-
Skeletal Radiology Jul 2020To identify abnormalities in asymptomatic sedentary individuals using 3.0 Tesla high-resolution MRI.
OBJECTIVE
To identify abnormalities in asymptomatic sedentary individuals using 3.0 Tesla high-resolution MRI.
MATERIALS AND METHODS
The cohort comprised of 230 knees of 115 uninjured sedentary adults (51 males, 64 females; median age: 44 years). All participants had bilateral knee 3.0 T MRIs. Two senior musculoskeletal radiologists graded all intraarticular knee structures using validated scoring systems. Participants completed Knee Injury and Osteoarthritis Outcome Score questionnaires at the time of the MRI scan.
RESULTS
MRI showed abnormalities in the majority (97%) of knees. Thirty percent knees had meniscal tears: horizontal (23%), complex (3%), vertical (2%), radial (2%) and bucket handle (1%). Cartilage and bone marrow abnormalities were prevalent at the patellofemoral joint (57% knees and 48% knees, respectively). Moderate and severe cartilage lesions were common, in 19% and 31% knees, respectively, while moderate and severe bone marrow oedema in 19% and 31% knees, respectively. Moderate-intensity lesion in tendons was found in 21% knees and high-grade tendonitis in 6% knees-the patellar (11% and 2%, respectively) and quadriceps (7% and 2%, respectively) tendons being most affected. Three percent partial ligamentous ruptures were found, especially of the anterior cruciate ligament (2%).
CONCLUSION
Nearly all knees of asymptomatic adults showed abnormalities in at least one knee structure on MRI. Meniscal tears, cartilage and bone marrow lesions of the patellofemoral joint were the most common pathological findings. Bucket handle and complex meniscal tears were reported for the first time in asymptomatic knees.
Topics: Adult; Anterior Cruciate Ligament Injuries; Asymptomatic Diseases; Bone Marrow Diseases; Cartilage Diseases; Female; Humans; Knee Injuries; Knee Joint; Magnetic Resonance Imaging; Male; Osteoarthritis, Knee; Prevalence; Sedentary Behavior; Surveys and Questionnaires; Tendinopathy
PubMed: 32060622
DOI: 10.1007/s00256-020-03394-z -
American Journal of Hematology Apr 2023Atypical chronic myeloid leukemia (aCML) and myelodysplastic/myeloproliferative (MDS/MPN) neoplasms, not otherwise specified (NOS), are MDS/MPN overlap neoplasms...
DISEASE OVERVIEW
Atypical chronic myeloid leukemia (aCML) and myelodysplastic/myeloproliferative (MDS/MPN) neoplasms, not otherwise specified (NOS), are MDS/MPN overlap neoplasms characterized by leukocytosis, in the absence of monocytosis and eosinophilia, with <20% blasts in the blood and bone marrow.
DIAGNOSIS
aCML, previously known as aCML, BCR::ABL1 negative, was renamed as aCML by the ICC classification, and as MDS/MPN with neutrophilia by the 5th edition of the WHO classification. This entity is characterized by dysplastic neutrophilia with immature myeloid cells comprising ≥10% of the white blood cell count, with prominent dysgranulopoiesis. MDS/MPN-NOS consists of MDS/MPN overlap neoplasms not meeting criteria for defined categories such as chronic myelomonocytic leukemia (CMML), MDS/MPN-ring sideroblasts-thrombocytosis (MDS/MPN-RS-T), and aCML.
MUTATIONS AND KARYOTYPE
Cytogenetic abnormalities are seen in 40-50% of patients in both categories. In aCML, somatic mutations commonly encountered include ASXL1, SETBP1, ETNK1, and EZH2 whereas MDS/MPN-NOS can be further stratified by mutational profiles into CMML-like, MDS/MPN-RS-T-like, aCML-like, TP35-mutated, and "others", respectively.
RISK STRATIFICATION
The Mayo Clinic aCML model stratifies patients based on age >67 years, hemoglobin <10 g/dl, and the presence of TET2 mutations into low-risk (0-1 points) and high-risk (>2 points) groups, with median survivals of 18 and 7 months, respectively. MDS/MPN-NOS patients have traditionally been risk stratified using MDS risk models such as IPSS and IPSS-R.
