360° approach to the patient with mite allergy: from scientific evidence to clinical practice.

In the recent years, several important advances have been made in the diagnosis of allergy using molecular techniques. The aetiological diagnosis of allergy using molecular components of allergens allows a more precise definition of the patient's IgE repertoire. Precision medicine is a structural model aimed at personalising healthcare and places the patient at the centre of the specialist's decision-making process. To this end, an accurate characterisation of the external exposome at a molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease, with a view to personalising diagnosis and therapy. It has been proposed a decision algorithm, the Top-Down approach, where the clinical history is set first and is followed by the use of skin tests or specific IgE techniques, which facilitates the clinicians to make decisions. The therapeutic intervention driven by the standard diagnostic approach, but supported by these innovative tools, can lead to a better phenotyping of highly complex patients, and a more appropriate prescription of AIT. To this end, the allergen extracts used for diagnosis require to be of proven quality and contain the most relevant allergens. Likewise, allergen vaccines must gather efficacy, safety, duration, and patient compliance, hence the demand for new vaccines to overcome these drawbacks.

Reliability of a point of care testing blood gas analyzer for measurement of lactate levels in cerebrospinal fluid.

Analysis of cerebrospinal fluid (CSF), including lactate, is key for diagnosis of acute meningitis. Since blood gas analyzers (BGA) enable rapid and safe blood-lactate measurements, we evaluated the reliability of RAPIDPoint 500 BGA to provide a fast and accurate measure of CSF lactate. In this study, CSF lactate levels were measured by a reference assay and on RAPIDPoint 500 BGA. Comparability was evaluated through difference analysis, using Bland Altman test, and linear regression analysis, using the Passing Bablok test. Agreement rate according to CSF lactate (≥3.5 and <3.5 mmol/L) was calculated using kappa (κ) statistic. Population study included 98 CSF samples. Concerning difference analysis, according to Bland-Altman test, bias was 0.13 mmol/L (CI 95%: -0.26 to 0.52 mmol/L. In regression analysis, according to Passing-Bablok equation a systematic difference between both assays was found. In concordance analysis, the interrate realibility was very high (κ: 0.964). According to our resuls, although a systematic difference was detected when lactate levels were measured on RAPIDPoint 500 BGA, the results from Bland-Altman test and the high agreement rate support that this POCT analyzer could be useful for a early and safe detection of patients with high probability of increased CSF lactate level.

Nurses' perspectives on ethical aspects of telemedicine. A scoping review.

BACKGROUND: Changes in health needs led to an increase in virtual care practices such as telemedicine. Nursing plays an essential role in this practice as it is the key to accessing the healthcare system. It is important that this branch of nursing is developed considering all the ethical aspects of nursing care, and not just the legal concepts of the practice. However, this question has not been widely explored in the literature and it is of crucial relevance in the new concept of care. OBJECTIVE: The purpose of this scoping review is to identify the ethical aspects of the development of telemedicine from a nursing practice perspective. METHODS: A scoping review of the literature based on Arksey and O'Malley's framework. The search was conducted in Scopus, PubMed/MEDLINE and CINAHL databases, from 2012 to 2022. A total of 1322 articles were retrieved, of which 12 met the inclusion criteria. ETHICAL CONSIDERATIONS: The research was conducted in accordance with the best scientific practices. FINDINGS: The most relevant aspects were the safety of the patient, the benefits for the user and the digital competence of the professionals. Informed consent and patient's willingness to use new technologies were relevant to the practice, as was person-centered care and how telemedicine can influence the quality of the therapeutic relationship. Another relevant issue was the concern about professional competence for optimal outcomes. CONCLUSION: It is necessary to further explore and develop the ethical aspects of the new practices, disassociating them from the legal aspects only. Professionals demand more training providing them with more competence and confidence.

Allergy to fungi: Advances in the understanding of fungal allergens.

