Plant-derived biostimulant as priming agents enhanced antioxidant and nutritive properties in brassicaceous microgreens.

BACKGROUND: Microgreens constitute dietary sources of bioactive compounds imparting numerous health benefits and enhancing sensory experience. They can be successfully cultivated in soilless systems where biostimulants can be easily integrated as seed-priming and post-germination agents improving the sustainability of a crop's final production. Compared to an untreated control, three priming agents (a commercial legume-derived protein hydrolysate (A250), a novel protein hydrolysate derived from peanut biomass (H250) and hydropriming (H2O)) were applied to Komatsuna and Mibuna seeds grown as microgreens and compared for their effects on yield parameters, mineral composition, ABTS and FRAP antioxidant capacity, carotenoid concentration and phenolic compounds. RESULTS: Significant effects of the main experimental factors and their interactions were identified on antioxidant capacity. Compared to the control and hydropriming, the highest ABTS and FRAP values were observed in Mibuna with the A250 and H250 treatments, respectively. Additionally, the H250 treatment increased the total concentrations of phenolic acid derivatives and flavonoid derivatives in Mibuna and Komatsuna, in tune with the levels of total flavonoids. Concerning mineral composition, the highest concentrations in both species were those of phosphorus and nitrate. CONCLUSION: These results highlight the potential of select plant-based biostimulants as priming agents to enhance the antioxidant capacity, nutrient content and bioactive compound content, thus further increasing their functional and nutritive quality. In the light of this, the possibility of reducing the application of fertilizers by promoting a green transition for the intensive production of microgreens could subsequently be evaluated. © 2024 Society of Chemical Industry.

Iodine-Biofortified Microgreens as High Nutraceutical Value Component of Space Mission Crew Diets and Candidate for Extraterrestrial Cultivation.

The success of Space missions and the efficacy of colonizing extraterrestrial environments depends on ensuring adequate nutrition for astronauts and autonomy from terrestrial resources. A balanced diet incorporating premium quality fresh foods, such as microgreens, is essential to the mental and physical well-being of mission crews. To improve the nutritional intake of astronaut meals, two levels of potassium iodide (KI; 4 µM and 8 µM) and an untreated control were assessed for iodine (I) biofortification, and overall nutraceutical profile of four microgreens: tatsoi (Brassica rapa L. subsp. narinosa), coriander (Coriandrum sativum L.), green basil, and purple basil (Ocimum basilicum L.). A dose-dependent increase in I was observed at 8 µM for all species, reaching concentrations of 200.73, 118.17, 93.97, and 82.70 mg kg-1 of dry weight, in tatsoi, coriander, purple basil, and green basil, respectively. Across species, I biofortification slightly reduced fresh yield (-7.98%) while increasing the antioxidant activity (ABTS, FRAP, and DPPH). LC-MS/MS Q extractive orbitrap analysis detected 10 phenolic acids and 23 flavonoids among microgreen species. The total concentration of phenolic acids increased (+28.5%) in purple basil at 8 µM KI, while total flavonoids in coriander increased by 23.22% and 34.46% in response to 4 and 8 µM KI, respectively. Both doses of KI increased the concentration of total polyphenols in all species by an average of 17.45%, compared to the control.

Frequency and type of domestic injuries among children during COVID-19 lockdown: what changes from the past? An Italian multicentre cohort study.