TREATMENT
Leukocytosis and anemia are managed like lower risk MPN and MDS. DNMT inhibitors have been used in both entities with suboptimal response rates. Allogeneic stem cell transplant remains the only curative strategy but is associated with high morbidity and mortality.
Topics: Humans; Aged; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myelodysplastic Syndromes; Leukocytosis; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myelomonocytic, Chronic; Thrombocytosis; Mutation; Risk Assessment
PubMed: 36601682
DOI: 10.1002/ajh.26828 -
Blood Mar 2019Myelodysplastic syndrome (MDS) is characterized by bone marrow failure and a strong propensity for leukemic evolution. Somatic mutations are critical early drivers of... (Review)
Review
Myelodysplastic syndrome (MDS) is characterized by bone marrow failure and a strong propensity for leukemic evolution. Somatic mutations are critical early drivers of the disorder, but the factors enabling the emergence, selection, and subsequent leukemic evolution of these "leukemia-poised" clones remain incompletely understood. Emerging data point at the mesenchymal niche as a critical contributor to disease initiation and evolution. Disrupted inflammatory signaling from niche cells may facilitate the occurrence of somatic mutations, their selection, and subsequent clonal expansion. This review summarizes the current concepts about "niche-facilitated" bone marrow failure and leukemic evolution, their underlying molecular mechanisms, and clinical implications for future innovative therapeutic targeting of the niche in MDS.
Topics: Disease Progression; Genetic Predisposition to Disease; Hematopoietic Stem Cells; Humans; Inflammation; Leukemia; Mesenchymal Stem Cells; Mutation; Myelodysplastic Syndromes; Signal Transduction; Stem Cell Niche
PubMed: 30670448
DOI: 10.1182/blood-2018-10-844639 -
Blood Apr 2023The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely,...
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.
Topics: Humans; Bone Marrow Diseases; Diagnosis, Differential; Anemia, Aplastic; Bone Marrow Failure Disorders; Pancytopenia
PubMed: 36542832
DOI: 10.1182/blood.2022017518 -
Blood Feb 2018Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179...
Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders (, ), telomeropathies (, , ), ribosome disorders (, , ), and DNA repair deficiency (). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as and (N = 16 of the 86 patients, 18.6%), (N = 6, 7.0%), and (N = 7, 8.1%), each of which was associated with a distinct natural history; and patients often experienced transient aplasia and monosomy 7, whereas patients presented early-onset severe aplastic anemia, and patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling.
Topics: Adolescent; Bone Marrow Diseases; Child; Child, Preschool; Cohort Studies; DNA Mutational Analysis; Female; Germ-Line Mutation; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Male; Myelodysplastic Syndromes; Exome Sequencing
PubMed: 29146883
DOI: 10.1182/blood-2017-09-806489 -
The Medical Clinics of North America Mar 2017Myelodysplastic syndrome (MDS) is a heterogeneous, clonal stem cell disorder of the blood and marrow typically diagnosed based on the presence of persistent... (Review)
Review
Myelodysplastic syndrome (MDS) is a heterogeneous, clonal stem cell disorder of the blood and marrow typically diagnosed based on the presence of persistent cytopenia(s), dysplastic cells, and genetic markers. Common issues that arise in the clinical management include difficulty confirming MDS diagnosis, lack of a standard approach with novel agents in MDS, and few prospective long-term, randomized controlled MDS clinical studies to guide allogeneic blood and marrow transplant. With the recent genetic characterization of MDS, certain aspects of these issues will be better addressed by integrating genetic data into clinical study design and clinical practice.
