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Journal of the American College of... Jan 2020The term embolic stroke of undetermined source (ESUS) was introduced in 2014 to describe patients with a nonlacunar ischemic stroke and no convincing etiology. The terms... (Review)
Review
The term embolic stroke of undetermined source (ESUS) was introduced in 2014 to describe patients with a nonlacunar ischemic stroke and no convincing etiology. The terms ESUS and cryptogenic stroke are not synonyms, as the latter also includes patients with multiple stroke etiologies or incomplete diagnostic work-up. ESUS involves approximately 17% of all ischemic stroke patients, and these patients are typically younger with mild strokes and an annual rate of stroke recurrence of 4% to 5%. It was hypothesized that oral anticoagulation may decrease the risk of stroke recurrence in ESUS, which was tested in 2 large randomized controlled trials: the NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) and the RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source). The present review discusses the trials of anticoagulation in patients with ESUS, suggests potential explanations for their neutral results, and highlights the rationale that supports ongoing and future research in this population aiming to reduce the associated risk for stroke recurrence.
Topics: Anticoagulants; Clinical Trials as Topic; Embolism; Humans; Platelet Aggregation Inhibitors; Stroke
PubMed: 31976872
DOI: 10.1016/j.jacc.2019.11.024 -
The Netherlands Journal of Medicine Sep 2019Monoclonal gammopathy of renal significance (MGRS) includes all kidney disorders caused by a monoclonal protein (M-protein) secreted by a small plasma cell clone or... (Review)
Review
Monoclonal gammopathy of renal significance (MGRS) includes all kidney disorders caused by a monoclonal protein (M-protein) secreted by a small plasma cell clone or other B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. The underlying disorder in patients with MGRS is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). MGRS-associated kidney disorders are various and the list is still expanding. The kidney disorders can manifest as glomerular diseases, tubulopathies, and vascular involvement with varying clinical presentations. Diagnosis is often challenging because of the wide spectrum of MGRS, and it is difficult to establish a pathogenic link between the presence of the M-protein or serum free light chains and kidney diseases; further complicating accurate diagnosis is the high incidence of MGUS and/or kidney disorders, independent of MGRS, in elderly patients. However, MGRS can significantly impair kidney function. Because treatment can stop and also reverse kidney disease, early recognition is of great importance. A combined haematologic and nephrologic approach is crucial to establish the causative role of the M-protein in the pathogenesis of kidney disease. Clone-directed therapy, which may include autologous stem cell transplantation in eligible patients, often results in improved outcomes. In this review, we discuss the histopathologic classification of MGRS lesions, provide a renal and haematologic diagnostic workup, discuss treatment options for MGRS, and introduce a Benelux MGRS Working Group.
Topics: Biopsy; Disease Management; Humans; Kidney Diseases; Monoclonal Gammopathy of Undetermined Significance; Stem Cell Transplantation; Transplantation, Autologous
PubMed: 31582582
DOI: No ID Found -
Blood Cancer Journal Sep 2022Smoldering multiple myeloma (SMM) is an asymptomatic condition that occupies a space between monoclonal gammopathy of undetermined significance (MGUS) and multiple... (Review)
Review
Smoldering multiple myeloma (SMM) is an asymptomatic condition that occupies a space between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) along the spectrum of clonal plasma cell proliferative disorders. It is not a biologic intermediate stage between MGUS and MM, but rather represents a heterogeneous clinically defined condition in which some patients (approximately two-thirds) have MGUS (pre-malignancy), and some (approximately one-third) have MM (biologic malignancy). Unfortunately, no single pathologic or molecular feature can reliably distinguish these two groups of patients. For purposes of practice and clinical trials, specific risk factors are used to identify patients with SMM in whom malignant transformation has already likely occurred (high risk SMM). Patients with newly diagnosed high risk SMM should be offered therapy with lenalidomide or lenalidomide plus dexamethasone (Rd) for 2 years, or enrollment in clinical trials. Patients with low risk SMM should be observed without therapy every 3-4 months.
Topics: Algorithms; Biological Products; Disease Progression; Humans; Lenalidomide; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Paraproteinemias; Smoldering Multiple Myeloma
PubMed: 36064707
DOI: 10.1038/s41408-022-00719-0 -
Leukemia Jun 2010Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of... (Review)
Review
Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management.
Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein <15 g/l, IgG type and a normal free light chain (FLC) ratio. Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2-3 years or when symptoms suggestive of a plasma cell malignancy arise. Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life. The risk of smoldering (asymptomatic) multiple myeloma (SMM) progressing to multiple myeloma or a related disorder is 10% per year for the first 5 years, 3% per year for the next 5 years and 1-2% per year for the next 10 years. Testing should be done 2-3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4-6 months for 1 year and, if stable, every 6-12 months.
Topics: Disease Progression; Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Practice Guidelines as Topic; Prognosis; Risk Factors
PubMed: 20410922
DOI: 10.1038/leu.2010.60 -
Mayo Clinic Proceedings May 2017Monoclonal gammopathies comprise a spectrum of clonal plasma cell disorders that include monoclonal gammopathy of undetermined significance, multiple myeloma, and... (Review)
Review
Monoclonal gammopathies comprise a spectrum of clonal plasma cell disorders that include monoclonal gammopathy of undetermined significance, multiple myeloma, and Waldenström macroglobulinemia. In this review, we outline the epidemiology, etiology, classification, diagnosis, and treatment of monoclonal gammopathy-associated peripheral neuropathy. Monoclonal gammopathy of undetermined significance is relatively common in the general population, with a prevalence of 3% to 4% among individuals older than age 50 years. Therefore, the presence of M protein in a patient with neuropathy does not automatically indicate a causal relationship. Monoclonal gammopathy-associated peripheral neuropathy is often a difficult diagnosis with limited treatment options. Studies addressing the optimal approach to diagnosis and management of this entity are limited. In addition to a review of the literature, we present a diagnostic approach to patients with monoclonal gammopathy-associated peripheral neuropathy and discuss available data and options for treatment.
Topics: Administration, Intravenous; Biomarkers; Demyelinating Autoimmune Diseases, CNS; Diagnosis, Differential; Glycoproteins; Humans; Immunoglobulins; Immunologic Factors; Monoclonal Gammopathy of Undetermined Significance; Myeloablative Agonists; Peripheral Nervous System Diseases; Plasmapheresis; Prognosis; Rituximab; Vidarabine
PubMed: 28473042
DOI: 10.1016/j.mayocp.2017.02.003 -
American Society of Clinical Oncology... Apr 2022Our knowledge of monoclonal gammopathies is continuously evolving. Once accepted as a possible precursor condition to multiple myeloma, monoclonal gammopathies as an... (Review)
Review
Our knowledge of monoclonal gammopathies is continuously evolving. Once accepted as a possible precursor condition to multiple myeloma, monoclonal gammopathies as an entity are now associated with many renal, neurologic, and dermatologic disorders of clinical significance. This change has created a challenge for patients and clinicians, as a monoclonal gammopathy may be a harbinger not of multiple myeloma but of other lymphoproliferative disorders such as light-chain amyloidosis and Waldenström macroglobulinemia. Early recognition of monoclonal gammopathies along with a careful workup are essential in determining the next steps in the care of a given patient. Recognition has become all the more important as we understand how to triage the 4% to 9% of patients with monoclonal gammopathies depending on age, with the goal of limiting overdiagnosis and misdiagnosis. In this review, we focus on treatment strategies for patients with monoclonal gammopathies that are not multiple myeloma, including smoldering multiple myeloma, light-chain amyloidosis, and Waldenström macroglobulinemia.
Topics: Amyloidosis; Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Paraproteinemias; Waldenstrom Macroglobulinemia
PubMed: 35394823
DOI: 10.1200/EDBK_349643 -
Blood Jul 2015Recent genetic analyses of large populations have revealed that somatic mutations in hematopoietic cells leading to clonal expansion are commonly acquired during human...
