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1.
Oncologist ; 25(2): 140-149, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32043775

RESUMO

BACKGROUND: Checkpoint inhibitor therapy is widely known to cause a number of immune-related adverse events. One rare adverse effect that is emerging is eosinophilic fasciitis, a fibrosing disorder causing inflammatory infiltration of subcutaneous fascia. It is characterized clinically by edema and subsequent induration and tightening of the skin and subcutaneous tissues. The condition is rare, yet at our institutions we have seen four cases in the past 3 years. We describe our 4 cases and review 11 other cases reported in the literature. CASE PRESENTATION: We present four cases of eosinophilic fasciitis following treatment with programmed cell death protein 1 or programmed cell death-ligand 1 blockade. All patients had extremity involvement with characteristic skin changes ranging from peripheral edema to induration, tightening, and joint limitation. The patients had varying degrees of peripheral eosinophilia. In two of our patients, the diagnosis was made by full-thickness skin biopsy showing lymphocytic infiltration of the subcutaneous fascia, with CD4+ T cells predominating in one case and CD8+ T cells in the other. In the other two cases, the diagnosis was made on the basis of characteristic imaging findings in the context of clinical features consistent with the diagnosis. All four patients were treated with glucocorticoids with varying degrees of success; immunotherapy had to be discontinued in all four. Patients with advanced melanoma who experienced this adverse effect had either a partial response or a complete response to therapy. CONCLUSION: Eosinophilic fasciitis can occur as a result of checkpoint inhibitor therapy. Although a tissue diagnosis is the gold standard, imaging studies may facilitate the diagnosis in the presence of consistent clinical features, but a degree of suspicion is key to recognizing the condition early. Therapy requires a collaborative approach by oncology, rheumatology, and dermatology; physical therapy is an important adjunct in treatment. For advanced melanoma, it may be a good prognostic indicator. IMPLICATIONS FOR PRACTICE: It is important for clinicians to recognize that eosinophilic fasciitis is a potential immune-related adverse event (irAE) as a consequence of immune checkpoint inhibitor therapy. The presentation is quite stereotypical; the diagnosis can be made by imaging in the absence of a full-thickness skin biopsy. Early intervention is important to limit morbidity. This irAE may be a good prognostic sign among patients with melanoma.

2.
Lancet Oncol ; 20(12): e699-e714, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31797796

RESUMO

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.

3.
Nat Med ; 25(12): 1839-1842, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31768065

RESUMO

Histiocytoses are clonal hematopoietic disorders frequently driven by mutations mapping to the BRAF and MEK1 and MEK2 kinases. Currently, however, the developmental origins of histiocytoses in patients are not well understood, and clinically meaningful therapeutic targets outside of BRAF and MEK are undefined. In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.


Assuntos
Quinase do Linfoma Anaplásico/genética , Histiocitose/genética , Proteínas Proto-Oncogênicas c-ret/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Adolescente , Adulto , Aminopiridinas/farmacologia , Benzotiazóis/farmacologia , Criança , Pré-Escolar , Feminino , Genoma Humano , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Histiocitose/tratamento farmacológico , Histiocitose/patologia , Humanos , Lactente , Masculino , Mutação , Ácidos Picolínicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Piridinas/farmacologia , Pirróis/farmacologia , Receptores Proteína Tirosina Quinases/genética , Gêmeos Monozigóticos , Sequenciamento Completo do Exoma , Adulto Jovem
4.
Oncologist ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615951

