CONSTANS, a HUB for all seasons: How photoperiod pervades plant physiology regulatory circuits.

How does a plant detect the changing seasons and make important developmental decisions accordingly? How do they incorporate daylength information into their routine physiological processes? Photoperiodism, or the capacity to measure the daylength, is a crucial aspect of plant development that helps plants determine the best time of the year to make vital decisions, such as flowering. The protein CONSTANS (CO) constitutes the central regulator of this sensing mechanism, not only activating florigen production in the leaves but also participating in many physiological aspects in which seasonality is important. Recent discoveries place CO in the center of a gene network that can determine the length of the day and confer seasonal input to aspects of plant development and physiology as important as senescence, seed size, or circadian rhythms. In this review, we discuss the importance of CO protein structure, function, and evolutionary mechanisms that embryophytes have developed to incorporate annual information into their physiology.

Factors influencing blood tumor marker concentrations in the absence of neoplasia.

BACKGROUND: Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells can either directly synthesize or induce the synthesis of TMs, and the release of these molecules into the bloodstream allows their quantification in biological fluids. Although very small concentrations of TMs are usually present in the serum or plasma of healthy subjects, increased concentrations may also be found in the presence of benign diseases or due to technical interference, producing false positive results. MATERIAL AND METHODS AND RESULTS: Our review analyses the causes of false positives described between January 1970 to February 2023 for the TMs most frequently used in clinical practice: α-fetoprotein (AFP), ß2-microglobulin (ß2-M), cancer antigen 15-3 (CA 15-3), cancer antigen CA 19-9 (CA 19-9), cancer antigen CA 72-4 (CA 72-4), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), chromogranin A (CgA), choriogonadotropin (hCG), cytokeratin 19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), human epididymis protein 4 (HE4), serum HER2 (sHER2), squamous cell carcinoma antigen (SCCA), protein induced by vitamin K absence-II (PIVKA-II), Pro-gastrin-releasing peptide (Pro-GRP), prostate-specific antigen (PSA), Protein S-100 (S-100) and thyroglobulin (Tg). A total of 247 references were included. CONCLUSIONS: A better understanding of pathophysiological processes and other conditions that affect the concentration of TMs might improve the interpretation of results and their clinical application.

The different response of Brassica napus genotypes to microspore embryogenesis induced by heat shock and trichostatin A is not determined by changes in cell wall structure and composition but by different stress tolerance.

During microspore embryogenesis, microspores are induced to develop into haploid embryos. In Brassica napus, microspore embryogenesis is induced by a heat shock (HS), which initially produces embryogenic structures with different cell wall architectures and compositions, and with different potentials to develop into embryos. The B. napus DH4079 and DH12075 genotypes have high and very low embryo yields, respectively. In DH12075, embryo yield is greatly increased by combining HS and the histone deacetylase (HDAC) inhibitor trichostatin A (TSA). However, we show that HS + TSA inhibits embryogenesis in the highly embryogenic DH4079 line. To ascertain why TSA has such different effects in these lines, we treated DH4079 and DH12075 microspore cultures with TSA and compared the cell wall structure and composition of the different embryogenic structures in both lines, specifically the in situ levels and distribution of callose, cellulose, arabinogalactan proteins and high and low methyl-esterified pectin. For both lines, HS + TSA led to the formation of cell walls unfavorable for embryogenesis progression, with reduced levels of arabinogalactan proteins, reduced cell adhesion of inner walls and altered pectin composition. Thus, TSA effects on cell walls cannot explain their different embryogenic response to TSA. We also applied TSA to DH4079 cultures at different times and concentrations before HS application, with no negative effects on embryogenic induction. These results indicate that DH4079 microspores are hypersensitive to combined TSA and HS treatments, and open up new hypotheses about the causes of such hypersensitivity.

Variations in tumor growth, intra-individual biological variability, and the interpretation of changes.

