Search

PURPOSETo better understand immigration disparities among a Spanish Early-Onset Colorectal Cancer (SECOC) subset, according to the country of origin.PATIENTS AND METHODSWe selected 250 consecutive participants from the SECOC consortium. Data on baseline patient and tumor characteristics, family history of colorectal cancer (CRC), and follow-up were collected. The presence of mismatch repair deficiency was also assessed. Special data regarding country of origin, time of stay in Spain in case of other different country, and a 10-year cutoff that specifies the obtaining of Spanish nationality defined the variables of interest for comparison.RESULTSSeventy-five percent of patients with early-onset CRC (EOCRC) (188) were born in Spain, whereas the other 25% were born outside of Spain. The mean time of living in Spain until the EOCRC diagnosis was 16.5 years. Comparatively, most of the analyzed features showed equivalent proportions between cohorts. Only Spanish patients appeared to have more familial cancer component in first degree in general (32.3%; P = .01), compared with non-Spaniards, which showed a predominant sporadic component (56.4%; P < .001). Among immigrants, those patients living in Spain before CRC diagnosis ≤10 years were younger at diagnosis (39.1 v 42.5), more frequently male (77.8 v 47.7), were in more advanced stages (88.8% diagnosed at stage III and IV [P = .01]), and had a worse prognosis regarding recurrence rates (29.4% v 6.3%).CONCLUSIONAlthough there were few differences between Spanish and non-Spanish EOCRC, the most remarkable difference was that linked with the situation of those immigrants who have recently arrived in Spain, in relation to their lower health coverage, which could be associated with the delay in the diagnosis and their subsequent worse prognosis.

Aim This study characterizes Colorectal Cancer (CRC) incidence in the University Hospital Ramon and Cajal, Madrid, and analyzes variations over time. It establishes risk groups, aiming to discover whether diagnosis can be determined in less advanced stages of disease. Method Evolutionary epidemiological study of genetic and environmental factors contributing to the development of CRC in this district that enables the comparison of two cohorts of patients separated by 37 years: G1 (patients of current group) and G2 (patients of historical group). The main risk variables gleaned retrospectively were analyzed and the statistical association between cohorts was determined. Results The mean age of patients increased significantly from 64 to 71 along with the incidence of ascending colon cancer. G1 scored higher than G2 for: the incidence of colon cancer in men, detection of adenomatous polyps (48.1%), percentage of resectability with curative intent (80.4%), and Dukes A stage (34.1%) (p < 0.001). Conclusion Biological aspects of CRC have been compared against its profile three decades earlier. We can confirm the existence of concrete changes in the manifestation and staging at the time of diagnosis or following earlier treatment.

Resumen Presentamos los fundamentos funcionales y reconstructivos en un caso de exenteración pélvica extendida. El propósito es analizar el defecto quirúrgico y los requerimientos reconstructivos, aspectos no suficientemente descritos en la literatura. Se trata de un varón de 62 años, con carcinoma epidermoide perineal de origen uretral (82x117x108 mm) que invadía vejiga, pelvis y fosa pararrectal. El defecto escisional fue reconstruido con un colgajo compuesto dorsal ancho-escapular-paraescapular y una malla bicapa (polipropileno y politetrafluoroetileno extendido). Describimos una reconstrucción multiplanar orientada a 3 requerimientos funcionales definidos: 1.- soporte visceral para evitar la herniación perineal; 2.- colapso del espacio muerto para minimizar el riesgo de infección; y 3.- cobertura cutánea estable en una región exigente. Sin complicaciones postoperatorias en el corto o largo plazo, el paciente puede deambular adecuadamente y se encuentra libre de enfermedad 1 año después de la intervención. Hasta donde hemos podido conocer, este caso presenta por primera vez el uso del colgajo compuesto descrito en la reconstrucción del defecto de exenteración pélvica.

Purpose The Spanish Early-onset Colorectal Cancer (SECOC) study is a multicentre prospective cohort established in Spain to investigate the molecular basis of early-onset colorectal cancer (EOCRC), including metabolic alterations.Participants 220 patients with EOCRC have been enrolled since January 2019 through 18 centres across Spain. Individual-level data were collected by questionnaire, including lifestyle and other colorectal cancer-related factors. Medical record review was performed to capture clinical, histopathological and familial cancer history data. Biospecimen collection (blood, stool, tissue) at diagnosis and at various time points across treatment, as applicable, is also completed.Findings to date Participants had a median age of 44 years (range 14–49), and the majority are men (60%), with individuals age 40–49 years at EOCRC diagnosis being over-represented. Forty-three per cent of participants were diagnosed with a tumour in the rectosigmoid junction/rectum. Nearly two-thirds of EOCRC cases (64%) were diagnosed with advanced stage (III–IV) disease, and 28% of cases had no reported familial history of cancer.Future plans We are actively recruiting and observing participants; we plan to administer follow-up questionnaires and perform additional biospecimen collection. This prospective cohort offers a unique, rich resource for research on EOCRC aetiologies and will contribute to larger international efforts to disentangle the rising disease burden.

RESUMEN Introducción: la endoprótesis como puente a cirugía curativa en pacientes con cáncer de colon izquierdo obstructivo es una alternativa al tratamiento clásico. El objetivo de nuestro estudio es evaluar la recidiva de la enfermedad así como la morbimortalidad del tratamiento. Pacientes y métodos: estudio retrospectivo observacional donde se analizan los pacientes que acudieron al Servicio de Urgencias con cuadro de obstrucción intestinal por tumoración en colon izquierdo entre junio de 2006 y enero de 2014. Se incluyó a los pacientes a los cuales se les colocó una endoprótesis por vía endoscópica y posteriormente fueron intervenidos con intención curativa. El periodo de observación fue hasta mayo de 2017. Resultados: cincuenta y tres pacientes fueron tratados con endoprótesis; de ellos, nueve fallecieron en el postoperatorio. Los pacientes fallecidos eran más frecuentemente varones (100% en fallecidos vs. 62% en no fallecidos, p = 0,02), con más edad (81,4 ± 5,1 vs. 71,6 ± 10,8, p < 0,001) y tenían hemoglobinas más bajas al ingreso (12,9 vs. 13,6, p < 0,001), mayor número de leucocitos (12.918 vs. 9.437, p < 0,001) y mayor coagulopatía (INR 1,6 vs. 1, p < 0,001). Tuvieron una recidiva a distancia ocho pacientes con una mediana de supervivencia libre de enfermedad de 19,1 meses. Se compararon las variables en función de la aparición de enfermedad a distancia y la media de edad fue menor en los pacientes que presentaron recidiva (65,9 ± 11,3 vs. 74,9 ± 9,9 p < 0,001). Conclusiones: el uso de endoprótesis como puente a cirugía curativa en los pacientes con cáncer de colon izquierdo obstructivo en nuestro hospital ha presentado unos resultados comparables a estudios previos.

