Impacto de la fracción de eyección del ventrículo izquierdo en el consumo de recursos, los costes y el pronóstico en pacientes con insuficiencia cardiaca / Differences in clinical outcomes, health care resource utilization and costs in heart failure patients according to left ventricular ejection fraction

Introducción y objetivos: No se conoce bien el impacto de la fracción de eyección del ventrículo izquierdo (FEVI) en el coste y la utilización de recursos sanitarios (URS) en la insuficiencia cardiaca (IC). El objetivo de nuestro trabajo es comparar el consumo de costes, la URS y el pronóstico según grupos de FEVI. Métodos: Estudio observacional retrospectivo que incluyó a todos los pacientes con diagnóstico principal de IC en urgencias o en una hospitalización en un centro terciario español durante 2018. Se excluyó la IC de nuevo diagnóstico. Se compararon los resultados clínicos, los costes y la URS según la FEVI (reducida [IC-FEr], ligeramente reducida [IC-FElr] y conservada [IC-FEc]) a 1 año. Resultados: De 1.287 pacientes con diagnóstico de IC en urgencias, 365 (28,4%) fueron dados de alta (grupo de urgencias [GU]) y 919 (71,4%), hospitalizados (GH). En total, 190 pacientes (14,7%) tenían IC-FEr; 146 (11,4%), IC-FElr y 951 (73,9%), IC-FEc. La media de edad fue 80,1±10,7 años, y el 57,1% eran mujeres. La mediana [intervalo intercuartílico] del coste por paciente-año fue de 1.889 [259-6.269] euros en el GU y 5.008 [2.747-9.589] euros en el GH (p <0,001). Los pacientes con IC-FEr del GU sufrieron más hospitalizaciones. El coste de la IC-FEr por paciente-año fue superior en ambos grupos: en el GU, 4.763 [2.076-17.155] euros con IC-FEr frente a 3.900 [590-8.013] euros con IC-FElr frente a 3.812 [259-5.486] euros con IC-FEc; en el GH, 6.321 [3.335-796] frente a 6.170 [3.189-10.484] frente a 4.636 [2.609-8.977] euros respectivamente; todos, p <0,001). Esta diferencia se debió a que los pacientes con IC-FEr ingresaron con mayor frecuencia en unidades de cuidados críticos y recibieron más pruebas diagnóstico-terapéuticas. Conclusiones: La FEVI influye significativamente en los costes y URS en la IC. Los pacientes con IC-FEr, especialmente los hospitalizados, concentran un mayor coste que aquellos con IC-FEc.(AU)

Introduction and objectives: The impact of left ventricular ejection fraction (LVEF) on health care resource utilization (HCRU) and cost in heart failure (HF) patients is not well known. We aimed to compare outcomes, HCRUs and costs according to LVEF groups. Methods: Retrospective, observational study of all patients with an emergency department (ED) visit or admission to a tertiary hospital in Spain 2018 with a primary HF diagnosis. We excluded patients with newly diagnosed heart failure. One-year clinical outcomes, costs and HCRUs were compared according to LVEF (reduced [HFrEF], mildly reduced [HFmrEF], and preserved [HFpEF]). Results: Among 1287 patients with a primary diagnosis of HF in the ED, 365 (28.4%) were discharged to home (ED group), and 919 (71.4%) were hospitalized (hospital group [HG]). In total, 190 patients (14.7%) had HFrEF, 146 (11.4%) HFmrEF, and 951 (73.9%) HFpEF. The mean age was 80.1±10.7 years; 57.1% were female. The median [interquartile range] of costs per patient/y was €1889 [259-6269] in the ED group and €5008 [2747-9589] in the HG (P <.001). Hospitalization rates were higher in patients with HFrEF in the ED group. The median costs of HFrEF per patient/y were higher in patients in both groups: €4763 [2076-17 155] vs €3900 [590-8013] for HFmrEF vs €3812 [259-5486] for HFpEF in the ED group, and €6321 [3335-796] vs €6170 [3189-10484] vs €4636 [2609-8977], respectively, in the hospital group (all P <.001). This difference was driven by the more frequent admission to intensive care units, and greater use of diagnostic and therapeutic tests among HFrEF patients. Conclusions: In HF, LVEF significantly impacts costs and HCRU. Costs were higher in patients with HFrEF, especially those requiring hospitalization, than in those with HFpEF.(AU)

Differences in clinical outcomes, health care resource utilization and costs in heart failure patients according to left ventricular ejection fraction.

