0000000000025819
AUTHOR
Evangelos Terpos
The Spectrum of Ocular Manifestations in Patients with Waldenström's Macroglobulinemia.
Purpose: To investigate the ocular manifestations in 91 Waldenstrom's macroglobulinemia (WM) patients.Methods: Retrospective, cross-sectional, observational analysis.Results: Ocular impairments, detected in 19 patients, included flame-shaped hemorrhages, venous sausaging, papilledema, macular detachments, or central retinal vein occlusion in 16 patients; paraproteinemic keratopathy in 2; and a CANOMAD syndrome in 1. Best-corrected visual acuity was ≥0.5 logMAR units in 11 of 38 eyes. Intraocular pressure was increased in seven eyes. Genetic analysis in seven patients showed a mutation in the MYD88 gene in six patients and a nonsense mutation in the CXCR4 gene in five patients. Plasmapheresi…
Molecular mechanisms of carfilzomib-induced cardiotoxicity in mice and the emerging cardioprotective role of metformin
AbstractCarfilzomib (Cfz), an irreversible proteasome inhibitor licensed for relapsed/refractory myeloma, is associated with cardiotoxicity in humans. We sought to establish the optimal protocol of Cfz-induced cardiac dysfunction, to investigate the underlying molecular-signaling and, based on the findings, to evaluate the cardioprotective potency of metformin (Met). Mice were randomized into protocols 1 and 2 (control and Cfz for 1 and 2 consecutive days, respectively); protocols 3 and 4 (control and alternate doses of Cfz for 6 and 14 days, respectively); protocols 5A and 5B (control and Cfz, intermittent doses on days 0, 1 [5A] and 0, 1, 7, and 8 [5B] for 13 days); protocols 6A and 6B (p…
CYP2C8 gene polymorphism and bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma
Osteonecrosis of the jaw is an uncommon but potentially serious complication of bisphosphonate therapy in multiple myeloma. Previous studies showed that the presence of one or two minor alleles of the cytochrome P450, subfamily 2C polypeptide 8 gene (CYP2C8) polymorphism rs1934951 was an independent prognostic marker associated with development of osteonecrosis of the jaw in multiple myeloma patients treated with bisphosphonates. The aim of this study was to validate the frequency of SNP rs193451 in 79 patients with multiple myeloma. In 9 (22%) patients developing osteonecrosis of the jaw, a heterozygous genotype was found, in contrast with those who did not develop osteonecrosis of the jaw…
Metformin Restores AMPK Alpha-Mediated Autophagy and Prevents Carfilzomib-Induced Cardiotoxicity In Vivo
Abstract Introduction: Carfilzomib (Cfz) significantly prolongs progression-free survival in relapsed or refractory multiple myeloma patients, as highlighted in the ENDEAVOR trial. However, Cfz has high incidences of cardiotoxicity and heart failure, leading to treatment cessation. Thus, there is an imperative need for preventive therapies. The study aimed to i) establish an in vivo Cfz cardiotoxicity protocol, ii) investigate the molecular mechanism, identify molecular targets and iii) based on initial results, investigate the potential protective effect and mechanism of Metformin (Met). Methods: Male, C57BL/6 mice, were randomized in groups as following: Acute protocol (6 days): Control (…
Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib
Background: Carfilzomib&rsquo
Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study.
© 2018 The Authors.
Longitudinal Immunogenomic Profiling of Tumor and Immune Cells for Minimally-Invasive Monitoring of Smoldering Multiple Myeloma (SMM): The Immunocell Study
Background: Although great strides were made in the management of MM, our best chances to eradicate this malignancy may lie in preventing its progression.Most current models to predict risk of transformation in SMM are commonly established at diagnosis and not reevaluated over time, because some parameters such as tumor burden or genetic abnormalities require invasive bone marrow (BM) aspirates. It could be hypothesized that periodic monitoring of tumor biomarkers is needed to improve risk-stratification of SMM patients, and so would be new minimally-invasive methods that can replace those performed in BM samples. Such methods should also monitor immune profiles, to identify patients with s…
Circulating tumor and immune cells for minimally invasive risk stratification of smoldering multiple myeloma
Abstract Purpose: Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under- and overtreatment. We hypothesized that replacing bone marrow (BM) plasma cells (PC) for circulating tumor cells (CTC), and adding immune biomarkers in peripheral blood (PB) for the identification of patients at risk of progression due to lost immune surveillance, could improve the International Myeloma Working Group 20/2/20 model. Experimental Design: We report the outcomes of 150 patients with SMM enrolled in the iMMunocell study, in which serial assessment of tumor and immune cells in PB was performed every 6 months for a period of 3 years since enrollment. Resul…
FlowCT for the analysis of large immunophenotypic data sets and biomarker discovery in cancer immunology
Key Points FlowCT is a new computational workspace for unveiling cellular diversity and objectively identifying biomarkers in large immune monitoring studies.FlowCT identified T-cell biomarkers predictive of malignant transformation and survival in SMM and active MM data sets.
Treatment of multiple myeloma-related bone disease
In this Policy Review, the Bone Working Group of the International Myeloma Working Group updates its clinical practice recommendations for the management of multiple myeloma-related bone disease. After assessing the available literature and grading recommendations using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method, experts from the working group recommend zoledronic acid as the preferred bone-targeted agent for patients with newly diagnosed multiple myeloma, with or without multiple myeloma-related bone disease. Once patients achieve a very good partial response or better, after receiving monthly zoledronic acid for at least 12 months, the treating…
Synergistic Effect of Carfilzomib and Metformin in Vascular Plasticity; The Emerging Role of Autophagy
Introduction: Carfilzomib (Cfz) correlates with a risk of reversible cardiotoxicity in 5-10% of multiple myeloma (MM) patients. We have recently shown that metformin (Met) has a prophylactic role against the Cfz-induced cardiotoxicity in vivo, through activation of AMPKα signaling (Blood 2019;133:710-23). However, the impact of Cfz on vascular function is obscure. Therefore, we sought to investigate: i) the acute, ii) the sub-chronic effect of Cfz on the vascular reactivity, iii) the effect of metformin co-administration on the vascular phenotype and iv) the impact of Cfz and Met co-administration on aged Human Aortic Smooth Muscle Cells (HAoSMCs). Methods: Forty male C57Bl/6 mice were assi…
Early prediction of COVID-19 outcome using artificial intelligence techniques and only five laboratory indices
We aimed to develop a prediction model for intensive care unit (ICU) hospitalization of Coronavirus disease-19 (COVID-19) patients using artificial neural networks (ANN). We assessed 25 laboratory parameters at first from 248 consecutive adult COVID-19 patients for database creation, training, and development of ANN models. We developed a new alpha-index to assess association of each parameter with outcome. We used 166 records for training of computational simulations (training), 41 for documentation of computational simulations (validation), and 41 for reliability check of computational simulations (testing). The first five laboratory indices ranked by importance were Neutrophil-to-lymphoc…