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1.
Impaired bone marrow microenvironment and stem cells in transfusion-dependent beta-thalassemia.
Zhou, X, Huang, L, Wu, J, Qu, Y, Jiang, H, Zhang, J, Qiu, S, Liao, C, Xu, X, Xia, J, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112548
Abstract
Beta-thalassemia (BT) is a hereditary disease caused by abnormal hemoglobin synthesis with consequent ineffective erythropoiesis. Patients with thalassemia major are dependent on long-term blood transfusions with associated long-term complications such as iron overload (IO). This excess iron can result in tissue damage, impaired organ function, and increased morbidity. Growing evidence has demonstrated that IO contributes to impairment of the bone marrow (BM) microenvironment that largely impacts the function of BM mesenchymal stem cells, hematopoietic stem cells, and endothelial cells. In this article, we review recent progress in the understanding of iron metabolism and the perniciousness induced by IO. We highlight the importance of understanding the cross-talk between BM stem cells and the BM microenvironment, particularly the pathological effect of IO on BM stem cells and BT-associated complications. We also provide an update on recent novel therapies to cure transfusion-dependent beta-thalassemia and iron overload-induced complications for their future clinical application.
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2.
Immunoglobulin D-kappa multiple myeloma in a patient with rheumatoid arthritis: a case report and review of the literature.
Tokunaga, T, Hashimoto, H, Yoshida, Y, Sugimoto, T, Mokuda, S, Kosaka, Y, Shimizu, R, Hirata, S, Kumagai, T, Komoto, K, et al
Modern rheumatology case reports. 2021;(1):22-28
Abstract
A 77-year-old Japanese woman with a 21-year history of seropositive, erosive rheumatoid arthritis (RA) and a 10-year history of methotrexate (MTX) therapy was admitted with malaise and mild consciousness disturbance. Laboratory data showed hypercalcemia, acute kidney injury, normocytic anaemia, and thrombocytopenia. As we first assumed drug-induced toxicity by MTX and eldecalcitol, both were discontinued and leucovorin rescue therapy and calcitonin were administered. However, her condition continued to worsen. Serum protein electrophoresis showed only a small M-peak, immunoelectrophoresis of both the serum and urine demonstrated Bence-Jones kappa (κ) type monoclonal protein without immunoglobulin heavy chain, and bone marrow examination revealed proliferation of plasma cells. We diagnosed her with Bence-Jones κ type multiple myeloma (MM) and transferred her to the department of haematology of a higher order medical institution. Conclusively, the diagnosis of immunoglobulin (Ig) D-κ type MM, a rare variant of this disorder, was determined in accordance with serum immunofixation. Several previous studies have suggested that pre-existing RA is a risk factor for MM. Although IgD MM is characterised by its clinical severity and poor prognosis compared to other subtypes, it is often misdiagnosed or mistaken as light chain type MM, as in the present case, because of the low level of IgD M-protein, resulting in delayed diagnosis. Physicians must take MM into consideration as a differential diagnosis when inactive RA patients present with inexplicable elevated calcium, renal failure, anaemia, and bone lesion symptoms and should be aware of IgD MM to establish the correct diagnosis promptly.
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3.
Radiotracers for Bone Marrow Infection Imaging.
Jødal, L, Afzelius, P, Alstrup, AKO, Jensen, SB
Molecules (Basel, Switzerland). 2021;(11)
Abstract
INTRODUCTION Radiotracers are widely used in medical imaging, using techniques of gamma-camera imaging (scintigraphy and SPECT) or positron emission tomography (PET). In bone marrow infection, there is no single routine test available that can detect infection with sufficiently high diagnostic accuracy. Here, we review radiotracers used for imaging of bone marrow infection, also known as osteomyelitis, with a focus on why these molecules are relevant for the task, based on their physiological uptake mechanisms. The review comprises [67Ga]Ga-citrate, radiolabelled leukocytes, radiolabelled nanocolloids (bone marrow) and radiolabelled phosphonates (bone structure), and [18F]FDG as established radiotracers for bone marrow infection imaging. Tracers that are under development or testing for this purpose include [68Ga]Ga-citrate, [18F]FDG, [18F]FDS and other non-glucose sugar analogues, [15O]water, [11C]methionine, [11C]donepezil, [99mTc]Tc-IL-8, [68Ga]Ga-Siglec-9, phage-display selected peptides, and the antimicrobial peptide [99mTc]Tc-UBI29-41 or [68Ga]Ga-NOTA-UBI29-41. CONCLUSION Molecular radiotracers allow studies of physiological processes such as infection. None of the reviewed molecules are ideal for the imaging of infections, whether bone marrow or otherwise, but each can give information about a separate aspect such as physiology or biochemistry. Knowledge of uptake mechanisms, pitfalls, and challenges is useful in both the use and development of medically relevant radioactive tracers.
