Resumen ejecutivo del documento de consenso sobre el manejo de la anemia perioperatoria en España / Executive summary of the consensus document on the management of perioperative anemia in Spain

La anemia perioperatoria constituye un factor independiente de riesgo de morbimortalidad posoperatoria. Sin embargo, persisten barreras conceptuales, logísticas y administrativas que dificultan la implementación generalizada de protocolos para su manejo. El coordinador del proyecto convocó a un grupo multidisciplinar de ocho profesionales para elaborar un documento de consenso sobre el manejo de la anemia perioperatoria, con base a en serie puntos claves (PCs) relativos a su prevalencia, consecuencias, diagnóstico y tratamiento. Estos PCs fueron evaluados utilizando una escala Likert de 5 puntos, desde «totalmente en desacuerdo [1]» a «totalmente de acuerdo [5]». Cada PC se consideró consensuado si recibía una puntuación de 4 o 5 por al menos siete participantes (> 75%). A partir de los 36 PCs consensuados, se construyeron algoritmos diagnóstico-terapéuticos que pueden facilitar la implementación de programas de identificación precoz y manejo adecuado de la anemia perioperatoria, adaptados a las características de las instituciones hospitalarias de nuestro país.(AU)

Perioperative anemia is an independent risk factor for postoperative morbidity and mortality. However, conceptual, logistical and administrative barriers persist that hinder the widespread implementation of protocols for their management. The project coordinator convened a multidisciplinary group of 9 experienced professionals to develop perioperative anemia management algorithms, based on a series of key points (KPs) related to its prevalence, consequences, diagnosis and treatment. These KPs were assessed using a 5-point Likert scale, from “strongly disagree [1]” to “strongly agree [5]”. For each KP, consensus was reached when receiving a score of 4 or 5 from at least 7 participants (>75%). Based on the 36 KPs agreed upon, diagnostic-therapeutic algorithms were developed that we believe can facilitate the implementation of programs for early identification and adequate management of perioperative anemia, adapted to the characteristics of the different institutions in our country.(AU)

Executive summary of the consensus document on the management of perioperative anemia in Spain.

Perioperative anemia is an independent risk factor for postoperative morbidity and mortality. However, conceptual, logistical and administrative barriers persist that hinder the widespread implementation of protocols for their management. The project coordinator convened a multidisciplinary group of 8 experienced professionals to develop perioperative anemia management algorithms, based on a series of key points (KPs) related to its prevalence, consequences, diagnosis and treatment. These KPs were assessed using a 5-point Likert scale, from "strongly disagree [1]" to "strongly agree [5]". For each KP, consensus was reached when receiving a score of 4 or 5 from at least 7 participants (>75%). Based on the 36 KPs agreed upon, diagnostic-therapeutic algorithms were developed that we believe can facilitate the implementation of programs for early identification and adequate management of perioperative anemia, adapted to the characteristics of the different institutions in our country.

Application of Accelerated Predictive Stability Studies in Extemporaneously Compounded Formulations of Chlorhexidine to Assess the Shelf Life.

Industrially fabricated medicines have a well-defined shelf life supported by rigorous studies before their approval for commercialization. However, the shelf life of extemporaneous compounding topical formulations prepared at hospitals tends to be shorter, especially when no data are available to prove a longer stability period. Also, the storage conditions are unknown in many circumstances. Accelerated Predictive Stability (APS) studies have been shown to be a useful tool to predict in a faster and more accurate manner the chemical stability of extemporaneously compounded formulations requiring a minimum amount of formulation, thereby reducing the chemical drug waste per study. Shelf life will be allocated based on scientific data without compromising drug efficacy or safety. In this work, the APS approach was applied to the commercially available Cristalmina® (CR) and an extemporaneously compounded formulation of chlorhexidine (DCHX). A different degradation kinetic was found between DCHX and CR (Avrami vs. zero-order kinetics, respectively). This can explain the different shelf life described by the International Council for Harmonisation of Technical Requirements Registration Pharmaceuticals Human Use (ICH) conditions between both formulations. A predicted stability for the DCHX solution was obtained from the extrapolation of the degradation rate in long-term conditions from the Arrhenius equation. The estimated degradation from the Arrhenius equation for DCHX at 5 °C, 25 °C, and 30 °C at 365 days was 3.1%, 17.4%, and 25.9%, respectively. The predicted shelf life, in which the DCHX content was above 90%, was 26.67 months under refrigerated conditions and 5.75 and 2.24 months at 25 and 30 °C, respectively. Currently, the Spanish National Formulary recommends a shelf life of no longer than 3 months at room temperature for DCHX solution. Based on the predicted APS and confirmed by experimental long-term studies, we have demonstrated that the shelf life of DCHX extemporaneously compounded formulations could be prolonged by up to 6 months.