OBJECTIVES: The identification of changes in tumor markers (TMs) in cancer patients that indicate response to treatment, stabilization or disease progression is a challenge for laboratory medicine. Several approaches have been proposed: assessing percentage increases, applying discriminant values, and estimating half-life (t1/2) or doubling time (DT). In all of them it is assumed that the TM is a surrogate of the variation in tumor size. In general this variation is time-dependent, but this is not the case of intraindividual biological variability (CVi), which can range from 6 % in CA15-3 to 22 % in CA125. When decisions are made on the basis of DT or t1/2, these values can be affected by the CVi; if it is very large, the growth rate very slow and the period of time between determinations very short, the result obtained for DT may be due mainly to the CVi. The aim of this study is to establish the relationship between the CVi and temporal variables. METHODS: We related equations for calculating DT and t1/2 to the reference change values in tumor markers. RESULTS: The application of the formula obtained allows the calculation of the optimal time between measurements to ensure that the influence of the CVi is minimal in different types of tumors and different scenarios. CONCLUSIONS: Intraindividual variation affects the calculation of DT and t1/2. It is necessary to establish the minimum time between two measurements to ensure that the CVi does not affect their calculation or lead to misinterpretation.

Novel method of removing metals from estuarine water using whole microbial mats.

This study addresses the limited understanding of chromium-microbial mat interactions in estuarine tidal flats. The aims were to evaluate (1) the efficiency of the microbial consortium in Cr(III) removal from seawater; (2) the elemental and mineralogical composition of the microbial mat as a natural system in the Cr removal, (3) the effects of metal on microphytobenthos, and (4) possible interactions of Cr with other metals present in the consortium. Microbial mats were exposed to Cr(III) solutions at different concentrations (2-30 mg Cr/L). Analysis such as metal concentration, organic matter content, chlorophyll a and phaeopigment concentrations, abundance of diatoms and cyanobacteria, SEM-EDS, and XRD were performed. Most of the Cr(III) was deposited, as chromium oxide/hydroxide, on the surface of all microbial mat components. The complete microbial mat, comprising sediments, detritus, EPS, and diverse microorganism communities, exhibited a remarkable capacity to accumulate Cr(III), retaining over 87% in the solution.

Infectious esophagitis in immunocompetent individuals: case series in a tertiary care hospital.

The prevalence of infectious esophagitis in immunocompetent people is low. The main etiological agent is HSV11,2, affecting mainly young men4 with intense odynophagia and dysphagia. It is unknown whether SARS-CoV-2 infection or its vaccine are predisposing factors. The objective is to determine the clinical, diagnostic, endoscopic and therapeutic characteristics of patients diagnosed with viral esophagitis since the beginning of the pandemic.

Chromium removal by microbial mats: understanding the effect of salinity and pH.

Environmental contamination by chromium represents a serious public health problem. Therefore, it is crucial to develop and optimize remediation technologies to reduce its concentration in the environment. The aims of this study were to evaluate the uptake of chromium by live and complete microbial mats in experimental mesocosms under different pH and salinity conditions to understand how these factors affect the microphytobenthic community and, consequently, how chromium removal process is influenced. Microbial mats from the estuarine environment were exposed to 15 mg Cr/L under different pH (2, 4, and 8) and salinity (2, 15, and 33) conditions. Salinity, redox potential, and pH were measured throughout the trial in solutions and in microbial mats, while total Cr determinations were performed at the end of the assay. The results demonstrated that the removal efficiency of Cr by microbial mats was significantly improved in solutions at pH 2, remaining unaffected by variations in salinity. Notably, both cyanobacteria and diatoms showed remarkable resistance to Cr exposure under all conditions tested, highlighting their exceptional adaptability. Microbial mats have proved to be effective filters for reducing the concentration of chromium in aqueous solutions with varying pH and salinity levels.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

Diagnostic trajectories of mental disorders in children and adolescents: a cohort study.

Mental disorders in children and adolescents may follow different trajectories, such as remission, change of diagnosis, or addition of two or more comorbid diagnoses, showing a heterotypic pattern. This study aims to describe the main diagnostic trajectories across a broad range of mental disorder diagnostic categories, from childhood to adolescence and from adolescence to young adulthood in a clinical population. A prospective study was conducted among a clinical sample of children and adolescents who were aged 3-17 years at the face-to-face baseline interview. Electronic health records of these participants were reviewed 10 years later. The diagnostic stability over time was examined using the kappa coefficient, and factors associated with stability were explored using simple logistic regression. The study included a sample of 691 participants. The kappa coefficient for diagnostic stability across all diagnoses was 0.574 for the transition from childhood to adulthood, 0.614 from childhood to adolescence, and 0.733 from adolescence to adulthood. Neurodevelopmental diagnoses had the highest stability. Factors associated with higher diagnostic stability included family history of mental disorders, receiving psychopharmacological treatment, and symptom severity at baseline. We found a variable diagnostic stability across different diagnoses and age categories. The different life transitions represent complex periods that should not be overlooked from a clinical standpoint. An appropriate transition from child and adolescent mental health services to adult mental health services may have a positive impact on children and adolescents with mental disorders.

