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1.
Vet Clin North Am Equine Pract ; 36(1): 35-52, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954548

RESUMO

This article describes the indications for sampling of bone marrow, the technical aspects of obtaining marrow core biopsies and aspirates, and the preparation of marrow smears. All aspects are illustrated with clinical cases. The information that can be expected from the pathologist's report of marrow samples is outlined, and the clinical features and prognosis of different types of leukemia are detailed.


Assuntos
Doenças da Medula Óssea/veterinária , Medula Óssea/patologia , Doenças dos Cavalos/patologia , Cavalos/sangue , Animais , Doenças da Medula Óssea/sangue , Doenças da Medula Óssea/patologia , Feminino , Doenças dos Cavalos/sangue , Leucemia/sangue , Leucemia/patologia , Leucemia/veterinária , Patologia Clínica , Prognóstico , Manejo de Espécimes
2.
Eur Radiol ; 30(1): 141-150, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31350586

RESUMO

OBJECTIVES: To evaluate the diagnostic accuracy of dual-energy computed tomography (CT) virtual non-calcium (VNCa) reconstructions for the depiction of traumatic knee bone marrow edema. METHODS: Fifty-seven patients (mean age, 50 years; range, 20-82 years) with acute knee trauma further divided into 30 women and 27 men, who had undergone third-generation dual-source dual-energy CT and 3-T magnetic resonance imaging (MRI) within 7 days between January 2017 and May 2018, were retrospectively analyzed. Six radiologists, blinded to clinical and MRI information, independently analyzed conventional grayscale dual-energy CT series for fractures; after 8 weeks, readers evaluated color-coded VNCa reconstructions for the presence of bone marrow edema in six femoral and six tibial regions. Quantitative analysis of CT numbers on VNCa reconstructions was performed by a seventh radiologist. Two additional radiologists, blinded to clinical and CT information, analyzed MRI series in consensus to define the reference standard. Sensitivity, specificity, and the area under the curve (AUC) were the primary metrics of diagnostic accuracy. RESULTS: MRI revealed 197 areas with bone marrow edema (91/342 femoral, 106/342 tibial). In the qualitative analysis, VNCa showed high overall sensitivity (1108/1182 [94%]) and specificity (2789/2922 [95%]) for depicting bone marrow edema. The AUC was 0.96 (femur) and 0.97 (tibia). A cutoff value of - 51 Hounsfield units (HU) provided high sensitivity (102/106 [96%]) and specificity (229/236 [97%]) for differentiating tibial bone marrow edema. CONCLUSIONS: In both quantitative and qualitative analyses, dual-energy CT VNCa reconstructions yielded excellent diagnostic accuracy for depicting traumatic knee bone marrow edema compared with MRI. KEY POINTS: • Dual-energy CT (DECT) virtual non-calcium (VNCa) reconstructions are highly accurate in depicting bone marrow edema of the femur and tibia. • Diagnostic confidence, image noise, and image quality were rated as equivalent in VNCa reconstructions and MRI (magnetic resonance imaging) series. • VNCa images may serve as an alternative imaging approach to MRI.


Assuntos
Doenças da Medula Óssea/patologia , Edema/patologia , Fraturas Ósseas/patologia , Traumatismos do Joelho , Tomografia Computadorizada por Raios X/métodos , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio , Feminino , Humanos , Traumatismos do Joelho/diagnóstico por imagem , Traumatismos do Joelho/patologia , Articulação do Joelho/patologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Tíbia/patologia , Adulto Jovem
3.
Toxicol Pathol ; 47(6): 665-783, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31526133

RESUMO

The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative changes in rats and mice. The purpose of this publication is to provide a standardized nomenclature for classifying changes observed in the hematolymphoid organs, including the bone marrow, thymus, spleen, lymph nodes, mucosa-associated lymphoid tissues, and other lymphoid tissues (serosa-associated lymphoid clusters and tertiary lymphoid structures) with color photomicrographs illustrating examples of the lesions. Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. The nomenclature for these organs is divided into 3 terminologies: descriptive, conventional, and enhanced. Three terms are listed for each diagnosis. The rationale for this approach and guidance for its application to toxicologic pathology are described in detail below.