RESUMO

BACKGROUND: Checkpoint inhibitor therapy is widely known to cause a number of immune-related adverse events. One rare adverse effect that is emerging is eosinophilic fasciitis, a fibrosing disorder causing inflammatory infiltration of subcutaneous fascia. It is characterized clinically by edema and subsequent induration and tightening of the skin and subcutaneous tissues. The condition is rare, yet at our institutions we have seen four cases in the past 3 years. We describe our 4 cases and review 11 other cases reported in the literature. CASE PRESENTATION: We present four cases of eosinophilic fasciitis following treatment with programmed cell death protein 1 or programmed cell death-ligand 1 blockade. All patients had extremity involvement with characteristic skin changes ranging from peripheral edema to induration, tightening, and joint limitation. The patients had varying degrees of peripheral eosinophilia. In two of our patients, the diagnosis was made by full-thickness skin biopsy showing lymphocytic infiltration of the subcutaneous fascia, with CD4+ T cells predominating in one case and CD8+ T cells in the other. In the other two cases, the diagnosis was made on the basis of characteristic imaging findings in the context of clinical features consistent with the diagnosis. All four patients were treated with glucocorticoids with varying degrees of success; immunotherapy had to be discontinued in all four. Patients with advanced melanoma who experienced this adverse effect had either a partial response or a complete response to therapy. CONCLUSION: Eosinophilic fasciitis can occur as a result of checkpoint inhibitor therapy. Although a tissue diagnosis is the gold standard, imaging studies may facilitate the diagnosis in the presence of consistent clinical features, but a degree of suspicion is key to recognizing the condition early. Therapy requires a collaborative approach by oncology, rheumatology, and dermatology; physical therapy is an important adjunct in treatment. For advanced melanoma, it may be a good prognostic indicator. IMPLICATIONS FOR PRACTICE: It is important for clinicians to recognize that eosinophilic fasciitis is a potential immune-related adverse event (irAE) as a consequence of immune checkpoint inhibitor therapy. The presentation is quite stereotypical; the diagnosis can be made by imaging in the absence of a full-thickness skin biopsy. Early intervention is important to limit morbidity. This irAE may be a good prognostic sign among patients with melanoma.

6.
Semin Cutan Med Surg ; 38(1): E38-E42, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31051022

RESUMO

In the past decade, machine learning and artificial intelligence have made significant advancements in pattern analysis, including speech and natural language processing, image recognition, object detection, facial recognition, and action categorization. Indeed, in many of these applications, accuracy has reached or exceeded human levels of performance. Subsequently, a multitude of studies have begun to examine the application of these technologies to health care, and in particular, medical image analysis. Perhaps the most difficult subdomain involves skin imaging because of the lack of standards around imaging hardware, technique, color, and lighting conditions. In addition, unlike radiological images, skin image appearance can be significantly affected by skin tone as well as the broad range of diseases. Furthermore, automated algorithm development relies on large high-quality annotated image data sets that incorporate the breadth of this circumstantial and diagnostic variety. These issues, in combination with unique complexities regarding integrating artificial intelligence systems into a clinical workflow, have led to difficulty in using these systems to improve sensitivity and specificity of skin diagnostics in health care networks around the world. In this article, we summarize recent advancements in machine learning, with a focused perspective on the role of public challenges and data sets on the progression of these technologies in skin imaging. In addition, we highlight the remaining hurdles toward effective implementation of technologies to the clinical workflow and discuss how public challenges and data sets can catalyze the development of solutions.


Assuntos
Algoritmos , Inteligência Artificial , Benchmarking , Dermatologia , Humanos , Aprendizado de Máquina
7.
Pediatr Dermatol ; 36(1): 9-15, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30152555

RESUMO

Despite the availability of effective medications for the management of atopic dermatitis and xerosis, patients may use nonconventional therapies such as topical oils. Patients choose these treatments because of the perceived lower risk of natural products and the fear of potential adverse effects of topical steroids. We review the use of topical olive, coconut, and sunflower seed oil in the treatment of atopic dermatitis and xerosis with a focus on children Currently available evidence suggests that olive oil may exacerbate xerosis and atopic dermatitis. Further studies are needed to make definitive recommendations regarding the use of coconut and sunflower seed oil.


Assuntos
Dermatite Atópica/terapia , Óleos Vegetais/administração & dosagem , Administração Tópica , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Óleos Vegetais/efeitos adversos
9.
J Pediatr ; 191: 266-269.e1, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29173316

RESUMO

We report a case of neonatal generalized erythema and epidermolysis resulting from a novel mutation in the junctional plakoglobin gene causing truncation of the plakoglobin protein. Expedited genetic testing enabled diagnosis while the patient was in the neonatal intensive care unit, providing valuable information for the clinicians and family.