Allergic diseases are a major health problem due to their increasing incidence and high prevalence worldwide. Asthma has several aetiologies, and allergy plays an important role in its development in approximately 60% of adults and 80% of children and adolescents. Although the link between aeroallergen sensitization and asthma exacerbations has been long recognized, the investigations of the triggering allergens may be superficial in many asthma cases. The main allergenic sources related to asthma, and other allergic diseases, are pollens, mites, fungi, and animal epithelia. Fungi are considered the third most frequent cause of respiratory pathologies. Asthma caused by several fungi species may have a bad prognosis in some cases due to its severity and difficulty in avoidance methods. Despite the recognised relevance of fungi in respiratory allergies, the knowledge about fungal allergens seems to be scarce, with few descriptions of new allergens, compared to other allergenic sources. The study of major, minor, and cross-reactive fungal allergens, and their relevance in the allergic disease, might be crucial, not only to accurately diagnose these allergies, but also to predict exacerbations and responses to therapies, as well as for the development of personalized treatment plans in a fast-changing climate scenario.

Recurrent Glioblastoma: A Review of the Treatment Options.

Glioblastoma is a disease with a poor prognosis. Multiple efforts have been made to improve the long-term outcome, but the 5-year survival rate is still 5-10%. Recurrence of the disease is the usual way of progression. In this situation, there is no standard treatment. Different treatment options can be considered. Among them would be reoperation or reirradiation. There are different studies that have assessed the impact on survival and the selection of patients who may benefit most from these strategies. Chemotherapy treatments have also been considered in several studies, mainly with alkylating agents, with data mostly from phase II studies. On the other hand, multiple studies have been carried out with target-directed treatments. Bevacizumab, a monoclonal antibody with anti-angiogenic activity, has demonstrated activity in several studies, and the FDA has approved it for this indication. Several other TKI drugs have been evaluated in this setting, but no clear benefit has been demonstrated. Immunotherapy treatments have been shown to be effective in other types of tumors, and several studies have evaluated their efficacy in this disease, both immune checkpoint inhibitors, oncolytic viruses, and vaccines. This paper reviews data from different studies that have evaluated the efficacy of different forms of relapsed glioblastoma.

Mitofusin-2 in nucleus accumbens D2-MSNs regulates social dominance and neuronal function.

The nucleus accumbens (NAc) is a brain hub regulating motivated behaviors, including social competitiveness. Mitochondrial function in the NAc links anxiety with social competitiveness, and the mitochondrial fusion protein mitofusin 2 (Mfn2) in NAc neurons regulates anxiety-related behaviors. However, it remains unexplored whether accumbal Mfn2 levels also affect social behavior and whether Mfn2 actions in the emotional and social domain are driven by distinct cell types. Here, we found that subordinate-prone highly anxious rats show decreased accumbal Mfn2 levels and that Mfn2 overexpression promotes dominant behavior. In mice, selective Mfn2 downregulation in NAc dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) induced social subordination, accompanied by decreased accumbal mitochondrial functions and decreased excitability in D2-MSNs. Instead, D1-MSN-targeted Mfn2 downregulation affected competitive ability only transiently and likely because of an increase in anxiety-like behaviors. Our results assign dissociable cell-type specific roles to Mfn2 in the NAc in modulating social dominance and anxiety.

Molecular Mapping of Allergen Exposome among Different Atopic Phenotypes.

Climate change and exposure to environmental pollutants play a key role in the onset and aggravation of allergic diseases. As different climate-dependent patterns of molecular immunoglobulin E (IgE) reactivity have been regionally described, we sought to investigate the evolving allergen exposome in distinctive allergic phenotypes and subtropical weather conditions through a Precision Allergy Molecular Diagnosis (PAMD@) model. Concurrent sensitization to several house dust mites (HDM) and storage mite molecules were broadly dominant in the investigated cohort, followed by the major cat allergen Fel d 1, and regardless of the basal allergic disease. Although a complex repertoire of allergens was recognized, a steadily increasing number of IgE binding molecules was associated with the complexity of the underlying atopic disease. Besides the highly prevalent IgE responses to major HDM allergens, Der p 21, Der p 5, and Der p 7 also showed up as serodominant molecules, especially in subjects bothered by asthma and atopic dermatitis. The accurate characterization of the external exposome at the molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease in terms of personalized diagnosis and therapy.