Co-Delivery of a High Dose of Amphotericin B and Itraconazole by Means of a Dry Powder Inhaler Formulation for the Treatment of Severe Fungal Pulmonary Infections.

Over the past few decades, there has been a considerable rise in the incidence and prevalence of pulmonary fungal infections, creating a global health problem due to a lack of antifungal therapies specifically designed for pulmonary administration. Amphotericin B (AmB) and itraconazole (ITR) are two antifungal drugs with different mechanisms of action that have been widely employed in antimycotic therapy. In this work, microparticles containing a high dose of AmB and ITR (20, 30, and 40% total antifungal drug loading) were engineered for use in dry powder inhalers (DPIs) with an aim to improve the pharmacological effect, thereby enhancing the existing off-label choices for pulmonary administration. A Design of Experiment (DoE) approach was employed to prepare DPI formulations consisting of AmB-ITR encapsulated within γ-cyclodextrin (γ-CD) alongside functional excipients, such as mannitol and leucine. In vitro deposition indicated a favourable lung deposition pattern characterised by an upper ITR distribution (mass median aerodynamic diameter (MMAD) ~ 6 µm) along with a lower AmB deposition (MMAD ~ 3 µm). This offers significant advantages for treating fungal infections, not only in the lung parenchyma but also in the upper respiratory tract, considering that Aspergillus spp. can cause upper and lower airway disorders. The in vitro deposition profile of ITR and larger MMAD was related to the higher unencapsulated crystalline fraction of the drug, which may be altered using a higher concentration of γ-CD.

Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition.

In inflammatory bowel disease (IBD), chronic inflammation in the gastrointestinal tract can lead to tissue damage and remodelling, which can ultimately result in fibrosis. Prolonged injury and inflammation can trigger the activation of fibroblasts and extracellular matrix (ECM) components. As fibrosis progresses, the tissue becomes increasingly stiff and less functional, which can lead to complications such as intestinal strictures, obstructive symptoms, and eventually, organ dysfunction. Epithelial cells play a key role in fibrosis, as they secrete cytokines and growth factors that promote fibroblast activation and ECM deposition. Additionally, epithelial cells can undergo a process called epithelial-mesenchymal transition, in which they acquire a more mesenchymal-like phenotype and contribute directly to fibroblast activation and ECM deposition. Overall, the interactions between epithelial cells, immune cells, and fibroblasts play a critical role in the development and progression of fibrosis in IBD. Understanding these complex interactions may provide new targets for therapeutic interventions to prevent or treat fibrosis in IBD. In this review, we have collected and discussed the recent literature highlighting the contribution of epithelial cells to the pathogenesis of the fibrotic complications of IBD, including evidence of EMT, the epigenetic control of the EMT, the potential influence of the intestinal microbiome in EMT, and the possible therapeutic strategies to target EMT. Finally we discuss the pro-fibrotic interactions epithelial-immune cells and epithelial-fibroblasts cells.

Mapping of Dietary Interventions Beneficial in the Prevention of Secondary Health Conditions in Spinal Cord Injured Population: A Systematic Review.