PALANTIR: An NFV-Based Security-as-a-Service Approach for Automating Threat Mitigation.

Small and medium enterprises are significantly hampered by cyber-threats as they have inherently limited skills and financial capacities to anticipate, prevent, and handle security incidents. The EU-funded PALANTIR project aims at facilitating the outsourcing of the security supervision to external providers to relieve SMEs/MEs from this burden. However, good practices for the operation of SME/ME assets involve avoiding their exposure to external parties, which requires a tightly defined and timely enforced security policy when resources span across the cloud continuum and need interactions. This paper proposes an innovative architecture extending Network Function Virtualisation to externalise and automate threat mitigation and remediation in cloud, edge, and on-premises environments. Our contributions include an ontology for the decision-making process, a Fault-and-Breach-Management-based remediation policy model, a framework conducting remediation actions, and a set of deployment models adapted to the constraints of cloud, edge, and on-premises environment(s). Finally, we also detail an implementation prototype of the framework serving as evaluation material.

Preliminary assessment of microbial mats in seawater metal remediation.

Microbial mats have a special role in the removal of metals in marine environment. This study aimed to experimentally determine the efficiency of Cr removal from seawater by microbial mats. The effect of Cr on the microphytobenthic community and the influence of an aerated condition on the removal of metal and microorganisms were also considered. Hence, microbial mat samples were subdivided in 4 groups: submerged in Cr (chromium 2 mg/L without aeration), Cr + O2 (chromium 2 mg/L with aeration), SW + O2 (filtered seawater with aeration), and a control: SW (filtered seawater with neither chromium nor aeration). Water and microbial mat subsamples were used to determine Cr concentrations, organic matter content, granulometry, physicochemical parameters, chlorophyll a, phaeopigments, and quantitative analysis of the microphytobenthic community. Cr removal efficiency from seawater was 95% for the Cr treatment and 99% for the Cr + O2 treatment. The abundance of cyanobacteria tended to decrease between the initial and final days of the assay, whereas the opposite trend was observed for diatoms. Two aspects are worth noting in the paper: microbial mats efficiently removed Cr from seawater at a concentration of 2 mg Cr/L and the removal of Cr by microbial mats was more efficient with water aeration.

Lung cancer tumor markers in serous effusions and other body fluids.

From its onset and during its progression, lung cancer may affect various extrapulmonary structures. These include the serous membranes, the pleura and pericardium, and less frequently the central nervous system, with leptomeningeal involvement. In these cases, fluid accumulates in the serous membranes which may contain substances secreted by the tumor. Measuring the concentrations of these substances can provide useful information for elucidating the origin of the fluid accumulation, either in pleural and pericardial effusions or in cerebrospinal fluid. This paper describes the histological types of lung cancer that most frequently affect the serosa and leptomeninges. It also reviews the literature on tumor markers in different fluids and makes recommendations for their interpretation.

[Functionality and seniors: where are we and where should we be going?Funcionalidade e pessoas idosas: onde estamos e para onde devemos ir?] / Funcionalidad y personas mayores: ¿dónde estamos y hacia dónde ir?

The process of population aging will lead to an increase in health problems in older people, mainly related to their functionality. Accordingly, the countries of the Region of the Americas must begin to act to meet this challenge. One of the fundamental tasks involves the ability to measure and monitor functionality in the population. The tools used to evaluate functionality focus mainly on the basic activities of daily living, which limits their preventive capacity, since instrumental activities provide a better prognosis. Using the case of Chile, challenges for the Region were identified, mainly related to the advantages of adopting new methodologies that not only evaluate functional capacity, as current strategies do, but also detect its deterioration early and monitor its stages throughout the dependence stage in older people. This will also make it possible to evaluate initiatives for the prevention and management of loss of functionality.

