Tromboprofilaxis en COVID-19. Nuevas evidencias / COVID-19 thromboprophylaxis: New evidences

Recientes publicaciones han puesto en duda la eficacia de la utilización de dosis terapéuticas o intermedias de heparina de bajo peso molecular (HBPM) en pacientes COVID-19, especialmente en los pacientes más graves. Con el objetivo de actualizar estas recomendaciones se ha realizado una revisión no sistemática en las principales bases de datos médicas. Se seleccionaron un total de 14 ensayos clínicos aleatorizados, 14 metaanálisis y las recomendaciones de 12 sociedades científicas, estratificadas según el tipo de paciente (ambulatorio, hospitalizado, ingresado en cuidados críticos o post-alta). Se ha analizado la eficacia de HBPM y también de otras aproximaciones terapéuticas (rivaroxabán, apixabán, sulodexida, ácido acetilsalicílico e inhibidores P2Y12). Los hallazgos recomiendan utilizar dosis estándar de HBPM como tromboprofilaxis en los pacientes COVID-19 hospitalizados críticos y dosis terapéutica en hospitalizados no críticos si el riesgo de sangrado es bajo. En los pacientes ambulatorios y dados de alta del hospital podría utilizarse HBPM a dosis profiláctica si existen factores de riesgo trombótico y el riesgo hemorrágico es bajo. No se recomienda asociar antiagregantes plaquetarios a la HBPM salvo indicación previa.(AU)

Recent publications have questioned the efficacy of using therapeutic or intermediate doses of low molecular weight heparin (LMWH) in COVID-19 patients, especially in the most severe patients. In order to update these recommendations, a non-systematic review has been carried out in the main medical databases. A total of 14 randomized clinical trials, 14 meta-analyses and the recommendations of 12 scientific societies were selected, stratified according to the type of patient (outpatient, hospitalized, admitted to critical care or post-discharge). The efficacy of LMWH and other therapeutic approaches (rivaroxaban, apixaban, sulodexide, acetylsalicylic acid and P2Y12 inhibitors) has been analyzed. The findings recommend using standard doses of LMWH as thromboprophylaxis in critically hospitalized COVID-19 patients and therapeutic doses in non-critically hospitalized patients with low bleeding risk. In outpatients and those discharged from the hospital, LMWH could be used at a prophylactic dose if there are thrombotic risk factors, and the bleeding risk is low. It is not recommended to associate antiplatelet agents with LMWH unless previously indicated.(AU)

COVID-19 thromboprophylaxis. New evidence.

Recent publications have questioned the efficacy of using therapeutic or intermediate doses of low molecular weight heparin (LMWH) in COVID-19 patients, especially in the most severe patients. In order to update these recommendations, a non-systematic review has been carried out in the main medical databases. A total of 14 randomized clinical trials, 14 meta-analyses and the recommendations of 12 scientific societies were selected, stratified according to the type of patient (outpatient, hospitalized, admitted to critical care or post-discharge). The efficacy of LMWH and other therapeutic approaches (rivaroxaban, apixaban, sulodexide, acetylsalicylic acid and P2Y12 inhibitors) has been analyzed. The findings recommend using standard doses of LMWH as thromboprophylaxis in critically hospitalized COVID-19 patients and therapeutic doses in non-critically hospitalized patients if the risk of bleeding is low. In outpatients and those discharged from the hospital, LMWH could be used at a prophylactic dose if there are thrombotic risk factors, and the bleeding risk is low. It is not recommended to associate antiplatelet agents with LMWH unless previously indicated.

Impacto clínico de no aplicar el protocolo ERAS en los pacientes sometidos a cistectomía durante la pandemia COVID-19 / Clinical impact of the suspension of the ERAS protocol on patients undergoing radical cystectomy during the COVID-19 pandemic

