Biofungicides Based on Plant Extracts: On the Road to Organic Farming.

Phytopathogenic fungi are responsible for diseases in commercially important crops and cause major supply problems in the global food chain. Plants were able to protect themselves from disease before humans played an active role in protecting plants. They are known to synthesize a variety of secondary metabolites (SMs), such as terpenes, alkaloids, and phenolic compounds, which can be extracted using conventional and unconventional techniques to formulate biofungicides; plant extracts have antifungal activity and various mechanisms of action against these organisms. In addition, they are considered non-phytotoxic and potentially effective in disease control. They are a sustainable and economically viable alternative for use in agriculture, which is why biofungicides are increasingly recognized as an attractive option to solve the problems caused by synthetic fungicides. Currently, organic farming continues to grow, highlighting the importance of developing environmentally friendly alternatives for crop production. This review provides a compilation of the literature on biosynthesis, mechanisms of action of secondary metabolites against phytopathogens, extraction techniques and formulation of biofungicides, biological activity of plant extracts on phytopathogenic fungi, regulation, advantages, disadvantages and an overview of the current use of biofungicides in agriculture.

Analysis of Diagnostic Delay and its Impact on Lung Cancer Survival: Results From the Spanish Thoracic Tumor Registry.

BACKGROUND: Early detection is crucial to improve lung cancer survival rates. Delays in diagnosis might negatively impact the prognosis of the disease. This study aims to analyze the diagnostic delay in lung cancer patients and describe if there is an association between delay and survival. METHODS: The data source used was the Thoracic Tumor Registry of the Spanish Lung Cancer Group. This analysis was restricted to lung cancer cases with information on the first date of consultation by symptoms and date of diagnosis. The delay was calculated as the number of days between the two dates. A descriptive analysis was performed, and ordinal logistic regressions were fitted with delay as the dependent variable. Kaplan-Meier survival analysis and Cox regression were performed. RESULTS: 22,755 lung cancer cases were included. Never smokers were 1.16 (95%CI: 1.06-1.27) times more likely to register longer delay than smokers. Stage 0-I-II cases had a 3.09 (95%CI: 2.88-3.32) higher risk of longer delay compared to III-IV stages. Overall, 5-year survival rate after diagnosis was 23.64% (95%CI: 22.88-24.41). In those categorized as having the shortest delay 5-year survival was 17.67% (95%CI: 16.31-19.07) and in the extreme delay it was 32.98% (95%CI: 31.28-34.69) (p<0.001). Adjusted mortality risk was higher in those with the shortest delay (HR 1.36, CI95%: 1.30-1.43) in comparison with the extreme delay. CONCLUSIONS: Diagnostic delay is short among Spanish lung cancer patients, indicating a relatively quick diagnostic process. Extreme delays appear to be associated with higher survival rates, possibly attributed to slow-growing tumors, earlier stage at diagnosis or basically the natural history of this disease.

Advanced non-squamous NSCLC with no actionable oncogenic driver in Spain: a cross-sectional descriptive analysis of data from the Thoracic Tumor Registry.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the vast majority of all diagnosed lung cancers. According to their histology, most NSCLCs are considered non-squamous cell carcinoma (NSCC), and up to 85% of the latter may lack either one of the two main actionable oncogenic drivers (i.e., EGFR mutations and ALK rearrangements). OBJECTIVE: Our analysis aimed to describe the clinical and epidemiological characteristics of Spanish patients suffering from NSCC with no actionable oncogenic driver in daily clinical practice. DESIGN: A retrospective, cross-sectional, descriptive analysis. METHODS: We analyzed the records of all Spanish patients with advanced NSCC diagnosed between January 2011 and January 2020 and included in the Spanish Thoracic Tumor Registry database. We evaluated the presence of metastasis and molecular profiling at the time of diagnosis and treatments received. We also assessed overall survival (OS) and progression-free survival (PFS) according to first-line treatment. RESULTS: One thousand seven hundred ninety-seven Spanish patients with NSCC were included. They were mainly men (73.2%), smokers (current [44.4%] and former [44.4%]) and presented adenocarcinoma histology (97.6%). Most patients had at least one comorbidity (80.4%) and one metastatic site (96.8%), and a non-negligible number of those tested were PD-L1 positive (35.2%). Notably, the presence of liver metastasis indicated a shorter median OS and PFS than metastasis in other locations (p < 0.001). Chemotherapy was more often prescribed than immunotherapy as first-, second-, and third-line treatment in that period. In first-line, the OS rates were similar in patients receiving either regimen, but PFS rates significantly better in patients treated with immunotherapy (p = 0.026). Also, a high number of patients did not reach second- and third-line treatment, suggesting the failure of current early diagnostic measures and therapies. CONCLUSIONS: This analysis of the most lethal tumor in Spain could highlight the strengths and the weaknesses of its clinical management and set the ground for further advances and research.

Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci.

BACKGROUND: Vision depends on the interplay between photoreceptor cells of the neural retina and the underlying retinal pigment epithelium (RPE). Most genes involved in inherited retinal diseases display specific spatiotemporal expression within these interconnected retinal components through the local recruitment of cis-regulatory elements (CREs) in 3D nuclear space. RESULTS: To understand the role of differential chromatin architecture in establishing tissue-specific expression at inherited retinal disease loci, we mapped genome-wide chromatin interactions using in situ Hi-C and H3K4me3 HiChIP on neural retina and RPE/choroid from human adult donor eyes. We observed chromatin looping between active promoters and 32,425 and 8060 candidate CREs in the neural retina and RPE/choroid, respectively. A comparative 3D genome analysis between these two retinal tissues revealed that 56% of 290 known inherited retinal disease genes were marked by differential chromatin interactions. One of these was ABCA4, which is implicated in the most common autosomal recessive inherited retinal disease. We zoomed in on retina- and RPE-specific cis-regulatory interactions at the ABCA4 locus using high-resolution UMI-4C. Integration with bulk and single-cell epigenomic datasets and in vivo enhancer assays in zebrafish revealed tissue-specific CREs interacting with ABCA4. CONCLUSIONS: Through comparative 3D genome mapping, based on genome-wide, promoter-centric, and locus-specific assays of human neural retina and RPE, we have shown that gene regulation at key inherited retinal disease loci is likely mediated by tissue-specific chromatin interactions. These findings do not only provide insight into tissue-specific regulatory landscapes at retinal disease loci, but also delineate the search space for non-coding genomic variation underlying unsolved inherited retinal diseases.

The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

Describing differences among populations of thoracic tumors patients under and over 80 years: Data analysis from the SLCG thoracic tumor registry.

OBJECTIVES: Cancer is a disease of old age; however, most studies usually included minority of patients fit elderly. The purpose is to investigate the clinical characteristics and genetic information of patients with thoracic tumors who are 80 years old or older compared to those under 80 years old. STUDY DESIGN AND METHODS: The Thoracic Tumor Registry (TTR) is a Spanish observational, prospective cohort study that included patients diagnosed with thoracic tumors. Data were collected from medical records related to sociodemographic, epidemiological, clinical, molecular/genetic, and treatment outcome variables. RESULTS: The total number of patients, recruited from August 2016 to April 2023, was 26.193 (93,1 % were younger than 80 years and 6,9 % were 80 years or older). In the group of older patients: the male ratio increased (72,9 % vs. 80 %); the number of elderly people who had never smoked or were ex-smokers increased (9,9 % vs. 21,1 % and 44,8 % vs. 61,3 %, respectively) and the number of current smokers decreased (43,3 % vs. 17,5 %); had higher ECOG performance status at diagnosis (for ECOG ≥ 2, 15 % vs. 32,9 %), and there were more patients with previous cancer (17,3 % vs. 28 %). The proportion of men is higher than that of women (73 % vs. 27 % in <80 years and 80 % vs. 20 % in ≥80 years). For all biomarkers, the proportion of patients who had a molecular determination was lower in older patients. There were no differences in terms of alterations in the biomarkers tested; except for EGFR, for which the positivity rate was higher in patients aged 80 years and older (25 % vs. 15,3 %). CONCLUSION: The proportion of older patients with targeted mutations is higher. So, at least at diagnosis, it should be proceeded in a standard way. Then, when it comes to treatment, comorbidities and patient's baseline situation should be considered. CLINICAL TRIAL REGISTRATION: NCT02941458.

