Implementació i resultats d'un programa d’optimització d’ús d’antimicrobians (PROA) pediàtric a un hospital infantil de tercer nivell

[cat] L'increment en les taxes de resistència antimicrobiana (RAM) és una causa important i creixent de morbimortalitat a tot el món a causa de la manca d'antibiòtics efectius per tractar aquestes infeccions. L'ús inadequat d'antimicrobians a l'entorn sanitari, molt prevalent en nens, contribueix a incrementar les RAM. Les situacions més freqüents són l'ús d'antimicrobians en situacions que no els requereixen, la prescripció de pautes antibiòtiques excessivament llargues, els tractaments empírics d'espectre antimicrobià massa ampli o un desescalat terapèutic tardà tot i conèixer el microorganisme causant de la infecció i el perfil de resistències. Hi ha múltiples iniciatives dirigides a frenar la propagació de les RAM, tant dins com fora de l’entorn de l’assistència sanitària. Els programes d'optimització d'ús d'antimicrobians (PROA) han demostrat ser una de les eines més efectives per millorar l'ús d'antimicrobians als hospitals, especialment a centres d'adults. La majoria de guies recomanen crear equips PROA multidisciplinaris capaços d'identificar necessitats concretes, dissenyar estratègies i intervencions específiques i avaluar els resultats amb l'objectiu final de millorar l'ús d'antimicrobians i els resultats clínics dels pacients al centre. L'evidència disponible sobre les millors intervencions i els indicadors PROA a utilitzar en pediatria, especialment en centres europeus, és encara escassa, més quan s'analitzen patologies pediàtriques concretes o unitats d'hospitalització determinades. Als articles que conformen aquesta Tesi Doctoral es descriu la instauració d'un programa PROA pediàtric dissenyat específicament per a l'Hospital Sant Joan de Déu, així com els principals resultats dels tres primers anys de funcionament. Durant el període d’intervenció del programa s’aconsegueix millorar de forma segura l’ús d’antimicrobians tant des del punt de vista quantitatiu com qualitatiu. Així mateix, s'aconsegueix disminuir la despesa en antimicrobians del centre. Aquest impacte s’observa tant a nivell global a l’hospital, com en grups concrets de patologies prevalents, com l’apendicitis aguda flegmonosa. Finalment, es descriu l'impacte important d'unitats específiques com la Unitat de Cures Intensives Pediàtriques, en l'ús global d'antimicrobians de l'hospital.[eng] Increasing rates of antimicrobial resistance (AMR) are a major and growing cause of morbidity and mortality worldwide due to the lack of effective antibiotics. Inappropriate use of antimicrobials in the healthcare setting, which is highly prevalent in children, contributes to the increase in AMR. The most frequent situations are the use of antimicrobials in situations that do not require them, the prescription of excessively long antibiotic regimens, empirical treatments with too broad antimicrobial spectrum or late therapeutic de-escalation despite knowing the micro-organism causing the infection and its resistance profile. There are multiple initiatives aimed at curbing the spread of AMR, both within and outside the healthcare setting. Antimicrobial stewardship programs (AMS) have proven to be one of the most effective tools to improve antimicrobial use in hospitals, especially in adult centres. Most guidelines recommend the creation of multidisciplinary AMS teams capable of identifying specific needs, designing specific strategies and interventions, and evaluating outcomes with the ultimate goal of improving antimicrobial use and clinical outcomes of patients in their facility. The available evidence on the best interventions and AMS indicators to use in paediatrics, especially in European centres, is still scarce, especially when analysing specific paediatric pathologies or specific hospitalisation units. The articles that make up this Doctoral Thesis describe the implementation of a paediatric AMS program designed specifically for the Hospital Sant Joan de Déu, as well as the main results of the first three years of its operation. During the program's intervention period, the use of antimicrobials was safely improved both quantitatively and qualitatively. In addition, the antimicrobial expenditure of the centre is reduced. This impact is observed both at the overall hospital level and in specific groups of prevalent pathologies, such as acute phlegmonous appendicitis. Finally, the important impact of specific units such as the Paediatric Intensive Care Unit on the overall use of antimicrobials in the hospital is described