Introducción Al inicio de la pandemia por COVID-19 no se pudo implementar ni prehabilitación ni rehabilitación multimodal por sobrecarga del sistema sanitario. Nuestro objetivo fue analizar evolución, complicaciones y supervivencia hasta el año de pacientes sometidos a cistectomía radical en nuestro centro desde el 1 de marzo hasta el 31 de mayo de 2020 (primera ola). Comparamos resultados con pacientes también cistectomizados fuera de pandemia donde sí estaba instaurado el protocolo ERAS. Material y métodos Estudio de cohortes retrospectivo, unicéntrico, de pacientes programados para cistectomía radical desde el 1 de marzo de 2020 hasta el 31 de mayo de 2020; se emparejaron con pacientes intervenidos anteriormente a través de score de emparejamiento por propensión 1:2. Las variables de emparejamiento fueron datos demográficos, condiciones clínicas preoperatorias e intraoperatorias. Resultados Se realizaron 23 cistectomía en este periodo; en ningún caso se aplicó ni prehabilitación ni seguimiento del protocolo ERAS, y esta fue la única diferencia en el tratamiento entre grupos. Tres pacientes se diagnosticaron de COVID-19 durante su ingreso presentando complicaciones respiratorias graves y alta mortalidad intrahospitalaria. La tasa de transfusión sanguínea fue mayor en el grupo pandemia. La estancia hospitalaria aumentó en tres días en grupo pandemia. Conclusiones Los pacientes sometidos a cistectomía en nuestro centro durante la primera ola de pandemia por COVID-19 presentaron complicaciones respiratorias y no respiratorias en mayor número y más graves que los cistectomizados fuera de este periodo. La no aplicación del protocolo ERAS fue la principal diferencia en el tratamiento entre grupos (AU)

Introduction During the beginning of the COVID-19 pandemic in our center, neither prehabilitation nor multimodal rehabilitation could be applied due to the excessive patient load on the health system and to reduce SARS-CoV-2 transmission. The objective of our study was to analyze the evolution, complications, and survival up to one year of patients who underwent radical cystectomy in our hospital from March 1st to May 31st, 2020 (period of the first wave COVID-19 pandemic in Spain). We also compared the results with cystectomized patients outside the pandemic period and with application of the ERAS (Enhanced Recovery After Surgery) protocol. Material and methods Single-center, retrospective cohort study of patients scheduled for radical cystectomy from March 1st,2020 to May 31st, 2020. They were matched with previously operated patients using a 1:2 propensity matching score. The matching variables were demographic data, preoperative and intraoperative clinical conditions. Results A total of 23 radical cystectomies with urinary diversion were performed in the period described. In none of the cases the prehabilitation or the follow-up of our ERAS protocol could be applied, and this was the only difference we found between the 2 groups. Although the minimally invasive approach was more frequent in the pandemic group, the difference was not statistically significant. Three patients were diagnosed with COVID-19 during their admission, presenting severe respiratory complications and high in-hospital mortality. Apart from respiratory complications secondary to SARS-CoV-2, we also found statistically significant differences in other postoperative complications. The hospital stay increased by 3 days in the pandemic group (AU)

Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

[CLINICAL IMPACT OF THE SUSPENSION OF THE ERAS PROTOCOL ON PATIENTS UNDERGOING RADICAL CYSTECTOMY DURING THE COVID-19 PANDEMIC.] / IMPACTO CLÍNICO DE NO APLICAR EL PROTOCOLO ERAS EN LOS PACIENTES SOMETIDOS A CISTECTOMÍA DURANTE LA PANDEMIA COVID-19.

INTRODUCTION: During the beginning of the COVID-19 pandemic in our center, neither prehabilitation nor multimodal rehabilitation could be applied due to the excessive patient load on the health system and to reduce SARS-CoV-2 transmission. The objective of our study was to analyze the evolution, complications, and survival up to one year of patients who underwent radical cystectomy in our hospital from March 1st to May 31st, 2020 (period of the first wave COVID-19 pandemic in Spain). We also compared the results with cystectomized patients outside the pandemic period and with application of the ERAS (Enhanced Recovery After Surgery) protocol. MATERIAL AND METHODS: Single-center, retrospective cohort study of patients scheduled for radical cystectomy from March 1st,2020 to May 31st, 2020. They were matched with previously operated patients using a 1:2 propensity matching score. The matching variables were demographic data, preoperative and intraoperative clinical conditions. RESULTS: A total of 23 radical cystectomies with urinary diversion were performed in the period described. In none of the cases the prehabilitation or the follow-up of our ERAS protocol could be applied, and this was the only difference we found between the 2 groups. Although the minimally invasive approach was more frequent in the pandemic group, the difference was not statistically significant. Three patients were diagnosed with COVID-19 during their admission, presenting severe respiratory complications and high in-hospital mortality. Apart from respiratory complications secondary to SARS-CoV-2, we also found statistically significant differences in other postoperative complications. The hospital stay increased by 3 days in the pandemic group. CONCLUSIONS: Patients who underwent radical cystectomy at our center during the first wave of the COVID-19 pandemic had a higher number and severity of respiratory and non-respiratory complications. Discontinuation of the ERAS protocol was the main difference in treatment between groups.

