RESUMO
Shwachman-Diamond syndrome (SDS) is an inherited multisystem ribosomopathy characterized by exocrine pancreatic deficiency, bone marrow failure, and predisposition to myeloid malignancies. The pathobiology of SDS results from impaired ribosomal maturation due to the deficiency of SBDS and the inability to evict the antiassociation factor eIF6 from the 60S ribosomal subunit. Clinical outcomes for patients with SDS who develop myeloid malignancies are extremely poor because of high treatment-related toxicities and a high rate of refractory disease/relapse even after allogeneic hematopoietic stem cell transplant (HSCT). Registry data indicate that outcomes are improved for patients with SDS who undergo routine bone marrow surveillance and receive an HSCT before developing an overt malignancy. However, the optimal approach to hematologic surveillance and the timing of HSCT for patients with SDS is not clearly established. Recent studies have elucidated distinct patterns of somatic blood mutations in patients with SDS that either alleviate the ribosome defect via somatic rescue (heterozygous EIF6 inactivation) or disrupt cellular checkpoints, resulting in increased leukemogenic potential (heterozygous TP53 inactivation). Genomic analysis revealed that most myeloid malignancies in patients with SDS have biallelic loss-of-function TP53 mutations. Single-cell DNA sequencing of SDS bone marrow samples can detect premalignant biallelic TP53-mutated clones before clinical diagnosis, suggesting that molecular surveillance may enhance the detection of incipient myeloid malignancies when HSCT may be most effective. Here, we review the clinical, genetic, and biologic features of SDS. In addition, we present evidence supporting the hematologic surveillance for patients with SDS that incorporates clinical, pathologic, and molecular data to risk stratify patients and prioritize transplant evaluation for patients with SDS with high-risk features.
Assuntos
Doenças da Medula Óssea , Insuficiência Pancreática Exócrina , Lipomatose , Transtornos Mieloproliferativos , Humanos , Síndrome de Shwachman-Diamond , Doenças da Medula Óssea/genética , Doenças da Medula Óssea/terapia , Doenças da Medula Óssea/diagnóstico , Insuficiência Pancreática Exócrina/genética , Insuficiência Pancreática Exócrina/terapia , Lipomatose/genética , Lipomatose/terapia , Recidiva Local de Neoplasia , Suscetibilidade a DoençasRESUMO
The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely, the misdiagnosis of inherited bone marrow failure (BMF) can expose patients to ineffectual and expensive therapies, toxic transplant conditioning regimens, and inappropriate use of an affected family member as a stem cell donor. To predict the likelihood of patients having acquired or inherited BMF, we developed a 2-step data-driven machine-learning model using 25 clinical and laboratory variables typically recorded at the initial clinical encounter. For model development, patients were labeled as having acquired or inherited BMF depending on their genomic data. Data sets were unbiasedly clustered, and an ensemble model was trained with cases from the largest cluster of a training cohort (n = 359) and validated with an independent cohort (n = 127). Cluster A, the largest group, was mostly immune or inherited aplastic anemia, whereas cluster B comprised underrepresented BMF phenotypes and was not included in the next step of data modeling because of a small sample size. The ensemble cluster A-specific model was accurate (89%) to predict BMF etiology, correctly predicting inherited and likely immune BMF in 79% and 92% of cases, respectively. Our model represents a practical guide for BMF diagnosis and highlights the importance of clinical and laboratory variables in the initial evaluation, particularly telomere length. Our tool can be potentially used by general hematologists and health care providers not specialized in BMF, and in under-resourced centers, to prioritize patients for genetic testing or for expeditious treatment.