Topics: Bone Marrow Cells; Chromatin Assembly and Disassembly; DNA Methylation; Hematologic Tests; Humans; Mutation; Myelodysplastic Syndromes; Prognosis; RNA Splicing
PubMed: 28189174
DOI: 10.1016/j.mcna.2016.09.006 -
Hematology/oncology Clinics of North... Aug 2018GATA2 deficiency is an immunodeficiency and bone marrow failure disorder caused by pathogenic variants in GATA2. It is inherited in an autosomal-dominant pattern or can... (Review)
Review
GATA2 deficiency is an immunodeficiency and bone marrow failure disorder caused by pathogenic variants in GATA2. It is inherited in an autosomal-dominant pattern or can be due to de novo sporadic germline mutation. Patients commonly have B-cell, dendritic cell, natural killer cell, and monocytopenias, and are predisposed to myelodysplastic syndrome, acute myeloid leukemia, and chronic myelomonocytic leukemia. Patients may suffer from disseminated human papilloma virus and mycobacterial infections, pulmonary alveolar proteinosis, and lymphedema. The bone marrow eventually takes on a characteristic hypocellular myelodysplasia with loss of monocytes and hematogones, megakaryocytes with separated nuclear lobes, micromegakaryocytes, and megakaryocytes with hypolobated nuclei.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; GATA2 Deficiency; GATA2 Transcription Factor; Genetic Predisposition to Disease; Germ-Line Mutation; Hemoglobinuria, Paroxysmal; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
PubMed: 30047422
DOI: 10.1016/j.hoc.2018.04.004 -
European Radiology Experimental Sep 2021Dual-energy CT (DECT) has emerged into clinical routine as an imaging technique with unique postprocessing utilities that improve the evaluation of different body areas.... (Review)
Review
Dual-energy CT (DECT) has emerged into clinical routine as an imaging technique with unique postprocessing utilities that improve the evaluation of different body areas. The virtual non-calcium (VNCa) reconstruction algorithm has shown beneficial effects on the depiction of bone marrow pathologies such as bone marrow edema. Its main advantage is the ability to substantially increase the image contrast of structures that are usually covered with calcium mineral, such as calcified vessels or bone marrow, and to depict a large number of traumatic, inflammatory, infiltrative, and degenerative disorders affecting either the spine or the appendicular skeleton. Therefore, VNCa imaging represents another step forward for DECT to image conditions and disorders that usually require the use of more expensive and time-consuming techniques such as magnetic resonance imaging, positron emission tomography/CT, or bone scintigraphy. The aim of this review article is to explain the technical background of VNCa imaging, showcase its applicability in the different body regions, and provide an updated outlook on the clinical impact of this technique, which goes beyond the sole improvement in image quality.
Topics: Bone Marrow; Bone Marrow Diseases; Calcium; Humans; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 34476640
DOI: 10.1186/s41747-021-00228-y -
Differentiation; Research in Biological... 2018Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative... (Review)
Review
Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic stem and progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and differentiation. We also discuss how both the increased risk of myelodysplastic syndromes and other hematological malignancies that is associated with telomere disorders and the discovery of cancer-associated somatic mutations in the shelterin components challenge the conventional interpretation that telomere defects are cancer-protective rather than cancer-promoting.
Topics: Animals; Bone Marrow Diseases; Hematopoietic Stem Cells; Humans; Telomere; Telomere Shortening
PubMed: 29331736
DOI: 10.1016/j.diff.2018.01.001 -
Experimental Hematology Jan 2022Bone marrow failure syndromes encompass a range of inherited and acquired hematological diseases that result in insufficient blood cell production, which leads to severe... (Review)
Review
Bone marrow failure syndromes encompass a range of inherited and acquired hematological diseases that result in insufficient blood cell production, which leads to severe complications including anemia, weakening of the immune system, impaired coagulation, and increased risk of cancer. Within inherited bone marrow failure syndromes, a number of genetically distinct diseases have been described including Shwachman-Diamond syndrome and Fanconi anemia. Given the genetic complexity and poor prognosis of these inherited bone marrow failure syndromes, there is increasing interest in both characterizing the genetic landscapes of these diseases and developing novel gene therapies to effectively monitor and cure patients. These topics were the focus of the winter 2021 International Society for Experimental Hematology New Investigator Webinar, which featured presentations by Dr. Akiko Shimamura and Dr. Paula Río. Here, we review the topics covered within this webinar.
Topics: Animals; Bone Marrow Failure Disorders; Clonal Evolution; Fanconi Anemia; Genetic Therapy; Humans; Shwachman-Diamond Syndrome; Translational Research, Biomedical
PubMed: 34801643
DOI: 10.1016/j.exphem.2021.11.004