INTRODUCTION AND OBJECTIVES: The impact of left ventricular ejection fraction (LVEF) on health care resource utilization (HCRU) and cost in heart failure (HF) patients is not well known. We aimed to compare outcomes, HCRUs and costs according to LVEF groups. METHODS: Retrospective, observational study of all patients with an emergency department (ED) visit or admission to a tertiary hospital in Spain 2018 with a primary HF diagnosis. We excluded patients with newly diagnosed heart failure. One-year clinical outcomes, costs and HCRUs were compared according to LVEF (reduced [HFrEF], mildly reduced [HFmrEF], and preserved [HFpEF]). RESULTS: Among 1287 patients with a primary diagnosis of HF in the ED, 365 (28.4%) were discharged to home (ED group), and 919 (71.4%) were hospitalized (hospital group [HG]). In total, 190 patients (14.7%) had HFrEF, 146 (11.4%) HFmrEF, and 951 (73.9%) HFpEF. The mean age was 80.1±10.7 years; 57.1% were female. The median [interquartile range] of costs per patient/y was €1889 [259-6269] in the ED group and €5008 [2747-9589] in the HG (P <.001). Hospitalization rates were higher in patients with HFrEF in the ED group. The median costs of HFrEF per patient/y were higher in patients in both groups: €4763 [2076-17 155] vs €3900 [590-8013] for HFmrEF vs €3812 [259-5486] for HFpEF in the ED group, and €6321 [3335-796] vs €6170 [3189-10484] vs €4636 [2609-8977], respectively, in the hospital group (all P <.001). This difference was driven by the more frequent admission to intensive care units, and greater use of diagnostic and therapeutic tests among HFrEF patients. CONCLUSIONS: In HF, LVEF significantly impacts costs and HCRU. Costs were higher in patients with HFrEF, especially those requiring hospitalization, than in those with HFpEF.

Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation.

Introduction: Chronic or uncontrolled activation of myeloid cells including monocytes, macrophages and dendritic cells (DCs) is a hallmark of immune-mediated inflammatory disorders. There is an urgent need for the development of novel drugs with the capacity to impair innate immune cell overactivation under inflammatory conditions. Compelling evidence pointed out cannabinoids as potential therapeutic tools with anti-inflammatory and immunomodulatory capacity. WIN55,212-2, a non-selective synthetic cannabinoid agonist, displays protective effects in several inflammatory conditions by mechanisms partially depending on the generation of tolerogenic DCs able to induce functional regulatory T cells (Tregs). However, its immunomodulatory capacity on other myeloid cells such as monocytes and macrophages remains incompletely understood. Methods: Human monocyte-derived DCs (hmoDCs) were differentiated in the absence (conventional hmoDCs) or presence of WIN55,212-2 (WIN-hmoDCs). Cells were stimulated with LPS, cocultured with naive T lymphocytes and their cytokine production and ability to induce T cell responses were analysed by ELISA or flow cytometry. To evaluate the effect of WIN55,212-2 in macrophage polarization, human and murine macrophages were activated with LPS or LPS/IFNγ, in the presence or absence of the cannabinoid. Cytokine, costimulatory molecules and inflammasome markers were assayed. Metabolic and chromatin immunoprecipitation assays were also performed. Finally, the protective capacity of WIN55,212-2 was studied in vivo in BALB/c mice after intraperitoneal injection with LPS. Results: We show for the first time that the differentiation of hmoDCs in the presence of WIN55,212-2 generates tolerogenic WIN-hmoDCs that are less responsive to LPS stimulation and able to prime Tregs. WIN55,212-2 also impairs the pro-inflammatory polarization of human macrophages by inhibiting cytokine production, inflammasome activation and rescuing macrophages from pyroptotic cell death. Mechanistically, WIN55,212-2 induced a metabolic and epigenetic shift in macrophages by decreasing LPS-induced mTORC1 signaling, commitment to glycolysis and active histone marks in pro-inflammatory cytokine promoters. We confirmed these data in ex vivo LPS-stimulated peritoneal macrophages (PMΦs), which were also supported by the in vivo anti-inflammatory capacity of WIN55,212-2 in a LPS-induced sepsis mouse model. Conclusion: Overall, we shed light into the molecular mechanisms by which cannabinoids exert anti-inflammatory properties in myeloid cells, which might well contribute to the future rational design of novel therapeutic strategies for inflammatory disorders.