Assuntos
Pesquisa Biomédica/normas , Doenças da Medula Óssea/classificação , Medula Óssea , Doenças Linfáticas/classificação , Tecido Linfoide , Animais , Animais de Laboratório , Medula Óssea/anatomia & histologia , Medula Óssea/patologia , Doenças da Medula Óssea/sangue , Doenças da Medula Óssea/imunologia , Doenças da Medula Óssea/patologia , Doenças Linfáticas/sangue , Doenças Linfáticas/imunologia , Doenças Linfáticas/patologia , Tecido Linfoide/anatomia & histologia , Tecido Linfoide/patologia , Camundongos , Ratos , Terminologia como Assunto
4.
Eur J Radiol ; 118: 207-214, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31439244

RESUMO

PURPOSE: To investigate the diagnostic accuracy of dual-energy computed tomography (CT) virtual non-calcium (VNCa) reconstructions for the depiction of traumatic bone marrow edema of the calcaneus. METHOD: Data from 62 patients (33 women, 29 men; mean age: 41 years, range: 19-84 years) with acute tarsal trauma who had undergone third-generation dual-source dual-energy CT and 3-T magnetic resonance imaging (MRI) within seven days between January 2017 and July 2018 were retrospectively analyzed. Five radiologists, blinded to clinical and MRI information, independently assessed conventional grayscale dual-energy CT series for the presence of fractures; after at least eight weeks, readers re-evaluated all cases using color-coded VNCa reconstructions for the presence of bone marrow edema. Quantitative analysis of CT numbers on VNCa reconstructions was performed by a sixth radiologist. Two additional experienced radiologists, blinded to clinical and CT information, assessed MRI series in consensus to define the reference standard. Sensitivity, specificity and the area under the curve (AUC) were the primary indices for diagnostic accuracy. RESULTS: MRI revealed 62 areas with bone marrow edema in 39 patients. In the qualitative analysis, VNCa showed high overall sensitivity (286/310 [92%]) and specificity (899/930 [97%]) for the depiction of bone marrow edema. A cut-off value of -53 Hounsfield units (HU) provided a sensitivity of 82% (51/62) and specificity of 95% (176/186]) for differentiating bone marrow edema. The overall AUC was 0.98. CONCLUSIONS: In both quantitative and qualitative analyses, dual-energy CT VNCa reconstructions show excellent diagnostic accuracy for the visualization of traumatic calcaneal bone marrow edema compared to MRI.


Assuntos
Medula Óssea/diagnóstico por imagem , Calcâneo/diagnóstico por imagem , Edema/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Doenças da Medula Óssea/patologia , Calcâneo/patologia , Cor , Edema/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
5.
Eur J Radiol ; 118: 223-230, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31439246

RESUMO

PURPOSE: To identify the predictors of bone-marrow DWI signals from anthropometric, complete blood count (CBC), and C-reactive protein (CRP), and to evaluate the association with fat-content in patients. METHOD: This retrospective study was approved by the institutional review board. A total of 113 consecutive tumor patients underwent whole-body PET/MRI. Apparent diffusion coefficient (ADC) and proton density fat fraction (PDFF) were measured and averaged in lumbar vertebrae (L3-5) and bilateral ilia. Due to respiratory motion, ribs were evaluated by 3-point visual scoring on DWI with b = 800 (1: invisible, 2: partially visible, 3: fully visible). The relationships between ADC/visual scores and anthropometric, CBC, CRP, and PDFF were examined. In females, the age-dependency was evaluated. RESULTS: Multi-regression analyses identified age as the strongest predictor of lumbar ADC (standardized coefficient: ß = 0.45), followed by red cell distribution width (RDW) (ß = -0.24), while age was the strongest predictor of iliac ADC (ß = 0.43), followed by hemoglobin (Hb) (ß = 0.22). RDW was the strongest predictor (ß = 0.47) for rib visual score and age was the second (ß = -0.39). ADC showed significant positive correlations with PDFF at L3-5 and ilium. Lumbar ADC showed a decreasing trend during middle age in females. CONCLUSIONS: Age, anemia (lower Hb), and increased hematopoietic activity (higher RDW) are the predominant predictors of ADC and the visibility of red marrow on DWI. Fat-suppression methods and bone-marrow physiology in middle-aged females may have affected the measured correlations between ADC and PDFF inconsistent with previous studies.