Cancer stem cells (CSCs) are a subset of tumor cells with capacity to self-renew and generate the diverse cells that make up the tumor. The aim of this study is to evaluate the prognostic value of CSCs in a highly homogeneous population of stage II colon cancer.One hundred stage II colon cancer patients treated by the same surgical team between 1977 and 2005 were retrospectively analyzed. None of the patients received adjuvant chemotherapy. Inmunohistochemistry expression of CD133, NANOG and CK20 was scored, using four levels: 50% positivity. Kaplan-Meier analysis and log rank test were used to compare survival.The average patient age was 68 years (patients were between 45-92 years of age) and median follow up was 5.8 years. There was recurrent disease in 17 (17%); CD133 expression (defined by >10% positivity) was shown in 60% of the tumors, in 95% for NANOG and 78% for CK20. No correlation was found among expression levels of CD133, NANOG or CK20 and relapse-free survival (RFS) or overall survival (OS). However, a statistical significant correlation was found between established pathological prognostic factors and RFS and OS.Stem Cell quantification defined by CD133 and NANOG expression has no correlation with RFS or OS in this cohort of Stage II colon cancer.

Squamous cell carcinoma of the rectum is one of the differential diagnoses of rectal tumors. It represents a low incidence in the population. The etiopathogenesis and the biology of these tumors are unclear, for this reason the gold standard treatment is difficult to establish. We present a 47-years-old woman who had a squamous cell carcinoma in medium rectum. She was treated with radiation therapy and chemotherapy and the treatment was followed by surgical excision.

Introduction: Chronic kidney disease (CKD) is associated with high cardiovascular disease (CVD) risk, and requires specific interventions to decreases CVD risk.The guidelines indicate that systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. The European Society Cardiology (ESC) guidelines, he European Renal Association (ERA) Council and the Spanish Society of Nephrology (S.E.N.) in collaboration with 15 Scientific Societies recommend assessing albuminuria in all these populations.We have evaluated current clinical practice regarding the assessment of CVD risk factors (blood pressure, albuminuria, serum cholesterol, glycemia and creatinine) in different adult health user populations, analyzing the results separately for men and women, given recent evidence on gender differences in the recognition, monitoring, and management of CKD. Methods: Observational, retrospective, non-interventional single center study performed in a hospital using Electronic Health Record (EHR) data. Results: Among 707,493 healthcare users, 612,619 were adults, and of these 332,943 (54.3%) females; 73,632 (12.0%) had DM and 121,445 (19.8%) hypertension. Mean (SD) age was 68.91 ± 21.4 years; 261,694 (36.9%) were older than 50 years.Only 8522 (1.39%) had undergone albuminuria testing as compared with 264,684 (43.21%) tested for serum creatinine, 140,492 (22.93%) for serum cholesterol, 263,381 (42.99%) for serum glucose, and 226,448 (36.96%) for blood pressure. Albuminuria was the only cardiovascular risk factor assessed more frequently in men than in women.Albuminuria, as other CVD risk factors, was more frequently assessed in patients with DM (6.71% of patients) or hypertension (4.81%), but albuminuria assessment remained suboptimal compared with 58–87% for other cardiovascular risk factors. For adults with diabetes or hypertension, albuminuria was assessed more frequently in men than in women.Albuminuria assessment in those older than 50 years was also suboptimal at 2.24%, as compared with 31–47% for other CVD risk factors.Albuminuria and EGFR are needed to screen for CKD, meaning that a urine test for albumin and creatinine and a serum test for creatinine are needed. To these, we may add assessment of blood pressure, serum cholesterol (for familial hypercholesterolemia) and serum glucose for Diabetes. Albuminuria was the only cardiovascular risk factor that was assessed more frequently in men (up to nearly 60% more frequently), indicating that screening for CKD and CVD risk in women is suboptimal. This result is surprisingly consistent across time and in all age groups. This is the first time that gender disparities in the assessment of albuminuria have been revealed. Conclusion: Albuminuria is assessed infrequently, even in patients with a high cardiovascular risk, especially in women. Resumen: Introducción: La enfermedad renal crónica (ERC) se asocia con un alto riesgo de enfermedad cardiovascular (ECV) y requiere intervenciones específicas para disminuir este riesgo.Las guías recomiendan una evaluación global sistemática del riesgo de ECV en personas con cualquier factor de riesgo vascular importante. Las guías de la Sociedad Europea de Cardiología (SEC), la Asociación Renal Europea (ERA) y la Sociedad Española de Nefrología (SEN), en colaboración con 15 sociedades científicas, recomiendan evaluar la albuminuria en todas estas poblaciones.Hemos evaluado la práctica clínica actual con respecto a la evaluación de los factores de riesgo de ECV (presión arterial, albuminuria, colesterol sérico, glucemia y creatinina) en diferentes poblaciones adultas de usuarios de salud, analizando los resultados por separado para los hombres y las mujeres, dada la evidencia reciente sobre las diferencias de género en el reconocimiento, el seguimiento y el tratamiento de la ERC. Métodos: Estudio observacional, retrospectivo, no intervencionista, unicéntrico, realizado en un hospital utilizando datos de la historia clínica electrónica. Resultados: De los 707.493 usuarios de atención sanitaria, 612.619 eran adultos. De ellos, 332.943 (54,3%) eran mujeres, 73.632 (12,0%) tenían DM y 121.445 (19,8%) tenían hipertensión. La edad media (DE) fue 68,91 ± 21,4 años; 261.694 (36,9%) eran mayores de 50 años.Solo 8.522 (1,39%) se habían sometido a pruebas de albuminuria en comparación con 264.684 (43,21%) de creatinina sérica, 140.492 (22,93%) de colesterol sérico, 263.381 (42,99%) de glucosa sérica y 226.448 (36,96%) de presión arterial. La albuminuria fue el único factor de riesgo cardiovascular evaluado con mayor frecuencia en hombres que en mujeres.La albuminuria, como otros factores de riesgo de ECV, se evaluó con mayor frecuencia en pacientes con DM (6,71% de los pacientes) o hipertensión (4,81%), pero la evaluación de la albuminuria siguió siendo subóptima en comparación con el 58% al 87% para otros factores de riesgo cardiovascular. Para los adultos con diabetes o hipertensión, la albuminuria se evaluó con mayor frecuencia en hombres que en mujeres.La evaluación de la albuminuria en los mayores de 50 años también fue subóptima, con un 2,24%, en comparación con un 31% a un 47% para otros factores de riesgo de ECV.La albuminuria y el FGe son necesarios para detectar ERC, lo que implica la determinación de albúmina y creatinina en orina y de creatinina en suero. A estos podemos agregar la evaluación de la presión arterial, el colesterol sérico (para la hipercolesterolemia familiar) y la glucosa sérica para la diabetes. La albuminuria fue el único factor de riesgo cardiovascular que se evaluó con mayor frecuencia en hombres (hasta casi un 60% más frecuentemente), lo que indica que la detección de ERC y riesgo de ECV en mujeres es subóptima. Este resultado es sorprendentemente consistente a lo largo del tiempo y en todos los grupos de edad. Esta es la primera vez que se revelan disparidades de género en la evaluación de la albuminuria. Conclusión: La albuminuria se evalúa con poca frecuencia, incluso en pacientes con alto riesgo cardiovascular, especialmente en mujeres.