Recent genetic analyses of large populations have revealed that somatic mutations in hematopoietic cells leading to clonal expansion are commonly acquired during human aging. Clonally restricted hematopoiesis is associated with an increased risk of subsequent diagnosis of myeloid or lymphoid neoplasia and increased all-cause mortality. Although myelodysplastic syndromes (MDS) are defined by cytopenias, dysplastic morphology of blood and marrow cells, and clonal hematopoiesis, most individuals who acquire clonal hematopoiesis during aging will never develop MDS. Therefore, acquisition of somatic mutations that drive clonal expansion in the absence of cytopenias and dysplastic hematopoiesis can be considered clonal hematopoiesis of indeterminate potential (CHIP), analogous to monoclonal gammopathy of undetermined significance and monoclonal B-cell lymphocytosis, which are precursor states for hematologic neoplasms but are usually benign and do not progress. Because mutations are frequently observed in healthy older persons, detection of an MDS-associated somatic mutation in a cytopenic patient without other evidence of MDS may cause diagnostic uncertainty. Here we discuss the nature and prevalence of CHIP, distinction of this state from MDS, and current areas of uncertainty regarding diagnostic criteria for myeloid malignancies.
Topics: Clonal Evolution; Diagnosis, Differential; Hematologic Neoplasms; Hematopoiesis; Humans; Monoclonal Gammopathy of Undetermined Significance; Mutation; Myelodysplastic Syndromes; Precancerous Conditions
PubMed: 25931582
DOI: 10.1182/blood-2015-03-631747 -
Blood Cancer Journal Apr 2022Monoclonal gammopathy associated with dermatological manifestations are a well-recognized complication. These skin disorders can be associated with infiltration and... (Review)
Review
Monoclonal gammopathy associated with dermatological manifestations are a well-recognized complication. These skin disorders can be associated with infiltration and proliferation of a malignant plasma cells or by a deposition of the monoclonal immunoglobulin in a nonmalignant monoclonal gammopathy. These disorders include POEMS syndrome, light chain amyloidosis, Schnitzler syndrome, scleromyxedema and TEMPI syndrome. This article provides a review of clinical manifestations, diagnostics criteria, natural evolution, pathogenesis, and treatment of these cutaneous manifestations.
Topics: Amyloidosis; Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Plasma Cells; Skin Diseases
PubMed: 35411042
DOI: 10.1038/s41408-022-00661-1 -
American Journal of Hematology Jul 2021Despite the benign nature of monoclonal gammopathy of undetermined significance (MGUS), mounting data are associating MGUS with the development of organ dysfunction,... (Review)
Review
Despite the benign nature of monoclonal gammopathy of undetermined significance (MGUS), mounting data are associating MGUS with the development of organ dysfunction, specifically monoclonal gammopathy of renal significance (MGRS) and monoclonal gammopathy of neurological significance (MGNS), which could be associated with substantial morbidity. Emerging evidence suggests that patients with MGRS and MGNS could benefit from treatments used for myeloma, Waldenström macroglobulinemia, or chronic lymphocytic leukemia, depending on the underlying pathology. However, the treatment of MGRS and MGNS is not standardized, and potentially effective therapies might not be reimbursed because these conditions do not formally meet the criteria for malignant processes. The present review aims at establishing standards for the evaluation and management of MGRS and MGNS, which can facilitate the diagnosis of and provide therapeutic options for treating practitioners and patients affected by these conditions. The careful design and execution of clinical trials for patients with MGRS and MGNS are positively encouraged.
Topics: Animals; Disease Management; Disease Progression; Humans; Kidney; Kidney Diseases; Monoclonal Gammopathy of Undetermined Significance; Nervous System; Nervous System Diseases
PubMed: 33709474
DOI: 10.1002/ajh.26155 -
Ugeskrift For Laeger Oct 2021Monoclonal gammopathies range from benign conditions to severe malignancies. A summary is given in this review. Overall, the prevalence is high; monoclonal gammopathies... (Review)
Review
Monoclonal gammopathies range from benign conditions to severe malignancies. A summary is given in this review. Overall, the prevalence is high; monoclonal gammopathies (MGUS) occur in > 3% of persons above 50 years of age. Approximately 400 new cases of multiple myeloma and 80 new cases of amyloid light-chain (AL) amyloidosis are diagnosed yearly in Denmark. MGUS is most often asymptomatic, but M-protein associated syndromes exist and should be considered when finding M-protein. Serum free light kappa and lambda chain analysis, CT, PET/CT and whole-body MRI have revolutionised diagnostics and monitoring of monoclonal gammopathies. New treatment modalities have improved outcome in multiple myeloma and AL amyloidosis.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Paraproteinemias; Positron Emission Tomography Computed Tomography
PubMed: 34709161
DOI: No ID Found