From strength to precision: A systematic review exploring the clinical utility of 7-Tesla magnetic resonance imaging in abdominal imaging.

BACKGROUND: After approval for clinical use in 2017 early investigations of ultra-high-field abdominal magnetic resonance imaging (MRI) have demonstrated the feasibility as well as diagnostic capabilities of liver, kidney, and prostate MRI at 7-Tesla. However, the elevation of the field strength to 7-Tesla not only brought advantages to abdominal MRI but also presented considerable challenges and drawbacks, primarily stemming from heightened artifacts and limitations in Specific Absorption Rate, etc. Furthermore, evidence in the literature is relatively scarce concerning human studies in comparison to phantom/animal studies which necessitates an investigation into the evidence so far in humans and summarizing all relevant evidence. AIM: To offer a comprehensive overview of current literature on clinical abdominal 7T MRI that emphasizes current trends, details relevant challenges, and provides a concise set of potential solutions. METHODS: This systematic review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A PubMed search, utilizing Medical Subject Headings terms such as "7-Tesla" and organ-specific terms, was conducted for articles published between January 1, 1985, and July 25, 2023. Eligibility criteria included studies exploring 7T MRI for imaging human abdominal organs, encompassing various study types (in-vivo/ex-vivo, method development, reviews/meta-analyses). Exclusion criteria involved animal studies and those lacking extractable data. Study selection involved initial identification via title/abstract, followed by a full-text review by two researchers, with discrepancies resolved through discussion. Data extraction covered publication details, study design, population, sample size, 7T MRI protocol, image characteristics, endpoints, and conclusions. RESULTS: The systematic review included a total of 21 studies. The distribution of clinical 7T abdominal imaging studies revealed a predominant focus on the prostate (n = 8), followed by the kidney (n = 6) and the hepatobiliary system (n = 5). Studies on these organs, and in the pancreas, demonstrated clear advantages at 7T. However, small bowel studies showed no significant improvements compared to traditional MRI at 1.5T. The majority of studies evaluated originated from Germany (n = 10), followed by the Netherlands (n = 5), the United States (n = 5), Austria (n = 2), the United Kingdom (n = 1), and Italy (n = 1). CONCLUSION: Further increase of abdominal clinical MRI field strength to 7T demonstrated high imaging potential, yet also limitations mainly due to the inhomogeneous radiofrequency (RF) excitation field relative to lower field strengths. Hence, further optimization of dedicated RF coil elements and pulse sequences are expected to better optimize clinical imaging at high magnetic field strength.

Human neutrophil elastase inhibitors: Classification, biological-synthetic sources and their relevance in related diseases.

BACKGROUND: Human neutrophil elastase is a multifunctional protease enzyme whose function is to break the bonds of proteins and degrade them to polypeptides or amino acids. In addition, it plays an essential role in the immune mechanism against bacterial infections and represents a key mediator in tissue remodeling and inflammation. However, when the extracellular release of this enzyme is dysregulated in response to low levels of its physiological inhibitors, it ultimately leads to the degradation of proteins, in particular elastin, as well as other components of the extracellular matrix, producing injury to epithelial cells, which can promote sustained inflammation and affect the innate immune system, and, therefore, be the basis for the development of severe inflammatory diseases, especially those associated with the cardiopulmonary system. OBJECTIVE: This review aims to provide an update on the elastase inhibitory properties of several molecules, either synthetic or biological sources, as well as their classification and relevance in related pathologies since a clear understanding of the function of these molecules with the inhibitory capacity of this protease can provide valuable information for the development of pharmacological therapies that manage to modify the prognosis and survival of various inflammatory diseases. METHODS: Collected data from scientific databases, including PubMed, Google Scholar, Science Direct, Nature, Wiley, Scopus, and Scielo. Articles published in any country and language were included. RESULTS: We reviewed and included 132 articles conceptualizing neutrophil elastase activity and known inhibitors. CONCLUSION: Understanding the mechanism of action of elastase inhibitors based on particular aspects such as their kinetic behavior, structure-function relationship, chemical properties, origin, pharmacodynamics, and experimental progress has allowed for a broad classification of HNE inhibitors.

Comparison of Clinical and Genetic Characteristics Between Younger and Older Lung Cancer Patients.

