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Asthma and rhinitis often co-exist in the same patient. Although some authors observed a higher prevalence and/or greater severity of asthma in patients with rhinitis, this view is not homogeneous and the debate continues. The aim of our study is to describe the prevalence of rhinitis in children and adolescents and to analyse their relationship with the prevalence of asthma. A multicentre study was conducted using the methodology of the International Study of Asthma and Allergies in Childhood (ISAAC). The target population of the study was all those school children aged 6–7 and 13–14 years from 6 of the main health catchment areas of Galicia (1.9 million inhabitants). The schools required were randomly selected, and all children in the targeted age ranges were included. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) between asthma symptoms of the schoolchildren and rhinitis prevalence. The results were adjusted for parental smoking habits, maternal education level, cat and dog exposure, and obesity. A total of 21,420 valid questionnaires were finally obtained. Rhinitis was associated with a significant increase in the prevalence of asthma in both age groups. The highest OR were 11.375 for exercise induced asthma (EIA) for children with recent rhinoconjunctivitis and 9.807 for children with recent rhinitis in 6–7 years old group. The prevalence OR’s are higher in EIA and severe asthmatics. Rhinitis in children and adolescents is associated with a higher prevalence and severity of asthma.

The specific metabolic contribution of consuming different energy-yielding macronutrients (namely, carbohydrates, protein and lipids) to obesity is a matter of active debate. In this Review, we summarize the current research concerning associations between the intake of different macronutrients and weight gain and adiposity. We discuss insights into possible differential mechanistic pathways where macronutrients might act on either appetite or adipogenesis to cause weight gain. We also explore the role of dietary macronutrient distribution on thermogenesis or energy expenditure for weight loss and maintenance. On the basis of the data discussed, we describe a novel way to manage excessive body weight; namely, prescribing personalized diets with different macronutrient compositions according to the individual’s genotype and/or enterotype. In this context, the interplay of macronutrient consumption with obesity incidence involves mechanisms that affect appetite, thermogenesis and metabolism, and the outcomes of these mechanisms are altered by an individual’s genotype and microbiota. Indeed, the interactions of the genetic make-up and/or microbiota features of a person with specific macronutrient intakes or dietary pattern consumption help to explain individualized responses to macronutrients and food patterns, which might represent key factors for comprehensive precision nutrition recommendations and personalized obesity management.This Review summarizes the process involved in the metabolism of macronutrients (carbohydrates, lipids and proteins) with a focus on the physiological and neuroendocrine aspects. The associations between macronutrients and obesity are also discussed in the context of factors such as genetics and the microbiome composition.

Patients with cirrhosis may show minimal hepatic encephalopathy (MHE), for which rifaximin is effective. Metabolic syndrome may be associated with cognitive impairment. Our aims were to evaluate the influence of metabolic syndrome features on response to rifaximin for neurological and inflammatory alterations in MHE. A prospective cohort study was conducted in 63 cirrhotic patients and 30 controls from two tertiary centres recruited between 2015 and 2019. Metabolic syndrome was defined according to the Adult Treatment Panel-III. Patients were classified into 31 without and 32 with MHE according to the Psychometric Hepatic Encephalopathy Score (PHES). All participants performed specific psychometric tests, and inflammatory parameters were studied. Patients with MHE received rifaximin (400 mg/8 h). Response was evaluated by PHES at 3 and 6 months. Response according to metabolic syndrome manifestations was compared. The response rate was 66%. Older age ( p  = 0.012) and all metabolic syndrome diseases ( p  < 0.05) were associated with non-response, plus an increase in risk as the number of manifestations rose ( p  < 0.001). Patients with metabolic manifestations exhibited worse processing speed ( p  = 0.011), working memory ( p  = 0.005), visual coordination ( p  = 0.013) and lower proportion of activated CD4 + lymphocytes ( p  = 0.039) at baseline, as well as worse concentration ( p  = 0.030), bimanual coordination ( p  = 0.004) and higher levels of intermediate monocytes ( p  = 0.026), CX3CL1 ( p  < 0.05), IL-17 ( p  = 0.022), AHR ( p  = 0.010) and IgG ( p  < 0.05) at 3 and/or 6 months of rifaximin. Patients with clinical signs of metabolic syndrome have poor response to rifaximin for MHE, with a higher proportion of neurological alterations associated with a pro-inflammatory environment.

Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from the Spanish Myeloma Group, involving a total of 1347 patients (847 transplant candidates). Regarding the GEM2010 > 65 trial, antibiotic prophylaxis was mandatory, so we excluded it from the final analysis. The incidence of severe infection episodes within the first 6 months was 13.8%, and majority of the patients experiencing the first episode before 4 months (11.1%). 1.2% of patients died because of infections within the first 6 months (1% before 4 months). Variables associated with increased risk of severe infection in the first 4 months included serum albumin ≤30 g/L, ECOG > 1, male sex, and non-IgA type MM. A simple risk score with these variables facilitated the identification of three risk groups with different probabilities of severe infection within the first 4 months: low-risk (score 0–2) 8.2%; intermediate-risk (score 3) 19.2%; and high-risk (score 4) 28.3%. Patients with intermediate/high risk could be candidates for prophylactic antibiotic therapies.

Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults ( n  = 4) and patients with precursor ( n  = 8) and full-blown MM ( n  = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27 − and CD27 + T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations. Myelomagenesis progresses through well-defined pre-malignant states. Here, using single-cell RNA sequencing and T cell receptor repertoire analysis of bone marrow T cells in patients at different stages of myelomagenesis, the authors identify large clonotypic expansions characterized by the expression of multiple immune checkpoints.

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P  < 0.001) and overall survival (HR: 0.73, P  = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that “real-world” assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.

Multimorbidity is one of the biggest challenges faced by modern medicine, especially when managing older patients who are also often taking multiple medications. Multimorbidity is influenced by social determinants of health, giving rise to health inequalities in the population. Here, we sought to determine the influence of social determinants of health on quality of life in patients with multimorbidity and polypharmacy. This cross-sectional observational study included 573 patients aged 65-74 with multimorbidity (≥3 diseases) and polypharmacy (≥5 drugs). Corresponding data was taken drawn from the Spanish MULTIPAP study, and included social and demographic variables, and data on health-related quality of life and overall self-perceived health status, assessed using the 5-level version of the EuroQol 5-dimensional questionnaire (EQ-5D-5L). Descriptive, bivariate and multivariate analyses with logistic regression models were performed. Mean patient age was 69.7 years, 55.8% of patients were female, 59.7% belonged to low social classes (V, VI), a monthly income of €1051-€1850 predominated, and the median number of diseases in the same patient was 6. Factors associated with higher quality of life were (odds ratio, OR) male gender (OR = 1.599, p = 0.013), a higher educational level (OR = 1.991, p = 0.036), an absence of urban vulnerability (OR = 1.605, p = 0.017), and the presence of medium social support (OR = 1.689, p = 0.017). Having a higher number of diseases was associated with poorer quality of life (OR = 0.912, p = 0.017). Our findings describe associations between social determinants of health and quality of life in patients aged 65-74 years with multimorbidity and polypharmacy. More illnesses, female gender, a lower education level, urban vulnerability, and less social support are associated with poorer quality of life, underscoring the need for a biopsychosocial approach in patient care.

To describe the prevalence of dementia and subtypes in a general elderly population in northwestern Spain and to analyze the influence of socio-demographic factors. Cross-sectional, two-phase, door-to-door, population-based study. A total of 870 individuals from a rural region and 2,119 individuals from an urban region of Valladolid, Spain, were involved. The seven-minute screen neurocognitive battery was used in the screening phase. A control group was included. A total of 2,170 individuals aged 65 to 104 years (57% women) were assessed. There were 184 subjects diagnosed with dementia. The crude prevalence was 8.5% (95% CI: 7.3-9.7). Age- and sex-adjusted prevalence was 5.5 (95% CI: 4.5-6.5). Main subtypes of dementia were: Alzheimer's disease (AD) 77.7%, Lewy Body disease, 7.6% and vascular dementia (VD) 5.9%. Crude prevalences were 6.6% (AD), 0.6% (Lewy Body disease), and 0.5% (VD). Dementia was associated with age (OR 1.14 for 1-year increase in age), female sex (OR 1.79) and the absence of formal education (OR 2.53 compared to subjects with primary education or more). The prevalence of dementia in the study population was lower than the most recent estimates for Western Europe. There was a high proportion of AD among all dementia cases and very low prevalence of VD. Old age, female sex, and low education level were independent risk factors for dementia and AD.

Wilson reviews A Reference Grammar of Spanish by R. E. Batchelor and Miguel Angel San Jose.