Assuntos
Anemia/patologia , Doenças da Medula Óssea/patologia , Hematopoese/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prótons , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Imagem Corporal Total/métodos , Adulto Jovem
9.
Eur J Radiol ; 113: 158-164, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30927942

RESUMO

BACKGROUND: Marrow fat accumulates in diabetic conditions but remains elusive. The published works on the relationships between marrow fat phenotypes and glucose homeostasis are controversial. PURPOSE: To detect the association of insulin resistance with marrow adiposity in postmenopausal women with newly diagnosed type 2 diabetes (T2D) using chemical shift-encoded water-fat MRI. METHODS: We measured vertebral proton density fat fraction (PDFF) by 3T-MRI in 75 newly diagnosed T2D and 20 nondiabetic postmenopausal women. Bone mineral density (BMD), whole body fat mass and lean mass were determined by dual-energy X-ray absorptiometry. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Lumbar spine PDFF was higher in women with T2D (65.9 ± 6.8%) than those without diabetes (59.5 ± 6.1%, P = 0.009). There was a consistent inverse association between the vertebral PDFF and BMD. PDFF had a positive association with glycated hemoglobin and HOMA-IR but not with fasting plasma glucose and insulin. PDFF was significantly increased, and BMD was decreased in a linear trend from the lowest (<1.90) to highest (≥2.77) HOMA-IR quartile. Multivariate linear regression analyses revealed a positive association between log-transformed HOMA-IR and PDFF after adjustment for multiple covariates (ß = 0.382, P < 0.001). The positive association of HOMA-IR with PDFF remained robust when total body lean mass and fat mass, BMD was entered into the multivariate regression model, respectively (ß = 0.293 and ß = 0.251, respectively; all P <0.05). CONCLUSIONS: Elevated HOMA-IR was linked to higher marrow fat fraction in postmenopausal women with newly diagnosed T2D independently of body compositions.


Assuntos
Adiposidade/fisiologia , Doenças da Medula Óssea/patologia , Diabetes Mellitus Tipo 2/patologia , Resistência à Insulina/fisiologia , Absorciometria de Fóton/métodos , Tecido Adiposo/patologia , Composição Corporal/fisiologia , Água Corporal/fisiologia , Medula Óssea/patologia , Estudos Transversais , Feminino , Homeostase/fisiologia , Humanos , Vértebras Lombares , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia
10.
J Am Acad Orthop Surg ; 27(20): 752-759, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30964755

RESUMO

Bone marrow lesions of the knee in patients with osteoarthritis (OA-BML) are an important clinical entity that may explain progressive pain, decreased quality of life, and impaired function. MRI of OA-BMLs demonstrates a region of subchondral bone with hyperintense marrow signal on T2-weighted images. Histopathology retrieval studies have demonstrated that these lesions correlate with microdamage of the trabecular bone, and subsequently, this leads to a vicious cycle of subchondral bone attrition, attempts at repair, pain, and progressive deformity. These lesions have also been linked to accelerated loss of adjacent articular cartilage and increases in the severity of knee pain, prompting patients to seek musculoskeletal care and treatment. Multiple studies have also correlated the presence of an OA-BML with an increased probability of seeking knee arthroplasty. Knowledge of these lesions is important in the context that knee OA is both a cartilage-based and bone-based disease. Further study of OA-BMLs may provide opportunities for early intervention and OA disease-modifying treatments.