INTRODUCTION: The aim of this study was to analyze the clinical and genetic characteristics of young lung cancer cases, and to compare them with those of older cases. METHODS: We used the Thoracic Tumors Registry (TTR) as a data source representative of lung cancer cases diagnosed in Spain, and included all cases registered until 9/01/2023 which had information on age at diagnosis or the data needed to calculate it. We performed a descriptive statistical analysis and fitted logistic regressions to analyze how different characteristics influenced being a younger lung cancer patient. RESULTS: A total of 26,336 subjects were included. Lung cancer cases <50 years old had a higher probability of being women (OR: 1.38; 95% CI: 1.21-1.57), being in stage III or IV (OR: 1.32; 95% CI: 1.08-1.62), not having comorbidities (OR: 5.21; 95% CI: 4.59-5.91), presenting with symptoms at diagnosis (OR: 1.53; 95% CI: 1.29-1.81), and having ALK translocation (OR: 7.61; 95% CI: 1.25-46.32) and HER2 mutation (OR: 5.71; 95% CI: 1.34-24.33), compared with subjects ≥50 years. Among subjects <35 years old (n=61), our study observed a higher proportion of women (59.0% vs. 26.6%; p<0.001), never smokers (45.8% vs. 10.3%; p<0.001), no comorbidities (21.3% vs. 74.0%; p<0.001); ALK translocation (33.3% vs. 4.4%; p<0.001) and ROS1 mutation (14.3% vs. 2.3%; p=0.01), compared with subjects ≥35 years. CONCLUSIONS: Lung cancer displays differences by age at diagnosis which may have important implications for its clinical management.

Olaparib maintenance versus placebo in platinum-sensitive non-small cell lung cancer: the Phase 2 randomized PIPSeN trial.

BACKGROUND: Platinum-sensitivity is a phenotypic biomarker of Poly (ADP-ribose) polymerase inhibitors (PARPi) sensitivity in histotypes where PARPi are approved. Approximately one-third of non-small cell lung cancers (NSCLC) are platinum-sensitive. The double-blind, randomized phase II PIPSeN (NCT02679963) study evaluated olaparib, a PARPi, as maintenance therapy for patients with platinum-sensitive advanced NSCLC. METHODS: Chemonaïve patients with ECOG performance status of 0-1, platinum-sensitive, EGFR- and ALK-wild-type, stage IIIB-IV NSCLC were randomized (R) to receive either olaparib (O) maintenance or a placebo (P). The primary objective was progression-free survival (PFS) from R. Secondary objectives included overall survival (OS) and safety. With an anticipated hazard ratio of 0.65, 144 patients were required to be randomized, and approximately 500 patients enrolled. RESULTS: The trial was prematurely terminated because anti-PD(L)1 therapy was approved during the trial recruitment. A total of 182 patients were enrolled, with 60 patients randomized: 33 and 27 in the O and P arms, respectively. Patient and tumor characteristics were well-balanced between arms, except for alcohol intake (33% vs 11% in the O and P arms, respectively, p = 0.043). The median PFS was 2.9 and 2.0 months in the O and P arms, respectively (logrank p = 0.99). The median OS was 9.4 and 9.5 months in the O and P arms, respectively (p = 0.28). Grade ≥3 toxicities occurred in 15 and 8 patients in O and P arms, with no new safety concerns. CONCLUSION: PIPSeN was terminated early after enrollment of only 50% of the pre-planned population, thus being statistically underpowered. Olaparib maintenance did neither improve median PFS nor OS in this patient population.

[Second victim experience and support from health professionals]. / Segunda víctima: experiencia y medidas de apoyo percibidas por los profesionales sanitarios.

INTRODUCTION: The second victims are those professionals who, when faced with a mistake, are traumatized, questioning their professional and personal skills. Knowledge of their experience allows institutions to understand the consequences of error in professionals to carry out care actions for the professionals involved, improving care security. The objective of this study is to characterize the phenomenon of second victims and to know the perceived support measures. METHOD: Cross-sectional descriptive observational quantitative study. Health professionals from five highly complex institutions participated through convenience sampling. The data collection instrument was the Second Victim Experience and Support Tool (SVEST) validated in Argentina, composed of impact dimensions (psychological, physical and professional skills) of support received (colleagues, supervisors, institutional and measures not related to the workplace) and two outcome dimensions (professional abandonment and absenteeism). RESULTS: 1134 professionals participated and 56% said they had made a mistake. The mean STEVS was 2.5, with the psychological impact dimension predominating (x = 3.4). As part of the support measures, professionals perceived greater support from family and friends (not related to work) (x = 3.1). The greater the impact, the lower the perception of support measures (Rho: -0.8, p = 0.047). DISCUSSION: More than half of the professionals refer to being second victim with a significant psychological impact, who, despite working in institutions that have patient safety protocols, received support from nonwork-related environments.