Accidents are the main cause of injury in children, more than half events happen at home. Aims of this study were to assess if SARS-CoV-2 lockdown influence emergency department (ED) visits due to children domestic accident (DAs) and to identify factors associated with hospitalization. This was a multicentre, observational, and retrospective cohort study involving 16 EDs in Italy and enrolling children (3-13 years) receiving a visit in ED during March-June 2019 and March-June 2020. Risk factors for hospitalization were identified by logistic regression models. In total, 8860 ED visits due to domestic accidents in children occurred before (4380) and during (4480) lockdown, with a mean incidence of DA of 5.6% in 2019 and 17.9% in 2020 (p < 0.001) (IRR: 3.16; p < 0.001). The risk of hospitalization was influenced by the type of occurred accident, with fourfold higher for poisoning and twofold lower risk for stab-wound ones. In addition, a higher risk was reported for lockdown period vs 2019 (OR: 1.9; p < 0.001), males (OR: 1.4; p < 0.001), and it increased with age (OR: 1.1; p < 0.001).    Conclusions: The main limitation of this study is the retrospective collection of data, available only for patients who presented at the hospital. This does highlight possible differences in the total number of incidents that truly occurred. In any case, the COVID-19 lockdown had a high impact on the frequency of DAs and on hospitalization. A public health campaign aimed at caregivers would be necessary to minimize possible risks at home. What is Known: • In Italy, domestic accidents are the second leading cause of paediatric mortality after cancer. • During the first SARS-CoV-2 lockdown in 2020, a sharp decrease in the total number of Emergency Departments visits for all causes was observed, both in children and in adults. What is New: • During the first SARS-CoV-2 lockdown in 2020, domestic accidents involving children increased threefold from the previous year. • Higher risk of hospitalization was showed in minors accessing during 2020 vs 2019, in males than in females and it increased with advancing age. Considering the type of injury, a significant higher risk of hospitalization for poisoning was observed.

Minor Variety of Campania Olive Germplasm ("Racioppella"): Effects of Kaolin on Production and Bioactive Components of Drupes and Oil.

The effects of climate change have a great impact on the Mediterranean regions which are experiencing an increase in drought periods with extreme temperatures. Among the various solutions reported to reduce the damage caused by extreme environmental conditions on olive plants, the application of anti-transpirant products is widespread. In an increasingly current scenario of climate change, this study was designed to evaluate the effect of kaolin on the quantitative and qualitative parameters of drupes and oil in a little-known olive cultivar known as "Racioppella", belonging to the autochthonous germplasm of Campania (Southern Italy). To this purpose, the determination of maturation index, olive yield/plant, and bioactive components analysis (anthocyanins, carotenoids, total polyphenols, antioxidant activity, and fatty acids) were carried out. Kaolin applications showed no statistically significant differences in terms of production/plant while a significant increase in the drupe oil content was observed. Kaolin treatments resulted in increased anthocyanins (+24%) and total polyphenols (+60%) content and at the same time a significant increase in the antioxidant activity (+41%) of drupes was recorded. As far as oil is concerned, the results showed an increase in monounsaturated fatty acids, oleic and linoleic acids, and total polyphenols (+11%). On the basis of the results obtained, we can conclude that kaolin treatment can be considered as a sustainable solution to improve qualitative parameters in olive drupes and oil.

Nutritive and Phytochemical Composition of Aromatic Microgreen Herbs and Spices Belonging to the Apiaceae Family.

Microgreens represent a new generation of food products, commonly used to garnish and embellish culinary dishes, and recently associated with an increasing interest in their nutraceutical and phytochemical profiles. Four Apiaceae species: Pimpinella anisum L. (anise), Anthriscus cerefolium L. (chervil), Carum carvi L. (caraway), and Anethum graveolens L. (dill) were assessed for fresh yield, macro- and microminerals, total chlorophylls, total ascorbic acid, carotenoids, polyphenols, and their antioxidant activity. Anise was the species yielding the most (2.53 kg m-2) and having the highest lutein content (18.4 µg g-1 dry weight (DW)). Chervil and dill were characterized by the highest total ascorbic acid content (~151 mg AA g-1 fresh weight (FW)). The phenolic profile highlighted the presence of five flavonoid derivatives and 12 phenolic acid derivatives, with quinic acid derivatives being the most abundant phenols in the species tested. In addition, anise, caraway, and dill proved to be considerably rich in total polyphenols (~11056 µg g-1 DW). Caraway and dill were characterized by the highest antioxidant activity measured by the DPPH and ABTS methods, whereas the FRAP method revealed caraway as having the highest antioxidant activity. Such results highlight the potential of Apiaceae species as an alternative to other families which are commonly used for microgreens production.