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4.
Marrow outside marrow: imaging of extramedullary haematopoiesis.
Malla, S, Razik, A, Das, CJ, Naranje, P, Kandasamy, D, Kumar, R
Clinical radiology. 2020;(8):565-578
Abstract
Extramedullary haematopoiesis (EMH) refers to the formation of non-neoplastic blood cell lines outside the bone marrow and is a common incidental finding when patients with haematological disorders are imaged. EMH presenting as mass (tumefactive EMH) has long been a radiological conundrum as it resembles neoplasms. Several imaging findings have been described in EMH, and these vary depending on the activity of the underlying haematopoiesis. The older lesions are easier to diagnose as they often demonstrate characteristic findings such as haemosiderin and fat deposition. In comparison, the newer, actively haematopoietic lesions often mimic neoplasms. Molecular imaging, particularly 99mTc labelled sulphur colloid scintigraphy, may be helpful in such cases. Although imaging is extremely useful in detecting and characterising EMH, imaging alone is often non-diagnostic as no single mass shows all the typical findings. Hence, a judgement based on the clinical background, combination of imaging findings, and slow interval growth may be more appropriate and practical in making the correct diagnosis. In every case, an effort has to be made in providing an imaging-based diagnosis as it may prevent a potentially risky biopsy. When confident differentiation is not possible, biopsy has to be resorted to. This article describes the causes, pathophysiology, and theories underlying the genesis of EMH, followed by the general and location-specific imaging findings. The purpose is to provide a thorough understanding of the condition as well as enable the clinical radiologist in making an imaging-based diagnosis whenever possible and identify the situations where biopsy has to be performed.
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5.
Metastatic Seeding Attacks Bone Marrow, Not Bone: Rectifying Ongoing Misconceptions.
Raynor, WY, Al-Zaghal, A, Zadeh, MZ, Seraj, SM, Alavi, A
PET clinics. 2019;(1):135-144
Abstract
Conventional modalities, such as bone scintigraphy, are commonly used to assess osseous abnormalities in skeletal metastasis. Fluorine-18 (18F)-sodium fluoride (NaF) PET similarly portrays osteoblastic activity but with improved spatial and contrast resolution and more accurate anatomic localization. However, these modalities rely on indirect evidence for tumor activity. PET imaging with 18F-fluorodeoxyglucose (FDG) and tumor-specific tracers may have an increased role by directly portraying the metabolic activity of cancer cells, which are often seeded in bone marrow and cause osseous disease after initial latency. This article describes the utility and limitations of these modalities in assessing skeletal metastases.
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6.
Physiology of Bone.
Grabowski, P
Endocrine development. 2015;:33-55
Abstract
Bone serves three main physiological functions: its mechanical nature provides support for locomotion and offers protection to vulnerable internal organs, it forms a reservoir for the storage of calcium and phosphate in the body, and it provides an environment for bone marrow production and haematopoietic cell development. The traditional view of bone as a passive tissue that responds to hormonal and dietary influences has changed over the past half century to one of bone as a dynamic adaptive tissue that responds to mechanical demands. This chapter gathers together some recent advances in bone physiology and molecular cell biology and discusses the potential application of the functional adaptation of bone to loading to enhance bone strength during childhood and adolescence.
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7.
[Pemetrexed nephrotoxicity].
Izzedine, H
Bulletin du cancer. 2015;(2):190-7
Abstract
Pemetrexed belongs to a new generation of multitargeted antifolate cytotoxic agents. It is increasingly used as first-line treatment in combination with cisplatin, and as second-line treatment or maintenance monotherapy mainly in metastatic non-small cell lung cancer and in malignant mesothelioma. It is increasingly used as first-line treatment in combination with cisplatin in lung adenocarcinoma, and as second-line treatment or maintenance monotherapy in patients mainly controlled by the first-line to progression or poor tolerance. In mesothelioma, pemetrexed is indicated only in first-line with a platinum salt. The main side effect of pemetrexed is myelosuppression, which may be prevented by folinic acid supplementation. This review focuses on the progressive and cumulative emerging renal toxicity of pemetrexed, affecting five to ten percent of "long-term" pemetrexed-treated patients.
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8.
Association of obesity and systemic factors with bone marrow lesions at the knee: a systematic review.