OBJECTIVES: Individuals with spinal cord injury are at risk of secondary health conditions (SHC) that develop as a consequence of autonomic dysfunction, prolonged oxidative stress and inflammation, and physical inactivity coupled with inadequate energy and nutritional intake. SHC can be debilitating and even life-threatening, and its prevention remains one of the major challenges in the continuum of medical care of aging SCI population. An unhealthy diet is a major driver of inflammation, oxidative stress, and unfavourable metabolic status and may be a practical preventive target to tackle increased SHC risk post-injury. AIMS: To provide a catalogue of dietary interventions beneficial in prevention of SHC among individuals with SCI by conducting a systematic review of the literature on dietary interventions and dietary supplementation in promoting health and well-being after the injury. In addition, we aimed to provide a summary of observational studies exploring the association between habitual diet (macro- and micronutrients intake and dietary patterns) and health patterns following the injury. METHOD: This review was registered at PROSPERO (University of York) with registration number CRD42022373773. Four medical databases (EMBASE.com, MEDLINE [Ovid], Cochrane CENTRAL, and Web of Science Core Collection) and Google Scholar were searched from inception until 11th July 2022. Studies were included if they were clinical trials or observational studies conducted in adult individuals with SCI and provided information of interest. Based on strength of the study design and risk of bias assessment (using the NIH tool), we classified studies from Level 1 (most reliable studies) to Level 4 (least reliable studies). RESULTS: Of 12,313 unique citations, 47 articles (based on 43 original studies) comprising 32 interventional (22 RCTs, 3 NRCT, and 7 pre-post studies) and 11 observational studies (2 cohort studies, 2 case-control, 1 post-intervention follow-up study, and 6 cross-sectional studies) were included in the present systematic review. Twenty studies (46.5%) were classified as Level 1 or 2, indicating high/moderate methodological quality. Based on those studies, dietary strategies including high protein diet, intermittent fasting, balanced diet in combination with physical conditioning and electrical stimulation, and dietary supplementation including alpha-lipoic acid, creatine, vitamin D, and cranberry-derived supplements and probiotics were mapped as the most promising in prevention of SHC among individuals with SCI. CONCLUSIONS: To develop timely and effective preventive strategies targeting major SHC (e.g., cardiometabolic diseases, urinary tract infections) in SCI, further research is warranted to confirm the effectiveness of dietary strategies/interventions identified through the current systematic review of the literature.

Brote de dermatofitosis en región de cabeza y cuello asociadas al rasurado en peluquerías: estudio descriptivo multicéntrico de una serie de casos / Outbreak of Dermatophyte Infections on the Head and Neck Related to Shave Haircuts: Description of a Multicenter Case Series

Introducción Desde 2021 se ha detectado un aumento de casos de tiñas del cuero cabelludo en adolescentes que se cortan el pelo mediante rasurado o degradado. Pacientes y métodos Estudio observacional retrospectivo multicéntrico de casos de dermatofitosis del polo cefálico con el antecedente de haber sido contraídas tras el rasurado frecuente en peluquería. Se realizó una llamada a dermatólogos de la Academia Española de Dermatología y Venereología (AEDV) para que aportaran casos observados entre enero de 2021 y diciembre de 2022. Se incluyeron pacientes con confirmación microbiológica mediante cultivo o examen directo con KOH. Resultados Se recogieron 107 casos, siendo 106 pacientes varones. Se observaron 78 formas no inflamatorias frente a 29 inflamatorias. El hongo aislado con mayor frecuencia fue Trichophyton tonsurans (75,7% de los casos). Las lesiones aparecieron predominantemente en la nuca y en el área temporal. Conclusiones La distribución por sexo, edad y localización lesional parece apuntar a que una nueva tendencia social, en la que adolescentes varones acuden asiduamente a peluquerías para el afeitado de las zonas occipital y temporal, sería la causante de esta agrupación de casos de tiña del cuero cabelludo. El microorganismo más frecuente en nuestro estudio (T.tonsurans) coincide con el más prevalente en nuestro medio. Con el presente estudio se evidencia un acúmulo de casos susceptible de ser tenido en cuenta por organismos competentes de salud pública, a los cuales corresponde velar por el cumplimiento de las normas de desinfección del material empleado para el rasurado (AU)

Introduction Since 2021, an increase in cases of tinea capitis has been detected in adolescents who shave their hair with fade haircut. Patients and methods Multicenter retrospective observational study of cases of cephalic pole dermatophytosis with a history of having been acquired after frequent shaving in hairdressing. A call was made to dermatologists from the Spanish Academy of Dermatology and Venereology (AEDV) to provide cases observed between January 2021 and December 2022. Patients with microbiological confirmation by culture or direct examination with KOH were included. Results 107 cases were collected, 106 of which were male. 78 non-inflammatory forms were observed, compared to 29 inflammatory. The most frequently isolated fungus was Trichophyton tonsurans (75.7% of cases). The lesions appeared predominantly on the nape of the neck and temporal area. Conclusions The distribution by sex, age and lesional location seems to indicate that a new social trend, in which male adolescents regularly go to hairdressers to shave the occipital and temporal areas, would be the cause of this grouping of cases of ringworm of the scalp. The most frequent microorganism in our study (T.tonsurans) coincides with the most prevalent in our environment. This study shows an accumulation of cases that can be taken into account by competent Public Health agencies, which are responsible for ensuring compliance with the rules of disinfection of the material used for shaving (AU)

