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1.
Nature ; 579(7797): 97-100, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32103182

RESUMO

The stiff human foot enables an efficient push-off when walking or running, and was critical for the evolution of bipedalism1-6. The uniquely arched morphology of the human midfoot is thought to stiffen it5-9, whereas other primates have flat feet that bend severely in the midfoot7,10,11. However, the relationship between midfoot geometry and stiffness remains debated in foot biomechanics12,13, podiatry14,15 and palaeontology4-6. These debates centre on the medial longitudinal arch5,6 and have not considered whether stiffness is affected by the second, transverse tarsal arch of the human foot16. Here we show that the transverse tarsal arch, acting through the inter-metatarsal tissues, is responsible for more than 40% of the longitudinal stiffness of the foot. The underlying principle resembles a floppy currency note that stiffens considerably when it curls transversally. We derive a dimensionless curvature parameter that governs the stiffness contribution of the transverse tarsal arch, demonstrate its predictive power using mechanical models of the foot and find its skeletal correlate in hominin feet. In the foot, the material properties of the inter-metatarsal tissues and the mobility of the metatarsals may additionally influence the longitudinal stiffness of the foot and thus the curvature-stiffness relationship of the transverse tarsal arch. By analysing fossils, we track the evolution of the curvature parameter among extinct hominins and show that a human-like transverse arch was a key step in the evolution of human bipedalism that predates the genus Homo by at least 1.5 million years. This renewed understanding of the foot may improve the clinical treatment of flatfoot disorders, the design of robotic feet and the study of foot function in locomotion.


Assuntos
Evolução Biológica , Fenômenos Biomecânicos , Pé/anatomia & histologia , Pé/fisiologia , Testes de Dureza , Animais , Cadáver , Extinção Biológica , Feminino , Pé/fisiopatologia , Hominidae/anatomia & histologia , Hominidae/fisiologia , Humanos , Pessoa de Meia-Idade , Pan troglodytes/anatomia & histologia , Pan troglodytes/fisiologia , Maleabilidade , Pé Cavo/fisiopatologia
2.
Skeletal Radiol ; 52(8): 1443-1463, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36656343

RESUMO

There are numerous bone tumors in the pediatric population, with imaging playing an essential role in diagnosis and management. Our understanding of certain bone tumors has rapidly evolved over the past decade with advancements in next-generation genetic sequencing techniques. This increased level of understanding has altered the nomenclature, management approach, and prognosis of certain lesions. We provide a detailed update of bone tumors that occur in the pediatric population with emphasis on the recently released nomenclature provided in the 5th edition of the World Health Organization Classification of Soft Tissue and Bone Tumours. We discuss other mesenchymal tumors of bone, hematopoietic neoplasms of bone, and WHO classification of undifferentiated small round cell sarcomas of bone. We have detailed osteogenic tumors and osteoclastic giant cell-rich tumors, as well as notochordal tumors, chondrogenic tumors, and vascular tumors of the bone in separate manuscripts.


Assuntos
Neoplasias Ósseas , Tumores de Células Gigantes , Neoplasias Hematológicas , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Criança , Neoplasias Ósseas/diagnóstico por imagem , Sarcoma/diagnóstico , Osso e Ossos/patologia , Neoplasias de Tecidos Moles/patologia , Organização Mundial da Saúde
3.
Skeletal Radiol ; 51(3): 477-504, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34191084

RESUMO

There are numerous soft tissue tumors and tumor-like conditions in the pediatric population. Magnetic resonance imaging is the most useful modality for imaging these lesions. Although certain soft tissue lesions exhibit magnetic resonance features characteristic of a specific diagnosis, most lesions are indeterminate, and a biopsy is necessary for diagnosis. We provide a detailed update of soft tissue tumors and tumor-like conditions that occur in the pediatric population, emphasizing each lesion's conventional magnetic resonance imaging appearance, using the recently released 5th edition of the World Health Organization Classification of Soft Tissue and Bone Tumors as a guide. In part one of this review, pediatric tumor-like lesions, adipocytic tumors, fibroblastic and myofibroblastic tumors, and perivascular tumors are discussed. In part two, vascular lesions, fibrohistiocytic tumors, muscle tumors, peripheral nerve sheath tumors, tumors of uncertain differentiation, and undifferentiated small round cell sarcomas are reviewed. Per the convention of the WHO, these lesions involve the connective, subcutaneous, and other non-parenchymatous-organ soft tissues, as well as the peripheral and autonomic nervous system.