Zinc biofortification of hydroponically grown basil: Stress physiological responses and impact on antioxidant secondary metabolites of genotypic variants.

Ocimum basilicum L. is an aromatic plant rich in bioactive metabolites beneficial to human health. The agronomic biofortification of basil with Zn could provide a practical and sustainable solution to address Zn deficiency in humans. Our research appraised the effects of biofortification implemented through nutrient solutions of different Zn concentration (12.5, 25.0, 37.5, and 50 µM) on the yield, physiological indices (net CO2 assimilation rate, transpiration, stomatal conductance, and chlorophyll fluorescence), quality, and Zn concentration of basil cultivars 'Aroma 2' and 'Eleonora' grown in a floating raft system. The ABTS, DPPH, and FRAP antioxidant activities were determined by UV-VIS spectrophotometry, the concentrations of phenolic acids by mass spectrometry using a Q Extractive Orbitrap LC-MS/MS, and tissue Zn concentration by inductively coupled plasma mass spectrometry. Although increasing the concentration of Zn in the nutrient solution significantly reduced the yield, this reduction was less evident in 'Aroma 2'. However, regardless of cultivar, the use of the maximum dose of Zn (50 µM) increased the concentration of carotenoids, polyphenols, and antioxidant activity on average by 19.76, 14.57, and 33.72%, respectively, compared to the Control. The significant positive correlation between Zn in the nutrient solution and Zn in plant tissues underscores the suitability of basil for soilless biofortification programs.

Hemp microgreens as an innovative functional food: Variation in the organic acids, amino acids, polyphenols, and cannabinoids composition of six hemp cultivars.

Hemp (Cannabis sativa L.) is a multi-functional crop cultivated for fiber, seeds, or phytochemical extraction. Once a major industrial crop in several agro-environments, its cultivation strongly declined in developed countries since World War II. Exploiting hemp vegetative tissue as innovative food has remained largely unexplored. The current work examined the potential production of hemp microgreens. Six cultivars were assessed for yield and composition of organic acids, amino acids, polyphenols and phytocannabinoids, through IC, FLD-HPLC and UHPLC-HRMS, respectively. Bioactive composition was strongly related to the hemp variety. 'Silvana' demonstrated the highest total content of amino acids and essential amino acids, high concentrations of cannflavin A and B, and moderate levels of cannabidiol and cannabigerol. 'Finola' distinguished by the highest concentration of cannflavins and total polyphenols, and the lowest levels of Δ9-THC. Regardless of varietal differences, hemp microgreens proved widely safe in terms of Δ9-THC content.

Development of a High Oleic Cardoon Cell Culture Platform by SAD Overexpression and RNAi-Mediated FAD2.2 Silencing.

The development of effective tools for the sustainable supply of phyto-ingredients and natural substances with reduced environmental footprints can help mitigate the dramatic scenario of climate change. Plant cell cultures-based biorefineries can be a technological advancement to face this challenge and offer a potentially unlimited availability of natural substances, in a standardized composition and devoid of the seasonal variability of cultivated plants. Monounsaturated (MUFA) fatty acids are attracting considerable attention as supplements for biodegradable plastics, bio-additives for the cosmetic industry, and bio-lubricants. Cardoon (Cynara cardunculus L. var. altilis) callus cultures accumulate fatty acids and polyphenols and are therefore suitable for large-scale production of biochemicals and valuable compounds, as well as biofuel precursors. With the aim of boosting their potential uses, we designed a biotechnological approach to increase oleic acid content through Agrobacterium tumefaciens-mediated metabolic engineering. Bioinformatic data mining in the C. cardunculus transcriptome allowed the selection and molecular characterization of SAD (stearic acid desaturase) and FAD2.2 (fatty acid desaturase) genes, coding for key enzymes in oleic and linoleic acid formation, as targets for metabolic engineering. A total of 22 and 27 fast-growing independent CcSAD overexpressing (OE) and CcFAD2.2 RNAi knocked out (KO) transgenic lines were obtained. Further characterization of five independent transgenic lines for each construct demonstrated that, successfully, SAD overexpression increased linoleic acid content, e.g., to 42.5%, of the relative fatty acid content, in the CcSADOE6 line compared with 30.4% in the wild type (WT), whereas FAD2.2 silencing reduced linoleic acid in favor of the accumulation of its precursor, oleic acid, e.g., to almost 57% of the relative fatty acid content in the CcFAD2.2KO2 line with respect to 17.7% in the WT. Moreover, CcSADOE6 and CcFAD2.2KO2 were also characterized by a significant increase in total polyphenolic content up to about 4.7 and 4.1 mg/g DW as compared with 2.7 mg/g DW in the WT, mainly due to the accumulation of dicaffeoyl quinic and feruloyl quinic acids. These results pose the basis for the effective creation of an engineered cardoon cells-based biorefinery accumulating high levels of valuable compounds from primary and specialized metabolism to meet the industrial demand for renewable and sustainable sources of innovative bioproducts.

