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Minimal Residual Disease-Adapted Therapy in Multiple Myeloma: Current Evidence and Opinions.

Purpose of reviewMultiple myeloma (MM) is a biologically heterogeneous malignancy with relatively uniform treatment paradigms. This review aims to assess the growing role of Minimal Residual Disease (MRD) assessment in facilitating response-adapted therapeutic decision making to individualize therapy in MM.Recent findingsMRD has been repeatedly demonstrated to provide strong prognostic information, superseding traditional IMWG response criteria. The use of MRD to modulate therapy remains controversial. Here, we review the existing landscape of MRD-adapted trial designs in both induction/consol

How we manage smoldering multiple myeloma.

Smoldering myeloma (SMM) is an asymptomatic stage characterized by bone marrow plasma cells infiltration between 10-60% in absence of myeloma-defining events and organ damage. Until the revision of criteria of MM to require treatment, two main prognostic models, not overlapping each other, were proposed and used differently in Europe and in US. Novel manageable drugs, like lenalidomide and monoclonal antibodies, with high efficacy and limited toxicity, improvement in imaging and prognostication, challenge physicians to offer early treatment to highrisk SMM. Taking advantage from the debates of

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… genes that can predict high risk of progression from smoldering to symptomatic MM. 61 However, these techniques are note reproducible in all centers, require a specific expertise, and are burdened with technical issue such as the necessity to enrich neoplastic plasma cells and to avoid bone marrow hemodilution …

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration.

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow-based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy-based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while othe

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… Furthermore, NGF MRD also provides information about the quality of the BM sample and the potential presence of hemodilution, which is critical for early identification of false-negative MRD results ( 23, 26, 27 ). …

Monitoring Minimal Residual Disease in Patients with Multiple Myeloma by Targeted Tracking Serum M-Protein Using Mass Spectrometry (EasyM).

PurposeWe investigated both the clinical utilities and the prognostic impacts of the clonotypic peptide mass spectrometry (MS)-EasyM, a blood-based minimal residual disease (MRD) monitoring protocol in multiple myeloma.Experimental designA total of 447 sequential serum samples from 56 patients with multiple myeloma were analyzed using EasyM. Patient-specific M-protein peptides were sequenced from diagnostic samples; sequential samples were quantified by EasyM to monitor the M-protein. The performance of EasyM was compared with serum immunofixation electrophoresis (IFE), bone marrow multiparame

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… However, these methods require costly and painful bone marrow aspiration, limiting their utility for repeated sampling, and are subject to the risk of false-negative results due to non-representative sampling of focally-distributed plasma cells and hemodilution ( 20 ). …

Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel.

Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on high-dose radi

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… Multiparametric flow cytometry uses a standard set of monoclonal PC-associated markers, is quantitative, includes an internal quality control of the sample cellularity and hemodilution, and is applicable for virtually every patient. …

Obesity and Cancer: Mechanisms, Epidemiological Evidence, and Potential Risk Reduction.

Obesity promotes carcinogenesis through interlocking metabolic, inflammatory, immune, and hormonal pathways. We narratively synthesize recent meta-analyses and selected cohort studies that examine adiposity-principally body mass index (BMI) and waist circumference-in relation to cancer incidence. Across the 13 cancers designated by the U.S. National Cancer Institute as obesity-associated, risk elevations are generally consistent, though magnitudes vary by histology (e.g., esophageal adenocarcinoma vs. squamous cell carcinoma), anatomic subsite (gastric cardia vs. non-cardia), sex or menopausal

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… Ramadani FG Perdana NR Ringoringo DR 2024 Body mass index, obesity and risk of prostate cancer: a systematic review and meta-analysis Cent European J Urol 77 176 88 10.5173/ceju.2023.162 PMC11428363 39345322 73 Grubb RL Black A Izmirlian G Hickey TP Pinsky PF Mabie JE 2009 Serum prostate-specific antigen hemodilution …

Risk and Response-Adapted Treatment in Multiple Myeloma.