O processo de envelhecimento populacional levará a um aumento de problemas de saúde nas pessoas idosas, principalmente relacionados à sua funcionalidade. Nesse sentido, os países da Região das Américas devem começar a agir para enfrentar esse desafio. Uma das tarefas fundamentais está relacionada à capacidade de medir e monitorar a funcionalidade da população. Os instrumentos utilizados para avaliá-la estão voltados principalmente para as atividades básicas da vida diária, o que limita sua capacidade preventiva, já que são as atividades instrumentais que permitem um melhor prognóstico. Utilizando o caso do Chile, identificamos desafios para a Região, principalmente relacionados às vantagens de incorporar novas metodologias de avaliação da capacidade funcional que não só habilitem as estratégias atuais, mas também detectem precocemente a deterioração da funcionalidade e monitorem suas fases ao longo da dependência das pessoas idosas. Isso permitirá, ao mesmo tempo, avaliar as iniciativas de prevenção e manejo da perda de funcionalidade.

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia.

On November 5, 2020, a marketing authorization valid through the European Union (EU) was issued for acalabrutinib monotherapy or acalabrutinib in combination with obinutuzumab (AcalaObi) in adult patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) and also for acalabrutinib monotherapy in adult patients with relapsed or refractory (RR) CLL. Acalabrutinib inhibits the Bruton tyrosine kinase, which plays a significant role in the proliferation and survival of the disease. Acalabrutinib was evaluated in two phase III multicenter randomized trials. The first trial (ACE-CL-007) randomly allocated acalabrutinib versus AcalaObi versus chlorambucil plus obinutuzumab (ChlObi) to elderly/unfit patients with TN CLL. The progression-free survival (PFS), as assessed by an independent review committee, was superior for both the AcalaObi (hazard ratio [HR], 0.1; 95% confidence interval [CI], 0.06-0.17) and acalabrutinib (HR, 0.2; 95% CI, 0.13-0.3) arms compared with the ChlObi arm. The second trial (ACE-CL-309) randomly allocated acalabrutinib versus rituximab plus idelalisib or bendamustine to adult patients with RR CLL. Also in this trial, the PFS was significantly longer in the acalabrutinib arm (HR, 0.31; 95% CI, 0.20-0.49). Adverse events for patients receiving acalabrutinib varied across trials, but the most frequent were generally headache, diarrhea, neutropenia, nausea, and infections. The scientific review concluded that the benefit-risk ratio of acalabrutinib was positive for both indications. This article summarizes the scientific review of the application leading to regulatory approval in the EU. IMPLICATIONS FOR PRACTICE: Acalabrutinib was approved in the European Union for the treatment of adult patients with chronic lymphocytic leukemia who have not received treatment before and for those who have received therapy but whose disease did not respond or relapsed afterward. Acalabrutinib resulted in a clinically meaningful and significant lengthening of the time from treatment initiation to further disease relapse or patient's death compared with standard therapy. The overall safety profile was considered acceptable, and the benefit-risk ratio was determined to be positive.

Characterization of Total and Unprotonated (Free) Nicotine Content of Nicotine Pouch Products.

INTRODUCTION: Nicotine pouch products, oral smokeless products that contain nicotine but no tobacco leaf material, have recently entered the US marketplace. Available data indicate sales of these products in the United States have increased since 2018; however, the extent of use among US youth and adults is uncertain. METHODS: To assay the chemistry of these emerging tobacco products, we analyzed 37 nicotine pouch brands from six total manufacturers. Almost all of the products had flavor descriptors (36 of 37), such as mint, licorice, coffee, cinnamon, and fruit. The amount of free nicotine, the form most easily absorbed, was calculated for each product using total nicotine, product pH, the appropriate pKa, and the Henderson-Hasselbalch equation. RESULTS: Nicotine pouch products varied in pouch content mass, moisture content (1.12%‒47.2%), alkalinity (pH 6.86‒10.1), and % free nicotine (7.7%‒99.2%). Total nicotine content ranged from 1.29 to 6.11 mg/pouch, whereas free nicotine ranged from 0.166 to 6.07 mg/pouch. These findings indicate that nicotine and pH levels found in some of these nicotine pouches are similar to conventional tobacco products, such as moist snuff and snus, and that most of these pouch products are flavored. CONCLUSIONS: Although these products likely lack many tobacco-related chemicals, each product analyzed contained nicotine, which is both addictive and can harm human health. Given that nicotine pouches may appeal to a spectrum of users, from novice to experienced users, it is important to include these emerging tobacco products in tobacco control research, policy, and practice. IMPLICATIONS: These "tobacco-free" nicotine pouches have similar pH and nicotine content to conventional tobacco products, such as moist snuff and snus. Although they lack many tobacco-related chemicals, most are highly flavored which could increase experimentation from new users. Given that nicotine pouches may appeal to a spectrum of users, from novice to experienced users, in terms of their flavors and nicotine content, it is important to examine and include these emerging tobacco products as they relate to tobacco control research, policy, and practice.

