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American Heart Journal Plus :... May 2024Patients with carpal tunnel syndrome (CTS) show manifestations of arterial abnormalities, including carotid intimal thickening and increased vascular stiffness. As...
STUDY OBJECTIVES
Patients with carpal tunnel syndrome (CTS) show manifestations of arterial abnormalities, including carotid intimal thickening and increased vascular stiffness. As carpal tunnel syndrome is associated with amyloidosis, we hypothesized that previously observed abnormalities can largely be related with concomitant amyloidosis rather than CTS itself.
DESIGN
Prospective observational study.
SETTING
Medeniyet University Goztepe Hospital.
PARTICIPANTS
61 patients with CTS (of whom 32 had biopsy-proven amyloidosis) and 36 healthy controls.
INTERVENTIONS
Subjects underwent ultrasound examinations for the measurement of coronary flow velocity reserve (CFVR), flow-mediated vasodilatation (FMD) and carotid intimal-media thickness (CIMT).
MAIN OUTCOME MEASURES
Comparison of CFVR, FMD and CIMT in CTS patients with or without amyloidosis.
RESULTS
Patients with either CTS or CTS with concomitant amyloidosis (CTS-A) had significantly lower FMD (9.7 % ± 4.0 % in CTS and 10.3 % ± 4.6 % in CTS-A groups, < 0.05 for both) and CFVR (2.4 (2.1-2.8) in CTS and 1.8 (1.6-2.1) in CTS-A groups, < 0.001 for both) as compared to controls, while CIMT was only increased in CTS-A group (0.70 (0.60-0.80), p < 0.001). The reduction in CFVR was solely related to an increased basal flow velocity in CTS patients while there was also a reduced hyperemic flow velocity in patients with CTS-A.
CONCLUSION
Most arterial phenomena in CTS patients could be attributable to concomitant amyloidosis, although endothelial dysfunction was present even in patients with CTS without amyloidosis.
PubMed: 38655035
DOI: 10.1016/j.ahjo.2024.100393 -
Current Oncology (Toronto, Ont.) Oct 2023While immunotherapies, such as CAR T therapy and bi-specific antibodies, have revolutionized the treatment of multiple myeloma (MM), patients with AL amyloidosis have...
Anti-B Cell Maturation Antigen Chimeric Antigen Receptor T Cell Therapy for the Treatment of AL Amyloidosis and Concurrent Relapsed/Refractory Multiple Myeloma: Preliminary Efficacy and Safety.
While immunotherapies, such as CAR T therapy and bi-specific antibodies, have revolutionized the treatment of multiple myeloma (MM), patients with AL amyloidosis have been excluded from trials with these agents due to concerns of underlying autonomic, cardiac, and renal dysfunction, leading to potentially fatal toxicities from these therapies. In this communication, we described the outcomes of two patients with AL amyloidosis and concurrent MM with underlying cardiac and/or renal dysfunction who underwent anti-BCMA CAR T cell therapy with ide-cel or cilta-cel, received cytokine release syndrome prophylaxis, and tolerated therapy well with manageable toxicities and achieved a MRD-negative state. We described the preliminary efficacy and safety of CAR T in patients with AL amyloidosis and highlighted the importance of patient selection and medical optimization of cardiac and renal function prior to CAR T.
Topics: Humans; Multiple Myeloma; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Immunoglobulin Light-chain Amyloidosis; B-Cell Maturation Antigen; Cell- and Tissue-Based Therapy; Kidney Diseases
PubMed: 37999117
DOI: 10.3390/curroncol30110697 -
Cancers Sep 2023There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the...
BACKGROUND
There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs.
RESULTS
165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger ( = 0.05) and more frequently had a prior AutoHCT ( = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32-14.21, < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19-0.95, = 0.037) predicted longer OS.
CONCLUSIONS
With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.
PubMed: 37686635
DOI: 10.3390/cancers15174359 -
Haematologica Jan 2024Treatment of patients with Mayo stage IIIb light chain (AL) amyloidosis is still challenging, and the prognosis remains very poor. Mayo stage IIIb patients were excluded...
Treatment of patients with Mayo stage IIIb light chain (AL) amyloidosis is still challenging, and the prognosis remains very poor. Mayo stage IIIb patients were excluded from the pivotal trial leading to the approval of daratumumab in combination with bortezomib-cyclophosphamide-dexamethasone. This retrospective, multicenter study evaluates the addition of daratumumab to first-line therapy in patients with newly diagnosed stage IIIb AL amyloidosis. In total, data from 119 consecutive patients were analyzed, 27 patients received an upfront treatment including daratumumab, 63 a bortezomibbased regimen without daratumumab, eight received therapies other than daratumumab or bortezomib and 21 pretreated patients or deceased prior to treatment were excluded. In the daratumumab group, median overall survival was not reached after a median follow-up time of 14.5 months, while it was significantly worse in the bortezomib- and the otherwise treated group (6.6 and 2.2 months, respectively) (P=0.002). Overall hematologic response rate at 2 and 6 months was better in the daratumumab group compared to the bortezomib group (59% vs. 37%, P=0.12, 67% vs. 41%, P=0.04, respectively). Landmark survival analyses revealed a significantly improved overall survival in patients with partial hematologic response or better, compared to non-responders. Cardiac response at 6 months was 46%, 21%, 0% in the daratumumab-, bortezomib- and otherwise treated groups, respectively (P=0.04). A landmark survival analysis revealed markedly improved overall survival in patients with cardiac very good partial response vs. cardiac non-responders (P=0.002). This study demonstrates for the first time the superiority of an upfront treatment with daratumumab over standard-of-care in stage IIIb AL amyloidosis.