[Translated article] Outbreak of Dermatophyte Infections on the Head and Neck Related to Shave Haircuts: Description of a Multicenter Case Series / Brote de dermatofitosis en región de cabeza y cuello asociadas al rasurado en peluquerías: estudio descriptivo multicéntrico de una serie de casos

Introduction Since 2021, an increase in cases of tinea capitis has been detected in adolescents who shave their hair with fade haircut. Patients and methods Multicenter retrospective observational study of cases of cephalic pole dermatophytosis with a history of having been acquired after frequent shaving in hairdressing. A call was made to dermatologists from the Spanish Academy of Dermatology and Venereology (AEDV) to provide cases observed between January 2021 and December 2022. Patients with microbiological confirmation by culture or direct examination with KOH were included. Results 107 cases were collected, 106 of which were male. 78 non-inflammatory forms were observed, compared to 29 inflammatory. The most frequently isolated fungus was Trichophyton tonsurans (75.7% of cases). The lesions appeared predominantly on the nape of the neck and temporal area. Conclusions The distribution by sex, age and lesional location seems to indicate that a new social trend, in which male adolescents regularly go to hairdressers to shave the occipital and temporal areas, would be the cause of this grouping of cases of ringworm of the scalp. The most frequent microorganism in our study (T.tonsurans) coincides with the most prevalent in our environment. This study shows an accumulation of cases that can be taken into account by competent Public Health agencies, which are responsible for ensuring compliance with the rules of disinfection of the material used for shaving (AU)

Introducción Desde 2021 se ha detectado un aumento de casos de tiñas del cuero cabelludo en adolescentes que se cortan el pelo mediante rasurado o degradado. Pacientes y métodos Estudio observacional retrospectivo multicéntrico de casos de dermatofitosis del polo cefálico con el antecedente de haber sido contraídas tras el rasurado frecuente en peluquería. Se realizó una llamada a dermatólogos de la Academia Española de Dermatología y Venereología (AEDV) para que aportaran casos observados entre enero de 2021 y diciembre de 2022. Se incluyeron pacientes con confirmación microbiológica mediante cultivo o examen directo con KOH. Resultados Se recogieron 107 casos, siendo 106 pacientes varones. Se observaron 78 formas no inflamatorias frente a 29 inflamatorias. El hongo aislado con mayor frecuencia fue Trichophyton tonsurans (75,7% de los casos). Las lesiones aparecieron predominantemente en la nuca y en el área temporal. Conclusiones La distribución por sexo, edad y localización lesional parece apuntar a que una nueva tendencia social, en la que adolescentes varones acuden asiduamente a peluquerías para el afeitado de las zonas occipital y temporal, sería la causante de esta agrupación de casos de tiña del cuero cabelludo. El microorganismo más frecuente en nuestro estudio (T.tonsurans) coincide con el más prevalente en nuestro medio. Con el presente estudio se evidencia un acúmulo de casos susceptible de ser tenido en cuenta por organismos competentes de salud pública, a los cuales corresponde velar por el cumplimiento de las normas de desinfección del material empleado para el rasurado (AU)

Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers.

The incidence of fungal pulmonary infections is known to be on the increase, and yet there is an alarming gap in terms of marketed antifungal therapies that are available for pulmonary administration. Amphotericin B (AmB) is a highly efficient broad-spectrum antifungal only marketed as an intravenous formulation. Based on the lack of effective antifungal and antiparasitic pulmonary treatments, the aim of this study was to develop a carbohydrate-based AmB dry powder inhaler (DPI) formulation, prepared by spray drying. Amorphous AmB microparticles were developed by combining 39.7 % AmB with 39.7 % γ-cyclodextrin, 8.1 % mannose and 12.5 % leucine. An increase in the mannose concentration from 8.1 to 29.8 %, led to partial drug crystallisation. Both formulations showed good in vitro lung deposition characteristics (80 % FPF < 5 µm and MMAD < 3 µm) at different air flow rates (60 and 30 L/min) when used with a DPI, but also during nebulisation upon reconstitution in water.

