonodos , Microbolhas , Ultrassonografia/métodos , Animais , Estudos de Viabilidade , Linfonodos/irrigação sanguínea , Linfonodos/diagnóstico por imagem , Masculino , Microvasos/diagnóstico por imagem , CoelhosRESUMO
In the original publication of the article, a part of acknowledgement section was missed out. The omitted acknowledgement is given below: 'The study was coordinated by the Imperial Clinical Trials Unit-Cancer, Imperial College London and Sponsored by Imperial College London. The Imperial Clinical Trials Unit receives funding from the National Institute for Health (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This study was supported by Imperial Experimental Cancer Medicine Centre and Cancer Research UK Imperial Centre'.
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Chemical peels belong to a group of cutaneous resurfacing procedures that are used in the treatment of photoageing, inflammatory dermatoses, epidermal proliferations, pigmentary disorders and scarring. This review describes best current practice, highlights recent advances in chemical peel technology and discusses the recommended uses for different peel types. It also presents the results of a survey of the chemical peeling practices of 30 Australian dermatologists.
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Cáusticos/uso terapêutico , Abrasão Química/métodos , Envelhecimento da Pele , Dermatopatias/terapia , Abrasão Química/efeitos adversos , Abrasão Química/classificação , Humanos , RejuvenescimentoRESUMO
PURPOSE: The FIGO score cannot accurately stratify low-risk gestational trophoblastic neoplasia (GTN) patients who develop chemoresistance to single agent methotrexate chemotherapy. Tumour vascularisation is a key risk factor and its quantification may provide non-invasive way of complementing risk assessment. MATERIALS AND METHODS: 187 FIGO-staged, low-risk GTN patients were prospectively recruited. Power Doppler ultrasound was analysed using a quantification program. Four diagnostic indicators were obtained comprising the number of colour pixels (NCP), mean dB, power Doppler quantification (PDQ), and percentage of colour pixels (%CP). Each indicator performance was assessed to determine if they could distinguish the subset of low-risk patients who became chemoresistant. RESULTS: There were 111 non-resistant and 76 resistant patients. NCP performed best at distinguishing these two groups where the non-resistant group had an average 3435 (±â2060) pixels and the resistant group 6151 (±â3192) pixels (pâ<â0.001). PDQ and %CP showed significant differences (pâ<â0.001) but had poorer performance (area under ROC curves were 72â% and 67â% respectively compared with 75â% for NCP). The mean dB index was not significantly different (pâ=â0.133). CONCLUSION: Power Doppler ultrasound quantification shows potential for non-invasive assessment of tumour vascularity and can distinguish low-risk GTN patients who become chemoresistant from those who have an uncomplicated course with first line treatment.
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Doença Trofoblástica Gestacional , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Metotrexato , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Ultrassonografia DopplerRESUMO
PURPOSE: Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit. EXPERIMENTAL DESIGN: Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled. The first-line AI was continued and Irosustat (40 mg orally daily) added. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included safety, tolerability, and pharmacodynamic end points. RESULTS: Twenty-seven women were recruited, four discontinued treatment without response assessment. Based on local reporting, the CBR was 18.5% (95% CI 6.3-38.1%) on an intent to treat basis, increasing to 21.7% (95% CI 7.4-43.7%) by per-protocol analysis. In those patients that achieved clinical benefit (n = 5), the median (interquartile range) duration was 9.4 months (8.1-11.3) months. The median progression-free survival time was 2.7 months (95% CI 2.5-4.6) in both the ITT and per-protocol analyses. The most frequently reported grade 3/4 toxicities were dry skin (28%), nausea (13%), fatigue (13%), diarrhoea (8%), headache (7%), anorexia (7%) and lethargy (7%). CONCLUSIONS: The addition of Irosustat to aromatase inhibitor therapy resulted in clinical benefit with an acceptable safety profile. The study met its pre-defined success criterion by both local and central radiological assessments.
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BACKGROUND/OBJECTIVES: Patients should be monitored post-laser resurfacing for reassurance and the early detection of adverse events. Smartphone monitoring in the post-laser resurfacing setting is an efficient and convenient tool that is well accepted by patients and dermatologists. The objective was to identify the benefits and barriers of, and patient attitudes towards, smartphone monitoring in the post-laser resurfacing setting. METHODS: A retrospective audit of 123 laser resurfacing patients was undertaken to determine the characteristics of this population. A web-based survey was used to determine patients' attitudes towards smartphone monitoring. RESULTS: The commonest indications for laser resurfacing were acne scarring and photoageing rejuvenation. 88% of patients either had no adverse outcomes or expected post-laser resurfacing side-effects such as erythema. 12% developed adverse effects requiring intervention. The survey showed that all patients who had used the smartphone monitoring service felt it was a positive initiative for post-laser patients. Of note, most patients not using the smartphone review service were simply unaware of its existence. Biases may have been introduced as staff were less likely to promote the review service to patients undergoing lower intensity procedures. CONCLUSIONS: Smartphone monitoring post-laser resurfacing is an efficient and convenient alternative to face-to-face review for both patients and dermatologists. As technology improves and patients' expectations increase we expect more patients will request teledermatology reviews in order to easily and rapidly access medical advice.
Assuntos
Assistência ao Convalescente/métodos , Atitude , Smartphone , Telemedicina/métodos , Adulto , Técnicas Cosméticas/efeitos adversos , Humanos , Terapia a Laser/efeitos adversos , Pessoa de Meia-Idade , Satisfação do Paciente , Fotografação , Estudos RetrospectivosRESUMO
Vulval lichen sclerosus is an uncommon skin condition that can usually be managed with topical corticosteroids to maintain remission. However, there is a subset of patients in whom it remains recalcitrant despite treatment with super-potent topical corticosteroids. We report a case series of four patients undergoing fractional carbon dioxide laser resurfacing and one with ablative carbon dioxide laser for severe, hyperkeratotic vulval lichen sclerosus not responding to super-potent topical corticosteroids. In these patients, carbon dioxide laser was successful in achieving remission. Their vulval lichen sclerosus was subsequently able to be maintained with topical corticosteroid treatment.