Assuntos
Anemia Aplástica , Doenças da Medula Óssea , Pancitopenia , Humanos , Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/genética , Doenças da Medula Óssea/terapia , Diagnóstico Diferencial , Anemia Aplástica/diagnóstico , Anemia Aplástica/genética , Anemia Aplástica/terapia , Transtornos da Insuficiência da Medula Óssea/diagnóstico , Pancitopenia/diagnósticoRESUMO
Immune aplastic anemia (AA) is a severe blood disease characterized by T-lymphocyte- mediated stem cell destruction. Hematopoietic stem cell transplantation and immunosuppression are effective, but they entail costs and risks, and are not always successful. The Janus kinase (JAK) 1/2 inhibitor ruxolitinib (RUX) suppresses cytotoxic T-cell activation and inhibits cytokine production in models of graft-versus-host disease. We tested RUX in murine immune AA for potential therapeutic benefit. After infusion of lymph node (LN) cells mismatched at the major histocompatibility complex [C67BL/6 (B6)âCByB6F1], RUX, administered as a food additive (Rux-chow), attenuated bone marrow hypoplasia, ameliorated peripheral blood pancytopenia, preserved hematopoietic progenitors, and prevented mortality, when used either prophylactically or therapeutically. RUX suppressed the infiltration, proliferation, and activation of effector T cells in the bone marrow and mitigated Fas-mediated apoptotic destruction of target hematopoietic cells. Similar effects were obtained when Rux-chow was fed to C.B10 mice in a minor histocompatibility antigen mismatched (B6âC.B10) AA model. RUX only modestly suppressed lymphoid and erythroid hematopoiesis in normal and irradiated CByB6F1 mice. Our data support clinical trials of JAK/STAT inhibitors in human AA and other immune bone marrow failure syndromes.
Assuntos
Anemia Aplástica , Doenças da Medula Óssea , Pancitopenia , Camundongos , Humanos , Animais , Pancitopenia/patologia , Anemia Aplástica/patologia , Transtornos da Insuficiência da Medula Óssea/patologia , Medula Óssea/patologia , Doenças da Medula Óssea/patologia , Janus Quinase 1RESUMO
Neutrophils are the shortest-lived blood cells, which requires a prodigious degree of proliferation and differentiation to sustain physiologically sufficient numbers and be poised to respond quickly to infectious emergencies. More than 107 neutrophils are produced every minute in an adult bone marrow-a process that is tightly regulated by a small group of cytokines and chemical mediators and dependent on nutrients and energy. Like granulocyte colony-stimulating factor, the primary growth factor for granulopoiesis, they stimulate signalling pathways, some affecting metabolism. Nutrient or energy deficiency stresses the survival, proliferation, and differentiation of neutrophils and their precursors. Thus, it is not surprising that monogenic disorders related to metabolism exist that result in neutropenia. Among these are pathogenic mutations in HAX1, G6PC3, SLC37A4, TAFAZZIN, SBDS, EFL1 and the mitochondrial disorders. These mutations perturb carbohydrate, lipid and/or protein metabolism. We hypothesize that metabolic disturbances may drive the pathogenesis of a subset of inherited neutropenias just as defects in DNA damage response do in Fanconi anaemia, telomere maintenance in dyskeratosis congenita and ribosome formation in Diamond-Blackfan anaemia. Greater understanding of metabolic pathways in granulopoiesis will identify points of vulnerability in production and may point to new strategies for the treatment of neutropenias.
Assuntos
Doenças da Medula Óssea , Anemia de Fanconi , Neutropenia , Adulto , Humanos , Doenças da Medula Óssea/genética , Anemia de Fanconi/genética , Medula Óssea/patologia , Transtornos da Insuficiência da Medula Óssea , Neutropenia/patologia , Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte de Monossacarídeos , AntiportersRESUMO
Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency and skeletal abnormalities. SDS bone marrow haematopoietic progenitors show increased apoptosis and impairment in granulocytic differentiation. Loss of Shwachman-Bodian-Diamond syndrome (SBDS) expression results in reduced eukaryotic 80S ribosome maturation. Biallelic mutations in the SBDS gene are found in ~90% of SDS patients, ~55% of whom carry the c.183-184TA>CT nonsense mutation. Several translational readthrough-inducing drugs aimed at suppressing nonsense mutations have been developed. One of these, ataluren, has received approval in Europe for the treatment of Duchenne muscular dystrophy. We previously showed that ataluren can restore full-length SBDS protein synthesis in SDS-derived bone marrow cells. Here, we extend our preclinical study to assess the functional restoration of SBDS capabilities in vitro and ex vivo. Ataluren improved 80S ribosome assembly and total protein synthesis in SDS-derived cells, restored myelopoiesis in myeloid progenitors, improved neutrophil chemotaxis in vitro and reduced neutrophil dysplastic markers ex vivo. Ataluren also restored full-length SBDS synthesis in primary osteoblasts, suggesting that its beneficial role may go beyond the myeloid compartment. Altogether, our results strengthened the rationale for a Phase I/II clinical trial of ataluren in SDS patients who harbour the nonsense mutation.