Assuntos
Granuloma de Células Plasmáticas , Neoplasias Lipomatosas , Sarcoma , Neoplasias de Tecidos Moles , Criança , Humanos , Imageamento por Ressonância Magnética , Neoplasias de Tecidos Moles/diagnóstico por imagem
4.
Skeletal Radiol ; 51(4): 701-725, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34297167

RESUMO

There are numerous soft tissue tumors and tumor-like conditions in the pediatric population. Magnetic resonance imaging is the most useful modality for imaging these lesions. Although certain soft tissue lesions exhibit magnetic resonance features characteristic of a specific diagnosis, most lesions are indeterminate, and a biopsy is necessary for diagnosis. We provide a detailed update of soft tissue tumors and tumor-like conditions that occur in the pediatric population, emphasizing each lesion's conventional magnetic resonance imaging appearance, using the recently released 5th edition of the World Health Organization Classification of Soft Tissue and Bone Tumors as a guide. In part one of this review, pediatric tumor-like lesions, adipocytic tumors, fibroblastic and myofibroblastic tumors, and perivascular tumors are discussed. In part two, vascular lesions, fibrohistiocytic tumors, muscle tumors, peripheral nerve sheath tumors, tumors of uncertain differentiation, and undifferentiated small round cell sarcomas are reviewed. Per the convention of the WHO, these lesions involve the connective, subcutaneous, and other non-parenchymatous organ soft tissues, as well as the peripheral and autonomic nervous system.


Assuntos
Neoplasias Musculares , Neoplasias de Bainha Neural , Sarcoma , Neoplasias de Tecidos Moles , Diferenciação Celular , Criança , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias de Bainha Neural/patologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico por imagem
5.
Skeletal Radiol ; 50(11): 2169-2184, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34131792

RESUMO

Spinal fusion is performed to eliminate motion at a degenerated or unstable segment. However, this is associated with loss of motion at the fused levels and increased stress on adjacent levels. Motion-preserving implants have been designed in effort to mitigate the limitations of fusion. This review will focus on posterior spinal motion-preserving technologies. In the cervical spine, laminoplasty is a posterior motion-preserving procedure used in the management of myelopathy/cord compression. In the lumbar spine, motion-sparing systems include interspinous process devices (also referred to as interspinous process spacers or distraction devices), posterior dynamic stabilization devices (also referred to as pedicle screw/rod fixation-based systems), and posterior element replacement systems (also referred to as total facet replacement devices). Knowledge of the intended physiologic purpose, hardware utilized, and complications is important in the assessment of imaging in those who have undergone posterior motion preservation procedures.


Assuntos
Fusão Vertebral , Espondilose , Fenômenos Biomecânicos , Vértebras Cervicais , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Radiologistas , Amplitude de Movimento Articular , Espondilose/diagnóstico por imagem , Espondilose/cirurgia
6.
Emerg Radiol ; 28(2): 259-264, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32844321

RESUMO

PURPOSE: To determine the negative predictive value of multidetector CT for radiographically occult fracture of the hip or pelvis in an elderly population presenting to the emergency department. METHODS: Two hundred thirty-seven elderly patients with suspected fracture were identified over a 5-year period with negative radiographs acquired in the emergency department followed by an index CT of the hip/pelvis within 24 h. There were 81 cases with a negative index CT, as determined by 2 musculoskeletal radiologists, and with some form of imaging follow-up (MRI, CT, or x-ray) performed within 18 months of the index CT. Follow-up imaging was reviewed by 2 musculoskeletal radiologists for the presence of fracture to determine the performance of the index CT. The electronic medical record was used to exclude the possibility of intervening trauma between the time of the index CT and follow-up imaging. RESULTS: There were 39 cases with follow-up imaging performed within 6 weeks of the negative index CT, and 42 with follow-up imaging within 6 weeks to 18 months of the negative index CT. Eight of 81 patients demonstrated a fracture on follow-up imaging, with 3 of 8 involving the femoral neck or intertrochanteric femur. The negative predictive value of the index CT for the detection of a radiographically occult hip or pelvic fracture was 90.1%. If considering only surgically relevant fractures (femoral neck and intertrochanteric fractures), the negative predictive value improved to 96.3%. CONCLUSION: Computed tomography for occult hip fractures has a high negative predictive value but there are cases not detected with surgical implications.


