Pharmacokinetics and Safety of Bilastine 10 mg/d in Children Aged 2 to 5 Years With Allergic Rhinoconjunctivitis or Urticaria: A Phase 3 Clinical Trial.

BACKGROUND: Bilastine is a second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis (ARC) and urticaria in adults, adolescents, and children. The pharmacokinetics and safety of oral bilastine 10 mg/d in children aged 2 to 5 years were evaluated. METHODS: This was a multicenter, open-label clinical trial in children aged 2 to 5 years with seasonal or perennial ARC or urticaria treated once daily with bilastine 10 mg orodispersible tablets. The safety evaluation included treatment-emergent adverse events (TEAEs), vital signs, and physical examination. Pharmacokinetic data were pooled with data from a prior pediatric study, and pharmacokinetic modeling was performed to assess consistency. RESULTS: A total of 37 children with ARC (81.1%), urticaria (8.1%), or both (10.8%) were included in the study, with a mean (SD) age of 3.7 (1.2) years. The highest plasma concentrations of bilastine were observed 1 hour after administration (634.91 ng/mL). Eight patients (21.6%) experienced 1 TEAE each, none of which was severe. Body weight and age were not covariates of variation in either systemic clearance or the volume of distribution in children aged 2 to 5 years and did not affect the pharmacokinetic parameters of bilastine. CONCLUSIONS: The pharmacokinetics of bilastine was linear and consistent with data from a previous trial, suggesting that a 10-mg dose may be used in children (2 to <12 years). No dose adjustments are deemed necessary. Oral once-daily bilastine 10 mg presented a good safety profile in children aged 2 to 5.

MGSurvE: A framework to optimize trap placement for genetic surveillance of mosquito populations.

Genetic surveillance of mosquito populations is becoming increasingly relevant as genetics-based mosquito control strategies advance from laboratory to field testing. Especially applicable are mosquito gene drive projects, the potential scale of which leads monitoring to be a significant cost driver. For these projects, monitoring will be required to detect unintended spread of gene drive mosquitoes beyond field sites, and the emergence of alternative alleles, such as drive-resistant alleles or non-functional effector genes, within intervention sites. This entails the need to distribute mosquito traps efficiently such that an allele of interest is detected as quickly as possible-ideally when remediation is still viable. Additionally, insecticide-based tools such as bednets are compromised by insecticide-resistance alleles for which there is also a need to detect as quickly as possible. To this end, we present MGSurvE (Mosquito Gene SurveillancE): a computational framework that optimizes trap placement for genetic surveillance of mosquito populations such that the time to detection of an allele of interest is minimized. A key strength of MGSurvE is that it allows important biological features of mosquitoes and the landscapes they inhabit to be accounted for, namely: i) resources required by mosquitoes (e.g., food sources and aquatic breeding sites) can be explicitly distributed through a landscape, ii) movement of mosquitoes may depend on their sex, the current state of their gonotrophic cycle (if female) and resource attractiveness, and iii) traps may differ in their attractiveness profile. Example MGSurvE analyses are presented to demonstrate optimal trap placement for: i) an Aedes aegypti population in a suburban landscape in Queensland, Australia, and ii) an Anopheles gambiae population on the island of São Tomé, São Tomé and Príncipe. Further documentation and use examples are provided in project's documentation. MGSurvE is intended as a resource for both field and computational researchers interested in mosquito gene surveillance.

[Self-sense and experiences of physical activity in breast cancer survivors: Qualitative evidence synthesis]. / Significados y experiencias de actividad física en mujeres sobrevivientes de cáncer de mama: síntesis cualitativa.

Breast cancer has a high incidence rate and a negative impact on women's lives. The practice of physical activity (PA) has shown strong evidence in controlling the side effects associated with the disease and its treatment. However, having an active lifestyle is influenced by socio-health inequities. The objective was to analyze the categories related to the meanings and perceived experiences with PA in breast cancer survivors (BCS). Protocol https://osf.io/7fwbs/. Articles describing the meanings of PA in BCS published after 2010 were included. Fourteen articles were analyzed using line-by-line coding. The emerging categories were: 1)PA as a strategy to re-signify and empower the body. 2)Cancer means a change in PA trajectories. 3)PA is a tool for a healthy and functional body in everyday life.