Introducción: Las segundas víctimas son aquellos profesionales que, ante un error, quedan traumatizados, cuestionándose sus habilidades profesionales y personales. El conocimiento de su experiencia permite a las instituciones entender las consecuencias del error en los profesionales para realizar acciones de atención a los profesionales involucrados mejorando la seguridad de atención. El objetivo de este estudio es caracterizar el fenómeno de segundas víctimas y conocer las medidas de apoyo percibidas. Métodos: Estudio cuantitativo observacional descriptivo transversal. Participaron profesionales de la salud de cinco instituciones de alta complejidad a través de un muestreo por conveniencia. El instrumento de recogida de datos fue el Second Victim Experience and Support Tool (SVEST) validado en Argentina, compuesta por dimensiones de impacto (psicológico, físico y de habilidades profesionales) de apoyo recibido (colegas, supervisores, institucional y medidas no relacionadas al ámbito laboral) y dos dimensiones de resultado (abandono profesional y ausentismo). Resultados: Participaron 1134 profesionales. El 56% manifestó haber cometido un error y completó el SVEST. La media del SVEST fue de 2.5 predominando la dimensión de impacto psicológico (x = 3.4). Como parte de las medidas de apoyo los profesionales percibieron mayor apoyo en familiares y amigos (x = 3.1). A mayor impacto menor percepción de las medidas de apoyo (Rho: -0.8, p = 0.047). Discusión: Más de la mitad de los profesionales refieren ser segundas víctimas con un impacto psicológico importante, los cuales, a pesar de trabajar en instituciones que cuentan con protocolos de seguridad del paciente, reciben el apoyo principalmente de entornos no relacionados al trabajo.

Segunda victima: experiencia y medidas de apoyo percibidas por los profesionales sanitarios / Second victim experience and support from health prof fessionals

Resumen Introducción : Las segundas víctimas son aquellos profesionales que, ante un error, quedan traumatizados, cuestionándose sus habilidades profesionales y perso nales. El conocimiento de su experiencia permite a las instituciones entender las consecuencias del error en los profesionales para realizar acciones de atención a los profesionales involucrados mejorando la seguridad de atención. El objetivo de este estudio es caracterizar el fenómeno de segundas víctimas y conocer las medidas de apoyo percibidas. Métodos : Estudio cuantitativo observacional descrip tivo transversal. Participaron profesionales de la salud de cinco instituciones de alta complejidad a través de un muestreo por conveniencia. El instrumento de recogida de datos fue el Second Victim Experience and Support Tool (SVEST) validado en Argentina, compuesta por dimen siones de impacto (psicológico, físico y de habilidades profesionales) de apoyo recibido (colegas, supervisores, institucional y medidas no relacionadas al ámbito la boral) y dos dimensiones de resultado (abandono pro fesional y ausentismo). Resultados : Participaron 1134 profesionales. El 56% manifestó haber cometido un error y completó el SVEST. La media del SVEST fue de 2.5 predominando la dimen sión de impacto psicológico (x = 3.4). Como parte de las medidas de apoyo los profesionales percibieron mayor apoyo en familiares y amigos (x = 3.1). A mayor impacto menor percepción de las medidas de apoyo (Rho: -0.8, p = 0.047). Discusión : Más de la mitad de los profesionales re fieren ser segundas víctimas con un impacto psicológico importante, los cuales, a pesar de trabajar en institu ciones que cuentan con protocolos de seguridad del paciente, reciben el apoyo principalmente de entornos no relacionados al trabajo.