Abstract Introduction Many immunization programs in Europe recommend quadrivalent meningococcal vaccinations, which are often administered concomitantly with other vaccines. We compared the immune response of a tetanus toxoid conjugated quadrivalent meningococcal vaccine (MenACYW-TT, MenQuadfi®) with another quadrivalent meningococcal conjugate vaccine (MCV4-TT; Nimenrix®) when administered alone or concomitantly with Tdap-IPV and 9vHPV vaccines in adolescents. Methods In this phase IIIb trial, healthy adolescents (MenC-naïve or MenC-primed before 2 years of age) from Spain, Italy, Hungary, and Singapore were randomized in a 3:3:2 ratio to receive either MenACYW-TT or MCV4-TT alone, or MenACYW-TT concomitantly with 9vHPV and Tdap-IPV. The primary objective was to demonstrate the non-inferiority of the seroprotection rate (human serum bactericidal assay [hSBA] titer ≥ 1:8) to serogroups A, C, W, and Y 30 days post-vaccination with a single dose of MenACYW-TT or MCV4-TT. Secondary objectives included describing hSBA titers for the four serogroups before and 1 month following vaccination and according to MenC priming status. Results A total of 463 participants were enrolled (MenACYW-TT, n = 173; MCV4-TT, n = 173; MenACYW-TT/9vHPV/Tdap-IPV n = 117). Non-inferiority based on seroprotection was demonstrated for MenACYW-TT versus MCV4-TT for all serogroups. Immune responses were comparable whether MenACYW-TT was administered alone or concomitantly with Tdap-IPV and 9vHPV. Post-vaccination hSBA GMTs were higher in MenACYW-TT vs. MCV4-TT for serogroups C, Y, and W and comparable for serogroup A. The percentages of participants with an hSBA vaccine seroresponse were higher in MenACYW-TT vs. MCV4-TT for all serogroups. For serogroup C, higher GMTs were observed in both MenC-naïve or -primed participants vaccinated with MenACYW-TT vs. MCV4-TT. Seroprotection and seroresponse were higher in MenC-naïve participants vaccinated with MenACYW-TT vs. MCV4-TT and comparable in MenC-primed. The safety profiles were comparable between groups and no new safety concerns were identified. Conclusions These data support the concomitant administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines in adolescents. Trial Registrations Clinicaltrials.gov, NCT04490018; EudraCT: 2020-001665-37; WHO: U1111-1249-2973.

Purpose: This study aims to minimize monitor units (MUs) of intensity-modulated treatments in the Monaco treatment planning system while preserving plan quality by optimizing the “Minimum Segment Width” (MSW) and “Fluence Smoothing” parameters. Materials and Methods: We retrospectively analyzed 30 prostate, 30 gynecological, 15 breast cancer, 10 head and neck tumor, 11 radiosurgery, and 10 hypo-fractionated plans. Original prostate plans employed “Fluence Smoothing” = Off and were reoptimized with Low, Medium, and High settings. The remaining pathologies initially used MSW = 0.5 cm and were reoptimized with MSW = 1.0 cm. Plan quality, including total MU, delivery time, and dosimetric constraints, was statistically analyzed with a paired t-test. Results: Prostate plans exhibited the highest MU variation when changing “Fluence Smoothing” from Off to High (average ΔMU = −5.1%; P < 0.001). However, a High setting may increase overall MU when MSW = 0.5 cm. Gynecological plans changed substantially when MSW increased from 0.5 cm to 1.0 cm (average ΔMU = −29%; P < 0.001). Organs at risk sparing and planning target volumes remained within 1.2% differences. Replanning other pathologies with MSW = 1.0 cm affected breast and head and neck tumor plans (average ΔMU = −168.38, average Δt = −11.74 s, and average ΔMU = −256.56, average Δt = −15.05 s, respectively; all with P < 0.004). Radiosurgery and hypofractioned highly modulated plans did not yield statistically significant results. Conclusions: In breast, pelvis, head and neck, and prostate plans, starting with MSW = 1.0 cm optimally reduces MU and treatment time without compromising plan quality. MSW has a greater impact on MU than the “Fluence Smoothing” parameter. Plans with high modulation might present divergent behavior, requiring a case-specific analysis with MSW values higher than 0.5 cm.