GALIPDIA study: Reaching lipid targets in a population with type 2 diabetes (T2DM) from the Northwest of Spain.

AIM: To assess the degree of compliance with the European ESC/EAS 2016 and 2019 dyslipidaemia guidelines in patients with type 2 diabetes mellitus (T2DM). METHODS: Multicentre retrospective cross-sectional study, conducted in 380 adults with T2DM and dyslipidaemia in 7 Spanish health areas. INCLUSION CRITERIA: minimum follow-up of one year in Endocrinology Units, at least one visit in 2020 and a lipid profile measurement in the last 3 months. EXCLUSION CRITERIA: familial hypercholesterolaemia, recent hospitalisation, active oncological pathology and dialysis. RESULTS: According to the 2016 and 2019 guidelines the majority of patients were classified as being at very high cardiovascular risk (86.8% vs. 72.1%, respectively). LDL-c compliance was adequate in 62.1% of patients according to the 2016 guidelines and 39.7% according to the 2019 guidelines (p<0.001). Clinical conditions such as history of cardiovascular disease and therapy-related aspects (use of statins, especially high-potency statins, combination therapies and good adherence) were significantly associated with greater achievement of lipid targets. CONCLUSION: There is a discrepancy between dyslipidaemia guideline recommendations and the reality of lipid control in patients with T2DM, despite most of these patients being at very high cardiovascular risk. Strategies to optimise lipid-lowering treatments need to be implemented.

Effects of academic self-regulation on procrastination, academic stress and anxiety, resilience and academic performance in a sample of Spanish secondary school students.

Introduction: One of the biggest challenges facing students today is procrastination, which is closely related to stress, anxiety and, in the most severe cases, depression. The aim of the present study is to analyze the influence of academic self-regulation on procrastination, academic anxiety and stress, academic resilience and academic performance. Method: The sample consisted of 991 high school students aged between 16 and 19 years (M = 17.25; SD = 3.45). A structural equation model was used to analyze the relationship between the study variables. Results: Analyzes showed that academic self-regulation negatively predicted procrastination. In turn, procrastination positively predicted academic stress and anxiety. However, resilience exerted a protective influence by being positively related to academic stress and anxiety. Finally, resilience positively predicted academic performance, whereas stress and anxiety negatively predicted academic performance. Conclusion: Thus, the importance of generating strategies for students to learn to self-regulate in academic contexts, manage emotions, foster motivation and develop strategies to help them overcome the vicissitudes they face is emphasized.

From trained immunity in allergy to trained immunity-based allergen vaccines.

Innate immune cells experience long lasting metabolic and epigenetic changes after an encounter with specific stimuli. This facilitates enhanced immune responses upon secondary exposition to both the same and unrelated pathogens, a process termed trained immunity. Trained immunity-based vaccines (TIbV) are vaccines able to induce innate immune memory, thus conferring heterologous protection against a broad range of pathogens. While trained immunity has been well documented in the context of infections and multiple immune-mediated diseases, the role of innate immune memory and its contribution to the initiation and maintenance of chronic allergic diseases remains poorly understood. Over the last years, different studies attempting to uncover the role of trained immunity in allergy have emerged. Exposition to environmental factors impacting allergy development such as allergens or viruses induces the reprogramming of innate immune cells to acquire a more pro-inflammatory phenotype in the context of asthma or food allergy. Several studies have convincingly demonstrated that prevention of viral infections using TIbV contributes to reduce wheezing attacks in children, which represent a high-risk factor for asthma development later in life. Innate immune cells trained with specific stimuli might also acquire anti-inflammatory features and promote tolerance, which may have important implications for chronic inflammatory diseases such as allergies. Recent findings showed that allergoid-mannan conjugates, which are next generation vaccines for allergen-specific immunotherapy (AIT), are able to reprogram monocytes into tolerogenic dendritic cells by mechanisms depending on metabolic and epigenetic rewiring. A better understanding of the underlying mechanisms of trained immunity in allergy will pave the way for the design of novel trained immunity-based allergen vaccines as potential alternative strategies for the prevention and treatment of allergic diseases.

Adaptation and Testing of the Factorial Structure of the Physical Education Grit Scale for Use in Secondary Education in Spain.