Abstract Introduction : The second victims are those profes sionals who, when faced with a mistake, are traumati zed, questioning their professional and personal skills. Knowledge of their experience allows institutions to understand the consequences of error in professionals to carry out care actions for the professionals involved, improving care security. The objective of this study is to characterize the phenomenon of second victims and to know the perceived support measures. Method : Cross-sectional descriptive observational quantitative study. Health professionals from five highly complex institutions participated through convenience sampling. The data collection instrument was the Second Victim Experience and Support Tool (SVEST) validated in Argentina, composed of impact dimensions (psychologi cal, physical and professional skills) of support received (colleagues, supervisors, institutional and measures not related to the workplace) and two outcome dimensions (professional abandonment and absenteeism). Results : 1134 professionals participated and 56% said they had made a mistake. The mean STEVS was 2.5, with the psychological impact dimension predominating (x = 3.4). As part of the support measures, professionals perceived greater support from family and friends (not re lated to work) (x = 3.1). The greater the impact, the lower the perception of support measures (Rho: -0.8, p = 0.047). Discussion : More than half of the professionals refer to being second victim with a significant psychological impact, who, despite working in institutions that have patient safety protocols, received support from non-work-related environments.

[Nutritional factors related to insulin resistance in children and adolescents]. / Factores nutricionales relacionados con la resistencia a la insulina en escolares y adolescentes.

Introduction: Insulin resistance is described as a defect in the binding of insulin to its receptor and is associated with several diseases, including obesity and type 2 diabetes. Insulin resistance has been linked to vitamin and mineral deficiencies, especially those involved in oxidative stress. The Mediterranean diet, a diet based on the Healthy Eating Index or the Dietary Approaches to Stop Hypertension (DASH) diet are dietary patterns that have been associated with a lower risk of developing insulin resistance in children. Therefore, a diet rich in antioxidant vitamins and minerals, fiber, calcium, and polyunsaturated fatty acids and low in free sugars, sodium and saturated fatty acids may decrease the risk of insulin resistance in this age group. In addition, other nutritional factors, such as avoiding fast food, eating dinner with the family, not eating while watching TV or eating a sufficient and healthy breakfast on a regular basis seem to be associated with a lower risk of insulin resistance. Therefore, it is important to establish balanced daily eating habits to prevent and treat insulin resistance in schoolchildren and adolescents.

Introducción: La resistencia a la insulina se explica como un defecto en la unión de la insulina con su receptor y está asociada con numerosas enfermedades, como la obesidad o la diabetes tipo 2, entre otras. La resistencia a la insulina se ha relacionado con la deficiencia de vitaminas y minerales, especialmente de aquellos involucrados en el estrés oxidativo. La dieta mediterránea, una dieta basada en el Healthy Eating Index o la dieta Dietary Approaches to Stop Hypertension (DASH) son patrones dietéticos que se han asociado con un menor riesgo de presentar resistencia a la insulina en edad infantil. Por tanto, una dieta rica en vitaminas y minerales antioxidantes, fibra, calcio y ácidos grasos poliinsaturados y baja en azucares libres, sodio y ácidos grasos saturados puede disminuir el riesgo de presentar resistencia a la insulina en este grupo de edad. Además, otros factores nutricionales, como evitar la comida rápida, cenar en familia, no comer mientras se ve la televisión o el consumo regular de un desayuno suficiente y saludable son hábitos que parecen estar relacionados con menor riesgo de presentar resistencia a la insulina. Por tanto, es importante establecer hábitos alimentarios diarios equilibrados para prevenir y tratar la resistencia a la insulina en escolares y adolescentes.

[Nutritional problems of vegetarian and vegan children]. / Problemática nutricional de los niños vegetarianos y veganos.

Introduction: The number of people following plant-based diets to a greater or lesser degree is increasing, but the more restrictive a diet, the greater the risk of nutritional deficiencies. The childhood stage is a stage of great physical and maturational growth, therefore, nutritional deficiencies at this stage can have serious and sometimes permanent consequences. People who follow restrictive diets of any kind, such as plant-based diets, should receive support from specialized staff to ensure that their diets are varied and balanced, as is desirable in any case.