The fungal pathogens Fusarium keratoplasticum and Fusarium falciforme are responsible for the emerging infectious disease named sea turtle egg fusariosis (STEF). This disease affects all sea turtle species throughout the world, causing low hatching success and mass mortalities. In this study, we investigated the potential use of widely available and easy-to-handle eggs of the invasive alien red-eared slider turtle, Trachemys scripta, as part of an in vivo host model to improve our knowledge of the biological properties of the pathogens responsible of the STEF. Specifically, we performed in vivo experiments, in which T. scripta eggs were challenged with conidia of F. keratoplasticum isolated from diseased sea turtle eggs. We found that the pathogen could colonize and develop similar signs to those observed in nature and fulfill Koch’s postulates. The pathogen showed high virulence properties (e.g., high disease incidence, severity, and low hatching success) and its ability to modify the pH in both the egg surface and culture media, confirming previously described fungal pathogen models. These results support the use of T. scripta as an experimental in vivo host model for studying the biological characteristics of STEF, thus providing valuable insights into the mechanisms underlying the emergence of this fungal disease.

Staphylococcus caprae is a coagulase-negative staphylococcus commonly associated with animals which can also be a zoonotic human pathogen. To date, there is little data available on S. caprae infections. The aim of this study was to characterize the S. caprae infections identified in two hospitals located, respectively, in rural and urban areas of Catalonia, Spain. In this retrospective, observational study, data were compiled from clinical records of all S. caprae infections diagnosed between January 2010 and December 2023. Over the study period, altogether 31 cases of S. caprae infection were identified, with most (23) of these cases occurring in the second half of the period (2017–2023). The mean age of patients was 58.87 ± 20.65 years, and 58.1% were males. Eight patients had had livestock exposure. The most frequent manifestation of infection was skin and soft subcutaneous tissue infections (10; 32.3%), osteomyelitis (6; 19.4%), and joint prosthetic infections (5; 16.1%). All the strains were susceptible to oxacillin, fluoroquinolones, rifampicin, and trimethoprim–sulfamethoxazole. Twenty-two (71%) of the patients required surgical treatment. Only one patient (3.2%) died, because of aortic prosthetic valve infective endocarditis. Skin and soft tissue infections were the most frequently identified manifestations of S. caprae infection. Over 75% of the cases occurred in the last six years, and 25.8% involved significant exposure to livestock. Ongoing surveillance is necessary to better understand the prevalence and transmission dynamics of this emerging zoonotic pathogen.

(1) Background: Alternative antibiotics are needed to treat infective endocarditis (IE) caused by non-faecalis/non-faecium enterococci; we aimed to assess the in vitro activity of ampicillin plus ceftriaxone (AMP + CTR) against these enterococci and to describe its clinical efficacy in IE cases. (2) Methods: Time–kill curves with standard (ISI) and high (IHI) inocula were performed to test VanC isolates [3 E. casseliflavus (ECAS) and 1 E. gallinarum (EGALL)] and non-VanC isolates [1 E. durans (EDUR), 1 E. hirae (EHIR) and 1 E. raffinosus (ERAF)]. The narrative literature review of IE cases treated with AMP + CTR was analyzed alongside three study cases. Clinical outcomes were relapse and death. (3) Results: Ampicillin plus gentamicin (AMP + GEN) showed synergistic and bactericidal activity against most isolates. AMP + CTR was synergistic at ISI for EGALL, EDUR, and EHIR and bactericidal against EHIR. At IHI, indifferent activity was observed for all isolates. In IE cases treated with AMP + CTR, it was only effective for EDUR and EHIR. Clinical information for EGALL IE is lacking. For IE caused by ECAS and ERAF, AMP + CTR seems suboptimal or ineffective, respectively. (4) AMP + CTR cannot be recommended for treating IE due to ECAS/ERAF. In contrast, this combination was effective in IE caused by EDUR/EHIR and could be recommended.

Background: A new monoclonal antibody (nirsevimab; Beyfortus®) and a bivalent prefusion RSV vaccine (Abrysvo®) for maternal immunization have been approved recently. This is a modelling study to estimate the potential impact of different immunization programs with these products on RSV-bronchiolitis. Methods: Population-based real-world data from primary care and hospitalizations were considered. RSV bronchiolitis dynamics in absence of these immunization scenarios were explained by a multivariate age-structured Bayesian model. Then, the potential impact was simulated under different assumptions including the most recent clinical trial data. Differences in endpoints, populations, and timeframes between trials make the two products’ efficacy difficult to compare. Results: A seasonal with catch-up program, assuming a constant effectiveness of 79.5 % during the first 5 months followed by a linear decay to 0 by month 10 with nirsevimab, would prevent between 5121 and 8846 RSV bronchiolitis per 100,000 infants-years. Assuming 77.3 % effectiveness with the same decay, between 976 and 1686 RSV-hospitalizations per 100,000 infants-years could be prevented depending on the uptake. A year-round maternal immunization program, with 51 % of effectiveness during the first 6 months followed by a linear decay to 0 by month 10 would prevent between 3246 and 5606 RSV bronchiolitis cases per 100,000 infants-years. Assuming 56.9 % effectiveness with the same decay, between 713 and 1231 RSV-hospitalizations per 100,000 infants-years could be prevented. Conclusions: Our results suggest that each strategy would effectively reduce RSV-bronchiolitis.