Toxic effects of chlorpyrifos, cypermethrin and glyphosate on the non-target organism Selenastrum capricornutum (Chlorophyta).

The toxic effects of the insecticides chlorpyrifos and cypermethrin, and the herbicide glyphosate on the growth, biovolume and ultrastructure of the green microalgae Selenastrum capricornutum were evaluated. Concentrations between 9.37-150 mg L-1 of chlorpyrifos, 3.12-100 mg L-1 of cypermethrin and 4.7-60 mg L-1 of glyphosate were assayed along with a control culture. The assayed concentrations were prepared using commercial formulations. After 48 h all tested concentrations of the three pesticides reduced significantly the population growth. The 96 h effective concentration 50 (EC50) was 14.45 mg L-1 for chlorpyrifos, 12.37 mg L-1 for cypermethrin and 15.60 mg L-1 for glyphosate. Cells exposed to the three pesticides showed an increase in the cellular size related to the increase in pesticide concentration and exposure time. The most significant damages observed on the ultrastructure of cells exposed to the three pesticides included thylakoids and mitochondria disruption, formation of electrodense bodies, accumulation of lipids and increase in the size and number of starch granules. The present study demonstrates that the effects of pesticides also extend to non-target organisms having significant ecological implications.

Short-term temporal dynamics of morphological and feeder functional groups and species richness in relation to seasonal changes.

This study examines the distribution of primary and secondary space holders integrated in morphological and feeder functional groups as well as the species richness over the seasons on northern Patagonian rocky shores. We also evaluated whether the temporal changes in species richness, assemblage structure and species turnover were related to seasonal changes. These patterns were studied by non-destructive samplings between December 2013 and March 2015. Thirty taxa were identified, including six algal morphological functional and three invertebrate feeder groups. The cover of seaweeds and invertebrates was positively correlated with changes in the environmental factors. The marked seasonality in this Patagonian zone changed between two contrasting periods. Species richness and assemblage structure were associated with seasonal changes and were influenced by the more abundant morphological and feeder functional groups. We suggest that habitat-formers, such as articulated calcareous and suspensor feeder groups, can expand and retract over time-scales of months to seasons, generating available space for the colonization and growth of other organisms. We conclude that seasonal changes and the dynamics of articulated calcareous and suspensor feeder groups drive changes in the algal and invertebrate abundances, in turn driving changes in species richness and assemblage structure.

Influence of microphytobenthos on the sedimentary organic matter composition in two contrasting estuarine microhabitats.

The influence of microphytobenthic community on the composition of sedimentary organic matter was evaluated in two Bahía Blanca estuary microhabitats contrasting in vegetation and hydrodynamic conditions; namely, S1 located in a Sarcocornia perennis saltmarsh with macroscopic microbial mats and S2 in a mudflat without macroscopic microbial mats or vegetation. Moisture, organic matter, chlorophyll a, phaeopigments, carbohydrates (CH), proteins (PRT), and abundance and structure of microphytobenthic community were evaluated in surface sediments. Higher moisture was observed at S2 and was related to the proximity of this site to the subtidal zone and the effect of the environmental variables temperature and rain. No significant differences were found in organic matter content between sites; however, at S1, a higher concentration was registered during winter and early spring associated to the period of higher microphytobenthic biomass. Chlorophyll a and phaeopigments were higher at S1, attributed to the higher microphytobenthos abundance at this site. Differences in microphytobenthos were observed not only in quantity but also in community structure since at S1 filamentous cyanobacteria dominated the community, whereas at S2, higher abundance of centric diatoms and the absence of cyanobacteria were observed during most of the study. S1 showed higher concentration of proteins and carbohydrates which could be attributed to the higher production of fresh organic matter by microphytobenthos. The total protein and carbohydrate concentrations allowed us to classify both microhabitats into the meso-oligotrophic category, contrasting with the classification made by other authors using water column proxies.

