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Abstract Background Intravenous administration of fibrinolytic drugs, such as recombinant tissue plasminogen activator (rtPA) is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and risk of hemorrhagic transformations. Platelet membrane-based nanocarriers have received increasing attention for ischemic stroke therapies, as they have natural thrombus-targeting activity, can prolong half-life of the fibrinolytic therapy, and reduce side effects. In this study we have gone further in developing platelet-derived nanocarriers (defined as cellsomes) to encapsulate and protect rtPA from degradation. Following lyophilization and characterization, their formulation properties, biocompatibility, therapeutic effect, and risk of hemorrhages were later investigated in a thromboembolic model of stroke in mice. Results Cellsomes of 200 nm size and loaded with rtPA were generated from membrane fragments of human platelets. The lyophilization process did not influence the nanocarrier size distribution, morphology, and colloidal stability conferring particle preservation and long-term storage. Encapsulated rtPA in cellsomes and administered as a single bolus showed to be as effective as a continuous clinical perfusion of free rtPA at equal concentration, without increasing the risk of hemorrhagic transformations or provoking an inflammatory response. Conclusions This study provides evidence for the safe and effective use of lyophilized biomimetic platelet-derived nanomedicine for precise thrombolytic treatment of acute ischemic stroke. In addition, this new nanoformulation could simplify the clinical use of rtPA as a single bolus, being easier and less time-consuming in an emergency setting than a treatment perfusion, particularly in stroke patients. We have successfully addressed one of the main barriers to drug application and commercialization, the long-term storage of nanomedicines, overcoming the potential chemical and physical instabilities of nanomedicines when stored in an aqueous buffer.

Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Design: Prospective case–control study involving 120 patients with imaging-confirmed LS and a 120 control group. Methods: We examined the relationship between Alzheimer’s disease biomarkers [amyloid beta (Aβ 1–40 , Aβ 1–42 )], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Results: Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p

Objetivo: Describir el uso de la terapia de presión negativa con (TPNi) y sin instilación (TPNs) como tratamiento adyuvante en el manejo de infecciones asociadas a dispositivo ortopédico (IADO). Método: Estudio observacional analítico de expedientes de pacientes con IADO manejados con TPNi y TPNs con solución salina al 0.9%, mayores de 18 años, operados en el periodo 2018-2021. Se evaluaron las características clínicas de infección, el agente infeccioso y las variables sociodemográficas. La TPN se realizó con sistema V.A.C.VERAFLO™. Para los análisis se emplearon las pruebas χ2, Fisher y t de Student. Valor estadísticamente aceptado: p < 0.05. Resultados: La muestra fue de 40 pacientes, el 75% masculinos. Fracturas: 42.5% expuestas y 57.5% cerradas. En el 92.5% se aplicó antibiótico profiláctico (30-120 min). Implantes: 35% placas, 12.5% clavo centromedular, 10% prótesis de rodilla y 12.5% cadera. El 47.5% con sangrado < 500 ml. En el 72.5% un tiempo quirúrgico de 2-4 horas. Tiempo de hospitalización previa: TPNs 3 semanas 55.9% y 4 semanas 26.5%; TPNi 3 semanas 50% y 4 semanas 33.3%. Conservación del implante: 73.5% TPNs y 50% TPNi (p = 0.341). Cierre de herida: 91.2% con TPNs y 100% con TPNi (p = 1.000). Conclusiones: El uso de TPNs y TPNi fue útil como tratamiento adyuvante en IADO, y además permitieron conservar el implante y el cierre de la herida en la mayoría de los pacientes.