Assuntos
Doenças da Medula Óssea , Insuficiência Pancreática Exócrina , Lipomatose , Humanos , Síndrome de Shwachman-Diamond , Proteína Supressora de Tumor p53/genética , Lipomatose/genética , Códon sem Sentido , Mielopoese , Neutrófilos/metabolismo , Quimiotaxia , Doenças da Medula Óssea/genética , Doenças da Medula Óssea/terapia , Insuficiência Pancreática Exócrina/genética , Ribossomos/metabolismoRESUMO
Inherited bone marrow (BM) failure syndromes are a diverse group of disorders characterized by BM failure, usually in association with ≥1 extrahematopoietic abnormalities. BM failure, which can involve ≥1 cell lineages, often presents in the pediatric age group. Furthermore, some children initially labeled as having idiopathic aplastic anemia or myelodysplasia represent cryptic cases of inherited BM failure. Significant advances in the genetics of these syndromes have been made, identifying more than 100 disease genes, giving insights into normal hematopoiesis and how it is disrupted in patients with BM failure. They have also provided important information on fundamental biological pathways, including DNA repair: Fanconi anemia (FA) genes; telomere maintenance: dyskeratosis congenita (DC) genes; and ribosome biogenesis: Shwachman-Diamond syndrome and Diamond-Blackfan anemia genes. In addition, because these disorders are usually associated with extrahematopoietic abnormalities and increased risk of cancer, they have provided insights into human development and cancer. In the clinic, genetic tests stemming from the recent advances facilitate diagnosis, especially when clinical features are insufficient to accurately classify a disorder. Hematopoietic stem cell transplantation using fludarabine-based protocols has significantly improved outcomes, particularly in patients with FA or DC. Management of some other complications, such as cancer, remains a challenge. Recent studies have suggested the possibility of new and potentially more efficacious therapies, including a renewed focus on hematopoietic gene therapy and drugs [transforming growth factor-ß inhibitors for FA and PAPD5, a human poly(A) polymerase, inhibitors for DC] that target disease-specific defects.
Assuntos
Anemia Aplástica , Doenças da Medula Óssea , Disceratose Congênita , Neoplasias , Pancitopenia , Anemia Aplástica/complicações , Anemia Aplástica/genética , Anemia Aplástica/terapia , Doenças da Medula Óssea/complicações , Doenças da Medula Óssea/genética , Doenças da Medula Óssea/terapia , Transtornos da Insuficiência da Medula Óssea , Criança , Disceratose Congênita/genética , Disceratose Congênita/terapia , Humanos , Neoplasias/complicações , Pancitopenia/complicaçõesRESUMO
There is no formally defined terminology for the related entities transient osteoporosis of the hip (TOH), localized or regional migratory osteoporosis (RMO) and bone marrow edema syndrome (BMES). This study aimed to map the diversity and frequency of diagnostic terms and vocabulary utilized in the literature. A comprehensive search of electronic databases and reference lists was conducted. Publications that reported on patients with TOH, RMO, BMES, or related variants were eligible for inclusion. The terminologies were categorized based on the wording of the titles, abstracts, or texts. We included 561 publications, of which 423 were case reports, involving 2921 patients. Overall, TOH was the most commonly used term, occurring in 257 (45.8%). RMO was used in 34 (6.1%) and BMES in 57 (10.2%). The remaining used various combinations of transient, migratory, and regional in conjunction with either osteoporosis or bone marrow edema. Localized osteoporosis was not used. We identified three different terms related to pregnancy. In 76.3% of the publications, the terminology was related to osteoporosis and in 18.2% to bone marrow edema, although terminology did not correspond to actual findings. Bone marrow edema occurred as often as osteoporosis, and osteoporosis was generally ascertained by visual inspection of radiographs, seldom by bone densitometry. Many publications used osteoporosis-related terms without evidence that osteoporosis had been detected. The terminology of these closely related entities is confusing and unstandardized. The lack of formal definitions impedes accurate diagnosis, research on disease mechanisms, and effective treatment.