Prediction model for lower limb amputation in hospitalized diabetic foot patients using classification and regression trees.

BACKGROUND: The decision to perform amputation of a limb in a patient with diabetic foot ulcer (DFU) is not an easy task. Prediction models aim to help the surgeon in decision making scenarios. Currently there are no prediction model to determine lower limb amputation during the first 30 days of hospitalization for patients with DFU. METHODS: Classification And Regression Tree analysis was applied on data from a retrospective cohort of patients hospitalized for the management of diabetic foot ulcer, using an existing database from two Orthopaedics and Traumatology departments. The secondary analysis identified independent variables that can predict lower limb amputation (mayor or minor) during the first 30 days of hospitalization. RESULTS: Of the 573 patients in the database, 290 feet underwent a lower limb amputation during the first 30 days of hospitalization. Six different models were developed using a loss matrix to evaluate the error of not detecting false negatives. The selected tree produced 13 terminal nodes and after the pruning process, only one division remained in the optimal tree (Sensitivity: 69%, Specificity: 75%, Area Under the Curve: 0.76, Complexity Parameter: 0.01, Error: 0.85). Among the studied variables, the Wagner classification with a cut-off grade of 3 exceeded others in its predicting capacity. CONCLUSIONS: Wagner classification was the variable with the best capacity for predicting amputation within 30 days. Infectious state and vascular occlusion described indirectly by this classification reflects the importance of taking quick decisions in those patients with a higher compromise of these two conditions. Finally, an external validation of the model is still required. LEVEL OF EVIDENCE: III.

Measurement of event-related potentials from electroencephalography to evaluate emotional processing in Fibromyalgia Syndrome: A systematic review and meta-analysis.

OBJECTIVE: The present systematic review and meta-analysis intended to: 1) determine the extent of abnormalities in emotional processing linked to emotional event-related potentials (ERPs) in Fibromyalgia Syndrome (FMS) and 2) integrate data from similar emotional tasks into a meta-analysis to clearly demonstrate the scientific and clinical value of measuring emotional ERPs by electroencephalography (EEG) in FMS. METHODS: A systematic review and meta-analysis of studies comparing emotional processing indicated by ERPs in FMS patients and healthy controls was conducted. Fifteen articles were included in the systematic review after applying the eligibility criteria. RESULTS: Nine articles demonstrated disturbances in emotional processing in FMS. These emotional disturbances were distributed over the whole range of ERP latencies, mainly over central, parietal, temporal and occipital areas. Despite of this, quantitative analysis revealed only significant differences in N250 and LPP/LPC between FMS patients and healthy controls, with smaller LPP/LPC and greater N250 seen in FMS. DISCUSSION: N250 and LPP/LPC seem to be the ERPs with the greatest potential to determine emotional alterations in FMS. These ERPs are related to complex cognitive processes such as decoding features relevant to affect recognition (N250) as well differentiation between emotions, persistent engagement, conflict resolution or evaluation of emotional intensity (LPC/LPP). However, differences in task setup had an important impact on the variation of ERP outcomes. Systematization of protocols and tasks is indispensable for future studies.

Impact of mediterranean diet promotion on environmental sustainability: a longitudinal analysis.

OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.

Retorno a la actividad completa tras cirugía de reconstrucción de ligamento cruzado anterior en personal militar: metaanálisis / Return to full duty after anterior cruciate ligament reconstruction surgery in military personnel: A meta-analysis