Abiotic Stresses Elicitation Potentiates the Productiveness of Cardoon Calli as Bio-Factories for Specialized Metabolites Production.

Cultivated cardoon (Cynara cardunculus L. var altilis) is a Mediterranean traditional food crop. It is adapted to xerothermic conditions and also grows in marginal lands, producing a large biomass rich in phenolic bioactive metabolites and has therefore received attention for pharmaceutical, cosmetic and innovative materials applications. Cardoon cell cultures can be used for the biotechnological production of valuable molecules in accordance with the principles of cellular agriculture. In the current study, we developed an elicitation strategy on leaf-derived cardoon calli for boosting the production of bioactive extracts for cosmetics. We tested elicitation conditions that trigger hyper-accumulation of bioactive phenolic metabolites without compromising calli growth through the application of chilling and salt stresses. We monitored changes in growth, polyphenol accumulation, and antioxidant capability, along with transcriptional variations of key chlorogenic acid and flavonoids biosynthetic genes. At moderate stress intensity and duration (14 days at 50-100 mM NaCl) salt exerted the best eliciting effect by stimulating total phenols and antioxidant power without impairing growth. Hydroalcoholic extracts from elicited cardoon calli with optimal growth and bioactive metabolite accumulation were demonstrated to lack cytotoxicity by MTT assay and were able to stimulate pro-collagen and aquaporin production in dermal cells. In conclusion, we propose a "natural" elicitation system that can be easily and safely employed to boost bioactive metabolite accumulation in cardoon cell cultures and also in pilot-scale cell culture production.

Lutein levels in arterial cord blood correlate with neurotrophic calcium binding S100B protein in healthy preterm and term newborns.

BACKGROUND: S100B is an established biomarker of brain development and damage. Lutein (LT) is a naturally occurring xanthophyll carotenoid mainly concentrated in the central nervous system (CNS), but its neurotrophic role is still debated. We investigated whether LT cord blood concentrations correlate with S100B in a cohort of preterm and term healthy newborns. METHODS: We conducted a prospective study on the distribution of LT and S100B in arterial cord blood of healthy preterm (n = 50) and term (n = 50) newborns. RESULTS: S100B and LT showed a pattern of concentration characterized by higher levels (P < 0.01, for all) at 33-36 weeks gestation (GA) followed by a progressive decrease (P < 0.01, for all) from 37 onwards with a dip at term. Both S100B and LT were gender-dependent with significantly (P < 0.01, for all) higher levels in females in preterm and term groups. S100B (R = 0.68; P < 0.001) and LT (R = 0.40; P = 0.005) correlated with GA at sampling. A positive significant correlation (R = 0.87; P < 0.001) between S100B and LT was found. CONCLUSIONS: The present data showing a correlation between S100B and LT supports the notion of a LT trophic role in the CNS. Further investigations in high-risk infants are needed to elucidate LT involvement in the pathophysiological cascade of events leading to CNS development and damage.