Assuntos
Doenças da Medula Óssea/patologia , Doenças das Cartilagens/patologia , Osteoartrite do Joelho/patologia , Doenças da Medula Óssea/diagnóstico por imagem , Doenças da Medula Óssea/cirurgia , Doenças das Cartilagens/diagnóstico por imagem , Doenças das Cartilagens/cirurgia , Humanos , Imagem por Ressonância Magnética , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Qualidade de Vida , Procedimentos Cirúrgicos Reconstrutivos
11.
Transpl Immunol ; 55: 101205, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30946889

RESUMO

Graft-versus-host disease (GVHD) constitutes the most frequent complications after the allogeneic hematopoietic stem cell transplantation for a variety of hematological malignancies. In the present study, we explored the prophylactic potential of adipose tissue-derived mesenchymal stem cells (AD-MSCs) in controlling GVHD in murine models with a special focus on bone marrow aplasia related with acute GVHD. The CB6F1 mice were induced GVHD by the injection intravenously of C57BL/6 (B6-Ly-5.1) splenocytes without conditioning irradiation or chemotherapy. AD-MSCs from C3H mice were injected intravenously via tail veins. GVHD was assessed using flowcytometry analysis of peripheral blood cells and histopathologic analysis of target organs. Histopathological analyses revealed that AD-MSCs markedly suppressed the infiltration of lymphocytes into liver as well as the aplasia in bone marrow. This study is the first to clarify the effectiveness of AD-MSCs against bone marrow aplasia in GVHD, supporting a rationale of AD-MSCs for ameliorating bone marrow suppression and infectivity after allo-HSCT in human clinics.


Assuntos
Doenças da Medula Óssea , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Tecido Adiposo , Aloenxertos , Animais , Doenças da Medula Óssea/etiologia , Doenças da Medula Óssea/imunologia , Doenças da Medula Óssea/patologia , Doenças da Medula Óssea/terapia , Modelos Animais de Doenças , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Células-Tronco Mesenquimais/patologia , Camundongos
13.
Skeletal Radiol ; 48(10): 1525-1539, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30903260

RESUMO

There is a large variety of conditions that can result in 'bone marrow edema' or 'bone marrow lesions' (BML) in the wrist on magnetic resonance imaging (MRI). The combination of clinical history and the distribution of the BML can serve as a valuable clue to a specific diagnosis. This article illustrates the different patterns of BML in the wrist to serve as a useful guide when reviewing wrist MRI studies. Imaging artefacts will also be briefly covered.


Assuntos
Doenças da Medula Óssea/diagnóstico por imagem , Edema/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Punho/diagnóstico por imagem , Doenças da Medula Óssea/patologia , Diagnóstico Diferencial , Edema/patologia , Humanos , Punho/patologia
14.
Eur J Radiol ; 112: 1-6, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30777197