Objetivo: Se realizó un metaanálisis para evaluar los resultados clínico-funcionales de la cirugía de ligamento cruzado anterior en militares, así como las complicaciones asociadas a la misma. Material y métodos: Se realizó una búsqueda en las 3 principales fuentes de bases de datos hasta diciembre de 2022 (PubMed, Google Scholar y ScienceDirect) en cuanto a los resultados tras la cirugía de ligamento cruzado anterior en personal militar. La revisión sistemática se realizó siguiendo las normas Preferred Reporting Items for Systematic Reviews and Meta-Analyses –PRISMA–, y los criterios de inclusión siguieron la estrategia PICO. Los datos de los estudios incluidos se analizaron mediante el software Review Manager 5.4. Resultados: Se seleccionaron un total de 7 estudios retrospectivos. La tasa general de retorno a la actividad completa en el personal militar fue del 62,3% (61,5% para el grupo de no oficiales frente a 68,3% para el grupo de oficiales), sin ser esta diferencia significativa (p=0,92). La tasa general de lesión meniscal en los militares fue del 58,8%, sin ser esta diferencia significativa (p=0,88). La homogeneidad en ambos casos fue buena (I2=0%, p=0,99). Conclusión: El regreso a la actividad militar completa puede usarse en la población militar como un marcador de éxito después de una reconstrucción de ligamento cruzado anterior. Hay que destacar que una gran cantidad de militares experimentan limitaciones permanentes en la actividad que impiden el regreso completo al servicio.(AU)

Objective: A meta-analysis was carried out to evaluate the clinical-functional results of anterior cruciate ligament surgery in military population, as well as the complications associated with it. Material and method: Three major database sources up to December 2022 (PubMed, Google Scholar, and ScienceDirect) were searched for outcomes after anterior cruciate ligament surgery in military personnel. The systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses –PRISMA– standards, and the inclusion criteria following the PICO strategy. Data from included studies were analyzed using Review Manager 5.4 software. Results: A total of 7 retrospective studies were selected. The general rate of return to full duty in military personnel was 62.3% (61.5% for the non-officer group vs. 68.3% for the officer group) without this difference being significant (p=0.92). The general rate of meniscal injury in the military was 58.8%, without this difference being significant (p=0.88). The homogeneity in both cases was good (I2=0%, p=0.99). Conclusion: Return to full military duty can be used in the military population as a marker of success after anterior cruciate ligament reconstruction. It should be noted that a large number of military personnel experience permanent activity limitations that prevent full return to service.(AU)

[Translated article] Return to full duty after anterior cruciate ligament reconstruction surgery in military personnel: A meta-analysis / Retorno a la actividad completa tras cirugía de reconstrucción del ligamento cruzado anterior en personal militar: metaanálisis

Objetivo: Se realizó un metaanálisis para evaluar los resultados clínico-funcionales de la cirugía de ligamento cruzado anterior en militares, así como las complicaciones asociadas a la misma. Material y métodos: Se realizó una búsqueda en las 3 principales fuentes de bases de datos hasta diciembre de 2022 (PubMed, Google Scholar y ScienceDirect) en cuanto a los resultados tras la cirugía de ligamento cruzado anterior en personal militar. La revisión sistemática se realizó siguiendo las normas Preferred Reporting Items for Systematic Reviews and Meta-Analyses –PRISMA–, y los criterios de inclusión siguieron la estrategia PICO. Los datos de los estudios incluidos se analizaron mediante el software Review Manager 5.4. Resultados: Se seleccionaron un total de 7 estudios retrospectivos. La tasa general de retorno a la actividad completa en el personal militar fue del 62,3% (61,5% para el grupo de no oficiales frente a 68,3% para el grupo de oficiales), sin ser esta diferencia significativa (p=0,92). La tasa general de lesión meniscal en los militares fue del 58,8%, sin ser esta diferencia significativa (p=0,88). La homogeneidad en ambos casos fue buena (I2=0%, p=0,99). Conclusión: El regreso a la actividad militar completa puede usarse en la población militar como un marcador de éxito después de una reconstrucción de ligamento cruzado anterior. Hay que destacar que una gran cantidad de militares experimentan limitaciones permanentes en la actividad que impiden el regreso completo al servicio.(AU)