Objectives: We aimed to compare the risk of herpes zoster (HZ) in adults with and without laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: This retrospective dynamic cohort study analyzed data from a public healthcare database in Spain between November 2020 and October 2021. The main outcome was incident cases of HZ in individuals ≥18-year-old. Relative risk (RR) of HZ in SARS-CoV-2-confirmed versus SARS-CoV-2-free individuals was estimated by a multivariable negative binomial regression adjusted by age, sex, and comorbidities. Results: Data from 4,085,590 adults were analyzed. The overall HZ incidence rate in adults was 5.76 (95% confidence interval [CI], 5.66-5.85) cases per 1000 person-years. Individuals ≥18-year-old with SARS-CoV-2-confirmed infection had a 19% higher risk of developing HZ versus SARS-CoV-2-free ≥18-year-olds (adjusted RR = 1.19; 95% CI, 1.09-1.29); this percentage was 16% (adjusted RR = 1.16; 95% CI, 1.05-1.29) in ≥50-year-olds. Severe (hospitalized) cases of SARS-CoV-2 infection had a 64% (if ≥18 years old) or 44% (if ≥50 years old) higher risk of HZ versus nonhospitalized cases. Conclusion: These results support an association between SARS-CoV-2 infection and HZ, with a greater HZ risk in severe cases of SARS-CoV-2 infection.

Abstract The scientific literature shows that children’s participation in video games is increasingly common. However, there is no analysis of the involvement of children in the development of video games promoting social science learning. The framework of the EU H2020 funded project “ALLINTERACT. Widening and diversifying citizen engagement in science” contributes to filling this gap by analysing the co-creation process between children, families, teachers, and researchers of a video game for children to distinguish between hoaxes and evidence to overcoming bullying. To this end, a 24-h Science Game Jam was recorded, which took place in a virtual space for group meetings in which five children, five family members, four teachers and four researchers participated in the co-creation of the video game and a collaborative document in the cloud including the guidelines of the video game, with their proposals for the development. Finally, they participated as well as in the co-creation of the video game itself. The key finding is that co-creation through an egalitarian dialogue, solidarity, and focus on scientific knowledge allowed these children to play a leading role in developing a video game where children of all educational stages learn to distinguish hoaxes and evidence in overcoming bullying. The involvement in science and the co-creation of science-based products benefited these children; as they were protagonists in science, they could express their concerns and the real problems they faced in their schools, which increased their scientific knowledge and strengthened their critical capacity about bullying. Furthermore, the adult participants also benefited from the knowledge provided by the children, especially in the development and creation of the video game.

Hostelry establishments face the challenge of devising a table and chair allocation for accommodating their customers on a daily basis. This problem scales significantly with the introduction of constraints, such as scenario obstacles or the requirement of a minimum distance separation. The TLP (Table Location Problem) and the CLP (Chair Location Problem) are NP-Hard complexity problems that aim to attain the optimal table and chair distribution for certain applications. Existing approaches to this problem fail to address both the TLP and CLP simultaneously, thus resulting in suboptimal solutions achieved by imposing optimization constraints. Therefore, in this paper, a sequential optimization methodology based on a GBLS MA (Gradient-Based Local Search Memetic Algorithm) optimizations is proposed for optimizing the table and chair disposition simultaneously while also considering scenario and distancing restrictions. The proposed methodology is then implemented into a realistic establishment, where different optimization strategies within the CLP are compared. Results prove the viability and flexibility of the proposed sequential optimization for complex hostelry scenarios.

Viral respiratory diseases place a heavy burden on the healthcare system, with children making up a significant portion of related hospitalizations. While comorbidities increase the risk of complications and poor outcomes, many hospitalized children lack clear risk factors. As new vaccines for respiratory viral diseases emerge, this study examined pediatric respiratory hospitalizations, focusing on viral etiology, complication rates, and the impact of comorbidities to guide future policy. Data were analyzed from eight pre-COVID influenza seasons (2011/2012–2018/2019) involving patients under 18 years hospitalized with respiratory complaints across 4–10 hospitals in Valencia, Spain. Respiratory specimens were tested for eight viral targets using multiplex real-time reverse-transcription polymerase chain reaction. Demographics, clinical outcomes, discharge diagnoses, and laboratory results were examined. Among the hospitalized children, 26% had at least one comorbidity. These children had higher rates of pneumonia, asthma exacerbation, and pneumothorax, and were twice as likely to require ICU admission, though mechanical ventilation and length of stay were similar to those without comorbidities. Respiratory syncytial virus (RSV) was the most common virus detected (23.1%), followed by rhinovirus/enterovirus (9.5%) and influenza (7.2%). Viral codetection decreased with age, occurring in 4.6% of cases. Comorbidities increase the risk of complications in pediatric respiratory illnesses, however, healthcare utilization is driven largely by otherwise healthy children. Pediatric viral vaccines could reduce this burden and should be further evaluated.

Background Informed consent (IC) is essential in defending the autonomy of potential participants in clinical research. Despite the advances in research ethics, particularly in IC, the different guidelines and codes have not been fully implemented. Several studies have presented consent deficiencies that have resulted in unethical practices or poor understanding of the IC. Main body This article reviews the evolution of IC, from its philosophical origins and initial use in the Ottoman Empire (16th century) to its use in clinical research today. It also presents the vision of the European project i-CONSENT (Grant Agreement number: 741856), whose main purpose is to improve the understanding of ICs in research and identifies the key components of a new paradigm to develop patient-centred ICs. Conclusions In many cases, the IC has served to protect the investigator or sponsor from complaints. Different ethical guidelines have sought to make the IC a more useful tool, with little success. Today’s IC is mainly a bureaucratic and legal process that fails to consider the patient’s point of view. In this context, the Guidelines for Tailoring the Informed Consent Process in Clinical Studies provide alternatives to the current IC process, focusing on the patient’s opinions and making them part of the process, thereby improving clinical research quality.

Numeracy is a critical competency needed by adults to navigate their way through tasks in their personal and professional lives. Hence, it is critical that efforts are made to identify and address challenges that prevent adults from developing the numeracy skills needed to engage in society. In this research we identify the challenges facing adult numeracy eduction across Europe. A survey, which sought to investigate the main challenges faced by adult educators and policy-makers when delivering numeracy programmes, was distributed to leading figures in adult numeracy education in EU states. Twelve countries responded and challenges identified related to the lack of a standardised definition of numeracy, the lack of a standardised framework to support adult numeracy education and the need for professional development for adult numeracy tutors. In this paper we look at how these challenges manifest themselves in different jurisdictions and offer suggestions for overcoming these challenges in future.