Biostimulatory Action of Vegetal Protein Hydrolysate Compensates for Reduced Strength Nutrient Supply in a Floating Raft System by Enhancing Performance and Qualitative Features of "Genovese" Basil.

The floating raft constitutes a valuable system for growing herbs as it effectuates high yield and prime functional quality. However, the pressing need for advancing sustainability in food production dictates the reduction of chemical fertilizer inputs in such intensive production schemes through innovative cultivation practices. In this perspective, our work appraised the productive and qualitative responses of two "Genovese" basil genotypes (Eleonora and Italiano Classico) grown in a floating raft system with nutrient solutions of varied electrical conductivity (EC; 2 and 1 dS m-1) combined with root application of protein hydrolysate biostimulant at two dosages (0.15 and 0.3 0 ml L-1 of Trainer®). The phenolic composition, aromatic profile, and antioxidant activities (ABTS, DPPH, and FRAP) of basil were determined by UHPLC/HRMS, GC/MS, and spectrophotometry, respectively. "Eleonora" demonstrated higher number of leaves (37.04 leaves per plant), higher fresh yield (6576.81 g m-2), but lower polyphenol concentration (1440.81 µg g-1 dry weight) compared to "Italiano Classico." The lower EC solution (1 dS m-1) increased total phenols (+32.5%), ABTS, DPPH, and FRAP antioxidant activities by 33.2, 17.1, and 15.8%, respectively, and decreased linalool relative abundance by 5.5%. Biostimulant application improved crop performance and increased total phenolic concentration in both genotypes, with the highest phenolic concentration (1767.96 µg g-1 dry weight) registered at the lowest dose. Significant response in terms of aromatic profile was detected only in "Eleonora." Our results demonstrate that the application of protein hydrolysate may compensate for reduced strength nutrient solution by enhancing yield and functional quality attributes of "Genovese" basil for pesto.

Nickel uptake in hydroponics and elemental profile in relation to cultivation reveal variability in three Hypericum species.

The Hypericum species (H. perforatum, H. olympicum, and H. orientale) were cultured in hydroponics with excess nickel (Ni, 1 or 100 µM Ni) to compare the metallic and metabolite content. Identical species were collected outdoor to assess the same parameters (including uranium and lanthanides) with total of 53 elements. The results showed that Ni was less accumulated in shoots in hydroponics (translocation factor of 0.01-0.25) and the highest absolute amount was detected in H. olympicum. Essential elements were typically depleted by Ni excess, but Co and Na increased. Soluble phenols, sum of flavonols and catechin rather increased in response to Ni but quercetin glycosides and free amino acids decreased in the shoots of H. olympicum mainly. Comparison of laboratory and outdoor growing plants showed more phenols in outdoor samples but not in H. olympicum and individual metabolites differed too. Plants cultured in hydroponics contained lower amount of non-essential, toxic and rare earth elements (30-100-fold) and shoot bioaccumulation factor in outdoor samples was low for most elements (<0.01) but not for Cd and Pt. Data reveal that H. olympicum is a potent source of phenolic metabolites whereas H. orientale accumulates many elements (38 out of 53 elements).

Bioactive Compounds and Antioxidant Activity of Lettuce Grown in Different Mixtures of Monogastric-Based Manure With Lunar and Martian Soils.