Objective: A meta-analysis was carried out to evaluate the clinical-functional results of anterior cruciate ligament surgery in military population, as well as the complications associated with it. Material and method: Three major database sources up to December 2022 (PubMed, Google Scholar, and ScienceDirect) were searched for outcomes after anterior cruciate ligament surgery in military personnel. The systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses –PRISMA– standards, and the inclusion criteria following the PICO strategy. Data from included studies were analyzed using Review Manager 5.4 software. Results: A total of 7 retrospective studies were selected. The general rate of return to full duty in military personnel was 62.3% (61.5% for the non-officer group vs. 68.3% for the officer group) without this difference being significant (p=0.92). The general rate of meniscal injury in the military was 58.8%, without this difference being significant (p=0.88). The homogeneity in both cases was good (I2=0%, p=0.99). Conclusion: Return to full military duty can be used in the military population as a marker of success after anterior cruciate ligament reconstruction. It should be noted that a large number of military personnel experience permanent activity limitations that prevent full return to service.(AU)

Estimating tongue deformation during laryngoscopy using a hybrid FEM-multibody model and intraoperative tracking - a cadaver study.

Throat tumour margin control remains difficult due to the tight, enclosed space of the oral and throat regions and the tissue deformation resulting from placement of retractors and scopes during surgery. Intraoperative imaging can help with better localization but is hindered by non-image-compatible surgical instruments, cost, and unavailability. We propose a novel method of using instrument tracking and FEM-multibody modelling to simulate soft tissue deformation in the intraoperative setting, without requiring intraoperative imaging, to improve surgical guidance accuracy. We report our first empirical study, based on four trials of a cadaveric head specimen with full neck anatomy, yields a mean TLE of 10.8 ± 5.5 mm, demonstrating methodological feasibility.

Targeting sex determination to suppress mosquito populations.

Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next-generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Ae. aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to effectively control wild populations of disease vectors.

Can We Do Anything Else before Removing a Button Battery from the Esophagus?-Hyaluronic Acid.

OBJECTIVE: This article tests the protective effect of a commercially available mixture of hyaluronic acid, chondroitin sulfate, and poloxamer 407 on the damage caused by the exposure of esophageal mucosa to button batteries in an animal model. METHODS: Experimental study. Sixty porcine esophageal samples were distributed in three groups: control (CG), exposure (EG), and exposure-protection (EPG). In EG and EPG, one CR2032 button battery per sample was inserted, both were subdivided into 2-, 4-, 6-, and 24-hour exposure subgroups, with subsequent battery removal. EPG samples were irrigated with the solution 1 hour after battery exposure. Esophageal pH and final voltage of the battery were measured. RESULTS: pH in CG remained stable. No significant differences in pH at 1 hour were found between EG and EPG. In EPG, the pH of the mucosa exposed to the anode was lower than in GE at 2 hours (12.44 vs. 11.89, p = 0.203) and 4 hours (13.78 vs. 11.77, p < 0.0001). In the cathode pH was significantly higher in EG at 2 hours (2.5 vs. 4.11, p < 0.0001), 4 hours (2.33 vs. 4.78, p < 0.0001), and 6 hours (2.17 vs. 2.91, p < 0.0001). Significant voltage reduction at 1 hour was found in EG compared to EPG (0.48 vs. 1.08 V, p = 0.004). CONCLUSION: Exposure to hyaluronic acid solution buffers the acidification on the side exposed to the cathode and basification on the anode. This effect can be maintained up to 3 to 5 hours, even after stopping its application. Our results suggest that a solution containing hyaluronic acid could be used as an esophageal protector after accidental ingestion of button batteries.

Return to full duty after anterior cruciate ligament reconstruction surgery in military personnel: A meta-analysis. / Retorno a la actividad completa tras cirugía de reconstrucción de ligamento cruzado anterior en personal militar: metaanálisis.

OBJECTIVE: A meta-analysis was carried out to evaluate the clinical-functional results of anterior cruciate ligament surgery in military population, as well as the complications associated with it. MATERIAL AND METHOD: Three major database sources up to December 2022 (PubMed, Google Scholar, and ScienceDirect) were searched for outcomes after anterior cruciate ligament surgery in military personnel. The systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses -PRISMA- standards, and the inclusion criteria following the PICO strategy. Data from included studies were analyzed using Review Manager 5.4 software. RESULTS: A total of 7 retrospective studies were selected. The general rate of return to full duty in military personnel was 62.3% (61.5% for the non-officer group vs. 68.3% for the officer group) without this difference being significant (p=0.92). The general rate of meniscal injury in the military was 58.8%, without this difference being significant (p=0.88). The homogeneity in both cases was good (I2=0%, p=0.99). CONCLUSION: Return to full military duty can be used in the military population as a marker of success after anterior cruciate ligament reconstruction. It should be noted that a large number of military personnel experience permanent activity limitations that prevent full return to service.