Assuntos
Fraturas Fechadas/diagnóstico por imagem , Fraturas do Quadril/diagnóstico por imagem , Ossos Pélvicos/lesões , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos
7.
Yale J Biol Med ; 94(1): 65-71, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33795983

RESUMO

Introduction: In controversial fashion, the presence of an enlarged external occipital protuberance has been recently linked to excessive use of handheld electronic devices. We sought to determine the prevalence of this protuberance in a diverse age group of adults from two separate time periods, before and approximately 10 years after the release of the iPhone, to further characterize this theory, as if indeed valid, such a relationship could direct preventative behavior. Materials and Methods: Eighty-two cervical spine radiographs between March 7, 2007 through June 29, 2007 and 147 cervical spine radiographs between October 25, 2017 through January 1, 2018 were reviewed for the presence or absence of an exophytic external occipital protuberance. Influence of sex and age were also assessed. Results: There were 41/82 (50%) patients within the 2007 pre-iPhone group with an exophytic external occipital protuberance, ranging from 2.7-33.8 mm in length. Twenty-seven out of 82 (32.9%) had an external occipital protuberance at or above 10 mm. There were 49/147 (33.3%) patients within the 2017 post-iPhone group with an exophytic external occipital protuberance, ranging from 4.4-53.8 mm in length. Thirty-three out of 147 (22.4%) had an external occipital protuberance at or above 10 mm. When considering accessibility to the iPhone, sex, and age to the presence of an exophytic external occipital protuberance, only sex has a statistically significant association, p=0.000000033. Conclusion: We found no significant association with iPhone accessibility and an exophytic external occipital protuberance. Due to inherent limitations in the retrospective nature of the study, future research is needed to better examine the association of handheld electronic devices with exophytic external occipital protuberances.


Assuntos
Osso Occipital , Adulto , Humanos , Prevalência , Estudos Retrospectivos
9.
Skeletal Radiol ; 46(6): 723-730, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28238017

RESUMO

Anterior hip dislocations are rare orthopedic emergencies resulting from high-energy trauma and have unique imaging characteristics on radiography, computed tomography (CT), and magnetic resonance imaging (MRI). Imaging findings on CT and MRI allow for the prompt recognition and classification of anterior hip dislocations, which guides patient management and reduces complications. The purpose of this article is to review imaging findings of anterior hip dislocations, specifically focusing on CT and MRI.


Assuntos
Luxação do Quadril/diagnóstico por imagem , Articulação do Quadril/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos
10.
J Spinal Disord Tech ; 28(4): 152-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-23168390

