Bioavailability of Bioactive Compounds from Reconstituted Grapefruit Juice as Affected by the Obtention Process

[EN] Much attention has been paid to the health benefits of including fruits and vegetables in the diet. However, for the compounds responsible for this beneficial effect to be effective at the level of the human organism, they must be available for absorption after digestion. In this sense, in vivo studies are needed to demonstrate the bioavailability of these compounds and their physiological activity. In order to provide information in this regard, this study collects data on the levels of vitamin C (VC) and naringenin (NAG) in the blood serum of the 11 volunteer participants in this trial, before and after consuming two different grapefruit juices. The juices were prepared by rehydrating the grapefruit powder obtained by freeze-drying (FD) the fruit puree or by spray-drying (SD) the liquefied grapefruit. No significant differences (p > 0.05) neither by juice nor by participant were observed in any case. The mean relative increase of VC, NAG and the radical scavenging ability (RSA) in blood serum due to grapefruit juices intake was 12%, 28% and 26%, respectively. Just VC showed a positive and significant Pearson¿s correlation with RSA. The mean bioavailability of VC was quantified as 1.529 +- 0.002 mg VC/L serum per 100 mg of VC ingested.This research was funded by Spanish Ministerio de Economía y Competitividad, Project AGL 2012-39103.Camacho Vidal, MM.; Martínez-Lahuerta, JJ.; García Martínez, EM.; Igual Ramo, M.; Martínez-Navarrete, N. (2023). Bioavailability of Bioactive Compounds from Reconstituted Grapefruit Juice as Affected by the Obtention Process. Molecules. 28(7). https://doi.org/10.3390/molecules2807290428

Bioavailability of freeze-dried and spray-dried grapefruit juice vitamin C

[EN] An alternative as to offer higher stable and easy handling than fresh fruit is in powdered form, as long as the process used to obtain it ensures a high quality product. The objective of this study was to compare the bioavailability of the vitamin C of a juice prepared from powdered grapefruit obtained by freeze-drying and by spray-drying. A trial was conducted with 11 healthy volunteers. A relative increase of 1,4 – 25,8 % of blood serum vitamin C concentration was quantified after juices intake, with no significant differences (p>0.05) due to the process used to obtain the powder. KThe authors thank the Ministerio de Economía y Competitividad for the financial support given through the Project AGL 2012-39103.Camacho Vidal, MM.; Igual Ramo, M.; Martínez-Lahuerta, JJ.; Martínez Navarrete, N. (2018). Bioavailability of freeze-dried and spray-dried grapefruit juice vitamin C. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 819-826. https://doi.org/10.4995/IDS2018.2018.7478OCS81982

Economic feasibility of freeze-drying to obtain powdered fruit

[EN] Fruit is a highly valuable food whose consumption should be encouraged. In addition, it would be desirable to design processes and products to channel the surplus and take advantage of the post-harvest losses that limit its fresh marketing. Freeze-drying is a known industrial process that permits the obtaining of high quality products, despite having always been labeled as very expensive. In this study, the economic feasibility of freeze-drying to obtain powdered fruit has been proven, as it yields a product more than twice as cheap as when obtained by spray-drying, recognized for its low cost.The authors thank the Ministerio de Economía y Competitividad for the financial support given through the Project AGL 2012-39103.Camacho Vidal, MM.; Casanova, MÁ.; Fenollosa Ribera, ML.; Ribal Sanchis, FJ.; Martínez-Lahuerta, JJ.; Martínez Navarrete, N. (2018). Economic feasibility of freeze-drying to obtain powdered fruit. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 827-834. https://doi.org/10.4995/IDS2018.2018.7479OCS82783

Circulating tumor cells for the staging of patients with newly diagnosed transplant-eligible multiple myeloma

