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BACKGROUND: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis. METHODS: Thirty-two patients with infective endocarditis were studied. Clinical data and a blood sample were collected at diagnosis, and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotypes EE1 and EE2). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression and molecular pathways involved were assessed. Identified endotypes were recapitulated in a cohort of COVID19 patients. RESULTS: 18 and 14 patients were assigned to EE1 and EE2 respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the STAT pathway, with higher counts of active T-cells and lower counts of neutrophils. Fourteen patients (9 in EE1 and 5 in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression towards a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, p=0.027) with adjusted hazard ratio of 12.987 (95% confidence interval 3.356 - 50]. Translation of these endotypes to COVID19 and non-COVID septic patients yielded similar results in cell populations and outcome. CONCLUSIONS: Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, response to surgery and outcome.

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This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and personalized therapies. The long-term survival rates for AML patients are low, and MRD assessment is crucial in predicting prognosis. Currently, the most common methods for MRD detection are flow cytometry and quantitative PCR, but NGS is being incorporated into clinical practice due to its ability to detect genomic aberrations in the majority of AML patients. Typically, bone marrow samples are used for MRD assessment, but using peripheral blood samples or liquid biopsies would be less invasive. Leukemia originates in the bone marrow, along with the cfDNA obtained from peripheral blood. This study aimed to assess the utility of cell-free DNA (cfDNA) from peripheral blood samples for MRD detection in AML patients. A cohort of 20 AML patients was analyzed using NGS, and a correlation between MRD assessment by cfDNA and circulating tumor cells (CTCs) in paired samples was observed. Furthermore, a higher tumor signal was detected in cfDNA compared to CTCs, indicating greater sensitivity. Challenges for the application of liquid biopsy in MRD assessment were discussed, including the selection of appropriate markers and the sensitivity of certain markers. This study emphasizes the potential of liquid biopsy using cfDNA for MRD detection in AML patients and highlights the need for further research in this area.

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[This corrects the article DOI: 10.3389/fimmu.2023.1188818.].

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Background: CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations. Method: Eleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death. Results: After a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression. Conclusion: This is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results.

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Introducción: El dolor de parto es uno de los aspectos que más preocupan a las futuras madres. La enfermería vela por el bienestar de las pacientes en todas sus vertientes y cabe tener presente que existen diversas opciones complementarias a la analgesia epidural. Objetivo: Identificar las terapias complementarias que puedan aplicarse de forma efectiva y segura en embarazadas, analizar los factores que contribuyan a un mayor bienestar para la parturienta y evaluar su utilidad. Método: Revisión integradora de la literatura realizada mediante la búsqueda en las bases de datos online: PubMed, Scopus y Dialnet. Se incluyeron artículos cuya fecha de publicación no fuese superior a los 10 años previos a la búsqueda, redactados en inglés, español o portugués y de acceso abierto. Resultados: Se analizaron un total de 16 artículos cuya temática giraba en torno a la aplicación de diferentes terapias complementarias utilizadas con seguridad en mujeres embarazadas. Se tuvieron en cuenta los resultados de la aplicación de diferentes técnicas complementarias en estudios previos y se agruparon según tipología: intervenciones cuerpo-mente, práctica médica alternativa, métodos de curación manual, inmersión en agua y pelota suiza, aromaterapia y auriculoterapia y estimulación nerviosa eléctrica transcutánea. Conclusión: Se evidencia la variedad de terapias complementarias cuya aplicación resulta efectiva y segura en el momento del parto, así como su utilidad para disminuir los inconvenientes presentes durante esta etapa, acrecentando así, la experiencia positiva del parto. (AU)