[Translated article] Return to full duty after anterior cruciate ligament reconstruction surgery in military personnel: A meta-analysis.

OBJECTIVE: A meta-analysis was carried out to evaluate the clinical-functional results of anterior cruciate ligament surgery in military population, as well as the complications associated with it. MATERIAL AND METHOD: Three major database sources up to December 2022 (PubMed, Google Scholar, and ScienceDirect) were searched for outcomes after anterior cruciate ligament surgery in military personnel. The systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses -PRISMA- standards, and the inclusion criteria following the PICO strategy. Data from included studies were analysed using Review Manager 5.4 software. RESULTS: A total of seven retrospective studies were selected. The general rate of return to full duty in military personnel was 62.3% (61.5% for the non-officer group versus 68.3% for the officer group) without this difference being significant (p=0.92). The general rate of meniscal injury in the military was 58.8%, without this difference being significant (p=0.88). The homogeneity in both cases was good (I2=0%, p=0.99). CONCLUSION: Return to full military duty can be used in the military population as a marker of success after anterior cruciate ligament reconstruction. It should be noted that a large number of military personnel experience permanent activity limitations that prevent full return to service.

A two-component model of hair cortisol concentration in fibromyalgia: Independent effects of pain chronicity and severity.

BACKGROUND: Fibromyalgia (FM) is a chronic pain disorder of unknown aetiopathogenesis, in which the role of activity of the hypothalamic-pituitary-adrenal (HPA) axis is not clearly established. METHODS: This study analysed the modulatory effects of disease chronicity and severity on cortisol levels. Hair cortisol concentrations (HCC) and clinical evaluation data (pain severity, impact of FM on daily activities, depression, anxiety, fatigue and insomnia) were collected from 47 female patients with FM and 36 healthy women (HW). RESULTS: The results showed that disease chronicity, with a negative effect, and symptom severity, with a positive effect, were independent predictors of HCC. Patients with a shorter disease duration had higher HCC than patients with a longer disease duration and healthy participants. Furthermore, patients with greater symptom severity had higher HCC than those patients with lower clinical severity and healthy participants. While disease chronicity in FM was associated with a decrease in HCC, clinical severity increased HCC. CONCLUSIONS: These results support the existence of a dysfunction in the regulation of the HPA axis in FM and its possible contribution to chronic pain development. SIGNIFICANCE: This is the first study to assess hair cortisol concentrations in a specific sample of patients with fibromyalgia (FM). This method is especially useful for the assessment of long-term regular cortisol excretion. Results showed a two-component model for explaining cortisol levels: disease chronicity, with a negative effect, and symptom severity, with a positive effect. This suggests that severe pain/stress evokes higher cortisol levels at earlier stages of FM, while in the longer term a decrease in cortisol levels was observed.

Influencia del ejercicio físico en la gravedad de la COVID-19 / Influence of physical exercise on the severity of COVID-19