Introducción: Está aumentando el número de personas que siguen dietas basadas en vegetales en mayor o menor grado, pero cuanto más restrictiva es una dieta, más riesgos existen de presentar deficiencias nutricionales. La etapa infantil es una etapa de gran crecimiento físico y madurativo, por ello, las deficiencias nutricionales en esta etapa pueden acarrear consecuencias graves y, en ocasiones, permanentes. Las personas que siguen dietas restrictivas de cualquier tipo, como son las dietas basadas en vegetales, deben recibir apoyo de personal especializado para conseguir que sus dietas sean variadas y equilibradas, como es deseable en cualquier caso.

[Properties of milk in sleep induction]. / Propiedades de la leche en la inducción del sueño.

Introduction: Sleep induction and its quality are issues of growing concern because its deterioration affects a large number of people and poses a risk to their well-being and quality of life and long-term health. There are several factors involved in the problem, but nutrition is one of them and in particular milk consumption has often been linked to sleep habits, sometimes as a promoter and sometimes as an inhibitor. The purpose of this review is to examine the matter further. On reaching the brain, tryptophan is the basis for the synthesis of serotonin and melatonin, which improve the induction and quality of sleep. But there is competition between tryptophan and other long-chain neutral amino acids (LNAA) (valine, leucine, isoleucine, tyrosine and phenylalanine) to cross the blood-brain barrier and reach the brain. In this sense, milk proteins with a high tryptophan content and the highest ratio between tryptophan and LNAA are very useful in promoting sleep. Moreover, milk also provides various micronutrients that help in the transformation of tryptophan into serotonin and melatonin, as well as antioxidant components, anti-inflammatory and bioactive peptides, and recent studies indicate that it favorably modulates the composition of the intestinal microbiota. Studies show that increasing milk consumption, up to the recommended intake and within a correct diet, favors the achievement and maintenance of quality sleep.

Introducción: La inducción del sueño y su calidad son temas de preocupación creciente porque su deterioro afecta a un número elevado de personas y supone un riesgo en su bienestar y calidad de vida y en la salud a largo plazo. Hay diversos factores implicados en el problema, pero la nutrición es uno de ellos y, en concreto, el consumo de leche se ha relacionado frecuentemente con los hábitos de sueño, a veces como factor promotor y otras como inhibidor. Profundizar en el tema es el objeto de la presente revisión. El triptófano, al llegar al cerebro, es la base para la síntesis de serotonina y melatonina, que mejoran la inducción y la calidad del sueño. Pero hay una competencia entre el triptófano y otros aminoácidos neutros de cadena larga (ANCL) (valina, leucina, isoleucina, tirosina y fenilalanina) para cruzar la barrera hematoencefálica y llegar al cerebro. En este sentido, las proteínas de la leche, con elevado contenido en triptófano y la relación más elevada entre triptófano y ANCL, son muy útiles en la promoción del sueño. Por otra parte, la leche también aporta diversos micronutrientes que ayudan en la transformación del triptófano en serotonina y melatonina, así como componentes antioxidantes, antiinflamatorios y péptidos bioactivos, y estudios recientes indican que modula favorablemente la composición de la microbiota intestinal. Los estudios realizados ponen de relieve que aumentar el consumo de leche, hasta el aporte aconsejado y dentro de una alimentación correcta, favorece el conseguir y mantener un sueño de calidad.

Acute pancreatitis due to osteosarcoma metastasis.

We present the case of a young patient with acute pancreatitis (AP) secondary to osteosarcoma metastasis. It is necessary to assess tumor etiology in the study of any acute pancreatitis without clear cause. Pancreatic metastases are rare and difficult to diagnose and differentiate from other primary tumors such as neuroendocrine tumors (NET). It is essential to have a high degree of clinical suspicion and the use of radiological and endoscopic ultrasound imaging techniques.

[Autologous hematopoietic stem cell transplantation in a patient with refractory Crohn's disease].

Crohn's disease is a chronic condition for which sometimes there is no effective medical or surgical treatment. Autologous hematopoietic stem cell transplantation may be a therapeutic option for these patients to restore immune tolerance. Consequently, this may lead to remission of the disease or decrease its activity, making drugs that have previously failed be effective. Due to the safety profile of the procedure and the fact that it is a non-curative treatment, patient selection must be rigorous. We report our experience with the first patient selected in our centre for autologous hematopoietic stem cell transplantation: 27 years old male with Crohn's disease (A1L3B1p) refractory to multiple lines of medical treatment and not a candidate for surgical treatment. Two years after the transplantation, the patient remains asymptomatic.

