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Reumatismo Jul 2014Bone marrow edema (BME) is a descriptive term which identifies a specific magnetic resonance imaging (MRI) pattern that can be observed in a number of clinical entities,... (Review)
Review
Bone marrow edema (BME) is a descriptive term which identifies a specific magnetic resonance imaging (MRI) pattern that can be observed in a number of clinical entities, which are often characterized by pain as their main symptom, but show significant differences in terms of histopathological findings, causal mechanisms and prognosis. Bone marrow lesions in the subchondral bone of subjects with knee osteoarthritis (OA) seem to be associated with pain and progression of cartilage damage over time. Some histopathological studies of advanced OA have shown a prevalent fibrosis and bone marrow necrosis. BME of the subchondral bone in rheumatoid arthritis is associated with an infiltrate of inflammatory cells and osteoclasts and has a predictive value of further development of erosions. In spondyloarthritis, BME of the sacroiliac joints identifies an active sacroiliitis and is associated with histological inflammation and radiographic progression, whereas the relationship between BME lesions of the spine and syndesmophyte development is still controversial. BME syndromes (BMES), such as transient osteoporosis of the hip, regional migratory osteoporosis, and transient post-traumatic BMES, are characterized by a BME pattern on MRI and a self-limiting course. The potential evolution of BMES toward osteonecrosis is still controversial.
Topics: Arthritis, Rheumatoid; Bone Marrow Diseases; Edema; Humans; Magnetic Resonance Imaging; Osteoarthritis; Spondylarthritis; Syndrome
PubMed: 25069499
DOI: 10.4081/reumatismo.2014.790 -
Advances in Clinical and Experimental... May 2022Anemia is a common finding among patients with liver diseases. Patients who suffer from anemia are at a higher risk of liver function decompensation and hospitalization.... (Review)
Review
Anemia is a common finding among patients with liver diseases. Patients who suffer from anemia are at a higher risk of liver function decompensation and hospitalization. It affects significantly their quality of life and contributes to mortality. Anemia is present in 70% of patients with liver cirrhosis and with varying incidence accompanies other liver disorders. As the etiology of anemia in liver diseases is multifactorial, various cases represent different clinical entities. Anemia accompanying hepatic disorders can be broadly divided into several types, such as anemia associated with blood loss, as well as aplastic, hemolytic and micronutrient deficiency anemia. However, it is sometimes difficult to delineate between those types in the clinical practice, as several pathophysiological causes can be present in one patient. It is reported that the most common cause of anemia in liver disease is blood loss and iron deficiency. Still, the incidence of unclear cases reaching over 50% suggests that other types of anemia can be underdiagnosed. This review comprehensively describes less frequent types of anemia associated with liver disease, namely hemolytic and aplastic anemia (AA). Hemolytic anemia can complicate autoimmune liver diseases or be a manifestation of membranopathy of red blood cells, dependent on severe hepatic function impairment or alcoholic liver disease. Aplastic anemia is best known as a sequela of viral hepatitis, but some degree of bone marrow inhibition can complicate virtually all advanced liver diseases.
Topics: Anemia, Aplastic; Bone Marrow; Humans; Iron Deficiencies; Liver Diseases; Quality of Life
PubMed: 35275448
DOI: 10.17219/acem/145984 -
Frontiers in Immunology 2022GATA2 deficiency is a disease with a broad spectrum of clinical presentation, ranging from lymphedema, deafness, pulmonary dysfunction to miscarriage and urogenital... (Review)
Review
GATA2 deficiency is a disease with a broad spectrum of clinical presentation, ranging from lymphedema, deafness, pulmonary dysfunction to miscarriage and urogenital anomalies, but it is mainly recognized as an immune system and bone marrow disorder. It is caused by various heterozygous mutations in the gene, encoding for a zinc finger transcription factor with a key role for the development and maintenance of a pool of hematopoietic stem cells; notably, most of these mutations arise . Patients carrying a mutated allele usually develop a loss of some cell populations, such as B-cell, dendritic cell, natural killer cell, and monocytes, and are predisposed to disseminated human papilloma virus and mycobacterial infections. Also, these patients have a predisposition to myeloid neoplasms, including myelodysplastic syndromes, myeloproliferative neoplasms, chronic myelomonocytic leukaemia. The age of symptoms onset can vary greatly even also within the same family, ranging from early childhood to late adulthood; incidence increases by age and most frequently clinical presentation is between the second and third decade of life. Currently, haematopoietic stem cell transplantation represents the only curative treatment, restoring both the hematopoietic and immune system function.