Parasitic infections are a major source of human suffering, mortality, and economic loss, but drug development for these diseases has been stymied by the significant expense involved in bringing a drug though clinical trials and to market. Identification of single compounds active against multiple parasitic pathogens could improve the economic incentives for drug development as well as simplifying treatment regimens. We recently performed a screen of repurposed compounds against the protozoan parasite Entamoeba histolytica, causative agent of amebic dysentery, and identified four compounds (anisomycin, prodigiosin, obatoclax and nithiamide) with low micromolar potency and drug-like properties. Here, we extend our investigation of these drugs. We assayed the speed of killing of E. histolytica trophozoites and found that all four have more rapid action than the current drug of choice, metronidazole. We further established a multi-institute collaboration to determine whether these compounds may have efficacy against other parasites and opportunistic pathogens. We found that anisomycin, prodigiosin and obatoclax all have broad-spectrum antiparasitic activity in vitro, including activity against schistosomes, T. brucei, and apicomplexan parasites. In several cases, the drugs were found to have significant improvements over existing drugs. For instance, both obatoclax and prodigiosin were more efficacious at inhibiting the juvenile form of Schistosoma than the current standard of care, praziquantel. Additionally, low micromolar potencies were observed against pathogenic free-living amebae (Naegleria fowleri, Balamuthia mandrillaris and Acanthamoeba castellanii), which cause CNS infection and for which there are currently no reliable treatments. These results, combined with the previous human use of three of these drugs (obatoclax, anisomycin and nithiamide), support the idea that these compounds could serve as the basis for the development of broad-spectrum anti-parasitic drugs.

IntroductionDynamic susceptibility-weighted contrast-enhanced (DSC) perfusion studies in magnetic resonance imaging (MRI) provide valuable data for studying vascular cerebral pathophysiology in different rodent models of brain diseases (stroke, tumor grading, and neurodegenerative models). The extraction of these hemodynamic parameters via DSC-MRI is based on tracer kinetic modeling, which can be solved using deconvolution-based methods, among others. Most of the post-processing software used in preclinical studies is home-built and custom-designed. Its use being, in most cases, limited to the institution responsible for the development. In this study, we designed a tool that performs the hemodynamic quantification process quickly and in a reliable way for research purposes.MethodsThe DSC-MRI quantification tool, developed as a Python project, performs the basic mathematical steps to generate the parametric maps: cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), signal recovery (SR), and percentage signal recovery (PSR). For the validation process, a data set composed of MRI rat brain scans was evaluated: i) healthy animals, ii) temporal blood–brain barrier (BBB) dysfunction, iii) cerebral chronic hypoperfusion (CCH), iv) ischemic stroke, and v) glioblastoma multiforme (GBM) models. The resulting perfusion parameters were then compared with data retrieved from the literature.ResultsA total of 30 animals were evaluated with our DSC-MRI quantification tool. In all the models, the hemodynamic parameters reported from the literature are reproduced and they are in the same range as our results. The Bland–Altman plot used to describe the agreement between our perfusion quantitative analyses and literature data regarding healthy rats, stroke, and GBM models, determined that the agreement for CBV and MTT is higher than for CBF.ConclusionAn open-source, Python-based DSC post-processing software package that performs key quantitative perfusion parameters has been developed. Regarding the different animal models used, the results obtained are consistent and in good agreement with the physiological patterns and values reported in the literature. Our development has been built in a modular framework to allow code customization or the addition of alternative algorithms not yet implemented.

Abstract Background Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. Methods 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. Results Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p

Resumen: Antecedentes: La dermatitis de las manos (DM) es frecuente en los pacientes con dermatitis atópica (DA). Pocos estudios describen las características de estos pacientes a partir de poblaciones amplias y representativas de ámbitos geográficos y laborales diferentes. Objetivos: Describir el perfil epidemiológico, clínico y alérgico de los pacientes con DM a los que se realizan pruebas epicutáneas, comparando los pacientes con DA con los pacientes sin DA. Métodos. El estudio se ha realizado a partir de los datos del REIDAC, un registro multicéntrico nacional de pacientes a los que se realizan pruebas epicutaneas. Resultados: Se incluyeron 1466 pacientes parcheados por DM desde enero de 2018 hasta junio de 2020. Los pacientes con DA fueron más jóvenes y con una duración de los síntomas mayor. Los antecedentes ocupacionales como desencadenantes se registraron en menor medida que en los pacientes no atópicos (38 vs 53%). La única profesión en la que se encontraron diferencias significativas fue la peluquería. Los alérgenos más detectados fueron el sulfato de níquel, la metilcloroisotiazolinona/metilisotiazolinona, el cloruro de cobalto, el dicromato potásico, mezcla de fragancias I y II, y el formaldehido. Los diagnósticos más frecuentes fueron dermatitis alérgica de contacto (DAC); 24% en atópicos vs 31% en no atópicos (p 0.0224) y el eccema de contacto irritativo; 18% atópicos vs 35% no atópicos (p