Myeloma therapeutic strategies have been adapted to patients' age and comorbidities for a long time. However, although cytogenetics and clinical presentations (plasmablastic cytology; extramedullary disease) are major prognostic factors, until recently, all patients received the same treatment whatever their initial risk. No strong evidence allows us to use a personalized treatment according to one cytogenetic abnormality in newly diagnosed myeloma. Retrospective studies showed a benefit of a double autologous transplant in high-risk cytogenetics according to the International Myeloma Working

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… For instance, hemodilution can lead to an underestimate of residual MM cells and false-negative results. Furthermore, MM presents a spatial heterogeneity with patchy bone marrow infiltration and potential extramedullary disease. …

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that govern the expression of genes responsible for energy metabolism, cellular development, and differentiation. Their crucial biological roles dictate the significance of PPAR-targeting synthetic ligands in medical research and drug discovery. Clinical implications of PPAR agonists span across a wide range of health conditions, including metabolic diseases, chronic inflammatory diseases, infections, autoimmune diseases, neurological and psychiatric disorders, and malignancies. In this review we aim to consolidate exist

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… Improved glycemic control and lipid profile ▪ Increased serum creatinine dose-dependently | [ 58 ] Aleglitazar | II (40) | ▪ Improved whole-body insulin sensitivity, hepatic insulin resistance index, and total glucose disposal | [ 59 ] II (332) | ▪ Reduced HbA1c dose-dependently ▪ Incidence of edema, hemodilution … effect on lowering CVD risk ▪ Induced side effects like gastrointestinal hemorrhages and renal dysfunction | [ 78 ] III-terminated (1999) | ▪ Reduced HbA1c and blood lipids ▪ Increased incidence of hypoglycemia and muscular events | [ 79 ] II (332) | ▪ Lowered HbA1c dose-dependently ▪ Caused edema, hemodilution …

Recent advances in use of fresh frozen plasma, cryoprecipitate, immunoglobulins, and clotting factors for transfusion support in patients with hematologic disease.

Hematologic diseases include a broad range of acquired and congenital disorders, many of which affect plasma proteins that control hemostasis and immune responses. Therapeutic interventions for these disorders include transfusion of plasma, cryoprecipitate, immunoglobulins, or convalescent plasma-containing therapeutic antibodies from patients recovering from infectious diseases, as well as concentrated pro- or anticoagulant factors. This review will focus on recent advances in the uses of plasma and its derivatives for patients with acquired and congenital hematologic disorders.

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… However, it is highly susceptible to hemodilution from fluid resuscitation and blood loss, both of which are common in the setting of massive transfusion. It is the earliest clotting factor to become depleted in hemorrhage and thus is targeted for replacement in such patients [55] . …

Sepsis in multimorbidity: a domain-based framework for systemic vulnerability and precision care.

Sepsis is a leading cause of morbidity and mortality, amplified by multimorbidity. This narrative review synthesizes epidemiological, pathophysiological, and immunological evidence to show how prevalent conditions-type 2 diabetes and obesity, heart failure and cerebrovascular disease, COPD, chronic kidney disease, cancer/HIV, and severe mental illness-reshape sepsis biology and outcomes. Convergent mechanisms include low-grade inflammation, impaired innate and adaptive immunity, endothelial injury with immunothrombosis/NETosis, barrier disruption with dysbiosis, and neuroendocrine maladaptatio

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… recurrent infections) | ↔, ↓ variable | ARDS risk, challenging ventilation; chronic colonization and macrophage dysfunction CKD/HFrEF | Similar peak; prolonged endothelial inflammation if congestion | ↑ with slower decline under volume overload | ↓ with slow recovery | ↓ mild; slow recovery (uremia, hemodilution …

Heart Failure in Older Patients: An Update.