Determination of chemical properties in ‘calçot’ (Allium cepa L.) by near infrared spectroscopy and multivariate calibration

‘Calçots’, the immature floral stems of second-year onion resprouts, are an economically important traditional crop in Catalonia (Spain). Classical approaches to evaluating the chemical properties of ‘calçots’ are time consuming and expensive; near-infrared spectroscopy (NIRS) may be faster and cheaper. We used NIRS to develop partial least square (PLS) models to predict dry matter, soluble solid content, titratable acidity, and ash content in cooked ‘calçots’. To guarantee the robustness of the models, calibration samples were grown and analyzed in a first season (2014–15) and validation samples in a second season (2015–16). NIRS on puree spectra estimated dry matter and soluble solid content with excellent accuracy (R2pred¿=¿0.953, 0.985 and RPD¿=¿4.571, 8.068, respectively). However, good estimation of titratable acidity and ash content required using ground dried puree spectra (R2pred¿=¿0.852, 0.820 and RPD¿=¿2.590, 1.987, respectively). NIRS can be a helpful tool for ‘calçots’ breeding and quality control.Peer ReviewedPostprint (author's final draft

From the Editors: Making Intangible Capital a better review in its third year

Con este número, Intangible Capital inicia su tercer año. Es un buen momento para reflexionar sobre cómo podemos mejorar la revista en este tercer volumen, y de reconsiderar los objetivos marcados en el segundo volumen.With this issue, Intangible Capital reaches its third year. It is a good moment to reflect on how can we make this review better one along this year, and to asses if we have achieved the second year’s goal

Hacia la evaluación de la calidad, el prestigio y la responsabilidad social de las revistas de acceso abierto

Peer Reviewe

Case report : Challenges in immune reconstitution following hematopoietic stem cell transplantation for CTLA-4 insufficiency-like primary immune regulatory disorders

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency is a T-cell hyperactivation disorder that can manifest with both immunodeficiency and immune dysregulation. Approximately one-third of patients may present mild symptoms and remain stable under supportive care. The remaining patients may develop severe multiorgan autoimmunity requiring lifelong immunosuppressive treatment. Hematopoietic stem cell transplantation (HSCT) is potentially curable for patients with treatment-resistant immune dysregulation. Nevertheless, little experience is reported regarding the management of complications post-HSCT. We present case 1 (CTLA-4 haploinsufficiency) and case 2 (CTLA-4 insufficiency-like phenotype) manifesting with severe autoimmunity including cytopenia and involvement of the central nervous system (CNS), lung, and gut and variable impairment of humoral responses. Both patients underwent HSCT for which the main complications were persistent mixed chimerism, infections, and immune-mediated complications [graft-versus-host disease (GVHD) and nodular lung disease]. Detailed management and outcomes of therapeutic interventions post-HSCT are discussed. Concretely, post-HSCT abatacept and human leukocyte antigen (HLA)-matched sibling donor lymphocyte infusions may be used to increase T-cell donor chimerism with the aim of correcting the immune phenotype of CTLA-4 haploinsufficiency

Reduced humoral response 3 months following BNT162b2 vaccination in SARS-CoV-2 uninfected residents of long-term care facilities

SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine. plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF. Neutralisation capacity was assessed in a pseudovirus neutralisation assay against the original WH1 and later B.1.617.2/Delta variants. A group of younger adults was used as a reference group. three months after vaccination, uninfected older adults presented reduced SARS-CoV-2-specific IgG levels and a significantly lower neutralisation capacity against the WH1 and Delta variants compared with vaccinated uninfected younger individuals. In contrast, COVID-19-recovered older adults showed significantly higher SARS-CoV-2-specific IgG levels after vaccination than their younger counterparts, whereas showing similar neutralisation activity against the WH1 virus and an increased neutralisation capacity against the Delta variant. Although, similarly to younger individuals, previously infected older adults elicit potent cross-reactive immune responses, higher quantities of SARS-CoV-2-specific IgG antibodies are required to reach the same neutralisation levels. although hybrid immunity seems to be active in previously infected older adults 3 months after mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected but vaccinated older residents of LTCF. These results suggest that a vaccine booster dose should be prioritised for this particularly vulnerable population