Outbreak of Dermatophyte Infections on the Head and Neck Related to Shave Haircuts: Description of a Multicenter Case Series. / Brote de dermatofitosis en región de cabeza y cuello asociadas al rasurado en peluquerías: estudio descriptivo multicéntrico de una serie de casos.

INTRODUCTION: Since 2021, an increase in cases of tinea capitis has been detected in adolescents who shave their hair with fade haircut. PATIENTS AND METHODS: Multicenter retrospective observational study of cases of cephalic pole dermatophytosis with a history of having been acquired after frequent shaving in hairdressing. A call was made to dermatologists from the Spanish Academy of Dermatology and Venereology (AEDV) to provide cases observed between January 2021 and December 2022. Patients with microbiological confirmation by culture or direct examination with KOH were included. RESULTS: 107 cases were collected, 106 of which were male. 78 non-inflammatory forms were observed, compared to 29 inflammatory. The most frequently isolated fungus was Trichophyton tonsurans (75.7% of cases). The lesions appeared predominantly on the nape of the neck and temporal area. CONCLUSIONS: The distribution by sex, age and lesional location seems to indicate that a new social trend, in which male adolescents regularly go to hairdressers to shave the occipital and temporal areas, would be the cause of this grouping of cases of ringworm of the scalp. The most frequent microorganism in our study (T.tonsurans) coincides with the most prevalent in our environment. This study shows an accumulation of cases that can be taken into account by competent Public Health agencies, which are responsible for ensuring compliance with the rules of disinfection of the material used for shaving.

Can amphotericin B and itraconazole be co-delivered orally? Tailoring oral fixed-dose combination coated granules for systemic mycoses.

The incidence and prevalence of invasive fungal infections have increased significantly over the last few years, leading to a global health problem due to the lack of effective treatments. Amphotericin B (AmB) and itraconazole (ITR) are two antifungal drugs with different mechanisms of action. In this work, AmB and ITR have been formulated within granules to elicit an enhanced pharmacological effect, while enhancing the oral bioavailability of AmB. A Quality by Design (QbD) approach was utilised to prepare fixed-dose combination (FDC) granules consisting of a core containing AmB with functional excipients, such as inulin, microcrystalline cellulose (MCC), chitosan, sodium deoxycholate (NaDC) and Soluplus® and polyvinyl pyrrolidone (PVP), coated with a polymeric layer containing ITR with Soluplus® or a combination of Poloxamer 188 and hydroxypropyl methyl cellulose-acetyl succinate (HPMCAS). A Taguchi design of experiments (DoE) with 7 factors and 2 levels was carried out to understand the key factors impacting on the physicochemical properties of the formulation followed by a Box-Behnken design with 3 factors in 3 levels chosen to optimise the formulation parameters. The core of the FDC granules was obtained by wet granulation and later coated using a fluidized bed. In vitro antifungal efficacy was demonstrated by measuring the inhibition halo against different species of Candida spp., including C. albicans (24.19-30.48 mm), C. parapsilosis (26.38-27.84 mm) and C. krusei (11.48-17.92 mm). AmB release was prolonged from 3 to 24 h when the AmB granules were coated. In vivo in CD-1 male mice studies showed that these granules were more selective towards liver, spleen and lung compared to kidney (up to 5-fold more selective in liver, with an accumulation of 8.07 µg AmB/g liver after twice-daily 5 days administration of granules coated with soluplus-ITR), resulting in an excellent oral administration option in the treatment of invasive mycosis. Nevertheless, some biochemical alterations were found, including a decrease in blood urea nitrogen (∼17 g/dl) and alanine aminotransferase (<30 U/l) and an increase in the levels of bilirubin (∼0.2 mg/dl) and alkaline phosphatase (<80 U/l), which could be indicative of a liver failure. Once-daily regimen for 10 days can be a promising therapy.