RESUMO

STUDY DESIGN: Retrospective diagnostic trial. OBJECTIVE: To determine the diagnostic performance of 3-dimensional isotropic fast/turbo spin-echo (3D-TSE) in routine lumbar spine magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: Conventional 2-dimensional fast spin-echo (2D-FSE) MRI requires independent acquisition of each desired imaging plane. This is time consuming and potentially problematic in spine imaging, as the plane of interest varies along the vertical axis due to lordosis, kyphosis, or possible deformity. 3D-TSE provides the capability to acquire volumetric data sets that can be dynamically reformatted to create images in any desired plane. METHODS: Eighty subjects scheduled for routine lumbar MRI were included in a retrospective trial. Each subject underwent both 3D-TSE and conventional 2D-FSE axial and sagittal MRI sequences. For each subject, the 3D-TSE and 2D-FSE sequences were separately evaluated (minimum 4 wk apart) in a randomized order and read independently by 4 reviewers. Images were evaluated using specific criteria for stenosis, herniation, and degenerative changes. RESULTS: The intermethod reliability for the 4 reviewers was 85.3%. Modified intermethod reliability analysis, disregarding disagreements between the lowest 2 descriptors for appropriate criteria (equivalent to "none" and "mild"), revealed average overall agreement of 94.6%. Using the above, modified criteria, interobserver variability for 3D-TSE was 89.1% and 88.3% for 2D-FSE (P=0.05), and intraobserver variability for 3D-TSE was 87.2% and 82.0% for 2D-FSE (P<0.01). The intermethod agreement between 3D-TSE and 2D-FSE was statistically noninferior to intraobserver 2D-FSE variability (P<0.01). CONCLUSIONS: This systematic evaluation showed that there is a very high degree of agreement between diagnostic findings assessed on 3D-TSE and conventional 2D-FSE sequences. Overall, intermethod agreement was statistically noninferior to the intraobserver agreement between repeated 2D-FSE evaluations. Overall, this study shows that 3D-TSE performs equivalently, if not superiorly to 2D-FSE sequences. Reviewers found particular utility for the ability to manipulate image planes with the 3D-TSE if there was greater pathology or anatomic variation.


Assuntos
Vértebras Lombares/patologia , Imageamento por Ressonância Magnética/métodos , Bases de Dados Factuais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estenose Espinal/patologia
11.
Blood Cells Mol Dis ; 53(1-2): 56-60, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24581483

RESUMO

BACKGROUND: Bone marrow infiltration by substrate-engorged "Gaucher" cells manifests early in Gaucher disease (GD). The impact of velaglucerase alfa on bone marrow burden (BMB) was evaluated as an exploratory assessment. METHODS: BMB scores were assessed using T1- and T2-weighted magnetic resonance images of the lumbar spine (LS) and femora among symptomatic GD patients who participated in the 9-month Phase I/II trial and long-term extension study for velaglucerase alfa. A post-hoc assessment of marrow involvement was performed. BMB scores per site are 0-8 (0/1=normal; 8=severe infiltration). RESULTS: The median LS-BMB score at baseline was 6 (n=12; range 3-8); at 9 months, compared with baseline, there was a median change of -2 (n=11; two-sided p-value=0.0078). LS-BMB scores continued to decrease through 5 years (n=8; median change from baseline -5 [p=0.0078], median score 1 [range 1-4]) and were subsequently sustained through 7 years (n=8). LS-BMB decreases of ≥2 points occurred in 6/11 patients at 9 months, and in all assessable patients (8/8) by 5 years. Long-term femoral BMB (F-BMB) assessment was possible for three patients; all experienced reductions of ≥2 points at 5 years with a total score (LS-BMB+F-BMB) decrease ≥4. CONCLUSIONS: This post hoc analysis suggests improvement in BMB scores through 5 years that was sustained through 7 years, despite dose reduction from 15 months. Prospective studies in a large cohort are needed to validate these findings.


Assuntos
Medula Óssea/efeitos dos fármacos , Terapia de Reposição de Enzimas , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/farmacologia , Glucosilceramidase/uso terapêutico , Adolescente , Adulto , Idoso , Medula Óssea/patologia , Feminino , Seguimentos , Humanos , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Curr Probl Diagn Radiol ; 53(3): 405-414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38246795

RESUMO

Adolescent idiopathic scoliosis is a commonly encountered condition often diagnosed on screening examination. Underlying, asymptomatic neural axis abnormalities may be present at the time of diagnosis. At certain institutions, total spine MRI is obtained preoperatively to identify these abnormalities. We provide a framework for the radiologist to follow while interpreting these studies. In part 1, we discuss Arnold Chiari malformations, syringomyelia, and the tethered cord. In part 2, we focus on spinal cord tumors, dysraphisms, to include diastematomyelia, and vertebral anomalies.