Assuntos
Doenças da Medula Óssea , Osteoporose , Gravidez , Feminino , Humanos , Medula Óssea , Osteoporose/diagnóstico , Osteoporose/terapia , Doenças da Medula Óssea/diagnóstico , Síndrome , Edema/etiologia , Edema/diagnóstico , Imageamento por Ressonância MagnéticaRESUMO
Diffusion-weighted imaging (DWI) is an established MRI technique that can investigate tissue microstructure at the scale of a few micrometers. Musculoskeletal tissues typically have a highly ordered structure to fulfill their functions and therefore represent an optimal application of DWI. Even more since disruption of tissue organization affects its biomechanical properties and may indicate irreversible damage. The application of DWI to the musculoskeletal system faces application-specific challenges on data acquisition including susceptibility effects, the low T2 relaxation time of most musculoskeletal tissues (2-70 msec) and the need for sub-millimetric resolution. Thus, musculoskeletal applications have been an area of development of new DWI methods. In this review, we provide an overview of the technical aspects of DWI acquisition including diffusion-weighting, MRI pulse sequences and different diffusion regimes to study tissue microstructure. For each tissue type (growth plate, articular cartilage, muscle, bone marrow, intervertebral discs, ligaments, tendons, menisci, and synovium), the rationale for the use of DWI and clinical studies in support of its use as a biomarker are presented. The review describes studies showing that DTI of the growth plate has predictive value for child growth and that DTI of articular cartilage has potential to predict the radiographic progression of joint damage in early stages of osteoarthritis. DTI has been used extensively in skeletal muscle where it has shown potential to detect microstructural and functional changes in a wide range of muscle pathologies. DWI of bone marrow showed to be a valuable tool for the diagnosis of benign and malignant acute vertebral fractures and bone metastases. DTI and diffusion kurtosis have been investigated as markers of early intervertebral disc degeneration and lower back pain. Finally, promising new applications of DTI to anterior cruciate ligament grafts and synovium are presented. The review ends with an overview of the use of DWI in clinical routine. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 3.
Assuntos
Doenças da Medula Óssea , Sistema Musculoesquelético , Fraturas da Coluna Vertebral , Criança , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Sistema Musculoesquelético/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Fraturas da Coluna Vertebral/patologiaRESUMO
Pure red cell aplasia (PRCA) is a rare bone marrow (BM) disorder characterized by ineffective erythropoiesis, reduced reticulocyte count, normocytic anemia, and the absence of erythroid precursors. Here, we present a rare instance of PRCA occurring after ABO-matched allo-HSCT in a refractory/relapsed acute myeloid leukemia (R/R AML) patient. In this case, the patient received a combination treatment of Gilteritinib, Venetoclax, and Azacitidine. Remarkably, this treatment not only reduced myeloblasts but also facilitated the restoration of erythroid hematopoiesis.
Assuntos
Compostos de Anilina , Doenças da Medula Óssea , Compostos Bicíclicos Heterocíclicos com Pontes , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Pirazinas , Aplasia Pura de Série Vermelha , Sulfonamidas , Humanos , Compostos de Anilina/uso terapêutico , Azacitidina/uso terapêutico , Doenças da Medula Óssea/complicações , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Pirazinas/uso terapêutico , Aplasia Pura de Série Vermelha/etiologia , Sulfonamidas/uso terapêuticoRESUMO
Haploidentical stem cell transplantation (haplo-SCT) represents the main alternative for children with inherited bone marrow failure syndrome (I-BMF) lacking a matched donor. This retrospective study, conducted on behalf of the EBMT SAAWP and PDWP, aims to report the current outcomes of haplo-SCT in I-BMFs, comparing the different in vivo and ex vivo T-cell depletion approaches. One hundred and sixty-two I-BMF patients who underwent haplo-SCT (median age 7.4 years) have been registered. Fanconi Anemia was the most represented diagnosis (70.1%). Based on different T-cell depletion (TCD) approaches, four categories were identified: (1) TCRαß+/CD19+-depletion (43.8%); (2) T-repleted with post-transplant Cyclophosphamide (PTCy, 34.0%); (3) In-vivo T-depletion with ATG/alemtuzumab (14.8%); (4) CD34+ positive selection (7.4%). The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 76% respectively, while that of primary and secondary graft failure was 10% and 8% respectively. The 100-day CI of acute GvHD grade III-IV(95% CI) was 13%, while the 24-month CI of extensive chronic GvHD was 4%. After a median follow-up of 43.4 months, the 2-year overall survival(OS) and GvHD/Rejection-free Survival (GRFS) probabilities are 67% and 53%, respectively. The TCR CD3+αß+/CD19+ depletion group showed a significantly lower incidence of both acute and chronic GvHD and higher OS (79%; p0.013) and GRFS (71%; p < .001), while no significant differences in outcomes have been observed by different diagnosis and conditioning regimens. This large retrospective study supports the safety and feasibility of haplo-SCT in I-BMF patients. TCRαß+/CD19+ depletion offers higher chances of patients' survival, with a significantly lower risk of severe a- and c-GvHD in I-BMFs compared to other platforms.