The supplementation of bioactive compounds in astronaut's diets is undeniable, especially in the extreme and inhospitable habitat of future space settlements. This study aims to enhance the Martian and Lunar regolith fertility (testing two commercial simulants) through the provision of organic matter (manure) as established by in situ resource utilization (ISRU) approach. In this perspective, we obtained 8 different substrates after mixing Mojave Mars Simulant (MMS-1) or Lunar Highlands Simulant (LHS-1), with four different rates of manure (0, 10, 30, and 50%, w/w) from monogastric animals. Then, we assessed how these substrates can modulate fresh yield, organic acid, carotenoid content, antioxidant activity, and phenolic profile of lettuce plants (Lactuca sativa L.). Regarding fresh biomass production, MMS-1-amended substrates recorded higher yields than LHS-1-ones; plants grown on a 70:30 MMS-1/manure mixture produced the highest foliar biomass. Moreover, we found an increase in lutein and ß-carotene content by + 181 and + 263%, respectively, when applying the highest percentage of manure (50%) compared with pure simulants or less-amended mixtures. The 50:50 MMS-1/manure treatment also contained the highest amounts of individual and total organic acids, especially malate content. The highest antioxidant activity for the ABTS assay was recorded when no manure was added. The highest content of total hydroxycinnamic acids was observed when no manure was added, whereas ferulic acid content (most abundant compound) was the highest in 70:30 simulant/manure treatment, as well as in pure LHS-1 simulant. The flavonoid content was the highest in pure-simulant treatment (for most of the compounds), resulting in the highest total flavonoid and total phenol content. Our findings indicate that the addition of manure at specific rates (30%) may increase the biomass production of lettuce plants cultivated in MMS-1 simulant, while the phytochemical composition is variably affected by manure addition, depending on the stimulant. Therefore, the agronomic practice of manure amendment showed promising results; however, it must be tested with other species or in combination with other factors, such as fertilization rates and biostimulants application, to verify its applicability in space colonies for food production purposes.

Use of Different Organic Carbon Sources in Cynara cardunculus Cells: Effects on Biomass Productivity and Secondary Metabolites.

Cynara cardunculus (Asteraceae family) is a perennial plant native to Mediterranean regions. This plant represents a source of high-value compounds, such as polyphenols and fatty acids that have several industrial applications. However, in vitro plant cell cultures can represent a valid alternative to in-field cultivation and facilitate the extraction of metabolites of commercial interest. Generally, sucrose is the main sugar used for plant cell cultures, but other carbon sources can be considered. Here, we investigated the potential use of alternative organic carbon sources, such as galactose, maltose, glucose, glycerol, fructose, lactose, and starch, for the cultivation of C. cardunculus cells. Moreover, cardoon cells were collected, and an extraction of polyphenols and oils was performed to study the effects of different carbon sources on the production of bioactive molecules. This study provided evidence that cardoon cell growth can be supported by carbon sources other than sucrose. However, the carbon source inducing optimum growth, did not necessarily induce the highest production of high-value compounds.

Photomicellar Catalyzed Synthesis of Amides from Isocyanides: Optimization, Scope, and NMR Studies of Photocatalyst/Surfactant Interactions.

The merging of micellar and photoredox catalysis represents a key issue to promote "in water" photochemical transformations. A photomicellar catalyzed synthesis of amides from N-methyl-N-alkyl aromatic amines and both aliphatic and aromatic isocyanides is herein presented. The mild reaction conditions enabled a wide substrate scope and a good functional groups tolerance, as further shown in the late-stage functionalization of complex bioactive scaffolds. Furthermore, solution 1D and 2D NMR experiments performed, for the first time, in the presence of paramagnetic probes enabled the study of the reaction environment at the atomic level along with the localization of the photocatalyst with respect to the micelles, thus providing experimental data to drive the identification of optimum photocatalyst/surfactant pairing.

Pearl Grey Shading Net Boosts the Accumulation of Total Carotenoids and Phenolic Compounds That Accentuate the Antioxidant Activity of Processing Tomato.