Assuntos
Malformação de Arnold-Chiari , Escoliose , Siringomielia , Humanos , Adolescente , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/cirurgia , Imageamento por Ressonância Magnética , Siringomielia/diagnóstico por imagem , Siringomielia/cirurgia , Programas de Rastreamento , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia
13.
Curr Probl Diagn Radiol ; 53(3): 415-421, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38262798

RESUMO

Adolescent idiopathic scoliosis is a commonly encountered condition often diagnosed on screening examination. Underlying, asymptomatic neural axis abnormalities may be present at the time of diagnosis. At certain institutions, total spine MRI is obtained preoperatively to identify these abnormalities. We provide a framework for the radiologist to follow while interpreting these studies. In part 1, we discuss Arnold Chiari malformations, syringomyelia, and the tethered cord. In part 2, we focus on spinal cord tumors, dysraphisms, to include diastematomyelia, and vertebral anomalies.


Assuntos
Malformação de Arnold-Chiari , Defeitos do Tubo Neural , Escoliose , Neoplasias da Medula Espinal , Humanos , Adolescente , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Defeitos do Tubo Neural/diagnóstico por imagem , Defeitos do Tubo Neural/patologia , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/patologia , Imageamento por Ressonância Magnética , Neoplasias da Medula Espinal/patologia , Medula Espinal/diagnóstico por imagem , Coluna Vertebral/patologia
14.
AJR Am J Roentgenol ; 201(3): W425-36, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23971473

RESUMO

OBJECTIVE: Classifying acetabular fractures can be an intimidating topic. However, it is helpful to remember that there are only three basic types of acetabular fractures: column fractures, transverse fractures, and wall fractures. Within this framework, acetabular fractures are classified into two broad categories: elementary or associated fractures. We will review the osseous anatomy of the pelvis and provide systematic approaches for reviewing both radiographs and CT scans to effectively evaluate the acetabulum. CONCLUSION: Although acetabular fracture classification may seem intimidating, the descriptions and distinctions discussed and shown in this article hopefully make the topic simpler to understand. Approach the task by recalling that there are only three basic types of acetabular fractures: column fractures (coronally oriented on CT images), transverse fractures (sagittally oriented on CT images), and wall fractures (obliquely oriented on CT images). We have provided systematic approaches for reviewing both conventional radiographs and CT scans to effectively assess the acetabulum. The clinical implications of the different fracture patterns have also been reviewed because it is critically important to include pertinent information for our clinical colleagues to provide the most efficient and timely clinical care.


Assuntos
Acetábulo/lesões , Fraturas Ósseas/classificação , Fraturas Ósseas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Acetábulo/anatomia & histologia , Fixação Interna de Fraturas/métodos , Humanos , Imageamento Tridimensional , Ossos Pélvicos/anatomia & histologia , Ossos Pélvicos/lesões
16.
Case Rep Surg ; 2022: 8440836, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402057

RESUMO

Introduction and Importance. Rosai-Dorfman disease (RDD) is a rare, benign type II histiocytosis characterized by the infiltration of S100+ histiocytes and emperipolesis. The disease may present in the lymph nodes (nodal RDD), in extranodal sites, or in both nodal and extranodal sites. Among those patients who present exclusively in extranodal sites, only a minority of cases present in the soft tissue. Case Presentation. An 18-year-old female presented to orthopedic oncology clinic with a chief complaint of a mass located in her lower back. The patient underwent excision of the lumbosacral mass. Pathologic review demonstrated emperipolesis of lymphocytes and plasma cells within enlarged, eosinophilic histiocytes in a background of lymphoplasmacytic infiltration and collagenous stroma. Immunohistochemical staining demonstrated S100+ and CD163+ histiocytes, consistent with diagnosis of soft tissue RDD. Clinical Discussion. Histologically, RDD is generally characterized by emperipolesis-the presence of intact lymphocytes within the histiocyte cytoplasm-and a mixed infiltrate of S100+ histiocytes, mononuclear cells, plasma cells, and lymphocytes. Although soft tissue RDD may histologically resemble nodal RDD, soft tissue RDD also demonstrates some notable histologic differences including the lack of nodal architecture, the presence of increased fibrosis and collagen deposition, and generally fewer RDD cells. Conclusion. This case presentation demonstrates one few reports of isolated soft tissue RDD within the lumbosacral region without associated lymphadenopathy or skin changes and highlights the heterogeneity that still exists in the treatment paradigm of extranodal RDD.