As a flagship of the Europe’s Beating Cancer Plan, the European Commission supports EU member states’ efforts to strengthen and expand the routine vaccination of girls and boys against human papillomavirus (HPV). Populations across Europe have grown in diversity, and health systems must adapt to meet the specific needs of increasing diversity. Healthcare professionals (HCPs) must strive to communicate HPV vaccine information in a culturally sensitive manner and address specific concerns related to cultural beliefs, trust in health systems and perceived risks. The objectives of this exploratory study are to identify which themes are most frequently raised during the recommendation of vaccination to minors based on the characteristics of the population (religion, region of origin, gender, level of education and language proficiency) and to collect strategies to improve communication with a diverse population. A survey was distributed through various European public health institutions to HCPs in the region and their networks. The survey included multi-response questions (themes addressed during vaccination recommendation based on population characteristics) and open-ended questions (own qualitative comments and strategies). The most common issues that arise during vaccine recommendation are a lack of knowledge, followed by misinformation. Differences were detected according to the population characteristics. Suggested strategies to improve HPV vaccine recommendation focused on the following aspects: affordability; sexuality and gender; communication platforms; multilingualism; quality of care; school collaboration. HCPs report differences according to the characteristics of the population receiving the recommendation. Personalisation of the recommendations would help to optimise the decision-making process for some groups.

There is an unmet need to create consensus documents on the management of cardiorenal patients since, due to the aging of the population and the rise of both pathologies, these patients are becoming more prevalent in daily clinical practice. Chronic kidney disease coexists in up to 40%–50% of patients with chronic heart failure cases. There have yet to be consensus documents on how to approach palliative care in cardiorenal patients. There are guidelines for patients with heart failure and chronic kidney disease separately, but they do not specifically address patients with concomitant heart failure and kidney disease. For this reason, our document includes experts from different specialties, who will not only address the justification of palliative care in cardiorenal patients but also how to identify this patient profile, the shared planning of their care, as well as knowledge of their trajectory and the palliative patient management both in the drugs that will help us control symptoms and in advanced measures. Dialysis and its different types will also be addressed, as palliative measures and when the decision to continue or not perform them could be considered. Finally, the psychosocial approach and adapted pharmacotherapy will be discussed.

Abstract Having a proper understanding of the impact of influenza is a fundamental step towards improved preventive action. This paper reviews findings from the Burden of Acute Respiratory Infections study on the burden of influenza in Iberia, and its potential underestimation, and proposes specific measures to lessen influenza’s impact.

Resumen: Las guías de 2021 sobre la prevención de la enfermedad vascular (EV) en la práctica clínica publicadas por la European Society of Cardiology (ESC) y apoyadas por otras 13 sociedades científicas europeas reconocen el papel clave de la detección de la enfermedad renal crónica (ERC) en la prevención de la EV. El riesgo vascular en la ERC se categoriza a partir de las medidas del filtrado glomerular estimado (FGe) y del cociente albúmina:creatinina en orina (ACRo). Así, la ERC moderada se asocia a un riesgo vascular alto y la ERC grave a un riesgo vascular muy alto, debiendo actuar en consecuencia desde el punto de vista terapéutico, sin que sea necesario aplicar otras puntuaciones de riesgo vascular cuando este ya es muy alto debido a la ERC. Es más, la ESC sitúa la medida del FGe y del ACRo en el inicio de la estimación del riesgo vascular y del algoritmo de decisión subsiguiente. A fin de optimizar la implementación de la guía 2021 de la ESC sobre la prevención de la EV en España, consideramos que: 1) El estudio de la orina para determinar la albuminuria mediante el ACRo debería formar parte de la rutina clínica al mismo nivel que el de la glucemia, la colesterolemia y la estimación del FG cuando estas se usan para tomar decisiones sobre el riesgo de EV. 2) Los servicios de salud públicos y privados españoles deberían disponer de los medios y recursos necesarios para implementar de forma óptima las Guías ESC 2021 de prevención de la EV en España, incluyendo la determinación del ACRo. Abstract: The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies, recognise the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorised based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimise the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolaemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing.

Background: This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription. Methods: A systematic search for relevant studies was performed in 3 databases. Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included: adiponectin, apelin, brain-derived neurotrophic factor, fetuin-A, fibroblast growth factor-21, follistatin, ghrelin, interleukin (IL)-6, IL-8, IL-10, IL-15, IL-18, leptin, myostatin, omentin, resistin, retinol-binding protein 4, tumor necrosis factor-α, and visfatin. Results: Forty randomized controlled trials were selected for data extraction (n = 2160). Exercise training induces changes in adiponectin, fetuin-A, fibroblast growth factor-21, IL-6, IL-10, leptin, resistin, and tumor necrosis factor-α levels but has no significant effects on apelin, IL-18, and ghrelin compared to controls. Physical exercise training favored large and positive changes in pooled exerkines (i.e., an overall effect size calculated from several exerkines) (Hedge's g = 1.02, 95% confidence interval (95%CI): 0.76−1.28), which in turn were related to changes in glycated hemoglobin (mean difference (MD) = −0.81%, 95%CI: −0.95% to −0.67%), fasting glucose (MD = −23.43 mg/dL, 95%CI: −30.07 mg/dL to −16.80 mg/dL), waist circumference (MD = −3.04 cm, 95%CI: −4.02 cm to −2.07 cm), and body mass (MD = −1.93 kg, 95%CI: −2.00 kg to −1.86 kg). Slightly stronger effects were observed with aerobic, resistance, or high-intensity interval protocols at moderate- to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session. Conclusion: Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies recognize the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorized based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimize the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing. Resumen: Las guías 2021 sobre la prevención de la enfermedad vascular (EV) en la práctica clínica publicadas por la European Society of Cardiology (ESC) y apoyadas por otras 13 Sociedades científicas europeas, reconocen el papel clave de la detección de la enfermedad renal crónica (ERC) en la prevención de la EV. El riesgo vascular en la ERC se categoriza a partir de las medidas del filtrado glomerular estimado (FGe) y del cociente albúmina:creatinina en orina (ACRo). Así, la ERC moderada se asocia a un riesgo vascular alto y la ERC grave a un riesgo vascular muy alto, debiendo actuar en consecuencia desde el punto de vista terapéutico y no siendo necesario aplicar otras puntuaciones de riesgo vascular cuando este ya es muy alto debido a la ERC. Es más, la ESC sitúa la medida del FGe y del ACRo en el inicio de la estimación del riesgo vascular y del algoritmo de decisión subsiguiente. A fin de optimizar la implementación de la guía 2021 de la ESC sobre la prevención de la EV en España, consideramos que: 1) El estudio de la orina para determinar la albuminuria mediante el ACRo debería formar parte de la rutina clínica al mismo nivel que las de la glucemia, la colesterolemia y la estimación del FG cuando estas se usan para tomar decisiones sobre el riesgo de EV. 2) Los servicios de salud públicos y privados españoles deberían disponer de los medios y recursos necesarios para implementar de forma óptima las Guías ESC 2021 de prevención de la EV en España, incluyendo la determinación del ACRo.