The challenges faced by students during Physical Education classes embrace both physical and academic aspects. Therefore, each individual possesses a series of internal psychological mechanisms, such as Grit, which allow them to adapt and overcome the vicissitudes. However, there are no scales that assess Grit in Span. Thus, the aim of the present study is to test the factor structure of the Physical Education Grit Scale in Span of Physical Education classes. For this purpose, 857 secondary school students took part in the present study. In order to test the factor structure, a confirmatory factor analysis, an exploratory factor analysis, an analysis of the reliability of the questionnaire and an analysis of temporal stability were carried out. The results showed that the factor structure consisted of two factors and four sub-factors (χ2/df = 2.17 (p = 0.001); CFI = 0.96; TLI = 0.96; IFI = 0.96; RMSEA = 0.051; SRMR = 0.037). In addition, the reliability and temporal stability analyses showed acceptable indices. Based on these results, evidence of reliability and validity of the Physical Education Grit Scale in Span of Physical Education is provided.

The Perception of Teaching, Learning Styles and Commitment to Learning and Their Influence on the Practice of Physical Activity and Eating Habits Related to the Mediterranean Diet in Physical Education Students.

Childhood obesity, linked to a sedentary lifestyle and an unbalanced diet, is one of the main problems in today's Western societies. In this sense, the aim of the study was to analyze students' perceived satisfaction in physical education classes with learning strategies and engagement in learning and critical thinking as determinants of healthy lifestyle habits. The study involved 2,439 high school students aged 12-18 years (M = 14.66, SD = 1.78). Structural equation modeling was conducted to analyze the predictive relationships between the study variables. The results showed that teaching, teaching mastery, and cognitive development are precursors to deep thinking on the part of students, indicators of the adoption of healthy lifestyle habits. These results reflect the importance of the methodology adopted by the teacher in order to positively influence the students' habits.

Primary vs. Secondary Heart Failure Diagnosis: Differences in Clinical Outcomes, Healthcare Resource Utilization and Cost.

Background: There is scarce information on patients with secondary heart failure diagnosis (sHF). We aimed to compare the characteristics, burden, and outcomes of sHF with those with primary HF diagnosis (pHF). Methods: Retrospective, observational study on patients ≥18 years with emergency department (ED) visits during 2018 with pHF and sHF in ED or hospital (ICD-10-CM) diagnostic codes. Baseline characteristics, 30-day and 1-year mortality, readmission and re-ED visit rates, and costs were compared between sHF and pHF. Results: Out of the 797 patients discharged home from the ED, 45.5% had sHF, and these presented lower 1-year hospitalization, re-ED visit rates, and costs. In contrast, out of the 2,286 hospitalized patients, 55% had sHF and 45% pHF. Hospitalized sHF patients had significantly (p < 0.01) greater comorbidity, lower use of recommended HF therapies, longer length of stay (10.8 ± 10.1 vs. 9.7 ± 7.9 days), and higher in-hospital and 1-year mortality (32 vs. 25.8%) with no significant differences in readmission rates and lower 1-year re-ED visit rate. Hospitalized sHF patients had higher total costs (€12,262,422 vs. €9,144,952, p < 0.001), mean cost per patient-year (€9,755 ± 13,395 vs. €8,887 ± 12,059), and average daily cost per patient. Conclusion: Hospitalized sHF patients have a worse initial prognosis, greater use of healthcare resources, and higher costs.

Bromhidrosis por trimetilaminuria. Dificultades en su diagnóstico y tratamiento / Bromhidrosis caused by trimethylaminuria. Difficulties in its diagnosis and treatment

La trimetilaminuria es una causa de bromhidrosis, que hay que tener en cuenta en niños prepúberes con un desarrollo normal. Su relación con la ingesta, sobre todo de pescado marino, nos hará sospechar su existencia, que deberemos confirmar mediante el análisis de la excreción urinaria de trimetilamina y el estudio genético. Presentamos cuatro casos de trimetilaminuria donde se analizan y discuten las fórmulas más empleadas para valorar una excreción urinaria aumentada de trimetilamina, su correlación con la gravedad del cuadro y con el rendimiento de las pruebas genéticas. Por último, se describen los tratamientos empleados y se realiza una propuesta de tratamiento, basada en las recomendaciones dietéticas y en el asesoramiento a los padres para un mejor conocimiento y manejo de la enfermedad (AU)

Trimethylaminuria is a cause of bromhidrosis to be considered in pre-pubertal children, with normal development. Its relation with the ingestion, especially of marine fish, will make us suspect its existence that we will have to confirm by means of the analysis of the urinary excretion of trimetilamine and the genetic study. We present four cases of trimethylaminuria where the most used formulas to assess increased urinary excretion of trimethylamine are analysed and discussed, as well as their correlation with the severity of the disease and with the performance of genetic tests. Finally, the used treatments are described, and a treatment proposal is made, based on dietary recommendations and advices to parents for a better understanding and management of the disease (AU)

LipoDDx: a mobile application for identification of rare lipodystrophy syndromes.