Interobserver Variability in Contouring Hepatocellular Carcinoma at a Tertiary Center.

BACKGROUND/AIM: The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance imaging (MRI) allows for better visualization of the extent of tumor and will optimize the accuracy of tumor delineation for liver stereotactic radiotherapy compared with computed tomography (CT) only. We evaluated the interobserver agreement in GTV of hepatocellular carcinoma in a multicenter panel and compared MRI and CT in GTV delineation. MATERIALS AND METHODS: After the institutional review boards approved the study, we analyzed anonymous CT and MRI obtained from five patients with hepatocellular carcinoma. Eight radiation oncologists at our center used CT and MRI to delineate five GTVs of liver tumors. In both CT and MRI, the GTV volumes were compared. RESULTS: The median GTV volume on MRI was 2.4 cm3 (range=0.59-15.6 cm3) compared to 3.5 cm3 (range=0.52-24.9 cm3) on CT (p=0.36). The GTV volume as defined on MRI was larger or at least as large as the GTV volume on CT in two cases. Variance and standard deviation between observers in CT and MRI were minor (6 vs. 7.87 cm3, and 2.5 vs. 2.8 cm3 respectively). CONCLUSION: In cases with well-defined tumors, CT is easier and reproducible. In cases with no defined tumor in CT, other tools are needed and MRI can be complementary. The interobserver variability in target delineation of hepatocellular carcinoma in this study is noteworthy.

Adsorption of multiple NO molecules on Au10- and Au9Zn- planar clusters. A comparative DFT study.

The doping of atomic clusters with transition-metal atoms modifies to a lesser or greater extent the catalytic properties of the pure forms. Here we study by means of density functional theory (DFT) the adsorption of up to six NO molecules on Au10- and Au9Zn- clusters, both with well-tested D3h planar geometry, to learn how precise modifications of the atomic and electronic environment, namely one atom and a valence electron, affect the bonding of multiple NO molecules to anionic gold clusters. First, we confirm that these clusters have D3h symmetry as determined by L. S. Wang and coworkers using photoelectron spectroscopy experiments [Kulichenko et al., J. Phys. Chem. A, 2021, 125, 4606]. Second, we verify that Au10(NO)n- with n ≤ 6 does not form adsorbed (NO)2 dimers, as realized by the experiments of Ma and coworkers [Ma et al., Phys. Chem. Chem. Phys., 2020, 22, 25227] using a mini flow-tube reactor at 150 K. Third, we discover that the ground state of the doped Au9Zn(NO)6- compound forms a (NO)2cis-dimer bridging two non-corner Au atoms of the Au9Zn(NO)4- compound. The discussion of adsorption energies, spin multiplicities, bond lengths, charge trends, vibrational strength frequencies of adsorbed NO's, and projected density of states (PDOS), brings additional testable differences between Au10(NO)n- and Au9Zn(NO)n- compounds (n ≤ 6).

pH-Activated Dissolvable Polymeric Coatings to Reduce Biofouling on Electrochemical Sensors.

Implantable electrochemical sensors that enable the real-time detection of significant biomarkers offer huge potential for the enhancement and personalisation of therapies; however, biofouling is a key challenge encountered by any implantable system. This is particularly an issue immediately after implantation, when the foreign body response and associated biofouling processes are at their most active in passivating a foreign object. Here, we present the development of a sensor protection and activation strategy against biofouling, based on coatings consisting of a pH-triggered, dissolvable polymer, that covered a functionalised electrode surface. We demonstrate that reproducible delayed sensor activation can be achieved, and that the length of this delay can be controlled by the optimisation of coating thickness, homogeneity and density through tuning of the coating method and temperature. Comparative evaluation of the polymer-coated and uncoated probe-modified electrodes in biological media revealed significant improvements in their anti-biofouling characteristics, demonstrating that this offers a promising approach to the design of enhanced sensing devices.

Going over Fungal Allergy: Alternaria alternata and Its Allergens.