Antecedentes La enfermedad por el nuevo coronavirus (COVID-19) fue declarada pandemia en marzo de 2020. Este estudio tiene como objetivo analizar la relación entre la práctica de ejercicio físico y la gravedad de la COVID-19. Método Estudio observacional en una cohorte de 29.875 personas de la Universidad de Salamanca (2.800 profesores/investigadores, 1.289 personal de servicio y 25.786 estudiantes) mediante la realización de una encuesta anónima telemática que recogió los datos sobre la realización de ejercicio, el diagnóstico de COVID-19 y sus síntomas. La encuesta fue realizada durante la primavera de 2021 y estuvo abierta un mes. Resultados Se recibieron 3.662 respuestas completas. Se utilizó la metodología «raking» para inferir los resultados a toda la población de estudio (29.875 personas). Se encontró una relación estadísticamente significativa (p<0,001) entre la presencia de síntomas y la práctica de ejercicio, la probabilidad de sufrir síntomas en personas que no practicaban ejercicio antes de COVID-19 fue 2,18 veces mayor que en aquellas que practicaban ejercicio (IC 95%; 1,825-2,611). La práctica de ejercicio más de 5 días/semana fue el factor más protector (Chi-cuadrado=134,22; gl=2; p<0,000). El ejercicio intenso fue más efectivo que el ejercicio moderado (Chi-cuadrado=36,88; gl=1; p<0,000) para prevenir los síntomas de COVID-19. Conclusión El ejercicio físico es un factor protector en la enfermedad COVID-19. El ejercicio regular, al menos 5 días/semana, resultó ser la opción más adecuada para prevenir los síntomas de la enfermedad. El ejercicio intenso logró mayor efectividad que el ejercicio moderado en el control de la gravedad de la enfermedad (AU)

Background Coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020. This study aims to clarify the relationship between physical exercise practice and the severity of COVID-19. Methods The present research is an observational, cross-sectional study. 29,875 people from the University of Salamanca were surveyed in March 2021 (2800 teacher and research staff, 1289 service staff and 25,786 students). The survey analysed the influence of physical exercise on COVID-19 symptoms. Results A total of 3662 complete responses were received. Raking methodology was used to extrapolate the results to the entire study population (29,875 people). A statistically significant relationship (P<.001) was recorded between developing symptoms and practicing physical exercise, the probability of suffering symptoms in people who did not practice exercise before COVID-19 was 2.18 times higher than those who practice exercise (95% CI, 1.825-2.611). Practising physical exercise more than 5 days/week was the most protective factor (Chi-square=134.22, gl=2; P<000). Intense physical exercise was more effective than moderate exercise (Chi-square=36.88, gl=1; P<.000) to prevent COVID-19 symptoms. Conclusion This study proved that physical exercise is a protective factor against SARS-CoV-2 infection. Regular exercise, at least 5 days/week, has been shown to be the most appropriate option to prevent disease symptoms. Intense exercise achieves greater effectiveness than moderate exercise in controlling the severity of the disease (AU)

Decoding clinical and molecular pathways of liver dysfunction in Psoriatic Arthritis: Impact of cumulative methotrexate doses.

BACKGROUND: The occurrence of liver abnormalities in Psoriatic Arthritis (PsA) has gained significant recognition. Identifying key factors at the clinical and molecular level can help to detect high-risk patients for non-alcoholic fatty liver disease in PsA. OBJECTIVES: to investigate the influence of PsA and cumulative doses of methotrexate on liver function through comprehensive in vivo and in vitro investigations. METHODS: A cross-sectional study involving 387 subjects was conducted, 200 patients with PsA, 87 NAFLD-non-PsA patients, and 100 healthy donors (HDs), age and sex-matched. Additionally, a retrospective longitudinal study was carried out, including 83 PsA patients since initiation with methotrexate. Detailed clinical, and laboratory parameters along with liver disease risk were analyzed. In vitro, experiments with hepatocyte cell line (HEPG2) were conducted. RESULTS: PsA patients present increased liver disease risk associated with the presence of cardiometabolic comorbidities, inflammatory markers, onychopathy, and psoriasis. The treatment with PsA serum on hepatocytes encompassed inflammatory, fibrotic, cell stress, and apoptotic processes. At the molecular level, methotrexate impacts liver biology, although the cumulative doses did not affect those alterations, causing any potential damage to liver function at the clinical level. Finally, anti-PDE-4 or anti-JAK decreased the inflammatory profile induced by PsA serum on hepatocytes. CONCLUSION: 1)This study identifies the complex link between liver disease risk, comorbidities, and disease-specific features in PsA patients. 2)Methotrexate dose in PsA patients had no significant effect on liver parameters, confirmed by hepatocyte in vitro studies. 3)Anti-PDE-4 and anti-JAK therapies show promise in reducing PsA serum-induced hepatocyte activation, potentially aiding liver complication management.