Tomato (Solanum lycopersicum L.) is one of the most consumed vegetables worldwide due to its low caloric intake and high fiber, minerals, and phenolic compounds, making it a high-quality functional food. However, fruit quality attributes can be affected by pre-harvest factors, especially environmental stresses. This research aimed to evaluate the influence of two shading nets (white net -30% and pearl grey net -40% shading degree) on the yield and phytochemical profile of tomato fruits grown in summer under the Mediterranean climate. Mineral and organic acid content (by ion chromatography-IC), phenolic profile (by ultra-high performance liquid chromatography-UHPLC coupled with an Orbitrap high-resolution mass spectrometry-HRMS), carotenoid content (by high-performance liquid chromatography with diode array detection-HPLC-DAD), and antioxidant activities DPPH, ABTS, and FRAP (by UV-VIS spectrophotometry) were determined. Tomato fruits grown under the pearl grey net recorded the highest values of total phenolic compounds (14,997 µg 100 g-1 of fresh weight) and antioxidant activities DPPH, ABTS, and FRAP, without affecting either fruit color or marketable yield. The reduction of solar radiation through pearl grey nets proved to be an excellent tool to increase the phytochemical quality of tomato fruits during summer cultivation in a Mediterranean environment.

Towards a Cardoon (Cynara cardunculus var. altilis)-Based Biorefinery: A Case Study of Improved Cell Cultures via Genetic Modulation of the Phenylpropanoid Pathway.

Cultivated cardoon (Cynara cardunculus var. altilis L.) is a promising candidate species for the development of plant cell cultures suitable for large-scale biomass production and recovery of nutraceuticals. We set up a protocol for Agrobacterium tumefaciens-mediated transformation, which can be used for the improvement of cardoon cell cultures in a frame of biorefinery. As high lignin content determines lower saccharification yields for the biomass, we opted for a biotechnological approach, with the purpose of reducing lignin content; we generated transgenic lines overexpressing the Arabidopsis thaliana MYB4 transcription factor, a known repressor of lignin/flavonoid biosynthesis. Here, we report a comprehensive characterization, including metabolic and transcriptomic analyses of AtMYB4 overexpression cardoon lines, in comparison to wild type, underlining favorable traits for their use in biorefinery. Among these, the improved accessibility of the lignocellulosic biomass to degrading enzymes due to depletion of lignin content, the unexpected increased growth rates, and the valuable nutraceutical profiles, in particular for hydroxycinnamic/caffeoylquinic and fatty acids profiles.

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors.

Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, bone lesions). When choosing RRMM-treatment, the biochemical markers for progression and severity of the disease, dynamic of disease relapse, type and number of prior therapy lines, including toxicity and underlying health status, need to be considered, and shared decision making should be pursued. Objectively characterizing health status via geriatric assessment (GA) at each multiple myeloma (MM) treatment decision point has been shown to be a better estimate than via age and comorbidities alone. The well-established national comprehensive cancer network, IMWG, European myeloma network and other national treatment algorithms consider these issues. Ideally, GA-based clinical trials should be supported in the future to choose wisely and efficaciously from available intervention and treatment options in often-older MM adults in order to further improve morbidity and mortality.

Geriatric assessments and frailty scores in multiple myeloma patients: a needed tool for individualized treatment?

PURPOSE OF REVIEW: Multiple myeloma is a disease of elderly adults. Improvement in survival has occurred because of biological insights and novel agents. Therapeutic options involve choices today, thus have become more complex. Demographics have led to an increased number of elderly patients and age may be associated with a poorer outcome but is not the only prognostic predictor today. RECENT FINDINGS: To evaluate patients' health status rather than their chronological age alone, frailty scores and functional geriatric assessments are used to identify prognostic groups, avoid adverse events, compare clinical trials and tailor treatment. As most clinical trials exclude frail elderly patients, those enrolled therein are often younger and healthier than the typical multiple myeloma patient. This represents a challenge for frail cohorts because of their increased risk of adverse events, overtreatment and undertreatment and/or therapy discontinuation, which may lead to poorer survival and quality of life (QoL). Reassessing patients' status via geriatric assessments is also relevant during treatment to adjust interventions appropriately. SUMMARY: Integrating geriatric assessments may lead to individual treatment decisions, dose adjustments, better clinical outcome and QoL. Prospective clinical trials that enroll elderly multiple myeloma patients with comorbidities, incorporate frailty scores/geriatric assessments and help with prognostication, adverse event avoidance and QoL maintenance, remain warranted.