Fungal allergy is the third most frequent cause of respiratory pathologies and the most related to a poor prognosis of asthma. The genera Alternaria and Cladosporium are the most frequently associated with allergic respiratory diseases, with Alternaria being the one with the highest prevalence of sensitization. Alternaria alternata is an outdoor fungus whose spores disseminate in warm and dry air, reaching peak levels in temperate summers. Alternaria can also be found in damp and insufficiently ventilated houses, causing what is known as sick building syndrome. Thus, exposure to fungal allergens can occur outdoors and indoors. However, not only spores but also fungal fragments contain detectable amounts of allergens and may function as aeroallergenic sources. Allergenic extracts of Alternaria hyphae and spores are still in use for the diagnosis and treatment of allergic diseases but are variable and insufficiently standardised, as they are often a random mixture of allergenic ingredients and casual impurities. Thus, diagnosis of fungal allergy has been difficult, and knowledge about new fungal allergens is stuck. The number of allergens described in Fungi remains almost constant while new allergens are being found in the Plantae and Animalia kingdoms. Given Alt a 1 is not the unique Alternaria allergen eliciting allergy symptoms, component-resolved diagnosis strategies should be applied to diagnose fungal allergy. To date, twelve A. alternata allergens are accepted in the WHO/IUIS Allergen Nomenclature Subcommittee, many of them are enzymes: Alt a 4 (disulfide isomerase), Alt a 6 (enolase), Alt a 8 (mannitol de-hydrogenase), Alt a 10 (aldehyde dehydrogenase), Alt a 13 (glutathione-S-transferase) and Alt a MnSOD (Mn superoxide dismutase), and others have structural and regulatory functions such as Alt a 5 and Alt a 12, Alt a 3, Alt a 7. The function of Alt a 1 and Alt a 9 remains unknown. Other four allergens are included in other medical databases (e.g., Allergome): Alt a NTF2, Alt a TCTP, and Alt a 70 kDa. Despite Alt a 1 being the A. alternata major allergen, other allergens, such as enolase, Alt a 6 or MnSOD, Alt a 14 have been suggested to be included in the diagnosis panel of fungal allergy.

Evaluación de la madurez del menor en el ámbito sanitario: la perspectiva de padres y pediatras / Assessment of the maturity of the minor in the health field: the perspective of parents and pediatricians

Introducción: el modelo de respeto a la autonomía y de participación progresiva en el contexto pediátrico requiere que el pediatra que atiende al paciente menor sea capaz de evaluar y decidir si este presenta suficiente madurez y es competente para tomar una decisión sanitaria, o en qué grado participa en la misma. El objetivo es determinar la correlación entre la valoración de la madurez del menor realizada por parte de pediatras y de padres de forma subjetiva, con la realizada mediante una prueba objetiva, la Escala de Valoración de la Madurez de Lleida, MadurTest. Material y métodos: estudio prospectivo, observacional y transversal; 199 adolescentes de entre 12 y 16 años, con patología aguda y crónica. Se evaluó la madurez de los pacientes con la escala MadurTest, y los pediatras y los padres valoraron la madurez del menor con preguntas de la escala Likert para madurez. Resultados: la media de la puntuación de MadurTest fue de 6,39, presentando las niñas un nivel de madurez superior a los niños en la mayoría de las franjas de edad. La valoración de madurez por parte de los pediatras fue de 3,18 de media y por parte de los padres de 3,18. No se observa correlación entre la puntuación obtenida en el MadurTest con la valoración por parte de los profesionales ni por parte de los padres. No obstante, se observa una correlación entre las valoraciones efectuadas por los padres y los profesionales (r = 0,73; p <0,00001). Conclusiones: la madurez de los menores valorada de forma subjetiva por pediatras y padres no se correlaciona con la madurez evaluada de forma objetiva mediante el test MadurTest (AU)