Topics: Humans; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Immunoglobulin Light-chain Amyloidosis; Retrospective Studies; Treatment Outcome
PubMed: 37439344
DOI: 10.3324/haematol.2023.283325 -
Blood Cancer Journal Nov 2023
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Immunoglobulin Light Chains; Antibodies, Bispecific; Antineoplastic Agents
PubMed: 38012151
DOI: 10.1038/s41408-023-00950-3 -
Kidney International Reports Jan 2024Although serum amyloid A (AA) amyloid may occasionally show nonspecific staining by immunofluorescence (IF), the correct diagnosis can usually be determined by...
INTRODUCTION
Although serum amyloid A (AA) amyloid may occasionally show nonspecific staining by immunofluorescence (IF), the correct diagnosis can usually be determined by integrating pathologic features and clinical scenario, and using AA amyloid immunohistochemistry (IHC) and/or mass spectrometry. A recent mass spectrometry-based study described false-positive Ig IF staining in a subset of AA amyloid cases.
METHODS
We sought to delineate clinicopathologic features of AA amyloid with Ig-dominant staining by using a retrospective review.
RESULTS
AA amyloid with Ig-dominant staining was identified in 10 patients from 5 institutions, representing 1.2% to 4% of AA amyloid kidney biopsies. Evidence of a monoclonal protein was documented in 0% to 2.7% of patients with AA amyloid screened for inclusion, but 30% of those with Ig-dominant staining. The patient population had equal sex distribution and presented at median age of 68.5 years with nephrotic proteinuria and kidney impairment. Etiologies of AA amyloid included injection drug use (30%), autoimmune disease (20%), and chronic infection (10%); 40% had no identified clinical association. On biopsy, heavy chain (co)dominant staining by IF (in 80%), discordant distribution in Ig staining (in 20%), tubulointerstitial nephritis (in 30%), and/or crescents (in 10%) were present. Two of 3 patients with paraproteinemia had concordant heavy and/or light chain dominant staining within the AA amyloid. Two cases were initially misdiagnosed as Ig-associated amyloidosis.
CONCLUSION
We describe the morphologic spectrum of AA amyloidosis with Ig-dominant staining which may have clinical, laboratory, and pathologic overlap with amyloid light chain (AL), amyloid heavy chain, and heavy and light chain (AHL) amyloidosis.
PubMed: 38312779
DOI: 10.1016/j.ekir.2023.10.005 -
Heart Failure Reviews Sep 2023Feature-tracking cardiac magnetic resonance (FT-CMR), with the ability to quantify myocardial deformation, has a unique role in the evaluation of subclinical myocardial... (Review)
Review
Feature-tracking cardiac magnetic resonance (FT-CMR), with the ability to quantify myocardial deformation, has a unique role in the evaluation of subclinical myocardial abnormalities. This review aimed to evaluate the clinical use of cardiac FT-CMR-based myocardial strain in patients with various systemic diseases with cardiac involvement, such as hypertension, diabetes, cancer-therapy-related toxicities, amyloidosis, systemic scleroderma, myopathies, rheumatoid arthritis, thalassemia major, and coronavirus disease 2019 (COVID-19). We concluded that FT-CMR-derived strain can improve the accuracy of risk stratification and predict cardiac outcomes in patients with systemic diseases prior to symptomatic cardiac dysfunction. Furthermore, FT-CMR is particularly useful for patients with diseases or conditions which are associated with subtle myocardial dysfunction that may not be accurately detected with traditional methods. Compared to patients with cardiovascular diseases, patients with systemic diseases are less likely to undergo regular cardiovascular imaging to detect cardiac defects, whereas cardiac involvement in these patients can lead to major adverse outcomes; hence, the importance of cardiac imaging modalities might be underestimated in this group of patients. In this review, we gathered currently available data on the newly introduced role of FT-CMR in the diagnosis and prognosis of various systemic conditions. Further research is needed to define reference values and establish the role of this sensitive imaging modality, as a robust marker in predicting outcomes across a wide spectrum of patients.
Topics: Humans; Magnetic Resonance Imaging, Cine; Ventricular Function, Left; Predictive Value of Tests; COVID-19; Magnetic Resonance Imaging; Reproducibility of Results
PubMed: 37191926
DOI: 10.1007/s10741-023-10321-6 -
Hellenic Journal of Cardiology : HJC =... 2023Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease associated with high mortality rates and the patient journey is characterized by increased... (Review)
Review
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease associated with high mortality rates and the patient journey is characterized by increased complexities. Accurate and timely diagnosis and prompt initiation of disease-modifying treatment constitute the contemporary unmet need in ATTR-CM. ATTR-CM diagnosis is characterized by considerable delays and high rates of misdiagnosis. The majority of patients present themselves to primary care physicians, internists, and cardiologists, and many have undergone repeated medical evaluations before an accurate diagnosis has been made. The disease is diagnosed mainly after the development of heart failure symptoms, reflecting a long course of missed opportunities before diagnosis and disease-modifying treatment initiation. Early referral to experienced centers ensures prompt diagnosis and therapy. Early diagnosis, better care coordination, acceleration of digital transformation and reference networks, encouragement of patient engagement, and implementation of rare disease registries are the key pillars to improve the ATTR-CM patient pathway and achieve important benefits in ATTR-CM outcomes.
Topics: Humans; Amyloid Neuropathies, Familial; Greece; Heart Failure; Heart Diseases; Early Diagnosis; Cardiomyopathies
PubMed: 37201632
DOI: 10.1016/j.hjc.2023.05.004 -
Endoscopic Manifestations and Clinical Characteristics of Localized Gastric Light-Chain Amyloidosis.Acta Medica Okayama Oct 2023To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine...
To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant.
Topics: Male; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Retrospective Studies; Amyloidosis; Stomach Diseases
PubMed: 37899266
DOI: 10.18926/AMO/65978