Introduction: Labour pain is one of the most worrying things for future mothers. Nurses ensure the well-being of patients in all these aspects and it should be noted that there are various complementary options to epidural analgesia. Objective: To identify the complementary therapies that could be applied effectively and safely in pregnant women, to analyse the contributing factors of greater well-being for the parturient and to evaluate their utility. Method: this integrative review were carried out in online databases: PubMed, Scopus and Dialnet, Articles whose publication date was not more than ten years ago, written in English, Spanish or Portuguese and open access were included. Results: 16 studies about the application of different complementary therapies used safely in pregnant were included and analysed. The obtained results of the application of complementary techniques in previous studies were taken into account and agruped according to typology: body-mind interventions, alternative medical practice, manual healing methods, immersion in water and swiss ball, aromatherapy and auriculotherapy and transcutaneous electrical nerve stimulation. Conclusion: The variety of effective and safe complementary therapies on labour is evidencied, as well as their usefulness to reduce the possible incoveniences that may appear during this process, increasing the positive experience of labour. (AU)

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In the present study, we screened 84 Follicular Lymphoma patients for somatic mutations suitable as liquid biopsy MRD biomarkers using a targeted next-generation sequencing (NGS) panel. We found trackable mutations in 95% of the lymph node samples and 80% of the liquid biopsy baseline samples. Then, we used an ultra-deep sequencing approach with 2 · 10-4 sensitivity (LiqBio-MRD) to track those mutations on 151 follow-up liquid biopsy samples from 54 treated patients. Positive LiqBio-MRD at first-line therapy correlated with a higher risk of progression both at the interim evaluation (HRINT 11.0, 95% CI 2.10-57.7, p = 0.005) and at the end of treatment (HREOT, HR 19.1, 95% CI 4.10-89.4, p < 0.001). Similar results were observed by PET/CT Deauville score, with a median PFS of 19 months vs. NR (p < 0.001) at the interim and 13 months vs. NR (p < 0.001) at EOT. LiqBio-MRD and PET/CT combined identified the patients that progressed in less than two years with 88% sensitivity and 100% specificity. Our results demonstrate that LiqBio-MRD is a robust and non-invasive approach, complementary to metabolic imaging, for identifying FL patients at high risk of failure during the treatment and should be considered in future response-adapted clinical trials.

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BACKGROUND: Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a severe disease, termed coronavirus disease 2019 (COVID-19), with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms and their modulation has shown a mortality benefit. METHODS: In a cohort of 56 critically ill COVID-19 patients, peripheral blood transcriptomes were obtained at admission to an intensive care unit (ICU) and clustered using an unsupervised algorithm. Differences in gene expression, circulating microRNAs (c-miRNAs) and clinical data between clusters were assessed, and circulating cell populations estimated from sequencing data. A transcriptomic signature was defined and applied to an external cohort to validate the findings. RESULTS: We identified two transcriptomic clusters characterised by expression of either interferon-related or immune checkpoint genes, respectively. Steroids have cluster-specific effects, decreasing lymphocyte activation in the former but promoting B-cell activation in the latter. These profiles have different ICU outcomes, despite no major clinical differences at ICU admission. A transcriptomic signature was used to identify these clusters in two external validation cohorts (with 50 and 60 patients), yielding similar results. CONCLUSIONS: These results reveal different underlying pathogenetic mechanisms and illustrate the potential of transcriptomics to identify patient endotypes in severe COVID-19 with the aim to ultimately personalise their therapies.

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Headache is among the most frequently reported symptoms after resolution of COVID-19. We assessed structural brain changes using T1- and diffusion-weighted MRI processed data from 167 subjects: 40 patients who recovered from COVID-19 but suffered from persistent headache without prior history of headache (COV), 41 healthy controls, 43 patients with episodic migraine and 43 patients with chronic migraine. To evaluate gray matter and white matter changes, morphometry parameters and diffusion tensor imaging-based measures were employed, respectively. COV patients showed significant lower cortical gray matter volume and cortical thickness than healthy subjects (p < 0.05, false discovery rate corrected) in the inferior frontal and the fusiform cortex. Lower fractional anisotropy and higher radial diffusivity (p < 0.05, family-wise error corrected) were observed in COV patients compared to controls, mainly in the corpus callosum and left hemisphere. COV patients showed higher cortical volume and thickness than migraine patients in the cingulate and frontal gyri, paracentral lobule and superior temporal sulcus, lower volume in subcortical regions and lower curvature in the precuneus and cuneus. Lower diffusion metric values in COV patients compared to migraine were identified prominently in the right hemisphere. COV patients present diverse changes in the white matter and gray matter structure. White matter changes seem to be associated with impairment of fiber bundles. Besides, the gray matter changes and other white matter modifications such as axonal integrity loss seemed subtle and less pronounced than those detected in migraine, showing that persistent headache after COVID-19 resolution could be an intermediate state between normality and migraine.