Abstract Objective: To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms. Design: An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used. Setting: Spanish older adults with metabolic syndrome (MetS). Participants: A total of 6625 adults aged 55–75 years from the PREDIMED-Plus study with overweight or obesity and MetS. Results: Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)). Conclusions: According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.

Abstract Introduction The informed consent process is key to safeguarding the autonomy of the participant in medical research. For this process to be valid, the information presented to the potential participant should meet their needs and be understood by them. The i‐CONSENT project has developed ‘Guidelines for adapting the informed consent process in clinical trials’ which aim to improve informed consent so that they are easier to understand and better adapted to the needs and preferences of the target population. The best way to tailor information to the characteristics and preferences of the target population is to involve the community itself. Methods Following guidelines developed by i‐CONSENT, assent materials were co‐created for a mock clinical trial of the human papillomavirus vaccine in adolescents. During the process, two design thinking sessions were conducted involving a total of 10 children and 5 parents. The objectives of the sessions were to find out the children's opinion of the informed consent (assent in their case) process in clinical trials, identify the parts that were most difficult to understand and alternatives for their presentation and wording, identify the preferred formats for receiving the information and the main characteristics of these formats, design a video explaining the clinical trial and evaluate a tool for assessing comprehension. Results Assent materials were co‐created in three formats: a web‐based material following a layered approach; a video in story format; a pdf document with an innovative way of presenting information compared to traditional assent documents. In addition, the Comprehension of Assent Questionnaire was co‐designed, based on the Quality of Informed Consent questionnaire. Conclusion The design thinking methodology has proven to be an easy and useful tool for involving children in designing information tailored to their needs and preferences. Patient or Public Contribution A sample of the target population participated in the design and piloting of the materials created using design thinking methodology. In addition, patient representatives participated in the design and evaluation of the guidelines developed by the i‐CONSENT project that were followed for the development of the materials in this study.

Smart Manufacturing is characterized by the digitization and massive communication of Cyber-Physical Systems under the Industrial Internet of Things paradigm. However, the heterogeneity of communication protocols hinders connectivity among assets due to lack of interoperability. Moreover, the decomposition of the classical production hierarchy towards decentralized self-organization makes the implementation of interoperability in industrial environments key to help decision-making. In this sense, the interoperability of heterogeneous assets (e.g., external, internal, and human) has been defined as hyperconnectivity and supposes a technological challenge in the scientific literature. To prove this novel hyperconnectivity definition, the authors propose and develop a novel hyperconnected demonstrator where all types of assets are interconnected in a case study consisting of the automation of an inspection process. For this purpose, an industrial internet platform has been used for connecting industrial equipment creating a collaborative environment through the use of interoperability. In this regard, it has been possible to communicate assets among the cloud, humans, and CPS with a processing time of less than 10 ms, which demonstrates that the technological challenge of implementing the hyperconnectivity concept of this paper has been successfully addressed.

Purpose: The study is intended to perform an end-to-end test of the entire intraoperative process using cadaver heads. A simulation of tumor removal was performed, followed by irradiation of the bed and measurement of absorbed doses with radiochromic films. Materials and Methods: Low-energy X-ray intraoperative radiotherapy (IORT) was used for irradiation. A computed tomography study was performed at each site and the absorbed doses calculated by the treatment planning system, as well as absorbed doses with radiochromic films, were studied. Results: The absorbed doses in the organs at risk (OAR) were evaluated in each case, obtaining maximum doses within the tolerance limits. The absorbed doses in the target were verified and the deviations were

Abstract Background Influenza is an acutely debilitating respiratory infection, contributing significantly to outpatient visits and hospitalizations. Spain lacks comprehensive and updated data on the burden of influenza, particularly in the outpatient setting. Our study aimed to fill this gap by estimating the clinical and economic burden of physician-diagnosed influenza cases in adults from four Spanish regions, stratified by age groups and presence of comorbidities. Methods A retrospective cost-of-illness study was conducted using data from an electronic medical records database from the National Healthcare Service (NHS) of four Spanish regions for individuals aged ≥ 18 years diagnosed for influenza during the 2017/2018 epidemic season. Health resource utilization and related cost data were collected, including primary care visits, referrals to other specialists, visits to the emergency department, hospitalizations, and prescribed medicines. Results The study reported a total of 28,381 patients aged ≥ 18 years diagnosed with influenza, corresponding to 1,804 cases per 100,000 population. Most patients were aged