Abstract Objective Leukoaraiosis (LA) refers to white matter lesions of undetermined etiology associated with the appearance and worsening of vascular pathologies. The aim is to confirm an increased frequency and intensity of LA in symptomatic patients with neurovascular pathology compared with asymptomatic subjects, and its association with circulating serum levels of soluble tumor necrosis factor‐like weak inducer of apoptosis (sTWEAK). Methods An observational study was conducted in which two groups of patients were compared. Group I (N = 242) comprised of asymptomatic subjects with arterial hypertension and/or diabetes or with a history of transient ischemic attacks, and Group II (N = 382) comprised patients with lacunar stroke or deep hemispheric intracerebral hemorrhage (ICH) of hypertensive origin. Serum levels of sTWEAK were analyzed and correlated with prevalence and intensity of LA according to the Fazekas scale. Results The prevalence of LA was higher in symptomatic (85.1%) versus asymptomatic patients (62.0%). Logistic regression model showed a significant relation of LA with neurovascular pathologies (OR: 2.69, IC 95%: 1.10–6.59, p = 0.003). When stratified according to the Fazekas scale, LA of grade II (OR: 3.53, IC 95%: 1.10–6.59, p = 0.003) and specially grade III (OR: 4.66, 95% CI: 1.09–19.84, p = 0.037) showed correlation with neurovascular pathologies. Increased sTWEAK levels were found in the symptomatic group in all LA grades (p

Abstract Background Ischemic stroke is the most common cerebrovascular disease and is caused by interruption of blood supply to the brain. To date, recombinant tissue plasminogen activator (rtPA) has been the main pharmacological treatment in the acute phase. However, this treatment has some drawbacks, such as a short half-life, low reperfusion rate, risk of hemorrhagic transformations, and neurotoxic effects. To overcome the limitations of rtPA and improve its effectiveness, we recently designed sonosensitive sub-micrometric capsules (SCs) loaded with rtPA with a size of approximately 600 nm, synthesized using the layer-by-layer (LbL) technique, and coated with gelatine for clot targeting. In this study, we evaluated the rtPA release of ultrasound (US)-responsive SCs in healthy mice and the therapeutic effect in a thromboembolic stroke model. Results In healthy mice, SCs loaded with rtPA 1 mg/kg responded properly to external US exposure, extending the half-life of the drug in the blood stream more than the group treated with free rtPA solution. The gelatine coating also contributed to stabilizing the encapsulation and maintaining the response to US. When the same particles were administered in the stroke model, these SCs appeared to aggregate in the ischemic brain region, probably generating secondary embolisms and limiting the thrombolytic effect of rtPA. Despite the promising results of these thrombolytic particles, at least under the dose and size conditions used in this study, the administration of these capsules represents a risk factor for stroke. Conclusions This is the first study to report the aggregation risk of a drug carrier in neurological pathologies such as stroke. Biocompatibility analysis related to the use of nano-and microparticles should be deeply studied to anticipate the limitations and orientate the design of new nanoparticles for translation to humans. Graphical Abstract

Objective: To evaluate the study habits in the academic performance of residents of the specialties of Orthopaedics and Trauma (OT) and Family Medicine (MF). Methods: An observational study was carried out with OT and MF medical residents. An online survey was applied to them, with response options on the Likert scale, to evaluate study habits. For the statistical analysis, measures of central tendency and dispersion were used, as well as correlations, P < 0.05. Results: A sample of 112 participants. 51% of participants were male. Mean age of 30.1±3. 75% of participants were single. 84.8% study one hour. 84.8% of respondents answered that they were pursuing the specialty they wanted. 80.4% always or constantly understand what they read. 45.5% of participants draw diagrams or charts. Writing summaries (82.1%) is the most used technique for memorisation. 93.7% always or constantly attend classes on a regular basis. 94.6% of participants strongly agree or agree that study habits can influence academic performance. 58% presented regular habits, 22% good habits and 18% bad habits. It was found that there is a correlation between age and average academic performance (P = 0.016). Conclusions: Age and marital status had a direct association with academic performance. Most of the residents are satisfied with the specialty they are studying. Memorisation and writing summaries are the most used study habits. In general, residents have regular study habits.