Plan de Intervención Comunitaria para el manejo de la EPOC estable: protocolo de coordinación asistencial y derivación entre farmacias comunitarias y centros de salud / Community Intervention Plan for the management of stable COPD: protocol for care coordination and referral between community pharmacies and health centres

La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad frecuente y progresiva, pero prevenible y tratable. Sin embargo, se han detectado importantes áreas de mejora en su diagnóstico, tratamiento y seguimiento, así como en la adherencia terapéutica. Con el propósito de aumentar la detección precoz de la EPOC y su manejo adecuado en España, se ha diseñado un Plan de intervención comunitaria (PIC) para la colaboración entre farmacias comunitarias y centros de salud de atención primaria. El PIC incluye un procedimiento normalizado de trabajo (PNT), desarrollado por un grupo de profesionales de farmacia comunitaria, medicina de familia, neumología y enfermería de atención primaria. En él se describe el algoritmo que guiará la actuación de los farmacéuticos comunitarios, incluyendo las pruebas y dispositivos para el cribado poblacional de la EPOC, la evaluación de la enfermedad, la adhesión a inhaladores y la detección de errores críticos en el uso de inhaladores entre otros aspectos. El PNT incluye también un formulario para la derivación del paciente al centro de salud correspondiente, donde se llevarán a cabo una serie de acciones preestablecidas en el plan de actuación según el escenario clínico. Además, se propone evaluar la efectividad de la intervención con unos indicadores recogidos en el centro de salud y en farmacia comunitaria. Por último, se recomienda establecer un plan formativo en EPOC para la óptima implementación del plan y una encuesta a pacientes sobre su grado de satisfacción con la intervención. En conclusión, la implantación del PIC podría reducir el infradiagnóstico en EPOC y optimizar el manejo de los pacientes diagnosticados en España, donde los farmacéuticos comunitarios tendrían una función esencial en el abordaje de estos pacientes. (AU)

Diagnostic study of pertussis using PCR in primary care clinics.

INTRODUCTION: Pertussis is a respiratory infection caused by bacteria of the genus Bordetella, mainly pertussis and parapertussis species. Despite the high vaccination coverage in developed countries, it is considered a re-emerging disease that is also underreported and underdiagnosed, especially in patients who do not require hospital referral. MATERIAL AND METHODS: Descriptive, prospective and multicentre study of pertussis diagnosis and contact investigation in 17 primary care paediatric clinics through collection of samples for polymerase chain reaction (PCR) testing over a period of 4 years and after the implementation of routine vaccination against pertussis during pregnancy. RESULTS: Pertussis was diagnosed in a total of 50 patients; the estimated incidence in these years was higher compared to previous rates in the paediatric age group. Fourteen percent of the cases occurred in children aged less than 1 year. The mean age was 6.7 years. Cough was present in 100% of cases, followed in frequency by vomiting and rhinorrhoea. Only 1 patient required hospital admission, and none died or developed complications. B. pertussis was the predominant causative agent. Only 40% knew the source of infection. In 26% of the cases, pertussis was confirmed in contacts of the patient by PCR, and in 46% it was suspected based on the clinical presentation but without microbiological confirmation. CONCLUSIONS: Access to diagnostic tests (PCR) for pertussis in primary care allows us to optimise its diagnosis and treatment, to break the chain of transmission, to know the real incidence rates and to assess the impact of routine vaccination of pregnant women on this disease.

Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos / Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients (AU)

La pandemia por COVID-19 ha provocado el ingreso de un elevado número de pacientes en UCI, generalmente por insuficiencia respiratoria severa. Desde la aparición de los primeros casos de infección por SARS-CoV-2, a finales de 2019, en China, se ha publicado una cantidad ingente de recomendaciones de tratamiento de esta entidad, no siempre respaldadas por evidencia científica suficiente ni con el rigor metodológico necesario. Gracias al esfuerzo de distintos grupos de investigadores, actualmente disponemos de resultados de ensayos clínicos, y otro tipo de estudios, de mayor calidad. Consideramos necesario realizar un documento que incluya recomendaciones que recojan estas evidencias en cuanto al diagnóstico y el tratamiento de COVID-19, pero también aspectos que otras guías no han contemplado y que consideramos fundamentales en el manejo del paciente crítico con COVID-19. Para ello se ha creado un comité redactor, conformado por miembros de los Grupos de Trabajo de SEMICYUC más directamente relacionados con diferentes aspectos específicos del manejo de estos pacientes (AU)

Deep Learning Adapted to Differential Neural Networks Used as Pattern Classification of Electrophysiological Signals.