BACKGROUND: Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx®. Our aim was to establish the effectiveness of LipoDDx®. Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx®. The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease. RESULTS: LipoDDx® provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx® the success rate was 17 ± 20%, while with LipoDDx® the success rate was 79 ± 20% (p < 0.01). CONCLUSIONS: LipoDDx® is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value.

Evaluación de las coberturas de vacunación antineumocócica y antigripal en pacientes reumatológicos con terapia biológica de un hospital autonómico de referencia / Evaluation of pneumococcal and influenza vaccination coverage in rheumatology patients receiving biological therapy in a regional referral hospital

OBJETIVO: Conocer las coberturas de vacunación frente a gripe estacional y neumococo en pacientes reumatológicos con terapia biológica. Identificar las variables que predicen adherencia a la vacunación. MATERIAL Y MÉTODO: Estudio transversal. Se incluyeron los pacientes reumatológicos que iniciaron terapia biológica entre el 01/01/2016 y el 31/12/2016 en un hospital autonómico de referencia. Se recogieron variables sociodemográficas, relacionadas con el diagnóstico, médico prescriptor, derivación a la Unidad de Vacunas y vacunación frente a neumococo con vacuna conjugada de 13 serotipos (VNC13) y polisacárida de 23 serotipos (VNP23), así como gripe estacional (2016/17). Se realizó análisis univariante, bivariante (Chi-cuadrado) y multivariante (regresión logística). Se consideró significativa una p < 0,05 y se utilizó el programa PASW V.18. RESULTADOS: Se incluyeron 222 pacientes. Las coberturas de vacunación fueron: VNC13, 80,2%; VNP23v, 77,9%; gripe 2016/17, 78,8%; VNC13 + VNP23, 75,2%; VNC13 + VNP23 + gripe 2016/17, 68,9%. La espondilitis axial registró las coberturas más altas (>80%) para la vacunación antineumocócica y en combinación con la antigripal. El 27% de los pacientes no fueron derivados a la Unidad. El médico prescriptor se asoció de manera estadísticamente significativa con cada una de las vacunas y sus combinaciones, pero fue la derivación a la Unidad de Vacunas la que se asoció de manera independiente con las mayores coberturas de vacunación (p < 0,001) en todos los casos. CONCLUSIONES: Comparando con la literatura científica, consideramos que las coberturas frente a neumococo y gripe en estos pacientes son elevadas. La derivación de estos pacientes a la Unidad de Vacunas resulta clave para garantizar una correcta inmunización y minimizar así algunos de los posibles efectos adversos infecciosos de las terapias biológicas

OBJECTIVE: Vaccination coverage for seasonal influenza and pneumococcus in rheumatology patients receiving biological treatment. To identify variables that predict vaccination adherence. MATERIAL AND METHOD: Descriptive cross-sectional study. The study involved rheumatology patients who initiated biological therapy between 01/01/2016 and 12/31/2016 in a regional referral hospital. Variables included sociodemographic information, diagnostic data, treating physician, referral to the vaccine unit and vaccination against pneumococcus with 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), as well as seasonal influenza (2016/17). Univariate, bivariate (Chi-square) and multivariate analysis (logistic regression) were performed. The differences were considered significant (P<.05) and the PASW V.18 software package was used. RESULTS: In all, 222 patients were included. Vaccination coverage was: PCV13, 80.2%; PPSV23, 77.9%; influenza 2016/17, 78.8%; PCV13 + PPSV23, 75.2%; PCV13 + PPSV23 + influenza 2016/17, 68.9%. Axial spondylitis had the highest coverage (>80%) for pneumococcal vaccination and combination of pneumococcal with influenza. Overall, 27% of the patients were not referred to the unit. The treating physician was associated with statistical significance in each vaccine alone or combined, but referral to the vaccine unit was independently associated with the highest vaccination coverage (P<.001) in all cases. CONCLUSIONS: Compared to the scientific literature, we consider that the coverage of our patients against pneumococcus and influenza is high. Referral of these patients to the vaccine unit is the key to guarantee a correct immunization and to minimize some of the possible infectious adverse effects of biological therapies

A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections.

Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ- and IL-17A-producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.

Evaluation of pneumococcal and influenza vaccination coverage in rheumatology patients receiving biological therapy in a regional referral hospital. / Evaluación de las coberturas de vacunación antineumocócica y antigripal en pacientes reumatológicos con terapia biológica de un hospital autonómico de referencia.

OBJECTIVE: Vaccination coverage for seasonal influenza and pneumococcus in rheumatology patients receiving biological treatment. To identify variables that predict vaccination adherence. MATERIAL AND METHOD: Descriptive cross-sectional study. The study involved rheumatology patients who initiated biological therapy between 01/01/2016 and 12/31/2016 in a regional referral hospital. Variables included sociodemographic information, diagnostic data, treating physician, referral to the vaccine unit and vaccination against pneumococcus with 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), as well as seasonal influenza (2016/17). Univariate, bivariate (Chi-square) and multivariate analysis (logistic regression) were performed. The differences were considered significant (P<.05) and the PASW v.18 software package was used. RESULTS: In all, 222 patients were included. Vaccination coverage was: PCV13, 80.2%; PPSV23, 77.9%; influenza 2016/17, 78.8%; PCV13+PPSV23, 75.2%; PCV13+PPSV23+influenza 2016/17, 68.9%. Axial spondylitis had the highest coverage (>80%) for pneumococcal vaccination and combination of pneumococcal with influenza. Overall, 27% of the patients were not referred to the unit. The treating physician was associated with statistical significance in each vaccine alone or combined, but referral to the vaccine unit was independently associated with the highest vaccination coverage (P<.001) in all cases. CONCLUSIONS: Compared to the scientific literature, we consider that the coverage of our patients against pneumococcus and influenza is high. Referral of these patients to the vaccine unit is the key to guarantee a correct immunization and to minimize some of the possible infectious adverse effects of biological therapies.

Evaluación de las coberturas de vacunación en pacientes con implante coclear de un hospital de referencia del norte de España / Evaluation of vaccination coverage in cochlear implant patients at a referral hospital in Northern Spain

Antecedentes y objetivo: El riesgo de meningitis bacteriana aumenta en los pacientes con implante coclear. Por ello, se indica la vacunación antineumocócica, antigripal y frente a Haemophilus influenzae tipo b en este grupo. El objetivo del presente estudio es conocer el cumplimiento del calendario vacunal en los pacientes implantados en un hospital de referencia. Materiales y métodos: Se incluyeron los pacientes con implante coclear intervenidos entre 2005 y 2015. Se evaluaron las coberturas vacunales frente a gripe estacional, Haemophilus influenzae tipo b, neumococo conjugada de 13 serotipos y neumococo polisacárida de 23 serotipos. Se dividió la muestra en 2 grupos por edad (< 14 años y ≥ 14 años). Se realizó un análisis univariante y bivariante. Resultados: De los 153 pacientes estudiados (28,01% 0-13 años y 71,9% ≥ 14), solo 2 (5,71%) tuvieron un 100% de adherencia al calendario vacunal, mientras que el 65,71% registró un cumplimiento del 50% o menor. Globalmente, la cobertura de vacunación frente a la pauta secuencial de neumococo fue del 48,57%. La población pediátrica superó el 90% de cobertura para la vacuna frente a Haemophilus influenzae tipo b y neumococo conjugada de 13 serotipos, mientras que en los mayores de 14 años apenas superó el 50%. La cobertura frente a gripe estacional fue inferior al 40%. Se obtuvo una correlación inversa entre la edad y el cumplimiento, aunque no estadísticamente significativa. Conclusiones. Las coberturas de vacunación en los pacientes con implante coclear evaluados son más bajas de lo esperado. Se propone la colaboración estrecha entre los servicios de Otorrinolaringología y las Unidades de Vacunas como principal estrategia para la mejora