Antecedentes: La displasia del desarrollo de la cadera (DDC) constituye una entidad clínica compleja que suele ser infradiagnosticada que, de no ser precozmente detectadas y manejadas, convertirán al individuo afectado en un ser discapacitado, con efecto negativo social, económico y emocional. Objetivo: Determinar la capacidad para la detección radiográfica oportuna de la DDC antes y después de una intervención educativa en médicos residentes de medicina familiar. Método: Se realizó una intervención educativa en residentes de medicina familiar, en la que se les dio capacitación sobre detección de DDC en proyecciones radiográficas. Se realizó una evaluación previa y posterior a la capacitación. El análisis estadístico se realizó mediante pruebas t de Student y χ2, tomando como significativo un valor de p ≤ 0.05. Resultados: Participaron 94 residentes. El 87.2% dijeron no conocer el protocolo radiológico de detección. En la evaluación preintervención, el 87.2% no tenían conocimiento del protocolo (p = 0.525). Se observó que el 98.9% trazaron de manera incorrecta la línea de Perkins (p = 0.427), el 96.8% la línea de Hilgenreiner (p = 0.177) y el 87.2% no consideraron los datos de displasia bilateral (p = 0.956). Posterior a la intervención educativa, el 87.2% trazaron de manera correcta la línea de Perkins (p = 0.926), el 97.8% la línea de Hilgenreiner (p = 0.325) y el 78.7% sí consideró los datos de displasia bilateral (p = 0.826). Conclusiones: Tras la capacitación, el 80% de los médicos residentes de medicina familiar fueron capaces de detectar oportunamente la DDC.

Objetivo: Describir y analizar la exposición a radiación ionizante de los residentes de ortopedia. Método: Se realizó un estudio prospectivo para evaluar el grado de exposición a radiación ionizante con un dosímetro de placa colocado debajo del mandil plomado a médicos residentes, por 10 meses. Mediante una encuesta en línea se midió el grado de conocimientos sobre seguridad radiológica. Resultados: Participaron 54 médicos residentes. El 55.6% refiere tener conocimiento de la existencia de equipo de protección radiológica y el 40.7% refiere que tuvo entrenamiento previo en su uso. El 77.8% utiliza el mandil plomado y el 31.5% la protección tiroidea. El 81.5% se posicionó a menos de 1 metro de la fuente de producción de rayos X del arco en C. La exposición a la radiación media total fue de 2.9 ± 2.17 mSv (intervalo de confianza del 95%: 1.25-14.28; p = 0.424). Conclusiones: Los médicos residentes de ortopedia presentan dosis de radiación menores que el límite recomendado por la International Commission on Radiological Protection. Sin embargo, existe una falta de conocimientos sobre protección radiológica, así como falta de interés e ignorancia de los efectos adversos de la radiación.