Clinical impact of the suspension of the ERAS protocol on patients undergoing radical cystectomy during the COVID-19 pandemic.

INTRODUCTION: During the beginning of the COVID-19 pandemic in our center, neither prehabilitation nor multimodal rehabilitation could be applied due to the excessive patient load on the health system and to reduce SARS-CoV-2 transmission. The objective of our study was to analyze the evolution, complications, and survival up to one year of patients who underwent radical cystectomy in our hospital from March 1st to May 31st, 2020 (period of the first wave COVID-19 pandemic in Spain). We also compared the results with cystectomized patients outside the pandemic period and with application of the ERAS (Enhanced Recovery After Surgery) protocol. MATERIAL AND METHODS: Single-center, retrospective cohort study of patients scheduled for radical cystectomy from March 1st, 2020 to May 31st, 2020. They were matched with previously operated patients using a 1:2 propensity matching score. The matching variables were demographic data, preoperative and intraoperative clinical conditions. RESULTS: A total of 23 radical cystectomies with urinary diversion were performed in the period described. In none of the cases the prehabilitation or the follow-up of our ERAS protocol could be applied, and this was the only difference we found between the 2 groups. Although the minimally invasive approach was more frequent in the pandemic group, the difference was not statistically significant. Three patients were diagnosed with COVID-19 during their admission, presenting severe respiratory complications and high in-hospital mortality. Apart from respiratory complications secondary to SARS-CoV-2, we also found statistically significant differences in other postoperative complications. The hospital stay increased by 3 days in the pandemic group. CONCLUSIONS: Patients who underwent radical cystectomy at our center during the first wave of the COVID-19 pandemic had a higher number and severity of respiratory and non-respiratory complications. Discontinuation of the ERAS protocol was the main difference in treatment between groups.

Evolución del hábito tabáquico en embarazadas del Área de Gestión Sanitaria de Jerez / Evolution of smoking habit in pregnant women of the Health Management Area of Jerez

Objetivo.Existe poca información actualizada sobre el consumo de tabaco durante el embarazo. El objetivo de este trabajo fue determinar la prevalencia de tabaquismo durante el embarazo en mujeres que se atienden en los distintos centros de salud dentro del Área de Gestión Sanitaria Jerez, costa noreste y sierra de Cádiz. Material y método.Estudio transversal mediante entrevistas de gestantes captadas en la visita realizada durante el primer trimestre del embarazo. El cuestionario incluía preguntas sobre características sociode mográficas, edad, antecedentes obstétricos, consumo de tabaco anterior al embarazo y abandono durante la gestación, así como hábito tabáquico en la pareja. Resultados. Se obtuvieron respuestas de 1.173 pacientes con edad media de 31 años. Se confesaron fumadoras activas el 31,2% de ellas, siendo exfumadoras el 9,5% y nunca fumadoras el 59,3%. El consumo medio de cigarrillos fue de 11 ± 7 diarios. Al conocer su estado de gestación dejaron su hábito el 50,8% (abandono espontáneo, n = 186). El porcentaje de fumadora durante la gestación asciende a un 15,5% del global,con un consumo medio de cigarrillos de 5 ± 4/día. En cuanto a las parejas el porcentaje de fumadores activos fue del 41,4%. Aunque solo un 12,4% de estas parejas refirieron seguir fumando en el domicilio conyugal,únicamente el 2,07 % consiguió cesar el consumo por completo. La prevalencia de tabaquismo respecto a un estudio previo en 2009 se redujo significativamente (18,9vs. 15,5 %, p < 0,009).Conclusión.Fumar durante el embarazo sigue siendoun comportamiento frecuente en nuestra área sanitaria. A pesar de que las gestantes reducen su consumo, solo la mitad abandona por completo su hábito. Este comportamiento es muy inferior si consideramos a sus parejas, donde el porcentaje de cesación es ínfimo. (AU)