Assuntos
Códon sem Sentido , Epidermólise Bolhosa Juncional/genética , Epidermólise Bolhosa Juncional/diagnóstico , Evolução Fatal , Marcadores Genéticos , Humanos , Recém-Nascido , Masculino , gama Catenina/genética
10.
J Biomech ; 46(11): 1875-81, 2013 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-23726184

RESUMO

Elevated hepatic venous pressure is the primary source of complications in advancing liver disease. Ultrasound imaging is ideal for potential noninvasive hepatic pressure measurements as it is widely used for liver imaging. Specifically, ultrasound based stiffness measures may be useful for clinically monitoring pressure, but the mechanism by which liver stiffness increases with hepatic pressure has not been well characterized. This study is designed to elucidate the nonlinear properties of the liver during pressurization by measuring both hepatic shear wave speed (SWS) and strain with increasing pressure. Tissue deformation during hepatic pressurization was tracked in 8 canine livers using successively acquired 3-D B-mode volumes and compared with concurrently measured SWS. When portal venous pressure was increased from clinically normal (0-5mmHg) to pressures representing highly diseased states at 20mmHg, the liver was observed to expand with axial strain measures up to 10%. At the same time, SWS estimates were observed to increase from 1.5-2m/s at 0-5mmHg (baseline) to 3.25-3.5m/s at 20mmHg.


Assuntos
Circulação Hepática/fisiologia , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Pressão na Veia Porta/fisiologia , Animais , Fenômenos Biomecânicos , Cães , Modelos Cardiovasculares , Dinâmica não Linear , Veia Porta/fisiologia , Ultrassonografia , Rigidez Vascular/fisiologia
11.
Ultrason Imaging ; 33(1): 1-16, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21608445

RESUMO

Ultrasound-guided needle placement is widely used in the clinical setting, particularly for central venous catheter placement, tissue biopsy and regional anesthesia. Difficulties with ultrasound guidance in these areas often result from steep needle insertion angles and spatial offsets between the imaging plane and the needle. Acoustic Radiation Force Impulse (ARFI) imaging leads to improved needle visualization because it uses a standard diagnostic scanner to perform radiation force based elasticity imaging, creating a displacement map that displays tissue stiffness variations. The needle visualization in ARFI images is independent of needle-insertion angle and also extends needle visibility out of plane. Although ARFI images portray needles well, they often do not contain the usual B-mode landmarks. Therefore, a three-step segmentation algorithm has been developed to identify a needle in an ARFI image and overlay the needle prediction on a coregistered B-mode image. The steps are: (1) contrast enhancement by median filtration and Laplacian operator filtration, (2) noise suppression through displacement estimate correlation coefficient thresholding and (3) smoothing by removal of outliers and best-fit line prediction. The algorithm was applied to data sets from horizontal 18, 21 and 25 gauge needles between 0-4 mm offset in elevation from the transducer imaging plane and to 18G needles on the transducer axis (in plane) between 10 degrees and 35 degrees from the horizontal. Needle tips were visualized within 2 mm of their actual position for both horizontal needle orientations up to 1.5 mm offset in elevation from the transducer imaging plane and on-axis angled needles between 10 degrees-35 degrees above the horizontal orientation. We conclude that segmented ARFI images overlaid on matched B-mode images hold promise for improved needle visibility in many clinical applications.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Aumento da Imagem/métodos , Agulhas , Ultrassonografia de Intervenção/métodos , Algoritmos , Técnicas de Imagem por Elasticidade/instrumentação , Humanos , Ultrassonografia de Intervenção/instrumentação
12.
Ultrason Imaging ; 33(4): 217-32, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22518953