This manuscript presents the design of a deep differential neural network (DDNN) for pattern classification. First, we proposed a DDNN topology with three layers, whose learning laws are derived from a Lyapunov analysis, justifying local asymptotic convergence of the classification error and the weights of the DDNN. Then, an extension to include an arbitrary number of hidden layers in the DDNN is analyzed. The learning laws for this general form of the DDNN offer a contribution to the deep learning framework for signal classification with biological nature and dynamic structures. The DDNN is used to classify electroencephalographic signals from volunteers that perform an identification graphical test. The classification results show exponential growth in the signal classification accuracy from 82 percent with one layer to 100 percent with three hidden layers. Working with DDNN instead of static deep neural networks (SDNN) represents a set of advantages, such as processing time and training period reduction up to almost 100 times, and the increment of the classification accuracy while working with less hidden layers than working with SDNN, which are highly dependent on their topology and the number of neurons in each layer. The DDNN employed fewer neurons due to the induced feedback characteristic.

[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Self-assembling, supramolecular chemistry and pharmacology of amphotericin B: Poly-aggregates, oligomers and monomers.

Antifungal drugs such as amphotericin B (AmB) interact with lipids and phospholipids located on fungal cell membranes to disrupt them and create pores, leading to cell apoptosis and therefore efficacy. At the same time, the interaction can also take place with cell components from mammalian cells, leading to toxicity. AmB was selected as a model antifungal drug due to the complexity of its supramolecular chemical structure which can self-assemble in three different aggregation states in aqueous media: monomer, oligomer (also known as dimer) and poly-aggregate. The interplay between AmB self-assembly and its efficacy or toxicity against fungal or mammalian cells is not yet fully understood. To the best of our knowledge, this is the first report that investigates the role of excipients in the supramolecular chemistry of AmB and the impact on its biological activity and toxicity. The monomeric state was obtained by complexation with cyclodextrins resulting in the most toxic state, which was attributed to the greater production of highly reactive oxygen species upon disruption of mammalian cell membranes, a less specific mechanism of action compared to the binding to the ergosterol located in fungal cell membranes. The interaction between AmB and sodium deoxycholate resulted in the oligomeric and poly-aggregated forms which bound more selectively to the ergosterol of fungal cell membranes. NMR combined with XRD studies elucidated the interaction between drug and excipient to achieve the AmB aggregation states, and ultimately, their diffusivity across membranes. A linear correlation between particle size and the efficacy/toxicity ratio was established allowing to modulate the biological effect of the drug and hence, to improve pharmacological regimens. However, particle size is not the only factor modulating the biological response but also the equilibrium of each state which dictates the fraction of free monomeric form available. Tuning the aggregation state of AmB formulations is a promising strategy to trigger a more selective response against fungal cells and to reduce the toxicity in mammalian cells.

COVID-19 pandemic. What have we learned?

Since the COVID-19 pandemic was declared in March 2020, we have learned a lot about the SARS-CoV-2 coronavirus, and its role in pediatric pathology. Children are infected in a rate quite similar to adults, although in most cases they suffer mild or asymptomatic symptoms. Around 1% of those infected require hospitalization, less than 0.02% require intensive care, and mortality is very low and generally in children with comorbidities. The most common clinical diagnoses are upper or lower respiratory infections, gastrointestinal infection and, more seriously, multisystemic inflammatory syndrome (MIS-C). Most episodes do not require treatment, except for MIS-C. Remdesivir has been widely used as a compassionate treatment and its role has yet to be defined. The newborn can become infected, although vertical transmission is very low (<1%) and it has been shown that the baby can safely cohabit with its mother and be breastfed. In general, neonatal infections have been mild. Primary care has supported a very important part of the management of the pandemic in pediatrics. There has been numerous collateral damage derived from the difficulty of access to care and the isolation suffered by children. The mental health of the pediatric population has been seriously affected. Although it has been shown that schooling has not led to an increase in infections, but rather the opposite. It is essential to continue maintaining the security measures that make schools a safe place, so necessary not only for children's education, but for their health in general.