Assuntos
Anemia Aplástica , Humanos , Criança , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Adolescente , Anemia Aplástica/terapia , Lactente , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transtornos da Insuficiência da Medula Óssea , Transplante Haploidêntico , Depleção Linfocítica , Condicionamento Pré-Transplante/métodos , Hemoglobinúria Paroxística/terapia , Anemia de Fanconi/terapia , Anemia de Fanconi/mortalidade , Doenças da Medula Óssea/terapia , Antígenos HLA/genética , Antígenos HLA/imunologiaRESUMO
OBJECTIVES: The study aimed to explore the value of texture analysis of radiomics based on the short tau inversion recovery (STIR) sequence to evaluate the activity of bone marrow oedema of sacroiliac joints in early AS. METHODS: 43 patients with early AS whose data were randomly divided into the training cohort (n=116) and verification cohort (n=56) according to the ratio of 7:3. The optimal feature subsets were obtained by Mann-Whitney U-test, the minimum-Redundancy Maximum-Relevancy (mRMR), and then least absolute shrinkage and selection operator (LASSO) using these texture feature parameters, which were used to construct the final prediction model and obtained the Radscore. The ROC curve was performed to evaluate the performance of the model. The Spearman correlation test was used to analyse the correlation of various indicators. RESULTS: In the training cohort, to differentiate early AS sacroiliac joint bone marrow oedema between the active and stable groups, the AUCs of the Radscore, SPARCC and ADC were 0.81, 0.91, 0.78, respectively. In the validation cohort, the AUCs were 0.87, 0.89, 0.85. In the two cohorts, there were no significant differences in AUCs between values of the Radscore and SPARCC, ADC (p>0.05). There was a significant difference in AUC between SPARCC and ADC in the training cohort (p<0.05), with no statistical significance in the validation cohort (p>0.05). The correlations were all low between the Radscore values and the values of ESR, CRP, tI, ASDAS-ESR and ASDAS-CRP (p<0.05). CONCLUSIONS: Radiomics analysis based on STIR texture analysis has a good prediction for the evaluation of bone marrow oedema activity of sacroiliac joints in AS. It can be a new non-invasive and objective evaluation method for AS activity.
Assuntos
Edema , Imageamento por Ressonância Magnética , Valor Preditivo dos Testes , Articulação Sacroilíaca , Espondilite Anquilosante , Humanos , Masculino , Feminino , Espondilite Anquilosante/diagnóstico por imagem , Articulação Sacroilíaca/diagnóstico por imagem , Adulto , Edema/diagnóstico por imagem , Edema/etiologia , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Doenças da Medula Óssea/diagnóstico por imagem , Curva ROC , Medula Óssea/diagnóstico por imagem , Adulto Jovem , Diagnóstico Precoce , Estudos Retrospectivos , Índice de Gravidade de Doença , RadiômicaRESUMO
BACKGROUND: Multisystemic findings of inherited bone marrow failure syndromes may cause difficulty in diagnosis. Exome sequencing (ES) helps to define the etiology of rare diseases and reanalysis offers a valuable new diagnostic approach. Herein, we present the clinical and molecular characteristics of a girl who was referred for cytopenia and frequent infections. CASE REPORT: A 5-year-old girl with cytopenia, dysmorphism, short stature, developmental delay, and myopia was referred for genetic counseling. Reanalysis of the ES data revealed a homozygous splice-site variant in the DNAJC21 (NM_001012339.3:c.983+1G>A), causing Shwachman-Diamond Syndrome (SDS). It was shown by the RNA sequencing that exon 7 was skipped, causing an 88-nucleotide deletion. CONCLUSIONS: Precise genetic diagnosis enables genetic counseling and improves patient management by avoiding inappropriate treatment and unnecessary testing. This report would contribute to the clinical and molecular understanding of this rare type of SDS caused by DNAJC21 variants and expand the phenotypic features of this condition.