Resumen: Antecedentes y objetivo: La actualización de las series estándar de pruebas epicutáneas debe basarse en datos objetivos de frecuencia de sensibilización de los alérgenos que componen cada batería. La última renovación de la batería estándar española se realizó en 2016 y de la europea en 2019, quedando pendiente valorar la inclusión de alérgenos emergentes. Material y método: Desarrollamos un estudio observacional, prospectivo y multicéntrico de los pacientes consecutivos del registro del Grupo Español de Investigación en Dermatitis y Alergia Cutánea sometidos a pruebas epicutáneas con hidroperóxido de linalool, hidroperóxido de limoneno, 2-hidroxi-etil-metacrilato, benzisotiazolinona, octilisotiazolinona, mezcla textil, metabisulfito sódico, propóleo, bronopol, mezcla de compuestas II, diazolidinil urea, imidazolidinil urea, decil glucósido y lauril glucósido, durante los años 2019 y 2020. Resultados: Se analizó una muestra de 4.654 pacientes estudiados con diazolidinil urea, imidazolidinil urea y bronopol, y de 1.890 pacientes con el resto de los alérgenos. El índice MOAHLFA fue: M 30%, O 18%, A 15%, H 29%, L 6,5%, F 23%, A 68%. Siete alérgenos mostraron una frecuencia de sensibilización mayor del 1%: hidroperóxido de linalool, 2-hidroxi-etil-metacrilato, benzisotiazolinona, hidroperóxido de limoneno, mezcla textil, metabisulfito sódico y propóleo. Tres alérgenos mostraron una frecuencia de relevancia presente superior al 1%: hidroperóxido de linalool, 2-hidroxi-etil-metacrilato e hidroperóxido de limoneno; para benzisotiazolinona y mezcla textil, esta frecuencia fue de entre el 0,9 y el 1%. Conclusiones: Nuestros resultados indican que debería valorarse la inclusión de siete nuevos alérgenos en la batería estándar española. Estos resultados podrían contribuir a la próxima actualización de la batería basal europea. Abstract: Background: Standard patch test series must be updated using objective data on allergen sensitization. The Spanish standard series was last updated in 2016 and the European series in 2019, and the inclusion of several emerging allergens needs to be evaluated. Material and methods: We conducted a prospective, observational, multicenter study of consecutive patients from the registry of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) who were patch tested in 2019 and 2020 with linalool hydroperoxide, limonene hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, octylisothiazolinone, textile dye mix (TDM), sodium metabisulfite, propolis, bronopol, Compositae mix II, diazolidinyl urea, imidazolidinyl urea, decyl glucoside, and lauryl glucoside. Results: We analyzed data for 4654 patients tested with diazolidinyl urea, imidazolidinyl urea, and bronopol, and 1890 tested with the other allergens. The values for the MOAHLFA index components were 30% for male, 18% for occupational dermatitis, 15% for atopic dermatitis, 29% for hand, 6.5% for leg, 23% for face, and 68% for age > 40 years. Sensitization rates above 1% were observed for 7 allergens: linalool hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, limonene hydroperoxide, TDM, sodium metabisulfite, and propolis. Three allergens had a current relevance rate of over 1%: linalool hydroperoxide, 2-hydroxyethyl-methacrylat, and limonene hydroperoxide. Benzisothiazolinone and TDM had a relevance rate of between 0.9% and 1%. Conclusions: Our results indicate that 7 new allergens should be considered when extending the Spanish standard patch test series. The data from our series could be helpful for guiding the next extension of the European baseline series.

Ischemic stroke is becoming one of the most common causes of death and disability in developed countries. Since current therapeutic options are quite limited, focused on acute reperfusion therapies that are hampered by a very narrow therapeutic time window, it is essential to discover novel treatments that not only stop the progression of the ischemic cascade during the acute phase, but also improve the recovery of stroke patients during the sub-acute or chronic phase. In this regard, several studies have shown that endothelial progenitor cells (EPCs) can repair damaged vessels as well as generate new ones following cerebrovascular damage. EPCs are circulating cells with characteristics of both endothelial cells and adult stem cells presenting the ability to differentiate into mature endothelial cells and self-renew, respectively. Moreover, EPCs have the advantage of being already present in healthy conditions as circulating cells that participate in the maintenance of the endothelium in a direct and paracrine way. In this scenario, EPCs appear as a promising target to tackle stroke by self-promoting re-endothelization, angiogenesis and vasculogenesis. Based on clinical data showing a better neurological and functional outcome in ischemic stroke patients with higher levels of circulating EPCs, novel and promising therapeutic approaches would be pharmacological treatment promoting EPCs-generation as well as EPCs-based therapies. Here, we will review the latest advances in preclinical as well as clinical research on EPCs application following stroke, not only as a single treatment but also in combination with new therapeutic approaches.