RESUMO

The goal of this work is to demonstrate the feasibility of using a diagnostic ultrasound system (Siemens Antares and CH6-2 curvilinear array) to ablate ex vivo liver with a custom M-mode sequence and monitor the resulting tissue stiffening with 2-D Acoustic Radiation Force Impulse (ARFI) imaging. Images were taken before and after ablation, as well as in 5- s intervals during the ablation sequence in order to monitor the ablation lesion formation temporally. Ablation lesions were generated at depths up to 1.5 cm from the surface of the liver and were not visible in B-mode. ARFI images showed liver stiffening with heating that corresponded to discolored regions in gross pathology. As expected, the contrast of ablation lesions in ARFI images is observed to increase with ablation lesion size. This study demonstrated the ability of a diagnostic system using custom beam sequences to localize an ablation site, heat the site to the point of irreversible damage and monitor the formation of the ablation lesion with ARFI imaging.


Assuntos
Ablação por Cateter/métodos , Técnicas de Imagem por Elasticidade/métodos , Interpretação de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Fígado/cirurgia , Animais , Bovinos , Estudos de Viabilidade
13.
Ultrasound Med Biol ; 36(5): 802-13, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20381950

RESUMO

The stiffness of tissue can be quantified by measuring the shear wave speed (SWS) within the medium. Ultrasound is a real-time imaging modality capable of tracking the propagation of shear waves in soft tissue. Time-of-flight (TOF) methods have previously been shown to be effective for quantifying SWS from ultrasonically tracked displacements. However, the application of these methods to in vivo data is challenging due to the presence of additional sources of error, such as physiologic motion or spatial inhomogeneities in tissue. This article introduces the use of random sample consensus (RANSAC), a model fitting paradigm robust to the presence of gross outlier data, for estimating the SWS from ultrasonically tracked tissue displacements in vivo. SWS reconstruction is posed as a parameter estimation problem and the RANSAC solution to this problem is described. Simulations using synthetic TOF data show that RANSAC is capable of good stiffness reconstruction accuracy (mean error 0.5 kPa) and precision (standard deviation 0.6 kPa) over a range of shear stiffness (0.6-10 kPa) and proportion of inlier data (50%-95%). As with all TOF SWS estimation methods, the accuracy and precision of the RANSAC reconstructed shear modulus decreases with increasing tissue stiffness. The RANSAC SWS estimator was applied to radiation force induced shear wave data from 123 human patient livers acquired with a modified SONOLINE Antares ultrasound system (Siemens Healthcare, Ultrasound Business Unit, Mountain View, CA, USA) in a clinical setting before liver biopsy was performed. Stiffness measurements were not possible in 19 patients due to the absence of shear wave propagation inside the liver. The mean liver stiffness for the remaining 104 patients ranged from 1.3 to 24.2 kPa and the proportion of inliers for the successful reconstructions ranged between 42% to 99%. Using RANSAC for SWS estimation improved the diagnostic accuracy of liver stiffness for delineating fibrosis stage compared with ordinary least squares (OLS) without outlier removal (AUROC = 0.94 for F >or= 3 and AUROC = 0.98 for F = 4). These results show that RANSAC is a suitable method for estimating the SWS from noisy in vivo shear wave displacements tracked by ultrasound.


Assuntos
Algoritmos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Fígado/fisiologia , Módulo de Elasticidade/fisiologia , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resistência ao Cisalhamento/fisiologia , Ultrassonografia
14.
Bioinformatics ; 21(10): 2539-40, 2005 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-15746286

RESUMO

UNLABELLED: The conservatism of conservatism (CoC) database presents statistically analyzed information about the conservation of residue positions in folds across protein families. AVAILABILITY: On the web at http://kulibin.mit.edu/coc/


Assuntos
Sistemas de Gerenciamento de Base de Dados , Bases de Dados de Proteínas , Proteínas/química , Proteínas/classificação , Alinhamento de Sequência/métodos , Análise de Sequência de Proteína/métodos , Interface Usuário-Computador , Sequência Conservada , Armazenamento e Recuperação da Informação/métodos , Dobramento de Proteína , Homologia de Sequência de Aminoácidos , Software
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