Introduction: the model of respect for autonomy and progressive participation in the pediatric context requires that attending pediatricians be able to assess minor maturity, and decide the degree of participation. The objective of this study is to determine the correlation between the assessment made subjectively by paediatricians and parents, with the maturity of the minor carried out by means of an objective test, the Lleida Maturity Assessment Scale, MadurTest.Material and methods: prospective, observational and cross-sectional study. 199 adolescents between 12 and 16 years old, affected by acute and chronic pathology. The maturity of the patients was evaluated with the MadurTest scale and pediatricians and parents assessed the maturity of the minor in the form of the Likert maturity scale.Results: the mean of the MadurTest score is 6.39, girls present a higher level of maturity than boys in most age groups. The maturity assessment by pediatricians is 3.18 on average and by parents 3.18. No correlation is observed between the score obtained with the MadurTest and the assessment by professionals or by parents. However, a correlation is observed between the assessments made by parents and professionals (r = 0.73, p <0.00001)Conclusions: the maturity of minors assessed subjectively by paediatricians and parents does not correlate with the maturity assessed objectively using the MadurTest. (AU)

Machine learning for industrial processes: Forecasting amine emissions from a carbon capture plant.

One of the main environmental impacts of amine-based carbon capture processes is the emission of the solvent into the atmosphere. To understand how these emissions are affected by the intermittent operation of a power plant, we performed stress tests on a plant operating with a mixture of two amines, 2-amino-2-methyl-1-propanol and piperazine (CESAR1). To forecast the emissions and model the impact of interventions, we developed a machine learning model. Our model showed that some interventions have opposite effects on the emissions of the components of the solvent. Thus, mitigation strategies required for capture plants operating on a single component solvent (e.g., monoethanolamine) need to be reconsidered if operated using a mixture of amines. Amine emissions from a solvent-based carbon capture plant are an example of a process that is too complex to be described by conventional process models. We, therefore, expect that our approach can be more generally applied.

SARS-CoV-2 Virus in Cancer Patients: A New Unknown in an Unsolved Equation.

INTRODUCTION: Cancer patients are more susceptible to infections, and infection can be more severe than in patients without cancer diagnosis. We conducted this retrospective study in patients admitted for SARS-CoV-2 infection in order to find differences in inflammatory markers and mortality in cancer patients compared to others. METHODS: We reviewed the electronic records of patients admitted for SARS-CoV-2 infection confirmed by PCR from March to September 2020. Data on socio-demographics, comorbidities, inflammatory makers, and cancer-related features were analyzed. RESULTS: 2,772 patients were admitted for SARS-CoV-2, to the Hospital Universitario Ramón y Cajal in Madrid during this period. Of these, 2,527 (91%) had no history of neoplastic disease, 164 (5.9%) patients had a prior history of cancer but were not undergoing oncological treatment at the time of infection, and 81 (2.9%) were in active treatment. Mortality in patients without a history of cancer was 19.5%, 28.6% for patients with a prior history of cancer, and 34% in patients with active cancer treatment. Patients in active oncology treatment with the highest mortality rate were those diagnosed with lung cancer (OR 5.6 95% CI: 2.2-14.1). In the multivariate study, active oncological treatment (OR 2.259 95% CI: 1.35-3.77) and chemotherapy treatment (OR 3.624 95% CI: 1.17-11.17), were statistically significant factors for the risk of death for the whole group and for the group with active oncological treatment, respectively. CONCLUSION: Cancer patients on active systemic treatment have an increased risk of mortality after SARS-CoV-2 infection, especially with lung cancer or chemotherapy treatment.

Interobserver variability in gross tumor volume contouring in non-spine bone metastases.