Introduction: Knee joint injection is a daily procedure in orthopedic outpatient visit. In order to obtain the maximum therapeutic benefit, it is necessary to perform the injection directly into the articular space and not into the adjacent structures. Objective: To establish the accuracy of the injection site into the knee joint in patients with grade II-III gonarthrosis. The portal approaches taken into consideration in this study were: Anterolateral (AL), Anteromedial (AM), Lateral Suprapatellar (LSP), Lateral mid-patellar (LMP), Medial mid-patellar (MMP) and Transtendinous (TT). Material and methods: A cross-sectional and descriptive study was conducted. A total of 123 knee joints were injected under fluoroscopy through the different approach portals. Variables: gender, positive arthrography at the first attempt, level of pain in patients during the procedure, as well as complications and side effects. Results: Lateral mid-patellar (LMP) approach was used on 20 knee joints with a 40% positive arthrography, 17 through LSP with 70.5%, 20 MMP with 90%, 21 AL with 61.3%, 26 M with 69.9%, 19 TT with 78.9%. Conclusion: The medial mid-patellar approach portal provides the greatest effectiveness in comparison to the other portals used on this study. Additionally, a greater percentage of positive arthrography was achieved at the first attempt.

Algunos contaminantes como las PM10, el NO2 o el O3 tienen influencia en la salud de las personas, tal y como apuntan numerosos estudios al relacionarse con la mortalidad tanto a corto como a largo plazo. Se estudió una muestra de 9 de las 52 provincias españolas. Se realizaron modelos lineales generalizados (GLM) con link Poisson en los periodos de la primera y segunda ola entre los valores medios diarios de las variables independientes (PM10, NO2 y O3 como contaminantes atmosféricos y variables meteorológicas (temperatura máxima diaria y humedad absoluta)) y la variable dependiente (tasa de mortalidad por COVID-19, TMC) durante la primera y segunda ola. Entre las variables independientes y la dependiente se establecieron los retardos estadísticamente significativos (lag). A partir de los estimadores obtenidos en los GLM se calcularon los riesgos relativos asociados, por aumentos de 10 μg/m3 para los contaminantes atmosféricos, 1 ºC para la temperatura máxima y 1 g/m3 para la humedad absoluta. Los resultados muestran que existe una mayor asociación del NO2 con la TMC que para el resto de los contaminantes atmosféricos. Las variables meteorológicas examinadas no han presentado una asociación robusta entre ambas olas, lo que indica un rol menor en relación a la TMC. En conclusión, la contaminación atmosférica por NO2 y PM10 presentan una asociación estadísticamente significativa con la TMC, aunque limitada y subordinada a otros factores como las medidas de salud pública adoptadas, la presencia de comorbilidades y la edad del paciente.

Abstract We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of mortality and morbidity 3-months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity according to the following groups: (1) IS + ICH, (2) IS, and (3) ICH. A total of 6022 patients were included: 4922 (mean age 71.9 ± 13.8 years) with IS and 1100 (mean age 73.3 ± 13.1 years) with ICH. NIHSS at 24, 48 h and axillary temperature at admission were the most important variables to consider for evolution of patients at 3-months. IS + ICH group was the most stable for mortality prediction [0.904 ± 0.025 of area under the receiver operating characteristics curve (AUC)]. IS group presented similar results, although variability between experiments was slightly higher (0.909 ± 0.032 of AUC). ICH group was the one in which RF had more problems to make adequate predictions (0.9837 vs. 0.7104 of AUC). There were no major differences between IS and IS + ICH groups according to morbidity prediction (0.738 and 0.755 of AUC) but, after checking normality with a Shapiro Wilk test with the null hypothesis that the data follow a normal distribution, it was rejected with W = 0.93546 (p-value

Abstract Functional impairment remains one of the most challenging issues for treatment in schizophrenia. However, previous studies have mainly focused on the negative impact of symptoms excluding variables that could positively impact functional outcome, such as creativity, which is considered an adaptive capacity for real-life problem-solving. This study analyzed the predictive role of creativity on functional outcome in 96 patients with schizophrenia through a mediational model, including sociodemographic, clinical, neurocognitive, and social cognitive variables. Path analysis revealed that creativity significantly mediated the relationship between neurocognition and functional outcome, and that creativity mediated between negative symptoms and functional outcome. Additionally, neurocognition was directly associated with functional outcome and social functioning was associated with creativity. The involvement of creativity in functional outcome could have relevant implications for the development of new interventions. These findings open up a new field of research on additional personal resources as possible factors of functional outcome in schizophrenia and other diseases.