[Purpose]: Patients with multiple myeloma (MM) may show patchy bone marrow (BM) infiltration and extramedullary disease. Notwithstanding, quantification of plasma cells (PCs) continues to be performed in BM since the clinical translation of circulating tumor cells (CTCs) remains undefined. [Patients and methods]: CTCs were measured in peripheral blood (PB) of 374 patients with newly diagnosed MM enrolled in the GEM2012MENOS65 and GEM2014MAIN trials. Treatment included bortezomib, lenalidomide, and dexamethasone induction followed by autologous transplant, consolidation, and maintenance. Next-generation flow cytometry was used to evaluate CTCs in PB at diagnosis and measurable residual disease (MRD) in BM throughout treatment. [Results]: CTCs were detected in 92% (344 of 374) of patients with newly diagnosed MM. The correlation between the percentages of CTCs and BM PCs was modest. Increasing logarithmic percentages of CTCs were associated with inferior progression-free survival (PFS). A cutoff of 0.01% CTCs showed an independent prognostic value (hazard ratio: 2.02; 95% CI, 1.3 to 3.1; P = .001) in multivariable PFS analysis including the International Staging System, lactate dehydrogenase levels, and cytogenetics. The combination of the four prognostic factors significantly improved risk stratification. Outcomes according to the percentage of CTCs and depth of response to treatment showed that patients with undetectable CTCs had exceptional PFS regardless of complete remission and MRD status. In all other cases with detectable CTCs, only achieving MRD negativity (and not complete remission) demonstrated a statistically significant increase in PFS. [Conclusion]: Evaluation of CTCs in PB outperformed quantification of BM PCs. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible MM.Supported by grants from the Centro de Investigación Biomédica en Red—Área de Oncología—del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00400, and CB16/12/00284); Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI19/01451, PI20/00048, and PI21/01816); the Cancer Research UK (C355/A26819); FCAECC and AIRC under the Accelerator Award Program (EDITOR); the ISCIII and FEDER foundations (AC17/00101) together with FCAECC for iMMunocell Transcan-2; the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT/680200); the CRIS Cancer Foundation (PR_EX_2020-02), the Leukemia Lymphoma Society, the Black Swan Research Initiative of the International Myeloma Foundation; and the Riney Family Multiple Myeloma Research Program Fund

A multiparameter flow cytometry immunophenotypic algorithm for the identification of newly diagnosed symptomatic myeloma with an MGUS-like signature and long-term disease control

GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group: et al.Achieving complete remission (CR) in multiple myeloma (MM) translates into extended survival, but two subgroups of patients fall outside this paradigm: cases with unsustained CR, and patients that do not achieve CR but return into a monoclonal gammopathy of undetermined significance (MGUS)-like status with long-term survival. Here, we describe a novel automated flow cytometric classification focused on the analysis of the plasma-cell compartment to identify among newly diagnosed symptomatic MM patients (N=698) cases with a baseline MGUS-like profile, by comparing them to MGUS (N=497) patients and validating the classification model in 114 smoldering MM patients. Overall, 59 symptomatic MM patients (8%) showed an MGUS-like profile. Despite achieving similar CR rates after high-dose therapy/autologous stem cell transplantation vs other MM patients, MGUS-like cases had unprecedented longer time-to-progression (TTP) and overall survival (OS; ∼60% at 10 years; P<0.001). Importantly, MGUS-like MM patients failing to achieve CR showed similar TTP (P=0.81) and OS (P=0.24) vs cases attaining CR. This automated classification also identified MGUS patients with shorter TTP (P=0.001, hazard ratio: 5.53) and ultra-high-risk smoldering MM (median TTP, 15 months). In summary, we have developed a biomarker that identifies a subset of symptomatic MM patients with an occult MGUS-like signature and an excellent outcome, independently of the depth of response.Peer Reviewe

Reference Values to Assess Hemodilution and Warn of Potential False-Negative Minimal Residual Disease Results in Myeloma