Assuntos
Doenças da Medula Óssea , Citopenia , Feminino , Humanos , Pré-Escolar , Síndrome Congênita de Insuficiência da Medula Óssea/genética , Exoma/genética , Síndrome de Shwachman-Diamond , Homozigoto , Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/genéticaRESUMO
We report 5 children with bone marrow failure (BMF) after primary varicella zoster virus (VZV) infection or VZV vaccination, highlighting the highly variable course. Two patients were treated with intravenous immunoglobulins; one had a slow hematologic recovery, and the other was rescued by allogeneic hematopoietic stem cell transplantation (HSCT). Of the 2 patients treated with immunosuppressive therapy with antithymocyte globulin and cyclosporine, one had a complete response, and the other was transplanted for nonresponse. One patient underwent a primary allograft. All patients are alive. This study demonstrated that VZV-associated BMF is a life-threatening disorder that often requires HSCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecção pelo Vírus da Varicela-Zoster , Humanos , Masculino , Feminino , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pré-Escolar , Herpesvirus Humano 3 , Transtornos da Insuficiência da Medula Óssea/etiologia , Vacinação/efeitos adversos , Doenças da Medula Óssea/etiologia , Vacina contra Varicela/efeitos adversos , Adolescente , Imunoglobulinas Intravenosas/uso terapêutico , LactenteRESUMO
BACKGROUND: Fat quantification methods in magnetic resonance imaging (MRI) have been studied to differentiate bone marrow pathologies in adult patients; however, scarce literature is available in pediatric patients. PURPOSE: To evaluate the efficacy of the T1 signal intensity value (T1-SIV), out-of-phase/in-phase signal ratio (OP/IP SR), and fat fraction (FF) to differentiate between normal, benign, and malignant pathological processes. MATERIAL AND METHODS: A total of 48 pediatric patients with lumbar and pelvic MRI were classified into three groups according to bone marrow pathology (group 1, normal; group 2, benign pathology/reconversion; group 3, malignant). The efficacy of T1-SIV, OP/IP SR, and FF values in differentiating these pathologies was evaluated using Kruskal-Wallis or analysis of variance and followed by Bonferroni or Dunn-Bonferroni tests. Cutoff values for malignant infiltration were defined using ROC analysis. RESULTS: Although these values were significantly different in all three groups (P = 0.001-0.008), this difference was not sufficient to discriminate between all groups. Subgroup analyses showed significant differences in T1-SIV between groups 1-3, in OP/IP SR between groups 1-3, 2-3, and 1-2, in FF between groups 1-2 and 1-3 in various regions (P = 0.001-0.049). Cutoff values had a sensitivity and specificity of 90%-100% for OP/IP SR and FF. CONCLUSION: T1-SIV, OP/IP SR, and FF may potentially distinguish normal from pathological bone marrow. OP/IP SR and FF values detected malignant infiltration with high sensitivity and specificity in this study. However, only OP/IP SR may significantly differentiate benign and malignant bone marrow pathologies which needs to be confirmed in the future study with a larger patient population.
Assuntos
Tecido Adiposo , Doenças da Medula Óssea , Medula Óssea , Imageamento por Ressonância Magnética , Humanos , Criança , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Diagnóstico Diferencial , Adolescente , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Pré-Escolar , Doenças da Medula Óssea/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Neoplasias da Medula Óssea/diagnóstico por imagem , Sensibilidade e Especificidade , Estudos Retrospectivos , LactenteRESUMO
BACKGROUND: Bone marrow lesions (BMLs) in knee osteoarthritis (OA) have been assessed histopathologically and by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); however, a direct comparison of the results has not been reported. PURPOSE: To evaluate and compare the findings by DCE-MRI and histopathology of subchondral BMLs in knee OA. MATERIAL AND METHODS: In total, 19 patients with medial tibiofemoral knee OA undergoing total knee arthroplasty were analyzed. Preoperative MRI, including a DCE sequence, was performed, and bone biopsies were obtained from the resected specimens corresponding to BML areas. The contrast enhancement by DCE-MRI was analyzed using semi-quantitative (area under the curve [AUC]), peak enhancement [PE]), and quantitative (Ktrans, Kep) methods. Enhancement in the medial OA compartment was compared with similar areas in a normal lateral compartment, and the DCE characteristics of BMLs were correlated with semi-quantitatively graded histopathological features. RESULTS: AUC and PE were significantly higher in medial tibial and femoral BMLs compared with the values in the lateral condyles; Ktrans and Kep were only significantly higher in the tibial plateau. In the tibia, AUC and PE were significantly correlated with the grade of vascular proliferation, and PE also with the degree of marrow fibrosis. There was no significant correlation between AUC/PE and histopathological findings in the femur and no correlation between quantitative DCE parameters and histopathological findings. CONCLUSION: BML characteristics by semi-quantitative DCE in the form of AUC and PE may be used as parameters for the degree of histopathological vascularization in the bone marrow whereas quantitative DCE data were less conclusive.