Background and Aim: The optimal imaging test for gross tumor volume (GTV) delineation in non-spine bone metastases has not been defined. The use of stereotactic body radiotherapy (SBRT) requires accurate target delineation. Magnetic resonance imaging (MRI) and/or 18fludesoxyglucose positron emission tomography (18FDG-PET) allow for better visualization of the extent of bone metastases and optimizes the accuracy of tumor delineation for stereotactic radiotherapy compared to computed tomography (CT) alone. We evaluated the interobserver agreement in GTV of non-spine bone metastases in a single center and compared MRI and/or 18FDG-PET and CT in GTV delineation. Methods: Anonymous CT and MRI and/or 18FDG-PET obtained from 10 non-spine bone metastases were analyzed by six radiation oncologists at our center. Images acquired by CT and MRI and/or 18FDG-PET were used to delineate 10 GTVs of non-spine bone metastases in the pelvis, extremities, and skull. The cases showed different characteristics: blastic and lytic metastases, and different primary cancers (lung, breast, prostate, rectum, urothelial, and biliary). In both CT and MRI and/or 18FDG-PET, the GTV volumes were compared. The index of agreement was evaluated according to Landis and Koch protocol. Results: The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT (P=0.25). The median GTV volume on MRI was 3.15 cc (0.027-70.64 cc) compared to 2.8 cc on CT (0.075-77.95 cc). Interobserver variance and standard deviation were lower in CT than MRI (576.3 vs. 722.2 and 24.0 vs. 26.9, respectively). The level of agreement was fair (kappa=0.36) between CT and MRI. The median GTV volume on 18FDG-PET in five patients was 5.8 cc (0.46-64.17 cc), compared to 4.1 cc on CT (0.99-54.2 cc) (P=0.236). Interobserver variance and standard deviation in CT, MRI, and 18FDG-PET were 576.3 versus 722.2 versus 730.5 and 24 versus 26.9 versus 27.0, respectively. The level of agreement was slight (kappa=0.08) between CT and 18FDG-PET. Conclusions: Interobserver variance in non-spine bone metastases was equal when MRI and PET were compared to CT. CT was associated with the lowest variance and standard deviation. Compared to CT GTVs, the GTVs rendered from MRI images had fair agreement, while the GTVs rendered from 18FDG-PET had only slight agreement. Relevance for Patients: The delimitation of the treatment volume in non-spine bone metastases with SBRT is important for the results determining its efficacy. It is therefore essential to know the variability and to manage it to achieve the highest quality of treatment.

Family presence during invasive procedures: a pilot study to test a tool.

BACKGROUND: Family Presence During Invasive Procedures (FPDI) generates controversy among healthcare professionals. Twibell and her team designed an instrument that measured nurses' Risk-Benefit and Self-Confidence perceptions regarding family presence during resuscitation and was used in numerous studies. OBJECTIVES: Evaluate the new tool for Family Presence Risk-Benefit and Family Presence Self-Confidence during invasive procedures and find out the opinions of the medical and nursing staff on FPDIP. METHOD: Cross-sectional methodological pilot study. Online and paper questionnaires modified from a previous translation. A factor analysis was performed for the validity of the indices and bivariate analysis for all the variables. Ethical approvals and research permissions were obtained according to national standards. RESULTS: One hundred twenty healthcare professionals (22.18%) answered the survey. Cronbach's α on the Family Presence Risk-Benefit scale was 0.877. Cronbach's α on the Family Presence Self-Confidence scale was 0.937. The correlation between the Risk-Benefit and Self-confidence variables is significant and with a moderate intensity of the relationship. A lower predisposition to Family Presence During Invasive Procedures is observed. Physicians are more reluctant than nurses. CONCLUSIONS: The FPDI generates controversy as it alters health professionals' routines when they decide whether to allow it or not. There is a tendency for younger professionals to support FPDI. In general, health professionals, mainly physicians, do not favor FPDI. Health workers who perceive fewer risks and more benefits in FPDI and have greater self-confidence are more in favor of FPDI. The psychometric properties and internal consistency of the questionnaire indicate the validity and reliability of this tool.

Glutathione in the nucleus accumbens regulates motivation to exert reward-incentivized effort.