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[This corrects the article DOI: 10.3389/fimmu.2023.1188818.].

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[This corrects the article DOI: 10.3389/fcell.2022.893099.].

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OBJECTIVE: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. METHODS: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. RESULTS: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. CONCLUSIONS: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

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BACKGROUND: Few studies have analyzed compulsive buying behavior in relation to a specific product. Smartphones are hugely popular products today, especially among young people. These two aspects have motivated this research into the compulsive buying behavior of Smartphones by university students. METHODS: To study this behavior, the main features that differentiate compulsive buyers from those that are not are analyzed, and their risk profiles are obtained through a discrete choice model. RESULTS: Sociodemographic features that define buyers with the greatest propensity to compulsiveness are younger age, longer time spent daily using social networks, higher spending on the acquisition of Smartphones and having owned a greater number of these devices. These buyers also show shopping addiction and greater feelings of guilt after the purchase as well as more positive and negative affective states when purchasing Smartphones. CONCLUSIONS: This analysis not only determines the characteristics that define young individuals with a tendency toward compulsiveness in Smartphone purchases, but also contributes to quantifying the probability of having this tendency.

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OBJETIVO: Analizar si los casos positivos de cribado combinado de trisomía 21 (t21) o trisomía 18 (t18) en ausencia de aneuploidía (falsos positivos- FP) se relacionan con complicaciones de la gestación, ajustando por factores demográficos y clínicos de riesgo. MATERIAL Y MÉTODOS: Estudio retrospectivo de casos y controles anidado en una cohorte de pacientes que acudieron para cribado del primer trimestre. Los casos fueron las pacientes con FP de riesgo combinado de t21 superior a 1/270 o riesgo de t18 superior a 1/100. Se consideraron complicaciones de la gestación: óbito fetal, parto prematuro menor de 34 semanas o prematuro menor de 37 semanas, preeclampsia, retrasos de crecimiento, pequeño para la edad gestacional (CIR, PEG) y diabetes gestacional (DG). Se ajustó por obesidad, edad, paridad, tabaquismo, y técnicas de reproducción asistida. RESULTADO: Se obtuvieron 204 casos de FP, 149 FP para trisomía 21, 41 para trisomía 18, y 14 FP para ambos riesgos. Se encontró asociación estadísticamente significativa de FP t21 con óbito fetal (OR=3,5; ic95% 1,4-8,7; p=0,01), parto prematuro menor de 37 semanas (OR=2,2; IC95% 1,4-3,4; p=0,001), preeclampsia (OR =2,6; IC95% 1,17-6,1; p=0,02), PEG (OR =2,2; IC95% 1,2-4,1; p=0,02), CIR (OR=2,8; IC95% 1,6-5,1; p=0,001), y DG (OR=2,1; IC95% 1,2-3,7; p=0,01). Los FP t18 se asociaron con óbito (OR=8,9; IC95% 2,9-27; p=0,002). CONCLUSIÓN: Los FP del cribado del primer trimestre, para trisomía 21 y trisomía 18, se asocian con resultados obstétricos adversos.