17.
J Magn Reson Imaging ; 33(1): 221-4, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21182143

RESUMO

Lipoma arborescens or synovial lipomatosis is a rare disorder characterized by mature fat infiltration of hypertrophic synovial villi, most frequently affecting the suprapatellar pouch of the knee. Involvement of the synovial tendon sheath is extremely rare with only a few reported cases in the literature. We present a case of lipoma arborescens involving the peroneal and flexor tendons sheaths of the ankle, review the few reported cases to date, and discuss MR imaging features of this rare entity.


Assuntos
Articulação do Tornozelo/patologia , Doenças do Tecido Conjuntivo/patologia , Lipomatose/patologia , Imageamento por Ressonância Magnética/métodos , Tendões/patologia , Humanos , Masculino , Pessoa de Meia-Idade
19.
Am J Phys Med Rehabil ; 100(5): e69-e72, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32769377

RESUMO

ABSTRACT: The knee extensor mechanism is a highly complex multilayered and reinforced structure. Quadriceps muscle injuries are considered to be common, particularly among athletes; however isolated rectus femoris injuries involving the distal myotendinous junction are considered to be exceedingly rare with very few case reports published to date. Thus, the presentation and diagnosis of this injury can be elusive and treatment is nonuniform. There is limited literature published advocating both nonsurgical and surgical management. We illustrate the clinical and radiologic presentation of a traumatic, nonsport-related distal rectus femoris muscle injury treated operatively. The presentation of this injury along with anatomical and clinical considerations is portrayed in detail. This case report contributes to the sparse literature regarding this injury and delineates management considerations.


Assuntos
Traumatismos do Joelho/cirurgia , Músculo Quadríceps/lesões , Músculo Quadríceps/cirurgia , Ruptura/cirurgia , Estética , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Inherit Metab Dis ; 33(6): 769-74, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20683668

RESUMO

Focal splenic lesions (FSL) occur in Gaucher disease type I (GD1), but their clinical significance is not known. Previous studies estimated the prevalence of FSL at 4% (pediatric) to 33% (adult) of GD1 patients and reported an association with splenomegaly. We tested the hypothesis that the presence of FSL is associated with suboptimal response to macrophage-directed enzyme replacement therapy (ERT). Additionally we investigated whether FSL were associated with other phenotypic features of GD1. The splenic parenchyma was assessed by MRI performed for routine evaluation of GD1 in 239 consecutive GD1 patients with intact spleens. The prevalence of FSL was 18.4% (44/239). Following a mean of 3.5 years of ERT, platelet response was inferior among patients with FSL (80,700 ± 9,600 to 90,100 ± 7,200/mm(3) , P = 0.2) compared to patients without FSL in whom there was a robust platelet response: 108,600 ± 5,670 to 150,200 ± 6,710/mm(3), P < 0.001. Compared to patients without FSL, patients harboring FSL had worse thrombocytopenia (platelet count: 83,700 ± 8,800 vs. 112,100 ± 4,200/mm(3), P = 0.004), greater frequency of pre-ERT splenomegaly, and greater post-ERT splenomegaly (8.5 ± 0.77 vs. 4.8 ± 0.25× normal, P < 0.001). Additionally, the prevalence of osteonecrosis was higher among patients with FSL compared to patients without FSL (38 vs. 20.7%, P = 0.026). FSL appear to be a determinant of response to ERT, suggesting studies comparing relative efficacy of newly emerging therapies for GD1 should adjust for this factor. Moreover, occurrences of FSL coincide with more severe manifestations of GD1 such as avascular osteonecrosis.


Assuntos
Transtornos Plaquetários/diagnóstico , Terapia de Reposição de Enzimas , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Macrófagos/efeitos dos fármacos , Baço/efeitos dos fármacos , Esplenopatias/diagnóstico , Adulto , Transtornos Plaquetários/patologia , Sistemas de Liberação de Medicamentos/métodos , Feminino , Seguimentos , Doença de Gaucher/sangue , Doença de Gaucher/diagnóstico , Doença de Gaucher/patologia , Glucosilceramidase/administração & dosagem , Glucosilceramidase/efeitos adversos , Humanos , Masculino , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Baço/patologia , Esplenopatias/patologia , Falha de Tratamento
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