Background and objective: The risk of bacterial meningitis increases in cochlear implant patients. Therefore, pneumococcal, influenza and Haemophilus influenzae type b vaccination is indicated in this group. The aim of this study was to determine compliance with the vaccination calendar in patients implanted in a referral hospital. Materials and methods: Patients with cochlear implant operated between 2005 and 2015 were included. Vaccine coverage for seasonal influenza, Haemophilus influenzae type b and pneumococcal conjugate 13-serotypes and pneumococcal polysaccharide 23-serotypes was evaluated. The sample was divided into 2 age groups (< 14 years and ≥ 14 years). A univariate and bivariate analysis was performed. Results: Of the 153 patients studied (28.01% 0-13 years old and 71.9% ≥ 14), only 2 (5.71%) had 100% adherence to the vaccination schedule, while 65.71% had compliance of 50% or less. Overall, vaccination coverage against the sequential pneumococcal pattern was 48.57%. The paediatric population exceeded 90% coverage for the vaccine against Haemophilus influenzae type b and pneumococcal conjugate 13-serotypes while in those over 14 years of age it barely exceeded 50%. Influenza coverage was less than 40%. An inverse correlation was obtained between age and compliance, although not statistically significant. Conclusions: Vaccination coverage in patients with cochlear implant is lower than expected. Close collaboration between Otolaryngology departments and the Vaccination Units is proposed as the main strategy for improvement

The Value of Adding Surveillance Cultures to Fluoroquinolone Prophylaxis in the Management of Multiresistant Gram Negative Bacterial Infections in Acute Myeloid Leukemia.

Multidrug resistant Gram-Negative Bacterial Infections (MR-GNBI) are an increasing cause of mortality in acute myeloid leukemia (AML), compromising the success of antineoplastic therapy. We prospectively explored a novel strategy, including mandatory fluoroquinolone prophylaxis, weekly surveillance cultures (SC) and targeted antimicrobial therapy for febrile neutropenia, aimed to reduce infectious mortality due to MR-GNBI. Over 146 cycles of chemotherapy, cumulative incidence of colonization was 50%. Half of the colonizations occurred in the consolidation phase of treatment. Application of this strategy led to a significant reduction in the incidence of GNB and carbapenemase-producing Klebisella pneumoniae (cpKp) species, resulting in a reduction of infectious mortality (HR 0.35 [95%, CI 0.13-0.96], p = 0.042). In multivariate analysis, fluroquinolone prophylaxis in addition to SC was associated with improved survival (OR 0.55 [95% CI 0.38-0.79], p = 0.001). Targeted therapy for colonized patients did not overcome the risk of death once cpKp or XDR Pseudomonas aeruginosa infections were developed. Mortality rate after transplant was similar between colonized and not colonized patients. However only 9% of transplanted patients were colonized by cpkp. In conclusion, colonization is a common phenomenon, not limited to the induction phase. This strategy reduces infectious mortality by lowering the global incidence of GN infections and the spread of resistant species.

Reacciones adversas asociadas a la vacunación en pacientes inmunodeprimidos y en situaciones especiales de una Unidad de Vacunas hospitalaria / Vaccine-related adverse reactions in immunocompromised patients and in special situations of a hospital Vaccine Unit

OBJETIVOS: Describir el tipo de vacunas administradas en la Unidad de Vacunas de un hospital de referencia y calcular la tasa de notificación global y específica de las reacciones adversas asociadas. MÉTODOS: Estudio observacional retrospectivo, realizado en el periodo entre noviembre de 2014 y noviembre de 2017, de los pacientes que desarrollaron una reacción adversa a medicamento (RAM) tras la administración de una vacuna y que fue notificada al Sistema Español de Farmacovigilancia. Las variables analizadas fueron edad, sexo, grupo de riesgo, tipo de vacuna, coadministración y tipo de RAM. Se llevó a cabo un análisis univariante y bivariante. Se calculó la tasa de notificación de RAM global y específica para cada vacuna. RESULTADOS: Se administraron un total de 18.123 vacunas de las que el 20,7% correspondían a la vacuna frente al virus de la hepatitis B. Se notificaron 53 sospechas de RAM. En el 64,2% de las ocasiones se había administrado solamente una vacuna. El 88,7% de las notificaciones correspondieron a vacunas inactivadas. La vacuna frente neumococo polisacárida de 23 serotipos fue la que generó el mayor número de notificaciones. La tasa de notificación global de RAM fue de 0,42%. La vacuna hexavalente fue la que registró la tasa de notificación más elevada (2,81%). El 49,1% de las RAM fueron de tipo sistémico. CONCLUSIONES: La tasa de notificación global fue baja aunque superior a la registrada por otros autores. La correcta notificación de posibles reacciones adversas postvacunales es imprescindible para contribuir a la seguridad vacunal y para aumentar la confianza de la población en las vacunas