Assuntos
Medula Óssea , Meios de Contraste , Imageamento por Ressonância Magnética , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Idoso , Pessoa de Meia-Idade , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Doenças da Medula Óssea/diagnóstico por imagem , Doenças da Medula Óssea/patologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Idoso de 80 Anos ou mais , Gadolínio DTPARESUMO
PURPOSE: To present the clinical features and treatment strategy of degenerative atlantoaxial subluxation (DAAS). METHODS: Patients with DAAS treated in our institution from 2003 to 2020 were retrospectively reviewed. We utilized the Japanese Orthopedic Association (JOA) scale to evaluate the neurologic status and distance of Ranawat et al. (DOR) to measure vertical migration. RESULTS: We recruited 40 patients with > 2 years of follow-up and an average age of 62.3 ± 7.7 years. All the patients had myelopathy; only one patient had moderate trauma before exacerbation of symptoms, and the duration of symptoms was 34 ± 36 months. The most frequent radiological features were vertical migration of C1 (100%), sclerosis (100%), and narrowing of the atlantoaxial lateral mass articulations (100%). Two patients underwent transoral release combined with posterior reduction and fusion, and 38 patients underwent posterior reduction and fusion with C1 lateral mass screws-C2 pedicle screws and plate systems only. Forty cases (100%) achieved a solid atlantoaxial fusion, and 38 cases (95%) achieved anatomic atlantoaxial reduction. The JOA score increased from 9.3 ± 2.6 to 14.8 ± 2.1 (P < 0.01). DOR increased from 14.5 ± 2.5 to 17.8 ± 2.2 mm at the final follow-up (P < 0.01). Loosening of the locking caps was detected in one case, bony fusion was achieved, and harvest-site pain was reported in five patients. CONCLUSION: DAAS differs from other types of AAS and presents with anterior subluxation combined with vertical subluxation arising from degenerative changes in the atlantoaxial joints. We recommend anatomic reduction as an optimal strategy for DAAS.
Assuntos
Articulação Atlantoaxial , Doenças da Medula Óssea , Luxações Articulares , Lesões do Pescoço , Parafusos Pediculares , Doenças da Medula Espinal , Fusão Vertebral , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Luxações Articulares/complicações , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Placas Ósseas , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
The paediatric metaphysis is afflicted by a wide range of pathological processes as it is the most metabolically active and well-vascularised part of the developing skeleton. This review focuses on metaphyseal marrow signal change detected with magnetic resonance imaging, which is most often occult on radiographs. When bilateral, these imaging appearances frequently present a diagnostic quandary. This review assists the radiologist to confidently dismiss physiological signal change and confidently work through the differential diagnosis. This is achieved by illustrating a practical method of classifying signal change into four categories: physiological red marrow, red marrow reconversion, marrow infiltration, and oedema-like marrow signal intensity. In doing so, various pathological entities are reviewed along with imaging pearls and next-step investigations.
Assuntos
Doenças da Medula Óssea , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Doenças da Medula Óssea/diagnóstico por imagem , Diagnóstico Diferencial , Criança , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Masculino , Feminino , Pré-Escolar , LactenteRESUMO
OBJECTIVE: Transient osteoporosis of the hip (TOH) is an uncommon, typically self-limited diagnosis of uncertain etiology. We hypothesize that TOH represents an underlying subchondral fracture, and a discrete fracture line can often be detected on high-resolution MRI. MATERIALS AND METHODS: A retrospective PACS query identified patients meeting imaging criteria for TOH with intense bone marrow edema (BME) in the femoral head on MRI. Those with poor quality studies, other underlying pathologies, or antecedent trauma were excluded. Three musculoskeletal radiologists independently reviewed each case for presence of a definite subchondral fracture line on small field of view (FOV) MR images of the affected hip. Extent of BME, reciprocal acetabular BME, and joint effusion size were also recorded. Binomial logistic regression was performed to determine statistically significant predictors of subchondral fracture. RESULTS: Fifty patients met inclusion criteria (29 females, 0 pregnant). Mean age was 62±12 years (range 35-84). Average duration of symptoms before MRI was 102±135 days. Ten patients had bone densitometry within 2 years of MRI, six demonstrating osteopenia or osteoporosis. Subchondral fractures were unanimously identified in 44/50 (88%). Interclass correlation coefficient with absolute agreement was 0.73, 95% CI (0.57-0.84), indicating near-excellent agreement. Most cases demonstrated a large joint effusion (23/50, 46%) and acetabular BME (31/50, 62%). Increasing size of joint effusion was a statistically significant predictor of subchondral fracture (p=0.05), with 6.9 higher odds. There was a strong correlation with osteopenia/osteoporosis and fracture (p<0.001). CONCLUSION: Discrete subchondral fractures were identified unanimously on small FOV imaging in the majority of TOH cases.