Emerging evidence is implicating mitochondrial function and metabolism in the nucleus accumbens in motivated performance. However, the brain is vulnerable to excessive oxidative insults resulting from neurometabolic processes, and whether antioxidant levels in the nucleus accumbens contribute to motivated performance is not known. Here, we identify a critical role for glutathione (GSH), the most important endogenous antioxidant in the brain, in motivation. Using proton magnetic resonance spectroscopy at ultra-high field in both male humans and rodent populations, we establish that higher accumbal GSH levels are highly predictive of better, and particularly, steady performance over time in effort-related tasks. Causality was established in in vivo experiments in rats that, first, showed that downregulating GSH levels through micro-injections of the GSH synthesis inhibitor buthionine sulfoximine in the nucleus accumbens impaired effort-based reward-incentivized performance. In addition, systemic treatment with the GSH precursor N-acetyl-cysteine increased accumbal GSH levels in rats and led to improved performance, potentially mediated by a cell-type-specific shift in glutamatergic inputs to accumbal medium spiny neurons. Our data indicate a close association between accumbal GSH levels and an individual's capacity to exert reward-incentivized effort over time. They also suggest that improvement of accumbal antioxidant function may be a feasible approach to boost motivation.

Variation in SARS-CoV-2 seroprevalence in children in the region of Asturias, Northern Spain.

BACKGROUND: Updated seroprevalence estimates are important to describe the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) landscape and to guide public health decisions. The aims are to describe longitudinal changes in seroprevalence in children in a region in Northern Spain and to analyze factors associated with SARS-CoV-2 seropositivity. METHODS: Prospective multicenter longitudinal study with subjects recruited from July to September 2020. Children (up to 14 years old) were included and followed up until September 2021. Venous blood samples were collected every six months during three testing rounds and were analyzed for SARS-CoV-2 antibodies. The data regarding epidemiological features, contact tracing, symptoms, and virological tests were collected. The evolution of SARS-CoV-2 seroprevalence during the study and the differences between children with positive and negative SARS-CoV-2 antibody tests were analyzed. RESULTS: Two hundred children were recruited (50.5% girls, median age 9.7 years). The overall seroprevalence increased from round 1 [1.5%, 95% confidence interval (CI) 0.3%-4.3%] to round 2 (9.1%, 95% CI 4.6%-12.7%) and round 3 (16.6%, 95% CI 9.5%-19.6%) (P < 0.001). Main changes occurred in children aged zero to four years (P = 0.001) who lived in urban areas (P < 0.001). None of the children who were previously positive became seronegative. Following multivariable analysis, three variables independently associated with SARS-CoV-2 seropositivity were identified: close contact with coronavirus disease 2019 (COVID-19) confirmed or suspected cases [odds ratio (OR) = 3.9, 95% CI 1.2-12.5], previous positive virological test (OR = 17.1, 95% CI 3.7-78.3) and fatigue (OR = 18.1, 95% CI 1.7-193.4). CONCLUSIONS: SARS-CoV-2 seroprevalence in children has remarkably increased during the time of our study. Fatigue was the only COVID-19-compatible symptom that was more frequent in seropositive than in seronegative children.

Biomarkers for Immunotherapy in Poorly Differentiated Sinonasal Tumors.

The sinonasal cavities harbor a wide variety of rare cancer types. Histopathological classification can be challenging, especially for poorly differentiated tumors. Despite advances in surgery and radio-chemotherapy, the 5-year survival rate is still very low. Thus, there is an unmet clinical need for new therapeutic options. We retrospectively evaluated poorly differentiated tumors of 9 different histological subtypes from 69 patients who had received conventional treatments for the presence of CD8+ tumor-infiltrating lymphocytes (TILs), as well as the expression of PD-L1 and microsatellite instability (MSI) markers MLH1, MSH2, MSH6 and PMS2, as biomarkers for immunotherapy. CD8+ TILs were present in 23/69 (33%) cases, PD-L1 expression was observed in 23/69 (33%), and markers for MSI positivity in 5/69 (7%) cases. CD8+ TILs correlated with PD-L1 positivity, while both were mutually exclusive with MSI markers. None of the biomarkers were associated with clinical features as age, gender or tumor stage. Cases with CD8+ TILs and PD-L1 positivity showed a tendency toward worse disease-specific survival. Immune checkpoint inhibitors are emerging as new options for treatment of many tumor types. Our results indicate that also a substantial subset of patients with poorly differentiated sinonasal tumors may be a candidate to be treated with this promising new therapy.