Resumen: Objetivo: Determinar la frecuencia de eventos adversos evitables (EAE) en atención primaria (AP). Diseño: Estudio retrospectivo de cohortes. Emplazamiento: consultas de medicina de familia y pediatría de Andalucía, Aragón, Castilla La Mancha, Cataluña, Madrid, Navarra y Comunidad Valenciana. Participantes: Se determinó revisar un mínimo de 2.397 historias clínicas (nivel de confianza del 95% y una precisión del 2%). La muestra se estratificó por grupos de edad de forma proporcional a su frecuentación y con revisión paritaria de historias de hombres y mujeres. Mediciones principales: Número y gravedad de los EAE identificados entre febrero de 2018 y septiembre de 2019. Resultados: Se revisaron un total de 2.557 historias clínicas (1.928, 75.4% de pacientes adultos y 629, 24.6% pediátricos). Se identificaron 182 EAE que afectaron a 168 pacientes (7,1%, IC 95% 6,1-8,1%); en adultos 7,6% (IC 95% 6,4-8,8%) y 5,7% (IC 95% 3,9-7,5%) en pacientes pediátricos. Las mujeres sufrieron más EAE que los hombres (p = 0,004). La incidencia de EAE en niños y niñas fue similar (p = 0,3). 6 (4.1%) de los EAE supusieron un daño permanente en pacientes adultos. Conclusiones: Buscar fórmulas para incrementar la seguridad en AP, particularmente en pacientes mujeres, debe seguir siendo un objetivo prioritario incluso en pediatría. Uno de cada 24 EAE supone un daño grave y permanente en el adulto. Abstract: Objective: To determine the frequency of avoidable adverse events (AAEs) in Primary Care (PC). Design: Retrospective cohort study. Location: Family medicine and paediatric clinics in Andalusia, Aragon, Castilla-La Mancha, Catalonia, Madrid, Navarre, and Valencia. Participants: A review was performed on a designated sample of 2,397 medical records (95% confidence level and 2% accuracy). The sample was stratified by age group as regards the frequency of physician consultations and considering equal distribution of male and female patients. Main measurements: Number and severity of identified AAEs from February 2018 to September 2019. Results: A total of 2,557 medical records were reviewed (1,928, 75.4% of adult patients, and 629, 24.6% paediatrics). A total of 182 (7.1%, 95% CI 6.1-8.1%) AAEs that affected 168 patients were identified, which included 7.6% (95% CI 6.4-8.8%) in adults and 5.7% (95% CI 3.9-7.5%) in paediatric patients. The number of AAEs in women was higher than in men (P = 0.006). The incidence of AAEs in boys and girls was similar (P = 0.3). Permanent damage was caused by AAEs in 6 (4.1%) adult patients. Conclusions: Seeking formulas to increase patient safety in PC should remain a priority objective, particularly in female patients and in paediatrics. One in 24 AAEs causes serious and permanent damage in adults.

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in worldwide. Although reperfusion therapies have shown efficacy in a limited number of patients with acute ischemic stroke, neuroprotective drugs and recovery strategies have been widely assessed, but none of them have been successful in clinical practice. Therefore, the search for new therapeutic approaches is still necessary. Sphingolipids consist of a family of lipidic molecules with both structural and cell signaling functions. Regulation of sphingolipid metabolism is crucial for cell fate and homeostasis in the body. Different works have emphasized the implication of its metabolism in different pathologies, such as diabetes, cancer, neurodegeneration, or atherosclerosis. Other studies have shown its implication in the risk of suffering a stroke and its progression. This review will highlight the implications of sphingolipid metabolism enzymes in acute ischemic stroke.