Assuntos
Doenças da Medula Óssea , Fraturas Ósseas , Osteoporose , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Acetábulo/patologia , Doenças da Medula Óssea/patologiaRESUMO
OBJECTIVE: To determine the prevalence of sacroiliac joint variants in patients with axial spondyloarthritis (axSpA) using MRI-based synthetic CT images and to evaluate their relationships with the presence of bone marrow edema, as this may potentially complicate diagnosing active sacroiliitis on MRI in patients with suspected axSpA. METHODS: 172 patients were retrospectively included. All patients underwent MRI because of clinical suspicion of sacroiliitis. The diagnosis of axSpA was made by a tertiary hospital rheumatologist. Two readers independently determined the presence of bone marrow edema and the presence of one or more of the nine known sacroiliac joint (SIJ) variants. RESULTS: SIJ variants were common in axSpA patients (82.9%) and the non-SpA group (85.4%); there were no significant differences in prevalence. Bone marrow edema was frequently found in axSpA (86.8%) and non-SpA patients (34%). AxSpA patients with SIJ variants (except for accessory joint) demonstrated 4 to 10 times higher odds for bone marrow edema, however not statistically significant. The more variants were present in this group, the higher the chance of bone marrow edema. However, some multicollinearity cannot be excluded, since bone marrow edema is very frequent in the axSpA group by definition. CONCLUSION: SIJ variants are common in axSpA and non-SpA patients. SIJ variants were associated with higher prevalence of bone marrow edema in axSpA patients, potentially due to altered biomechanics, except for accessory joint which may act as a stabilizer.
Assuntos
Espondiloartrite Axial , Doenças da Medula Óssea , Sacroileíte , Espondilartrite , Humanos , Articulação Sacroilíaca/diagnóstico por imagem , Sacroileíte/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Estudos Retrospectivos , Doenças da Medula Óssea/diagnóstico por imagem , Doenças da Medula Óssea/complicações , Imageamento por Ressonância Magnética/métodos , Edema/diagnóstico por imagem , Edema/complicações , Espondilartrite/diagnóstico por imagemRESUMO
OBJECTIVE: To identify bone marrow lesion (BML) trajectories over 4 years and their demographic and structural predictors in middle-aged and older adults with or at increased risk of knee osteoarthritis (OA). METHODS: A total of 614 participants (mean age 61 years, 62% female) from the Osteoarthritis Initiative cohort (OAI) were included. BMLs in 15 anatomical locations of the knee were measured annually from baseline to 4 years using the Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) method. BML trajectories were determined using latent class mixed models (LCMMs). Multinomial logistic regression was used to examine baseline characteristics that predicted BML trajectories. RESULTS: Three distinct BML trajectories were identified: "Mild-stable BMLs" (25.9%), "Moderate-stable BMLs" (66.4%), and "Rapid-rise BMLs" (7.7%). Compared to the "Mild-stable BMLs" trajectory, current smokers were more likely to be in the "Moderate-stable BMLs" (odds ratio [OR] 2.089, P < 0.001) and "Rapid-rise" (OR 2.462, P < 0.001) trajectories. Moreover, female sex and meniscal tears were associated with an increased risk of being in the "Rapid-rise BMLs" trajectory (OR 2.023 to 2.504, P < 0.05). Participants who had higher education levels and drank more alcohol were more likely to be in the "Rapid-rise BMLs" trajectory (OR 1.624 to 3.178, P < 0.05) and less likely to be in the "Moderate-stable BMLs" trajectory (OR 0.668 to 0.674, P < 0.05). CONCLUSIONS: During the 4-year follow-up, most participants had relatively stable BMLs, few had enlarged BMLs, and no trajectory of decreased BMLs was identified. Sociodemographic factors, lifestyle, and knee structural pathology play roles in predicting distinct BML trajectories.