Factores asociados al tratamiento crónico no justificado con digoxina en pacientes con insuficiencia cardiaca aguda y relación con el pronóstico a corto plazo / Factors associated with unjustified chronic treatment with digoxin in patients with acute heart failure and relationship with short-term prognosis

Objetivos Analizar los factores relacionados con el tratamiento crónico inadecuado con digoxina, y si esta inadecuación impacta en la evolución a corto plazo. Método Se incluyeron pacientes diagnosticados de insuficiencia cardiaca aguda (ICA) en tratamiento crónico con digoxina, y se clasificaron como con tratamiento indicado o no indicado, investigándose los factores asociados a este hecho, y si se asociaba a mortalidad intrahospitalaria a 30 días, estancia hospitalaria prolongada (>7 días) y evento adverso combinado (reconsulta a urgencias, hospitalización por ICA o muerte por cualquier causa) durante los 30 días postalta. Resultados Se analizaron 2.366 pacientes en tratamiento crónico con digoxina (mediana=83 años, mujeres=61%): adecuado en 1.373 casos (58,0%), inadecuado en 993 (42,0%). La inadecuación se asoció con mayor edad, menor comorbilidad, menor tratamiento con betabloqueantes e IECA, mejor función ventricular y peor índice de Barthel. La mortalidad intrahospitalaria y a 30 días fue mayor en pacientes con tratamiento inadecuado (9,9 versus 7,6%, p=0,05; y 12,6 versus 9,1%, p<0,001; respectivamente); no hubo diferencias en estancia prolongada (35,7 versus 33,8%) ni en eventos adversos posalta (32,9 versus 31,8%). Ajustando las diferencias basales y del episodio de descompensación, el tratamiento crónico inadecuado con digoxina no se asoció con ningún resultado, con odds ratio de 1,31 (IC 95%: 0,85-2,03) para mortalidad intrahospitalaria, 1,29 (0,74-2,25) para mortalidad a 30 días; 1,07 (0,82-1,40) para estancia prolongada y 0,88 (0,65-1,19) para evento adverso posalta. Conclusión Existe un perfil de paciente que recibe de forma inadecuada tratamiento crónico con digoxina, si bien ello no se asocia con resultados adversos a corto plazo durante los episodios de ICA (AU)

Objectives To analyze the factors related to inadequate chronic treatment with digoxin and whether the inadequacy of treatment has an impact on short-term outcome. Method Patients diagnosed with AHF who were in chronic treatment with digoxin were selected. Digoxin treatment was classified as adequate or inadequate. We investigated factors associated to inadequacy and whether such inadequacy was associated with in-hospital and 30-day mortality, prolonged hospital stay (>7 days) and combined adverse event (re-consultation to the ED or hospitalization for AHF or death from any cause) during the 30 days after discharge. Results We analyzed 2366 patients on chronic digoxin treatment (median age=83 years, women=61%), which was considered adequate in 1373 cases (58.0%) and inadequate in 993 (42.0%). The inadequacy was associated with older age, less comorbidity, less treatment with beta-blockers and renin–angiotensin inhibitors, better ventricular function, and worse Barthel index. In-hospital and 30-day mortality was higher in patients with inadequate digoxin treatment (9.9% vs. 7.6%, p=0.05; and 12.6% vs. 9.1%, p<0.001, respectively). No differences were recorded in prolonged stay (35.7% vs. 33.8%) or post-discharge adverse events (32.9% vs. 31.8%). In the model adjusted for baseline and decompensation episode differences, inadequate treatment with digoxin was not significantly associated with any outcome, with an odds ratio of 1.31 (95% CI=0.85-2.03) for in-hospital mortality; 1.29 (0.74-2.25) for 30-day mortality; 1.07 (0.82-1.40) for prolonged stay; and 0.88 (0.65-1.19) for post-discharge adverse event. Conclusion There is a profile of patients with AHF who inadequately receive digoxin, although this inadequateness for chronic digitalis treatment was not associated with short-term adverse outcomes (AU)