Heart failure (HF) is a clinical syndrome with high incidence and prevalence and high morbidity and death rate, even in the short term, representing a serious public health issue, mainly in older people. It is a growing cause for hospital admission in this age group, being frequently associated with several comorbidities, further aggravating the disease's course. Moreover, older HF patients are usually affected by clinical conditions, like frailty, malnutrition, and cachexia, which significantly impact the overall management of HF and need to be properly identified and treated. Diagnosing and

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… In addition, laboratory exams may reveal peculiar findings in elderly HF patients, as routine tests often show reduced hemoglobin (Hb) levels and impaired serum sodium levels, both in term of hyponatremia, due to hemodilution by fluid retention-congestion or loop-diuretics therapy, and of hypernatremia …

Lipocalin 2-not only a biomarker: a study of current literature and systematic findings of ongoing clinical trials.

Lipocalin 2 (Lcn2), also known as neutrophil gelatinase-associated lipocalin, is an innate immune protein encoded by the LCN2 gene. In this study, we investigated various roles and functions of Lcn2 characterized in a systems-based format and evaluated its therapeutic potentials and clinical relevance for diagnosis and prognosis. An additional systematic presentation was presented for 70 ongoing clinical trials utilizing Lcn2 in the diagnostic and prognostic setting as a key outcome measure. With trials being conducted through December 2030, Lcn2 will become all the more relevant given its ass

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… .; performance of urinary NGAL; performance of Doppler echography NCT05349292 | Acute Normovolemic Hemodilution on Urine Neutrophil Gelatinase-associated Lipocalin Levels | Not yet recruiting | Acute kidney injury | Other: ANH | Urinary biomarkers NGAL and KIM-1; AKI by KDIGO criteria NCT05374759 | NGAL …

37th International Symposium on Intensive Care and Emergency Medicine (part 2 of 3) : Brussels, Belgium. 21-24 March 2017

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COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches.

Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated with more severe outcomes among patients living with haematological disorders and malignancies (HDMs). Because individuals with moderate to severe immunodeficiency are likely to undergo persistent infections, shed virus particles for prolonged periods, and lack an inflammatory or abortive phase, this represents an overall risk of morbidity and mortality from COVID-19. In cases suffering from HDMs, further investigation is needed to achi

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… Hemodilution with interplacental transfer of vitamin B12 further contributes to the physiological reduction of vitamin B12 levels. In addition, pancytopenia is a rare manifestation of some viral infections, including the novel COVID-19 [ 109 ]. …

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: children and adolescents.

The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Children and Adolescents was developed by dietitians, physicians, and pediatric hematologists from 10 Brazilian reference centers in hematopoietic stem cell transplantation. The aim was to emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to patient´s nutritional assessment. This consensus is intended to improve and standardize nutrition therapy during hematopoietic stem cell transplantation. The consensus was approved by the Brazilian

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… 5-10 Severe depletion: <5 Transferrin, mg/dL | Normal: 200-400 | Transporting certain nutrients, particularly iron Mild depletion: 150-120 Moderate depletion: 100-150 Severe depletion: <100 However, it is important to bear in mind that these proteins have a limited role in severe patients, due to hemodilution …

Abstract Book for the 3rd European Myeloma Network Meeting

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The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases.

PurposeIn 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121-167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper.MethodsA literature search mainly focusing on the role of the glycocalyx in the

Haematological Diseases in the Tropics

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36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

P001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP efflux R. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. Ellis P002 - Lower serum immunoglobulin G2 level does not predispose to severe flu. J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez Gallego P003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsis F. Esen

Наномедицина - мощная терапия CAR-T для множественной миеломы: к программируемой, долговременной и точной иммунотерапии.

Множественная миелома (ММ) по-прежнему является трудновыполнимой гематологией. Несмотря на то, что терапия против созревания клеток B (BCMA), ориентированная на химерик антигенный рецептор Т-клектор (CAR-T), существенно углубила клиническую реакцию у пациентов с рецидивом/переносом MM, ее более широкое клиническое применение по-прежнему сдерживается рецидивом после лечения, недостаточной устойчивостью реакции, длительными сроками производства и ограниченной доступностью. Растущие данные свидетельствуют о том, что рецидив после лечения CAR-T в MM происходит не из одного механизма, а из конверге