We have studied whether positive cases of combined trisomy 21 (t21) or 18 (t18) screening in the absence of aneuploidy (false positives -FP-) are related to pregnancy complications adjusting for demographic and clinical risk factors. METHODS: Retrospective case-control study nested in a cohort of patients who came for first trimester aneuploidy screening. The cases were patients with FP combined risk of t21 (greater than 1/270) or t18 risk (greater than 1/100). The control group was a sample of patients with low-risk screening. We considered pregnancy complications: stillbirth, premature delivery before 34 and 37 weeks, preeclampsia, growth retardation, small for gestational age (FGR, SGA), and gestational diabetes (GD). Or were adjusted for obesity, age, parity, smoking, and assisted reproduction techniques. RESULTS: 204 cases of FP were obtained, 149 FP for trisomy 21, 41 for trisomy 18, and 14 FP for both risks. A statistically significant association between t21 FP was found with stillbirth (OR = 3.5; 95% CI 1.4-8.7; p = 0.01), preterm delivery less than 37 weeks (OR = 2.2; 95% CI 1.4-3.4; p = 0.001), preeclampsia (OR = 2.6; 95% CI 1.17-6.1; p = 0.02), SGA (OR = 2.2; 95% CI 1, 2-4.1; p = 0.02), FGR (OR = 2.8; 95% CI 1.6-5.1; p = 0.001), and GD (OR = 2.1; 95% CI 1.2 −3.7; p = 0.01). FP t18s were associated with fetal loss (OR= 8.9 (95% CI 2.9-27) p = 0.002. CONCLUSION: FP from first trimester screening for t21 and t18 are associated with adverse obstetric outcomes.

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It is known that the harmful presence of the wild cochineal (Dactylopius opuntiae), unlike the fine cochineal (Dactylopius coccus), in prickly pear crops of farmers leads to consider it as one of the major pests for this crop. In this study, we present the implementation of an optical setup that ensures the measurement of the in-vivo fluorescence spectra of wild cochineals ranging in size from 440 to 1190 µm in their natural habitat achieved by developing a reproduction model adopted from available literature. It was observed that in-vivo fluorescence spectra of these insects were comprised in the spectral region of 570-760 nm, showing a proportional dependence between the fluorescence intensity emitted and the cochineal size. In addition, we have considered other spectral parameters to perform the comparison between fluorescence spectra of the different cochineal sizes. These results provide the basis for the development of novel methodologies and equipment aimed towards the early detection of this pest in prickly pear crops from its early growth stages (nymph I and II).

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Los hospitales municipales y provinciales representaron un papel clave en la confi-guración histórica del sistema hospitalario en España hasta la segunda mitad del siglo XX. Su papel estratégico en la beneficencia del siglo XIX para la cobertura de los pobres se modificó con el avance y la configuración del hospital moderno ubicado en nuevos edificios y técnicas de gestión, con una estructura interna jerarquizada y avances en ámbito diagnóstico-terapéutico para la cobertura de cada vez más porcentaje de población. Partiendo de esta idea, este trabajo se centra en el estudio histórico de las infraestructuras hospitalarias públicas vinculadas a los municipios y diputaciones en España con dos objetivos. De un lado, trata de analizar cómo se configuraron, qué servicios prestaron y cómo afrontaron su financiación hasta la dictadura de Franco. De otro, aborda los efectos que tuvo la puesta en marcha del Seguro Obligatorio de Enfermedad (SOE), en 1944, y la construcción de su propia red de hospitales, conocidos como residencias sanitarias, en el funcionamiento y supervivencia de estas viejas infraestructuras municipales y provinciales. Finalmente se analiza su práctica desaparición tras la cesión de las competencias sanitarias en la transición democrática (AU)