OBJECTIVES: The aim of the study was to describe the type of vaccines administered in the Vaccine Unit at a reference hospital. Calculate the overall and specific reporting rate of adverse reactions. METHODS: Retrospective observational study for the period between November 2014 and November 2017, on patients who developed an adverse drug reaction (ADR) after the administration of a vaccine and who were notified to the Spanish Pharmacovigilance System. The variables analyzed were age, sex, risk group, vaccine class, co-administration and type of ADR. A univariate and bivariate analysis was performed. The global and vaccine specific rate of ADR notification was calculated. RESULTS: A total of 18,123 vaccines were administered, of which 20.7% corresponded to hepatitis B virus vaccine. Fifty-three RAM suspects were reported. In 64.2% of cases only one vaccine was administered. Inactivated vaccines accounted for 88.7% of notifications. The highest number of notifications was generated by the 23 serotypes pneumococcal polysaccharide vaccine. The overall reporting rate was 0.42%. The hexavalent vaccine had the highest reporting rate (2.81%).49.1% of the ADR were systemic. CONCLUSIONS: The overall reporting rate was low but higher than that of other authors. Proper reporting of possible adverse post-vaccine reactions is essential to contribute to vaccine safety and to increase public confidence in vaccines

A Modular Vector Toolkit with a Tailored Set of Thermosensors To Regulate Gene Expression in Thermus thermophilus.

Modular plasmid architectures have shown to be a very useful resource to standardize, build, share, and compare biological parts and functional vectors, and are being applied in an increasing number of microorganisms. Here, we present a modular plasmid toolkit for Thermus thermophilus, a species considered as a workhorse for biotechnology and a model for high-temperature biology. Apart from integrating improved versions of already existing parts, we have characterized specific promoters and developed a thermosensor-based palette that restricts the expression to Thermus and, at the same time, controls protein expression in this organism in a temperature-dependent manner.

Lesion location and other predictive factors of dysphagia and its complications in acute stroke.

BACKGROUND AND AIMS: Early detection of dysphagia is crucial in stroke patients as a result of increased morbidity and mortality due to malnutrition and respiratory tract infections. The aim of this study was to identify possible predictors of the onset of dysphagia following stroke in order to be able to act precociously. METHODS: Observational, prospective study in which a Volume-Viscosity Swallow Test (V-VST) was carried out in the first 72 h following admission to assess dysphagia in acute stroke patients with a previous result of <3 in the Eating Assessment Tool-10. Lesions were analysed by computed tomography and/or magnetic resonance, using the ABC/2 formula to calculate their volume. Likewise, 3-month follow-up was carried out for the evaluation of the occurrence of respiratory tract infections and deaths. RESULTS: Out of 106 patients admitted for acute stroke, 60 (56.60%) presented dysphagia (44.40% showing alterations in the effectiveness of swallowing and 33.30% in its safety). The factors that were related to dysphagia were: older age (76.40 ± 11.50 vs 66.37 ± 13.85 years, p = 0.0001), stroke severity as measured on the National Institute of Health Stroke Scale (6.81 ± 5.83 vs 3.38 ± 3.46, p = 0.001) and greater volume of the lesion (23.47 ± 47.15 vs 7.50 ± 14.53 ml, p = 0.042). The variables that were influenced by a greater lesion size were the presence of cough, oxygen desaturation and impaired labial seal. Dysphagia was not affected by the lateralization of the lesion or by the type of stroke (ischaemic/haemorrhagic). Despite the fact that 68.80% of the patients with a temporoparietal lesion presented dysphagia, no significant differences were observed regarding the location of the lesion in the regions studied. 27.3% of the patients with frontal lesions presented respiratory infections after discharge (p = 0.018), a condition which was also observed in 20.0% of patients with dysphagia (p = 0.044). Mortality during the 3-month follow-up period was 20.0% for patients with a positive V-VST (p = 0.005), due to respiratory infection in 66.6% of the cases (p = 0.0001). CONCLUSIONS: Post-stroke dysphagia was associated with the occurrence of respiratory tract infection and mortality. Our study also provides more information about how certain demographic and clinical factors, as well as neuroimaging patterns, influence dysphagia. This fact may help to identify at an early stage those patients with a greater risk of developing swallowing alterations.