This article belongs to the Special Issue Advances in Multiple Myeloma Research and Treatment.[Simple Summary] Although the majority of patients with myeloma who achieve undetectable minimal residual disease show prolonged survival, some of them relapse shortly afterwards. False-negative results due to hemodiluted bone marrow samples could explain this inconsistency, but there is no guidance on how to evaluate them. We analyzed three cell populations normally absent in peripheral blood in 1404 aspirates obtained in numerous disease settings and in 85 healthy adults. Pairwise comparisons according to age and treatment showed significant variability, thus suggesting that hemodilution should be preferably evaluated with references obtained after receiving identical regimens. Leveraging the minimal residual disease results from 118 patients, we showed that a comparison with age-matched healthy adults could also inform on potential hemodilution. Our study supports the routine assessment of bone marrow cellularity to evaluate hemodilution, using as reference values either treatment-specific or from healthy adults if the former are unavailable.[Abstract] Background: Whereas, in most patients with multiple myeloma (MM), achieving undetectable MRD anticipates a favorable outcome, some others relapse shortly afterwards. Although one obvious explanation for this inconsistency is the use of nonrepresentative marrow samples due to hemodilution, there is no guidance on how to evaluate this issue. Methods: Since B-cell precursors, mast cells and nucleated red blood cells are normally absent in peripheral blood, we analyzed them in 1404 bone marrow (BM) aspirates obtained in numerous disease settings and in 85 healthy adults (HA). Results: First, we confirmed the systematic detection of the three populations in HA, as well as the nonreduced numbers with aging. Pairwise comparisons between HA and MM patients grouped according to age and treatment showed significant variability, suggesting that hemodilution should be preferably evaluated with references obtained from patients treated with identical regimens. Leveraging the MRD results from 118 patients, we showed that a comparison with HA of similar age could also inform on potential hemodilution. Conclusions: Our study supports the routine assessment of BM cellularity to evaluate hemodilution, since reduced BM-specific cell types as compared to reference values (either treatment-specific or from HA if the former are unavailable) could indicate hemodilution and a false-negative MRD result.This study was supported by grants from the Centro de Investigación Biomédica en Red—Área de Oncología—del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00400, CB16/12/00233 and CB16/12/00284); Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria and co-financed by FEDER funds (FIS No. PI15/01956, PI15/02049, PI15/02062, PI18/01709, PI18/01673 and PI19/01451); the Cancer Research UK (C355/A26819), FCAECC and AIRC under the Accelerator Award Programme (EDITOR); the Black Swan Research Initiative of the International Myeloma Foundation and the European Research Council (ERC) 2015 Starting Grant (Contract 680200 MYELOMANEXT). This study was supported by the Riney Family Multiple Myeloma Research Program Fund

Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiplemyeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes werecompared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admittedat six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients weremale; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity wasmoderate-severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was requiredby 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasiveventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients,inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM athospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independentprognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifiespredictors of inpatient mortality among MM patients hospitalized with COVID-19

MM, SARS-CoV-2 infection, and inpatient mortality

There is limited information on the characteristics, pre-admission prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with coronavirus disease 2019 (COVID-19). This retrospective case series investigated characteristics and outcomes of 167 MM patients hospitalized with COVID-19 reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in Spain between March 1 and April 30, 2020. Outcomes were compared with a randomly selected contemporary cohort of 167 age-/sex-matched non-cancer patients with COVID-19 admitted at 6 participating hospitals. Common demographic, clinical, laboratory, treatment, and outcome variables were collected; specific disease status and treatment data were collected for MM patients. Among the MM and non-cancer patients, median age was 71 years and 57% of patients were male in each series, and 75% and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77% and 89% of patients and critical in 8% and 4%, respectively. Supplemental oxygen was required by 47% and 55% of MM and non-cancer patients, respectively, and 21%/9% vs 8%/6% required non-invasive/invasive ventilation. Inpatient mortality was 34% and 23% in MM and non-cancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors of inpatient mortality on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.This study was supported by PETHEMA FoundationN

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

Spanish Myeloma Group (GEM) and Grupo Castellano-Leones de Gammapatias Monoclonales, cooperative study groups: et al.Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapsefree survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8 + T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and recovery of B-cell production and homing, suggesting improved immune surveillance.This work was supported by the Cooperative Research Thematic Network (RTICCs; RD06/0020/0006 and G03/136), Instituto de Salud Carlos III/ Subdirección General de Investigación Sanitaria (FIS: PI060339; 06/1354; 02/0905; 01/0089/01-02; PS09/01897/01370) and Consejeria de Educacion (GR37) and Consejería de Sanidad, Junta de Castilla y León, Valladolid, Spain (557/A/10). The authors also thank the Fundación Carolina-BBVA for supporting and promoting the exchange of medical researchers from Latin America to Spain.Peer Reviewe

Validation of the International Myeloma Working Group standard response criteria in the PETHEMA/GEM2012MENOS65 study: are these times of change?

Induction and consolidation based on proteasome inhibitors, immunomodulatory drugs, and corticoids integrated with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT), are showing complete response (CR) rates >50% in multiple myeloma (MM).1-3 The addition of anti-CD38 monoclonal antibodies may increase these unprecedented CR rates.4-6 When more than half of transplant-eligible patients with MM achieve CR with frontline therapy, it is reasonable to ask, what other tests are clinically relevant after negative immunofixation. The achievement of deep responses with modern therapy led the International Myeloma Working Group (IMWG) to propose new guidelines that included definitions of negative minimal residual disease (MRD) for standard response criteria.7 Indeed, recent studies have reported nearly 50% MRD− rates,5,8,9 and, more importantly, the prognostic value of MRD criteria was validated in clinical trials8,10-12 and routine practice...