Background: Hand eczema is common in patients with atopic dermatitis (AD), but few studies have described the characteristics of these patients in large, representative populations from different geographic regions and occupational settings. Objective: To describe the epidemiological, clinical, and allergy profile of patients with hand eczema who underwent patch testing and compare patients with and without AD. Methods: Analysis of data from the Spanish Contact Dermatitis Registry, a multicenter registry of patients who undergo patch testing in Spain. Results: We included 1466 patients with hand eczema who were patch tested between January 2018 and June 2020. Those with AD were younger and had had symptoms for longer before testing. They were also more likely to have been exposed to occupational triggers (38% vs 53% for patients without AD). The only profession for which significant differences were found was hairdressing. The most common allergens were nickel sulfate, methylchloroisothiazolinone/methylisothiazolinone, cobalt chloride, potassium dichromate, fragrance mixes I and II, and formaldehyde. The most common diagnoses were allergic contact dermatitis (24% vs 31% in patients with and without AD, P = .0224) and irritant contact dermatitis (18% and 35% respectively, P

ObjectiveThis study aimed to explore the association between smoking habit and the serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), in relation with the functional outcome of patients with acute ischemic stroke undergoing reperfusion treatment.MethodsObservational and retrospective study of a series of patients with acute ischemic stroke subjected to reperfusion treatments. Clinical, analytical, and neuroimaging parameters were analyzed. The main endpoint was the functional outcome at 3 months, measured by the modified Ranking Scale (mRS). Logistic regression models were used to analyze the association between smoking and sTWEAK levels with functional outcome and leukoaraiosis.ResultsThe results showed that smoking habit was associated with a good functional outcome at 3 months in patients with stroke (OR: 3.52; 95% CI: 1.03–11.9; p = 0.044). However, this independent association was lost after adjusting by sTWEAK levels (OR 1.73; 95% CI: 0.86–13.28; p = 0.116). sTWEAK levels were significantly lower in smoker patients [4015.5 (973.66–7921.83) pg/ml vs. 5,628 (2,848–10,202) pg/ml, p < 0.0001], while sTWEAK levels were significantly higher in patients with poor functional outcomes at 3 months [10,284 (7,388–13.247) pg/ml vs. 3,405 (2,329–6,629) pg/ml, p < 0.0001].ConclusionThe decrease in sTWEAK levels was associated with a good functional outcome in smoker patients with stroke undergoing reperfusion therapy.

Abstract Objective To investigate whether elevated serum levels of sTWEAK (soluble tumor necrosis factor‐like inducer of apoptosis) might be involved in a higher frequency of symptomatic hemorrhagic transformation (HT) through the presence of leukoaraiosis (LA) in patients with acute ischemic stroke (IS) undergoing reperfusion therapies. Methods This is a retrospective observational study. The primary endpoint was to study the sTWEAK‐LA‐HT relationship by comparing results with biomarkers associated to HT and evaluating functional outcome at 3‐months. Clinical factors, neuroimaging variables and biomarkers associated to inflammation, endothelial/atrial dysfunction or blood‐brain barrier damage were also investigated. Results We enrolled 875 patients (mean age 72.3 ± 12.2 years; 46.0% women); 710 individuals underwent intravenous thrombolysis, 87 endovascular therapy and 78 both. HT incidence was 32%; LA presence was 75.4%. Patients with poor functional outcome at 3‐months showed higher sTWEAK levels at admission (9844.2 [7460.4–12,542.0] vs. 2717.3 [1489.7–5852.3] pg/mL, P

Abstract Background Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients. Methods A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72 h and at day 7 after stroke onset. Results Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48 h were independently associated with good functional outcome (OR, 3.5; CI: 1.9–7.8) after adjusting by confounding factors. Patients with lower Treg at 48 h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48 h (r = − 0.414) and 72 h (r = − 0.418) and infarct volume. Conclusions These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke.

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644