Objetive. There is little up-to-date information on tobacco 11 use during pregnancy. The objective of this work was to determine the prevalence of smoking during pregnancy in women who are cared for in the different Health Centers within the Jerez Health Management Area, northeast coast and sierra of Cadiz. Material and method. Cross-sectional study through interviews of pregnant women enrolled duringthe visit during the first trimester of pregnancy. The questionnaire included questions about sociodemo-graphic characteristics, age, obstetric history, tobacco consumption prior to pregnancy and cessation during pregnancy, as well as smoking habits in the couple. Results. Responses were obtained from 1,173 patients,with a mean age of 31 years. 31.2% of them confessed to being active smokers, 9.5% being ex-smokers and 59.3% never smokers. The average consumption ofcigarettes was 11 ± 7 per day. When knowing theirstate of pregnancy, 50.8% of them quit their habit(spontaneous quitters, n = 186). The percentage ofsmokers during pregnancy amounts to 15.5% of theglobal with an average cigarette consumption of 5 ±4/day. As for couples, the percentage of active smokerswas 41.4%. Although only 12.4% of these couples reported continuing to smoke at their marital home,only 2.07% managed to stop using them completely.The prevalence of smoking compared to a previousstudy in 2009 was significantly reduced (18.9 vs.15.5%, p < 0.009).Conclusion.Smoking during pregnancy continues tobe a frequent behavior in our healthcare area. Despitethe fact that pregnant women reduce their consump-tion, only half abandon their habit completely. Thisbehavior is much lower if we consider their partnerswhere the percentage of cessation is negligible. (AU)

Real-world evidence from a European cohort study of patients with treatment resistant depression: Healthcare resource utilization.

BACKGROUND: Treatment resistant depression (TRD) is diagnosed when patients experiencing a major depressive episode fail to respond to ≥2 treatments. Along with substantial indirect costs, patients with TRD have higher healthcare resource utilization (HCRU) than other patients with depression. However, research on the economic impact of this HCRU, and differences according to response to treatment, is lacking. METHODS: This multicenter, observational study documented HCRU among patients with TRD in European clinical practice initiating new antidepressant treatments. Data regarding access to outpatient consultations and other healthcare resources for the first 6 months, collected using a questionnaire, were analyzed qualitatively according to response and remission status. The economic impact of HCRU, estimated using European costing data, was analyzed quantitatively. RESULTS: Among 411 patients, average HCRU was higher in non-responders, attending five times more general practitioner (GP) consultations and spending longer in hospital (1.7 versus 1.1 days) than responders. Greater differences were observed according to remission status, with non-remitters attending seven times more GP consultations and spending approximately three times longer in hospital (1.7 versus 0.6 days) than remitters. Consequently, the estimated economic impacts of non-responders and non-remitters were significantly greater than those of responders and remitters, respectively. LIMITATIONS: Key limitations are small cohort size, absence of control groups and generalizability to different healthcare systems. CONCLUSION: Patients with TRD, particularly those not achieving remission, have considerable HCRU, with associated economic impact. The costs of unmet TRD treatment needs are thus substantial, and treatment success is fundamental to reduce individual needs and societal costs.

Effect of Two Unique Nanoparticle Formulations on the Efficacy of a Broadly Protective Vaccine Against Pseudomonas Aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of infections in humans. In addition to its innate antibiotic resistance, P. aeruginosa is very effective in acquiring resistance resulting in the emergence of multi-drug resistance strains and a licensed vaccine is not yet available. We have previously demonstrated the protective efficacy of a novel antigen PaF (Pa Fusion), a fusion of the type III secretion system (T3SS) needle tip protein, PcrV, and the first of two translocator proteins, PopB. PaF was modified to provide a self-adjuvanting activity by fusing the A1 subunit of the heat-labile enterotoxin from Enterotoxigenic E. coli to its N-terminus to give L-PaF. In addition to providing protection against 04 and 06 serotypes of P. aeruginosa, L-PaF elicited opsonophagocytic killing and stimulated IL-17A secretion, which have been predicted to be required for a successful vaccine. While monomeric recombinant subunit vaccines can be protective in mice, this protection often does not transfer to humans where multimeric formulations perform better. Here, we use two unique formulations, an oil-in-water (o/w) emulsion and a chitosan particle, as well as the addition of a unique TLR4 agonist, BECC438 (a detoxified lipid A analogue designated Bacterial Enzymatic Combinatorial Chemistry 438), as an initial step in optimizing L-PaF for use in humans. The o/w emulsion together with BECC438 provided the best protective efficacy, which correlated with high levels of opsonophagocytic killing and IL-17A secretion, thereby reducing the lung burden among all the vaccinated groups tested.