Mutational Landscape and tumor burden assessed by cell-free DNA in Diffuse Large B-Cell Lymphoma in a population-based study

Purpose: We analyzed the utility of cell-free DNA (cfDNA) in a prospective population-based cohort to determine the mutational profile, assess tumor burden, and estimate its impact in response rate and outcome in patients with diffuse large B-cell lymphoma (DLBCL). Experimental design: A total of 100 patients were diagnosed with DLBCL during the study period. Mutational status of 112 genes was studied in cfDNA by targeted next-generation sequencing. Paired formalin-fixed, paraffin-embedded samples and volumetric PET/CT were assessed when available. Results: Appropriate cfDNA to perform the analyses was obtained in 79 of 100 cases. At least one mutation could be detected in 69 of 79 cases (87%). The sensitivity of cfDNA to detect the mutations was 68% (95% confidence interval, 56.2-78.7). The mutational landscape found in cfDNA samples was highly consistent with that shown in the tissue and allowed genetic classification in 43% of the cases. A higher amount of circulating tumor DNA (ctDNA) significantly correlated with clinical parameters related to tumor burden (elevated lactate dehydrogenase and β2-microglobulin serum levels, advanced stage, and high-risk International Prognostic Index) and total metabolic tumor volume assessed by PET/CT. In patients treated with curative intent, high ctDNA levels (>2.5 log hGE/mL) were associated with lower complete response (65% vs. 96%; P < 0.004), shorter progression-free survival (65% vs. 85%; P = 0.038), and overall survival (73% vs. 100%; P = 0.007) at 2 years, although it did not maintain prognostic value in multivariate analyses. Conclusions: In a population-based prospective DLBCL series, cfDNA resulted as an alternative source to estimate tumor burden and to determine the tumor mutational profile and genetic classification, which have prognostic implications and may contribute to a future tailored treatment

Functional and structural findings of neurodegeneration in early stages of diabetic retinopathy:cross-sectional analyses of baseline data of the EUROCONDOR project

Cross-sectional study evaluating the relationship between: a) functional and structural measurements of neurodegeneration in initial stages of diabetic retinopathy (DR); and b) presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of patients with type 2 diabetes (n=449) enrolled in the EUROCONDOR study (NCT01726075). Functional studies by multifocal ERG (mfERG) evaluated neurodysfunction and structural measurements using spectral domain optical-coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time (IT), and was lower in patients with ETDRS 20-35 than in patients with ETDRS <20 (p=0.005). In 58% of cases, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements which increases with the presence of microvascular impairment. However, in our particular study population (ETDRS ≤ 35) a significant proportion of patients had normal GC-IPL thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many, but not in all type 2 diabetic patients

Workshops interdisciplinares: implementación de metodologías de aprendizaje basado en proyectos y cooperativo

Los workshops interdisciplinares son un modelo de enseñanza-aprendizaje con capacidad para integrar otras modalidades –como trabajo en grupo, autónomo, clases prácticas u otras– y pueden ser implementados a través de metodologías de aprendizaje basado en proyectos y cooperativo. Presentamos el workshop Arqueología del Presente, en el cual los estudiantes crearon y publicaron webdocs sobre la desaparición de la industria lanar en la región de Beiras, y el workshop Teatro de Igualdad de Género del Empowerment Lab –subvencionado por las EEA-Grants–, en el que se desarrolló una performance teatral. Ambos workshops fueron desarrollados en la Universidad de Beira Interior, Portugal.Interdisciplinary workshops are a model of teaching-learning with ability to integrate other modalities such as group/autonomous work, laboratory practices and others. They can be implemented using the methodologies of cooperative and project base learning.We present the workshop Archaeology of the Present, in which students developed and published online webdocs about the demise of the wool industry in the region of Beiras, and the Empowerment Lab’s Theater workshop on gender identity –funded by the EEA-grants– in which a theatrical performance was developed. Both workshops were developed at the University of Beira Interior, Portugal