Real-world treatment patterns and survival outcomes for patients with stage III non-small cell lung cancer in Spain: a nationwide cohort study.

Background: The burden of non-small cell lung cancer (NSCLC) remains high in Spain, with lung cancer accounting for 20% of cancer-related deaths annually. Programs such as the Spanish Thoracic Tumour Registry (TTR) and the global I-O Optimise initiative have been developed to observe patients in clinical practice with the aim of improving outcomes. This analysis examined treatment patterns and survival in patients with stage III NSCLC from the TTR. These patients represent a heterogenous group with complex treatment pathways. Methods: The TTR is an ongoing, observational, prospective, and retrospective cohort multicentre study (NCT02941458) that follows patients with thoracic cancer in Spain. Adults aged ≥18 years with stage IIIA/IIIB NSCLC enrolled in the TTR between 01 Jan 2010 and 31 Oct 2019 were included in this analysis. Initial treatment received was described by cancer stage and histology (squamous and non-squamous NSCLC). Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were calculated over a 5-year period. Results: A total of 1,838 patients were included in the cohort, including 1,082 with stage IIIA (58.9%) and 756 with stage IIIB (41.1%). Median follow-up was 18.3 months. The median age of patients was 66 years, and most had non-squamous NSCLC (54.0%), were male (81.2%), and were active or former smokers (93.4%). Overall, 26.3% of patients received surgical resection (37.0% for stage IIIA and 11.1% for stage IIIB). The most frequent initial treatment received was concurrent chemoradiotherapy for stage IIIA (30.2%) and stage IIIB (37.0%) patients. Median OS was lower in patients with stage IIIB than stage IIIA (28 vs. 37 months) disease and was lower for patients with squamous than non-squamous histology (19 vs. 26 months). Median PFS and OS varied when patients were stratified by initial treatment. Conclusions: This TTR analysis describes the clinical reality surrounding the initial management and survival outcomes for stage III NSCLC in Spain and presents survival outcomes comparable with other real-world evidence. It provides insights into the diverse approaches used before the availability of immunotherapies and targeted treatments in the non-metastatic NSCLC setting.

Endometrial receptivity tests in reproduction: a SWOT analysis.

Endometrial receptivity and its management in assisted reproduction is now a significant focus of research interest. Endometrial receptivity tests, which analyze different panels of gene expression, are usually offered in fertility clinics to determine the women's individual 'window of implantation', providing a personalized timing for embryo transfer. However, there are still no definite indications on whether its inclusion in the study of the infertile couple or the study of patients with repeated implantation failure is essential.

Machine Learning-Assisted Recurrence Prediction for Patients With Early-Stage Non-Small-Cell Lung Cancer.

PURPOSE: Stratifying patients with cancer according to risk of relapse can personalize their care. In this work, we provide an answer to the following research question: How to use machine learning to estimate probability of relapse in patients with early-stage non-small-cell lung cancer (NSCLC)? MATERIALS AND METHODS: For predicting relapse in 1,387 patients with early-stage (I-II) NSCLC from the Spanish Lung Cancer Group data (average age 65.7 years, female 24.8%, male 75.2%), we train tabular and graph machine learning models. We generate automatic explanations for the predictions of such models. For models trained on tabular data, we adopt SHapley Additive exPlanations local explanations to gauge how each patient feature contributes to the predicted outcome. We explain graph machine learning predictions with an example-based method that highlights influential past patients. RESULTS: Machine learning models trained on tabular data exhibit a 76% accuracy for the random forest model at predicting relapse evaluated with a 10-fold cross-validation (the model was trained 10 times with different independent sets of patients in test, train, and validation sets, and the reported metrics are averaged over these 10 test sets). Graph machine learning reaches 68% accuracy over a held-out test set of 200 patients, calibrated on a held-out set of 100 patients. CONCLUSION: Our results show that machine learning models trained on tabular and graph data can enable objective, personalized, and reproducible prediction of relapse and, therefore, disease outcome in patients with early-stage NSCLC. With further prospective and multisite validation, and additional radiological and molecular data, this prognostic model could potentially serve as a predictive decision support tool for deciding the use of adjuvant treatments in early-stage lung cancer.