Real-world evidence from a European cohort study of patients with treatment resistant depression: Treatment patterns and clinical outcomes.

BACKGROUND: Treatment resistant depression (TRD) characterizes a subgroup of 10-30% of patients with major depressive disorder, and is associated with considerable morbidity and mortality. A consensus treatment for TRD does not exist, which often leads to wide variations in treatment strategies. Real-world studies on treatment patterns and outcomes in TRD patients in Europe are lacking and could help elucidate current treatment strategies and their efficacy. METHODS: This non-interventional cohort study of patients with TRD (defined as treatment failure on ≥2 oral antidepressants given at adequate dose and duration) with moderate to severe depression collected real-world data on treatment patterns and outcomes in several European countries. Patients were started on a new treatment for depression according to routine clinical practice. RESULTS: Among 411 patients enrolled, after 6 months, only 16.7% achieved remission and 73.5% showed no response. At Month 12, while 19.2% achieved remission and 69.2% showed no response, 33.3% of those in remission at Month 6 were no longer in remission. Pharmacological treatments employed were heterogenous; 54 different drugs were recorded at baseline, and the top 5 treatment types according to drug classes accounted for 40.0% of patients. Even though remission rates were very low, at Month 12, 60.0% of patients had not changed treatment since enrolment. CONCLUSIONS: The heterogeneity of treatments highlights a lack of consensus. Moreover, despite low response rates, patients often remained on treatments for substantial periods of time. These data further support existence of an unmet treatment need for TRD patients in Europe.

Real-world evidence from a European cohort study of patients with treatment resistant depression: Baseline patient characteristics.

BACKGROUND: Treatment resistant depression (TRD; failure to respond to ≥2 treatments) affects ~20% of patients with major depressive disorder (MDD). Real-world data could help describe patient characteristics and TRD disease burden, to assess the unmet needs of TRD patients in Europe. METHODS: This observational study collected data from adults with moderate to severe TRD initiating a new treatment for depression, according to local standards of care. At baseline, socio-demographic characteristics, medical history, prior and current treatments were recorded. Disease severity, health-related quality of life (HRQoL), functionality and productivity were assessed. RESULTS: Overall, 411 eligible patients were enrolled across seven European countries. Mean (standard deviation [SD]) patient age was 51.0 (10.8) years; 62.3% were female. Long-term sick leave was reported by 19.0% of patients; 30.2% were unemployed. The mean (SD) duration of the current episode was 2.6 (3.9) years. At baseline, mean (SD) HRQoL scores for EuroQoL 5-dimension 5-level (UK tariff) and EQ-Visual Analog Scale were 0.41 (0.25) and 41.1 (18.7), respectively. The Work Productivity and Activity Impairment questionnaire demonstrated mean (SD) absenteeism of 57.0% (44.9%) and presenteeism of 54.7% (29.5%); mean (SD) overall work impairment was 60.5% (29.9%). LIMITATIONS: Key limitations are small cohort size, absence of a control group and generalizability to countries with different healthcare models. CONCLUSIONS: TRD patients had a high disease burden, low HRQoL and reduced function and productivity, with a substantial proportion unable to work. This demonstrates an unmet treatment need in TRD patients that, if addressed, could reduce the heavy personal and societal burden.