RESUMO

PURPOSE: The purpose of this study was to assess the differences in magnetic resonance (MR) findings between the symptomatic and asymptomatic pre-collapse stage of osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: This study reviewed 123 consecutive hips in 91 patients in the pre-collapse stage of ONFH based on plain radiographic findings. These 123 hips were divided into symptomatic and asymptomatic groups according to the pain domain score in the Harris hip score system. Bone marrow edema (BME), synovial fluid effusion, and subchondral fracture were evaluated using MR imaging. Odds ratios (ORs) were calculated between these three parameters and symptoms. The subsequent clinical course after MR examination was also assessed for each hip that could be followed more than 1 year. RESULTS: Forty-six hips (37.4%) were categorized as symptomatic and 77 hips (62.6%) as asymptomatic. The prevalence of BME, synovial fluid effusion, and subchondral fracture were 87.0% (40/46), 80.4% (37/46), and 34.8% (16/46), respectively, in the symptomatic group, and 0%, 28.6% (22/77), and 0%, respectively, in the asymptomatic group, indicating significant differences between the two groups (p < 0.0001). Among these parameters, BME showed the highest OR with regard to the presence or absence of symptoms (BME, 965.8; joint effusion, 10.3; subchondral fracture, 83.9). Due to persistent pain and subsequent collapse, 30 of 35 (85.7%) symptomatic hips with BME subsequently underwent surgical treatment at a mean interval of 3.47 months after MR examination, while 25 of 66 (37.9%) asymptomatic hips without BME underwent surgical treatment at a mean interval of 20.7 months after MR examination. CONCLUSIONS: This study demonstrated that symptomatic pre-collapse ONFH diagnosed based on plain radiographic findings could be distinguished from asymptomatic pre-collapse ONFH by the presence of BME on MR imaging, and thus BME may be a sign of occult fracture.


Assuntos
Doenças da Medula Óssea/patologia , Necrose da Cabeça do Fêmur/patologia , Adolescente , Adulto , Idoso , Edema/patologia , Feminino , Fraturas Ósseas/patologia , Articulação do Quadril/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dor/patologia , Prevalência , Radiografia , Estudos Retrospectivos , Adulto Jovem
15.
Exp Hematol ; 71: 32-42, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30664904

RESUMO

The plasticity of induced pluripotent stem cells (iPSCs) with the potential to differentiate into virtually any type of cells and the feasibility of generating hematopoietic stem progenitor cells (HSPCs) from patient-derived iPSCs (iPSC-HSPCs) has many potential applications in hematology. For example, iPSC-HSPCs are being used for leukemogenesis studies and their application in various cell replacement therapies is being evaluated. The use of iPSC-HSPCs can now provide an invaluable resource for the study of diseases associated with the destruction of HSPCs, such as bone marrow failure syndromes (BMFSs). Recent studies have shown that generating iPSC-HSPCs from patients with acquired aplastic anemia and other BMFSs is not only feasible, but is also a powerful tool for understanding the pathogenesis of these disorders. In this article, we highlight recent advances in the application of iPSCs for disease modeling of BMFSs and discuss the discoveries of these studies that provide new insights in the pathophysiology of these conditions.


Assuntos
Anemia Aplástica/etiologia , Anemia Aplástica/metabolismo , Doenças da Medula Óssea/etiologia , Doenças da Medula Óssea/metabolismo , Hematopoese , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Hemoglobinúria Paroxística/etiologia , Hemoglobinúria Paroxística/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Modelos Biológicos , Anemia Aplástica/patologia , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Doenças da Medula Óssea/patologia , Diferenciação Celular , Evolução Clonal , Hemoglobinúria Paroxística/patologia , Humanos
16.
J Cancer Res Clin Oncol ; 145(2): 535-542, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30603901

RESUMO

PURPOSE: Multicolor flow cytometry (MFC) is widely available, fast and has an easy-to perform approach for finding neuroblastoma (NB) cells among normal bone marrow (BM) hematopoietic cells. Aim of the study was to investigate prognostic significance of initial MFC tumor cells' detection in BM of children with NB. METHODS: 51 patients (24 boys and 27 girls) aged from 6 days to 15 years (median age 1 year 3 months) with NB were included in the study. BM samples at the time of diagnosis were obtained from 2 to 5 aspiration sites per patient. CD45(-)CD56(+)CD81(+)GD2(+)-cells were evaluated by MFC. RESULTS: NB cells were detected in BM by FC more frequently compared to conventional cytomorphology (49.0% and 29.4% patients, respectively, р = 0.043). Patients with NB cells detected in BM by MFC had significantly worse event-free survival and cumulative incidence of relapse/progression [0.24(0.08) and 0.60(0.10), respectively] compared to children with negative result of immunophenotyping [0.85(0.07) and 0.12(0.06), respectively, p < 0.001 in both cases]. BM involvement detection by MFC maintained its prognostic significance in various patients groups. In multivariate analysis, immunophenotyping proved to be an independent prognostic factor when analyzed jointly with other NB risk factors. In 42 patients BM involvement was also studied by RQ-PCR for PHOX2B and TH genes expression. Within groups of patients divided by RQ-PCR positivity, MFC-positivity retained prognostic significance. CONCLUSIONS: Thus flow cytometric BM involvement detection has very strong prognostic impact even stronger than RQ-PCR. It could be used in combination with other parameters for the treatment strategy choice in patients with NB.