Abstract Aims In people at risk of heart failure (HF) enrolled in the Heart ‘OMics’ in AGEing (HOMAGE) trial, spironolactone reduced circulating markers of collagen synthesis, natriuretic peptides, and blood pressure and improved cardiac structure and function. In the present report, we explored factors associated with dyskalaemia. Methods and results The HOMAGE trial was an open‐label study comparing spironolactone (up to 50 mg/day) versus standard care in people at risk for HF. After randomization, serum potassium was assessed at 1 and 9 months and was defined as low when ≤3.5 mmol/L (hypokalaemia) and high when ≥5.5 mmol/L (hyperkalaemia). Multivariable logistic regression models were constructed to identify clinical predictors of dyskalaemia. A total of 513 participants (median age 74 years, 75% men, median estimated glomerular filtration rate 71 mL/min/1.73 m2) had serum potassium available and were included in this analysis. At randomization, 88 had potassium 5.0 mmol/L. During follow‐up, on at least one occasion, a serum potassium 5.0 mmol/L was observed in 38 (8%) and >5.5 mmol/L in 5 (1.0%) participants. The median (percentile25−75) increase in serum potassium with spironolactone during the study was 0.23 (0.16; 0.29) mmol/L. Because of the low incidence of dyskalaemia, for regression analysis, hypokalaemia and hyperkalaemia thresholds were set at 5.0 mmol/L, respectively. The occurrence of a serum potassium > 5.0 mmol/L during follow‐up was positively associated with the presence of diabetes mellitus {odds ratio [OR]: 1.21 [95% confidence interval (CI) 2.14; 3.79]} and randomization to spironolactone (OR: 2.83 [95% CI 1.49; 5.37]). Conversely, the occurrence of a potassium concentration

IntroductionThe contemporary scientific literature indicates that numeracy is a multifaceted concept. The ongoing societal and technological transformations underscore the imperative to re-evaluate the attributes characterizing a numerate individual and the strategic initiatives that policymakers should devise and implement to ensure that individuals are not marginalized from participation in public and private domains due to their lack of numeracy proficiency. Numerous empirical investigations on numeracy consistently affirm its pivotal role in enabling individuals to engage autonomously across diverse contexts within their daily lives. However, numeracy’s fundamental role has often been neglected in our societies. The present study scrutinizes the overarching challenges associated with numeracy, particularly emphasizing the challenges regarding healthcare, finance, and the critical utilization and interpretation of data awareness.MethodsA two-phase research framework was adopted to address this inquiry. A comprehensive literature review was conducted to discern the prevalent challenges regarding numeracy awareness. Subsequently, two illustrative case studies were undertaken in Slovenia and Spain to contrast and deliberate upon the insights derived from the literature review. Qualitative research methods were employed to engage in a nuanced exploration of the gathered data.ResultsThis empirical analysis deduced guidelines aimed at enhancing awareness and ameliorating some of these challenges.Discussion and ConclusionWe conclude that making visible the awareness that adults already have about numeracy in aspects of their lives, such as finance, health, or the use and critical interpretation of data, can give policymakers and curriculum developers clues to design effective numeracy programs to address the multifaceted challenges confronting contemporary society, both in the immediate and foreseeable future.

Abstract The Sixth Assessment Report (AR6) of the Intergovernmental Panel on Climate Change (IPCC) has adopted the FAIR Guiding Principles. We present the Atlas chapter of Working Group I (WGI) as a test case. We describe the application of the FAIR principles in the Atlas, the challenges faced during its implementation, and those that remain for the future. We introduce the open source repository resulting from this process, including coding (e.g., annotated Jupyter notebooks), data provenance, and some aggregated datasets used in some figures in the Atlas chapter and its interactive companion (the Interactive Atlas), open to scrutiny by the scientific community and the general public. We describe the informal pilot review conducted on this repository to gather recommendations that led to significant improvements. Finally, a working example illustrates the re-use of the repository resources to produce customized regional information, extending the Interactive Atlas products and running the code interactively in a web browser using Jupyter notebooks.

BackgroundDiffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor–neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD.MethodsRole of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan.DiscussionREVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810.

IntroductionDevelopment of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public–private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017–2018 to its final season in 2021–2022.MethodsIn 2021–2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving >1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis.ResultsIn 2021–2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%−93%) for any vaccine and 81% (22%−95%) for Vaxigrip Tetra in adults ≥65 years old and 64% (25%−83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%−97%) for any vaccine in adults 18–64 years (TND hospital setting), and 38% (1%−62%) in children 6 months−6 years (population-based cohort, mixed setting).DiscussionOver five seasons, DRIVE collected data on >35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE.

Background: Methicillin-resistant S. aureus (MRSA) especially ST398, is a zoonotic agent. This study aimed to determine the prevalence of methicillin-susceptible S. aureus (MSSA) and MRSA among workers in the pork production chain. Methods: 659 workers associated with 123 pig farms, livestock transporters, one pig slaughterhouse, pork transporters and 23 pork butcheries were studied for S. aureus recovery, and all isolates were characterized (antibiotic resistance, MLST and spa-typing). Results: The prevalence of S. aureus was 35.5%, 75.6% of isolates being MRSA. The prevalence of MRSA was 68.7% (149/217) among pig farm, 33.9% (19/56) livestock transporters, 2.9% (9/306) slaughterhouse, 0% in pork transporters (0/36) and butchery workers (0/44). Of the 234 S. aureus-positive workers, 100% (149/149) of pig farm workers, 82.6% (19/23) of livestock transporters, and 16.4% (9/55) of slaughterhouse workers carried MRSA isolates (p

Abstract Background Since cardiovascular magnetic resonance (CMR) imaging allows comprehensive quantification of both myocardial function and structure we aimed to assess myocardial remodeling processes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods CMR imaging was performed in 40 patients with severe AS before and 1 year after TAVR. Image analyses comprised assessments of myocardial volumes, CMR-feature-tracking based atrial and ventricular strain, myocardial T1 mapping, extracellular volume fraction-based calculation of left ventricular (LV) cellular and matrix volumes, as well as ischemic and non-ischemic late gadolinium enhancement analyses. Moreover, biomarkers including NT-proBNP as well as functional and clinical status were documented. Results Myocardial function improved 1 year after TAVR: LV ejection fraction (57.9 ± 16.9% to 65.4 ± 14.5%, p = 0.002); LV global longitudinal (− 21.4 ± 8.0% to -25.0 ± 6.4%, p