EMA Review of Daratumumab (Darzalex) for the Treatment of Adult Patients Newly Diagnosed with Multiple Myeloma.

The use of daratumumab in combination with established regimens for the treatment of newly diagnosed multiple myeloma has recently been authorized by the European Medicines Agency based on results from three separate phase III randomized, active controlled, open-label studies that have confirmed enhanced efficacy and tolerability in both transplant-ineligible (MMY3008 and MMY3007) and transplant-eligible (MMY3006) patients, without compromising transplant ability. Trial MMY3008 showed an improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone; the median PFS had not been reached in the daratumumab arm and was 31.9 months in the control arm (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.43-0.73; p < .0001). Trial MMY3007 showed an improvement in PFS when daratumumab was added to bortezomib, melphalan, and prednisone compared with bortezomib, melphalan, and prednisone; PFS had not been reached in the daratumumab arm and was 18.1 months in the control arm (HR, 0.5; 95% CI, 0.38-0.65; p < .0001). In trial MMY3006, daratumumab added to bortezomib, thalidomide, and dexamethasone was compared with bortezomib, thalidomide, and dexamethasone as induction and consolidation treatment prior to autologous stem cell transplant. The stringent complete response rate at day 100 after transplant in the daratumumab group was 29% compared with 20% in the control group (odds ratio, 1.60; 1.21-2.12 95% CI; p = .0010). Overall adverse events were manageable, with an increased rate of neutropenia and infections in the daratumumab arms. Regulatory assessment of efficacy and safety results from trials MMY3006, MMY3007, and MMY3008 confirmed a positive benefit-risk ratio leading to an approval of the extensions of indication. IMPLICATIONS FOR PRACTICE: A set of extensions of indication was recently approved for daratumumab (Darzalex) in the setting of newly diagnosed multiple myeloma in combination with established regimens. Results of the MMY3006, MMY3007, and MMY3008 trials have shown enhanced efficacy and a favorable side effect profile of several daratumumab-based combinations in patients both ineligible and eligible for transplant, without compromising transplant ability. The combinations of daratumumab with either lenalidomide and low-dose dexamethasone or bortezomib, melphalan, and prednisone were approved for transplant-ineligible patients. The combination of daratumumab with bortezomib, thalidomide, and dexamethasone was approved for transplant-eligible patients. These combinations are expected to improve the survival outlook for patients with multiple myeloma, without an unacceptable risk of increase in adverse events, and updated information on progression-free survival and overall survival is expected from the above trials.

Children and adolescents with eating disorders during COVID-19 confinement: Difficulties and future challenges.

OBJECTIVE: To present the adaptations to treatment protocols made in a child and adolescent eating disorders (ED) unit during the eight-week confinement period mandated in response to the COVID-19 pandemic and examine clinical and treatment variables in the outpatient, day hospital, and inpatient care programs. METHOD: Description of the implementation of a combined teletherapy program for outpatient and day-hospital patients and the adaptations made to the inpatient protocol. Retrospective review of medical records and analysis of general and specific variables related to the pandemic and confinement. RESULTS: We held 1,329 (73.10%) telehealth consultations and 489 (26.9%) face-to-face outpatient visits with 365 patients undergoing treatment in the outpatient clinic or day hospital. Twenty-eight (7.67%) were initial evaluations. Twenty-two patients were newly admitted and 68 ED-related emergencies were attended. Almost half of the children and adolescents studied experienced reactivation of ED symptoms despite treatment, and severe patients (25%) presented self-harm and suicide risk. CONCLUSIONS: The implementation of a combined teletherapy program has enabled continuity of care during confinement for children and adolescents with ED. Delivery of treatment to adolescents in the day hospital program posed the biggest challenge due to their greater degrees of severity and higher hospitalization rates. An adapted inpatient program should be maintained throughout confinement, as the need for hospitalization of children and adolescents with ED does not decrease with lockdown.