Assuntos
Antígenos CD/análise , Biomarcadores Tumorais/análise , Doenças da Medula Óssea/patologia , Medula Óssea/patologia , Citometria de Fluxo/métodos , Imunofenotipagem/métodos , Neuroblastoma/patologia , Adolescente , Medula Óssea/metabolismo , Doenças da Medula Óssea/metabolismo , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neuroblastoma/metabolismo , Prognóstico , Taxa de Sobrevida
17.
Pediatr Blood Cancer ; 66(5): e27597, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30604473

RESUMO

Shwachman-Diamond syndrome (SDS) is one of the more common inherited bone marrow failure syndromes, characterized by neutropenia, occasional thrombocytopenia, and anemia. Bone marrow evaluation reveals an increased number of monocytes and mature B cells along with decreased granulocytes. However, little is known about the subpopulations of peripheral blood cells, and few previous publications have been based on a small number of patients. Here, we report a comprehensive immunophenotypic analysis from a cohort of 37 SDS patients who display impairment mostly in the myeloid compartment with a deficiency also in the number of B cells and CD4/CD8 double-negative T cells.


Assuntos
Linfócitos B/imunologia , Doenças da Medula Óssea/sangue , Doenças da Medula Óssea/imunologia , Insuficiência Pancreática Exócrina/sangue , Insuficiência Pancreática Exócrina/imunologia , Imunofenotipagem/métodos , Leucócitos Mononucleares/imunologia , Lipomatose/sangue , Lipomatose/imunologia , Adolescente , Adulto , Doenças da Medula Óssea/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Insuficiência Pancreática Exócrina/patologia , Feminino , Seguimentos , Humanos , Lactente , Lipomatose/patologia , Masculino , Prognóstico , Adulto Jovem
18.
J Pediatr Hematol Oncol ; 41(2): 137, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30475299

RESUMO

Macropolycytes are tetraploid neutrophils produced during accelerated myelopoiesis. They have been reported in adults with pernicious anemia, sepsis, and after cytotoxic chemotherapy. Two pediatric cases are reported, one after granulocyte colony-stimulating factor treatment and the other following Kawasaki disease, respectively.


Assuntos
Doenças da Medula Óssea/patologia , Insuficiência Pancreática Exócrina/patologia , Lipomatose/patologia , Síndrome de Linfonodos Mucocutâneos/patologia , Neutrófilos/patologia , Adolescente , Doenças da Medula Óssea/sangue , Doenças da Medula Óssea/tratamento farmacológico , Criança , Insuficiência Pancreática Exócrina/sangue , Insuficiência Pancreática Exócrina/tratamento farmacológico , Humanos , Lipomatose/sangue , Lipomatose/tratamento farmacológico , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Neutrófilos/metabolismo
19.
Rheumatology (Oxford) ; 58(2): 274-283, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30247727