Lim, YZ, Wang, Y, Wluka, AE, Davies-Tuck, ML, Hanna, F, Urquhart, DM, Cicuttini, FM
Seminars in arthritis and rheumatism. 2014;(5):600-12
Abstract
OBJECTIVE The objective of this study was to systematically review the literature to determine whether obesity and systemic factors, including age, gender, heritability, dietary factors, smoking, serum and urine biomarkers of cartilage or bone metabolism, bone-related factors, and medication, are associated with knee bone marrow lesions (BMLs) identified on magnetic resonance imaging in asymptomatic pre-osteoarthritis and osteoarthritis populations. METHODS Electronic searches of MEDLINE and EMBASE were performed from January 1, 1996 to September 30, 2012 using the following keywords: bone marrow lesion(s), bone marrow (o)edema, osteoarthritis, and knee. Studies examining obesity and non-biomechanical factors in relation to the presence, incidence, or change in BMLs were included. Two independent reviewers extracted data and assessed methodological quality of selected studies. Due to the heterogeneity of the studies, we performed a best evidence synthesis. RESULTS Among 30 studies, 17 were considered high quality. The study populations were heterogeneous in terms of symptoms and radiographic knee osteoarthritis. There was strong evidence for an association between serum lipids and BMLs and no association between age and BMLs. There was moderate evidence for a relationship between obesity and BMLs. There was limited evidence for gender, smoking, C-telopeptide of type I collagen, anti-bone-resorptive treatments, licofelone, and chondroitin sulfate. There was a paucity of evidence for heritability and conflicting evidence for dietary fatty acids. CONCLUSION There is strong evidence for serum lipids and moderate evidence for obesity as risk factors for knee BMLs. Given the role of BMLs in the pathogenesis of knee osteoarthritis, identification of modifiable risk factors of BMLs and therapeutic interventions targeting BMLs has the potential to reduce the burden of knee osteoarthritis.
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9.
[Pathomechanism and clinical impact of myelofibrosis in neoplastic diseases of the bone marrow].
Bedekovics, J, Méhes, G
Orvosi hetilap. 2014;(10):367-75
Abstract
Polyclonal mesenchymal cells (fibroblasts, endothelial cells, pericytes, osteoblasts, reticular cells, adipocytes, etc.) of the bone marrow create a functional microenvironment, which actively contributes to the maintenance of hemopoesis. This takes place through cellular interactions via growth factors, cytokines, adhesion molecules and extracellular matrix components, as well as through the control of calcium and oxygen concentration. Inflammatory and neoplastic diseases of the bone marrow result in pathologic interaction between hemopoietic progenitors and stromal cells. This may lead to the activation and expansion of the stroma and to the accumulation of reticulin and collagen fibers produced by mesenchymal cells. Clinically relevant fiber accumulation, termed as myelofibrosis accompanies many diseases, although, the extent and the consequence of myelofibrosis are variable in different disorders. The aim of this review is to summarize basic features of the normal bone marrow mesenchymal environment and the pathological process leading to myelofibrosis. In addition, the special features of myelofibrosis in bone marrow diseases, including myeloproliferative neoplasia, myelodysplastic syndrome and other neoplastic conditions are discussed.
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10.
Prominent gelatinous bone marrow transformation presenting prior to myelodysplastic syndrome: a case report with review of the literature.
Nakanishi, R, Ishida, M, Hodohara, K, Yoshida, T, Yoshii, M, Okuno, H, Horinouchi, A, Iwai, M, Yoshida, K, Kagotani, A, et al
International journal of clinical and experimental pathology. 2013;(8):1677-82
Abstract
Gelatinous bone marrow transformation (GMT) is a rare disorder characterized by the presence of fat cell atrophy, loss of hematopoietic cells, and deposition of extracellular gelatinous materials. GMT is not a specific disease, but is strongly associated with malnutrition and drugs. Albeit extremely rare, GMT has been reported in patients with myeloproliferative disorders. Herein, we report the second documented case of hypoplastic myelodysplastic syndrome (MDS) accompanying GMT. A 73-year-old Japanese male with excellent nutrition status and no history of alcohol or drug intake was detected with pancytopenia. The initial bone marrow aspirate specimen reveled hypocellular marrow without dysplastic signs in the myeloid cells. Bone marrow biopsy demonstrated hypocellular bone marrow with prominent GMT. He received blood transfusions, however, pancytopenia continued to progress. The second bone marrow aspirate specimen showed dysplastic changes, such as pseudo-Pelger-Huët cells, hypogranular or agranular granulocytes, and megakaryocytes with multiple small nuclei. Cytogenetic study demonstrated deletion of chromosome 7. Therefore, an ultimate diagnosis of hypoplastic MDS accompanying GMT was made. Only a limited number of cases of myeloproliferative disorders with GMT have been reported. Our analysis of these cases revealed that chromosome 7 abnormality is frequently observed in this condition. Moreover, findings from the current case suggested that myeloproliferative disorders including MDS must be included in the differential diagnostic considerations of GMT patients, who have no history of malnutrition or drugs, and careful examination of the bone marrow smear specimen and cytogenetic analysis are necessary for early detection of underlying myeloproliferative disorders.