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INTRODUCCIÓN: El delirium es un trastorno neuropsiquiátrico muy frecuente en pacientes ingresados en unidades de cuidados paliativos. OBJETIVOS: Estudiar la incidencia de delirium en una población de pacientes ingresados en una unidad de cuidados paliativos (UCP); analizar los posibles factores sociodemográficos, clínicos, funcionales y mentales que pudieran asociarse al riesgo de delirium. MATERIAL Y MÉTODOS: Estudio epidemiológico longitudinal sobre una población de pacientes hospitalizados en la UCP entre el 13 de marzo y el 13 de abril de 2019. Se recogieron variables sociodemográficas, clínicas, funcionales (índice de Barthel y Karnofsky) y mentales (Global Deterioration Scale). El diagnóstico de delirium se realizó en base al Confussional Assessment Method (CAM) y se clasificó en hiperactivo, hipoactivo y mixto. RESULTADOS: 35 sujetos fueron incluidos en el estudio (77,69 ± 11,66 años; 51,4 % mujeres; Barthel 35,14 ± 31,54 y Karnofsky 30 ± 19,40). Se detectó una incidencia de delirium del 65,7 % (11,4 % hiperactivo, 20,4 % hipoactivo y 34,3 % mixto). Se objetivó asociación estadística con delirium de: puntuación en el Barthel y Karnofsky, presencia de metástasis cerebrales y ser tratados con antidepresivos. CONCLUSIONES: Para nuestra población de estudio, el 65,7 % de los sujetos ingresados en la UCP desarrolla un delirium. Según los resultados obtenidos, la puntuación en Barthel y el Karnofsky, así como la existencia de metástasis cerebrales y la prescripción de antidepresivos, son factores que se asocian a un aumento del riesgo de sufrir delirium

INTRODUCTION: Delirium is a very common neuropsychiatric disorder in patients admitted to palliative care units. OBJECTIVES: To study the incidence of delirium in a population of patients admitted to a Palliative Care Unit (PCU); to analyze the sociodemographic, clinical, functional, and mental factors associated with the risk of delirium. MATERIAL AND METHODS: A longitudinal epidemiological study in a population of patients hospitalized in the PCU between March 13 and April 13, 2019. Sociodemographic, clinical, functional (Barthel and Karnofsky Index), and mental variables were collected (Global Deterioration Scale). The diagnosis of delirium was made based on the Confussional Assessment Method (CAM), and was then classified as hyperactive, hypoactive, or mixed. RESULTS: A total of 35 subjects were included in the study (77.69 ± 11.66 years, 51.4 % women, Barthel: 35.14 ± 31.54, Karnofsky: 30 ± 19.40). The incidence of delirium was 65.7 % (11.4 % hyperactive, 20.4 % hypoactive, 34.3 % mixed). A statistical association with delirium was observed for: Barthel and Karnofsky scores, presence of brain metastases, and treatment with antidepressants. CONCLUSIONS: In all, 65.7 % of the subjects admitted to the PCU developed delirium. Barthel and Karnofsky scores, as well as the existence of brain metastases and the prescription of antidepressants were factors associated with the risk of delirium

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OBJECTIVE: This study evaluates different parameters describing the gray matter structure to analyze differences between healthy controls, patients with episodic migraine, and patients with chronic migraine. DESIGN: Cohort study. SETTING: Spanish community. SUBJECTS: Fifty-two healthy controls, 57 episodic migraine patients, and 57 chronic migraine patients were included in the study and underwent T1-weighted magnetic resonance imaging acquisition. METHODS: Eighty-four cortical and subcortical gray matter regions were extracted, and gray matter volume, cortical curvature, thickness, and surface area values were computed (where applicable). Correlation analysis between clinical features and structural parameters was performed. RESULTS: Statistically significant differences were found between all three groups, generally consisting of increases in cortical curvature and decreases in gray matter volume, cortical thickness, and surface area in migraineurs with respect to healthy controls. Furthermore, differences were also found between chronic and episodic migraine. Significant correlations were found between duration of migraine history and several structural parameters. CONCLUSIONS: Migraine is associated with structural alterations in widespread gray matter regions of the brain. Moreover, the results suggest that the pattern of differences between healthy controls and episodic migraine patients is qualitatively different from that occurring between episodic and chronic migraine patients.

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