Topics: Disease Susceptibility; GATA2 Deficiency; GATA2 Transcription Factor; Humans; Immune System
PubMed: 35769478
DOI: 10.3389/fimmu.2022.865773 -
Frontiers in Endocrinology 2023
Topics: Humans; Bone Neoplasms; Bone and Bones; Bone Marrow Diseases
PubMed: 37564977
DOI: 10.3389/fendo.2023.1256406 -
British Journal of Haematology May 2017The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to... (Review)
Review
The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to pancytopenia, and are associated with increased risk of cancer. Although the clinical features of the IBMFS are often diagnostic, variable disease penetrance and expressivity may result in diagnostic dilemmas. The discovery of the genetic aetiology of the IBMFS has been greatly facilitated by next-generation sequencing methods. This has advanced understanding of the underlying biology of the IBMFS and been essential in improving clinical management and genetic counselling for affected patients. Herein we review the clinical features, underlying biology, and new genomic discoveries in the IBMFS, including Fanconi anaemia, dyskeratosis congenita, Diamond Blackfan anaemia, Shwachman Diamond syndrome and some disorders of the myeloid and megakaryocytic lineages.
Topics: Anemia, Aplastic; Anemia, Diamond-Blackfan; Blood Platelet Disorders; Bone Marrow Diseases; Bone Marrow Failure Disorders; DNA Repair-Deficiency Disorders; Dyskeratosis Congenita; Exocrine Pancreatic Insufficiency; Fanconi Anemia; Genetic Counseling; Genomics; Hemoglobinuria, Paroxysmal; Humans; Lipomatosis; Neutropenia; Ribosomes; Shwachman-Diamond Syndrome; Telomere
PubMed: 28211564
DOI: 10.1111/bjh.14535 -
Frontiers in Immunology 2021Myeloid neoplasms, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), feature clonal dominance and... (Review)
Review
Myeloid neoplasms, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), feature clonal dominance and remodeling of the bone marrow niche in a manner that promotes malignant over non-malignant hematopoiesis. This take-over of hematopoiesis by the malignant clone is hypothesized to include hyperactivation of inflammatory signaling and overproduction of inflammatory cytokines. In the -negative MPNs, inflammatory cytokines are considered to be responsible for a highly deleterious pathophysiologic process: the phenotypic transformation of polycythemia vera (PV) or essential thrombocythemia (ET) to secondary myelofibrosis (MF), and the equivalent emergence of primary myelofibrosis (PMF). Bone marrow fibrosis itself is thought to be mediated heavily by the cytokine TGF-β, and possibly other cytokines produced as a result of hyperactivated JAK2 kinase in the malignant clone. MF also features extramedullary hematopoiesis and progression to bone marrow failure, both of which may be mediated in part by responses to cytokines. In MF, elevated levels of individual cytokines in plasma are adverse prognostic indicators: elevated IL-8/CXCL8, in particular, predicts risk of transformation of MF to secondary AML (sAML). Tumor necrosis factor (TNF, also known as TNFα), may underlie malignant clonal dominance, based on results from mouse models. Human PV and ET, as well as MF, harbor overproduction of multiple cytokines, above what is observed in normal aging, which can lead to cellular signaling abnormalities separate from those directly mediated by hyperactivated JAK2 or MPL kinases. Evidence that NFκB pathway signaling is frequently hyperactivated in a pan-hematopoietic pattern in MPNs, including in cells outside the malignant clone, emphasizes that MPNs are pan-hematopoietic diseases, which remodel the bone marrow milieu to favor persistence of the malignancy. Clinical evidence that JAK2 inhibition by ruxolitinib in MF neither reliably reduces malignant clonal burden nor eliminates cytokine elevations, suggests targeting cytokine mediated signaling as a therapeutic strategy, which is being pursued in new clinical trials. Greater knowledge of inflammatory pathophysiology in MPNs can therefore contribute to the development of more effective therapy.
Topics: Age Factors; Biomarkers; Cell Transformation, Neoplastic; Cytokines; Disease Susceptibility; Humans; Inflammation Mediators; Models, Biological; Myeloproliferative Disorders; Primary Myelofibrosis; Signal Transduction
PubMed: 34140953
DOI: 10.3389/fimmu.2021.683401 -
Blood Oct 2014Our understanding of the pathophysiology of aplastic anemia is undergoing significant revision, with implications for diagnosis and treatment. Constitutional and... (Review)
Review
Our understanding of the pathophysiology of aplastic anemia is undergoing significant revision, with implications for diagnosis and treatment. Constitutional and acquired disease is poorly delineated, as lesions in some genetic pathways cause stereotypical childhood syndromes and also act as risk factors for clinical manifestations in adult life. Telomere diseases are a prominent example of this relationship. Accelerated telomere attrition is the result of mutations in telomere repair genes and genes encoding components of the shelterin complex and related proteins. Genotype-phenotype correlations show genes responsible for X-linked (DKC1) and severe recessive childhood dyskeratosis congenita, typically with associated mucocutaneous features, and others (TERC and TERT) for more subtle presentation as telomeropathy in adults, in which multiorgan failure may be prominent. Telomerase mutations also are etiologic in familial pulmonary fibrosis and cryptic liver disease. Detection of a telomere disease requires awareness in the clinic, appropriate laboratory testing of telomere content, and genetic sequencing. In treatment decisions, genetic screening of related donors for hematopoietic stem cell transplantation is critical, and androgen therapy may be helpful. Telomeres shorten normally with aging, as well as under environmental circumstances, with regenerative stress and oxidative damage. Telomere biology is complexly related to oncogenesis: telomere attrition is protective by enforcing senescence or apoptosis in cells with a long mitotic history, but telomere loss also can destabilize the genome by chromosome rearrangement and aneuploidy.