RESUMO

Objective: To identify and validate knee pain phenotypes in an older population across different pain-related domains over 10.7 years. Methods: A total of 963 participants (mean age 63 years) from a population-based older adult cohort study were studied at baseline and followed up at 2.6 (n = 875), 5.1 (n = 768) and 10.7 years (n = 563). Baseline demographic, psychological, lifestyle and comorbidities data were obtained and MRI was performed to measure knee structural pathology. WOMAC pain and pain at multiple sites were assessed by questionnaires at each time-point. Latent class analysis was used to identify knee pain phenotypes, considering sex, BMI, emotional problems, education level, comorbidities, number of painful sites and knee structural pathology. Results: Three pain phenotypes were identified: Class 1: high prevalence of emotional problems and low prevalence of structural damage (25%); Class 2: high prevalence of structural damage and low prevalence of emotional problems (20%); Class 3: low prevalence of emotional problems and low prevalence of structural damage (55%). Participants within Class 1 and 2 had greater BMI, more comorbidities, a higher prevalence of radiographic knee OA and knee structural pathology compared with Class 3. Furthermore, compared with Class 2 and 3, WOMAC pain and number of painful sites were consistently greater at each time-point over 10.7 years in Class 1. Results were similar when the analyses were restricted to participants with radiographic knee OA. Conclusion: Psychological and structural factors interact with each other to exacerbate pain perception, suggesting that tailored treatment approaches for older people with knee pain in clinical practice are needed.


Assuntos
Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/complicações , Dor/etiologia , Sintomas Afetivos/complicações , Idoso , Idoso de 80 Anos ou mais , Doenças da Medula Óssea/diagnóstico por imagem , Doenças da Medula Óssea/patologia , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Estudos de Coortes , Escolaridade , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Dor/diagnóstico por imagem , Dor/patologia , Dor/psicologia , Medição da Dor/métodos , Percepção da Dor , Fenótipo , Estudos Prospectivos , Radiografia , Sinovite/diagnóstico por imagem , Sinovite/patologia
20.
Blood ; 133(2): 107-120, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30413413

RESUMO

Hematopoiesis is a dynamic system that requires balanced cell division, differentiation, and death. The 2 major modes of programmed cell death, apoptosis and necroptosis, share molecular machinery but diverge in outcome with important implications for the microenvironment; apoptotic cells are removed in an immune silent process, whereas necroptotic cells leak cellular contents that incite inflammation. Given the importance of cytokine-directed cues for hematopoietic cell survival and differentiation, the impact on hematopoietic homeostasis of biasing cell death fate to necroptosis is substantial and poorly understood. Here, we present a mouse model with increased bone marrow necroptosis. Deletion of the proapoptotic Bcl-2 family members Bax and Bak inhibits bone marrow apoptosis. Further deletion of the BH3-only member Bid (to generate Vav CreBaxBakBid triple-knockout [TKO] mice) leads to unrestrained bone marrow necroptosis driven by increased Rip1 kinase (Ripk1). TKO mice display loss of progenitor cells, leading to increased cytokine production and increased stem cell proliferation and exhaustion and culminating in bone marrow failure. Genetically restoring Ripk1 to wild-type levels restores peripheral red cell counts as well as normal cytokine production. TKO bone marrow is hypercellular with abnormal differentiation, resembling the human disorder myelodysplastic syndrome (MDS), and we demonstrate increased necroptosis in MDS bone marrow. Finally, we show that Bid impacts necroptotic signaling through modulation of caspase-8-mediated Ripk1 degradation. Thus, we demonstrate that dysregulated necroptosis in hematopoiesis promotes bone marrow progenitor cell death that incites inflammation, impairs hematopoietic stem cells, and recapitulates the salient features of the bone marrow failure disorder MDS.


Assuntos
Doenças da Medula Óssea/etiologia , Medula Óssea/patologia , Células-Tronco Hematopoéticas/patologia , Inflamação/etiologia , Síndromes Mielodisplásicas/etiologia , Necrose , Animais , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/fisiologia , Medula Óssea/metabolismo , Doenças da Medula Óssea/metabolismo , Doenças da Medula Óssea/patologia , Células Cultivadas , Citocinas/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologia , Proteína Killer-Antagonista Homóloga a bcl-2/fisiologia
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