Efecto de los fármacos modificadores del PH sobre los inhibidores de la tirosin quinasa: contrastando información / Effect of gastric-acid-reducing agents on the tyrosine kinasa inhibitors: contrasting information

Objetivos: Los inhibidores de la tirosin quinasa (ITK) comprenden un conjunto de moléculas ampliamente utilizadas actualmente en onco-hematología. Los ITK han supuesto una ventaja para los pacientes, de forma que la administración oral favorece su autonomía, pero a su vez, su absorción gastrointestinal y, por ende, su biodisponibilidad, puede verse alterada por el PH-gástrico. Las interacciones con los fármacos modificadores del PH son un problema conocido y una consulta frecuente. El objetivo del estudio fue analizar las interacciones ITK-fármacos modificadores del PH-gástrico y las discrepancias en diferentes bases de datos. Con los resultados, se elaboró una tabla, para proporcionar a los pacientes la información correcta y consensuada, y no generar así inseguridad que comprometa la adherencia al tratamiento o confianza hacia el profesional sanitario. Métodos: Se exportaron de la web de la Agencia Española del Medicamento y Productos Sanitarios los fármacos clasificados como ITK directos (ATC: L01XE). Se consultó la interacción de éstos con los IBP, Anti-H2 y antiácidos en diversas fuentes y se resumieron los hallazgos.Resultados y conclusiones: Para establecer una fuerte recomendación, es necesario consultar varias bases de datos, ya que las discrepancias o la información insuficiente pueden llevar a recomendaciones erróneas. Es importante establecer un consenso entre profesionales para realizar la recomendación correcta, y no ver comprometida la eficacia del tratamiento, con las importantes consecuencias que ello conllevaría. (AU)

Objectives: Tyrosine kinase inhibitors (TKIs) include a group of molecules widely used in oncohematology today. Using the oral administration route of TKIs offers an advantage for the patient; favoring patient autonomy, however, oral administration also causes relevant new problems. Gastrointestinal absorption and, therefore, bioavailability, can be altered by gastric PH. Interactions of these TKIs with gastric acid reducing (GAR) drugs are a known problem and a frequent query in clinical practice. The aim was to analyze ITK-GAR drugs interactions and discrepancies in different databases. Based on the results, a table was elaborated to provide the correct and consensed information, and thus not generate insecurity that compromises the adherence to the treatment or trust towards the healthcare professional.Methods: Drugs classified as direct ITKs (ATC: L01XE) were exported from the Spanish Agency for Medicines and Health Products website. Their interaction with PPIs, Anti-H2 and antacids was consulted in different databases and findings were summarized.Results and conclusions: To establish a strong recommendation, it is necessary to consult several databases, because of discrepancies or insufficient information can lead to erroneous recommendations. It is important to establish a consensus among professionals to make the correct recommendation, and not compromising the effectiveness of the treatment, which would entail important consequences. (AU)

Recomendaciones de consenso SEDAR-SEMICYUC sobre el manejo de las alteraciones de la hemostasia en los pacientes graves con infección por COVID-19 / SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection

La infección por el coronavirus SARS-CoV-2, causante de la enfermedad denominada COVID-19, provoca alteraciones fundamentalmente en el sistema respiratorio. En los pacientes graves, con frecuencia la enfermedad evoluciona a un síndrome de distrés respiratorio agudo que puede predisponer a los pacientes a un estado de hipercoagulabilidad, con trombosis tanto a nivel venoso como arterial. Esta predisposición presenta una fisiopatología multifactorial, relacionada tanto con la hipoxia como con el grave proceso inflamatorio ligado a esta patología, además de los factores trombóticos adicionales presentes en muchos de los pacientes.Ante la necesidad de optimizar el manejo de la hipercoagulabilidad, los grupos de trabajo de las sociedades científicas de Anestesiología-Reanimación y Terapéutica del Dolor (SEDAR) y de Medicina Intensiva, Crítica y de Unidades Coronarias (SEMICYUC) han desarrollado un consenso para establecer unas pautas de actuación frente a las alteraciones de la hemostasia observadas en los pacientes graves COVID-19. Estas recomendaciones incluyen la profilaxis de la enfermedad tromboembólica venosa en pacientes graves y en el periparto, el manejo de los pacientes en tratamiento crónico con fármacos antiagregantes o anticoagulantes, de las complicaciones hemorrágicas en la evolución de la enfermedad y de la interpretación de las alteraciones generales de la hemostasia

The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients. In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis

Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium.

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.

SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection. / Recomendaciones de consenso SEDAR-SEMICYUC sobre el manejo de las alteraciones de la hemostasia en los pacientes graves con infección por COVID-19.

The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients. In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis.

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.

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