Topics: Animals; Bone Marrow; Bone Marrow Diseases; Genetic Association Studies; Humans; Neoplasms; Telomerase; Telomere
PubMed: 25237198
DOI: 10.1182/blood-2014-05-526285 -
Journal of Clinical and Experimental... 2018Myelodysplastic syndromes (MDS) are clonal diseases characterized by cytopenia and dysplasia in the peripheral blood, and risk of transition to acute myeloid leukemia... (Review)
Review
Myelodysplastic syndromes (MDS) are clonal diseases characterized by cytopenia and dysplasia in the peripheral blood, and risk of transition to acute myeloid leukemia (AML) in the bone marrow. In the current revision of the World Health Organization (WHO) classification for hematopoietic tissues, MDS are divided into low-, intermediate-, and high- risk groups according to their frequency of leukemic transformation and other biological indicators. Accuracy in histological evaluation plus blast counting on bone marrow biopsy is essential for the differentiation of high-risk MDS from AML. In this review, the value of histopathology in the diagnosis of high-risk MDS is discussed.
Topics: Bone Marrow; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
PubMed: 29998976
DOI: 10.3960/jslrt.18009 -
Annals of Medicine Sep 2014The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples... (Review)
Review
The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital neutropenia, and Shwachman-Diamond syndrome. The management of these disorders was once the exclusive domain of pediatric subspecialists, but increasingly physicians who care for adults are being called upon to diagnose or treat these conditions. Through a series of patient vignettes, we highlight the clinical manifestations of inherited bone marrow failure syndromes in adolescents and young adults. The diagnostic and therapeutic challenges posed by these diseases are discussed.
Topics: Adolescent; Adult; Anemia, Aplastic; Anemia, Diamond-Blackfan; Bone Marrow Diseases; Bone Marrow Failure Disorders; Congenital Bone Marrow Failure Syndromes; Dyskeratosis Congenita; Exocrine Pancreatic Insufficiency; Fanconi Anemia; Hemoglobinuria, Paroxysmal; Humans; Lipomatosis; Neutropenia; Radius; Shwachman-Diamond Syndrome; Thrombocytopenia; Upper Extremity Deformities, Congenital; Young Adult
PubMed: 24888387
DOI: 10.3109/07853890.2014.915579 -
Frontiers in Immunology 2021Immune phenomena are increasingly reported in myeloid neoplasms, and include autoimmune cytopenias/diseases and immunodeficiency, either preceding or complicating acute... (Review)
Review
Immune phenomena are increasingly reported in myeloid neoplasms, and include autoimmune cytopenias/diseases and immunodeficiency, either preceding or complicating acute myeloid leukemia, myelodysplastic syndromes (MDS), chronic myeloproliferative neoplasms, and bone marrow failure (BMF) syndromes. Autoimmunity and immunodeficiency are the two faces of a dysregulated immune tolerance and surveillance and may result, along with contributing environmental and genetic factors, in an increased incidence of both tumors and infections. The latter may fuel both autoimmunity and immune activation, triggering a vicious circle among infections, tumors and autoimmune phenomena. Additionally, alterations of the microbiota and of mesenchymal stem cells (MSCs) pinpoint to the importance of a permissive or hostile microenvironment for tumor growth. Finally, several therapies of myeloid neoplasms are aimed at increasing host immunity against the tumor, but at the price of increased autoimmune phenomena. In this review we will examine the epidemiological association of myeloid neoplasms with autoimmune diseases and immunodeficiencies, and the pivotal role of autoimmunity in the pathogenesis of MDS and BMF syndromes, including the paroxysmal nocturnal hemoglobinuria conundrum. Furthermore, we will briefly examine autoimmune complications following therapy of myeloid neoplasms, as well as the role of MSCs and microbiota in these settings.
Topics: Autoimmune Diseases; Bone Marrow Diseases; Humans; Mesenchymal Stem Cells; Microbiota; Primary Immunodeficiency Diseases
PubMed: 34659257
DOI: 10.3389/fimmu.2021.751630