Effectiveness of internet-delivered psychological treatments for children and adolescents with anxiety and/or depressive disorders: Systematic review and network meta-analysis.

Background: Anxiety and depression symptomatology has increased in the child and adolescent population. Internet-delivered psychological treatments (IDPT) can help to reduce this symptomatology, attending to the largest possible population. Aim: To conduct a systematic review and network meta-analysis of IDPT to reduce anxiety and depression symptoms in children and adolescents. Methods: The search for studies was conducted in SCOPUS, PsycINFO, PSICODOC, PsycARTICLES and Medline, between 2000 and 2022, in December 2022. Studies were selected if they were conducted with a sample of children and/or adolescents with previous symptoms of anxiety and depression, had applied IDPT, and included at least two comparative groups with pretest-posttest measures. Network meta-analyses were separately performed for anxiety and depression outcomes. Publication bias was analyzed using Egger's test and funnel plots, and mixed-effects meta-regression models were applied to account for heterogeneity. Results: 37 studies were included in the meta-analysis, providing a total of 74 comparative groups. IDPT exhibited low-to-moderate, statistically significant average effect sizes when compared to both inactive and active controls. No statistical significance was found when IDPT was compared with other types of interventions. Discussion: IDPT is recommended to reduce anxiety and depression symptomatology in children and adolescents, but more studies are needed which compare treatments with other types of interventions, such as face-to-face therapy.

Cognitive Function with PCSK9 Inhibitors: A 24-Month Follow-Up Observational Prospective Study in the Real World-MEMOGAL Study.

INTRODUCTION: The cognitive safety of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has been established in clinical trials, but not yet in real-world observational studies. We assessed the cognitive function in patients initiating PCSK9i, and differences in cognitive function domains, to analyze subgroups by the low-density lipoprotein cholesterol (LDL-C) achieved, and differences between alirocumab and evolocumab. METHODS: This has a multicenter, quasi-experimental design carried out in 12 Spanish hospitals from May 2020 to February 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Among 158 patients followed for a median of 99 weeks, 52% were taking evolocumab and 48% alirocumab; the mean change from baseline in MoCA score at follow-up was + 0.28 [95% CI (- 0.17 to 0.73; p = 0.216)]. There were no significant differences in the secondary endpoints-the visuospatial/executive domain + 0.04 (p = 0.651), naming domain - 0.01 (p = 0.671), attention/memory domain + 0.01 (p = 0.945); language domain - 0.10 (p = 0.145), abstraction domain + 0.03 (p = 0.624), and orientation domain - 0.05 (p = 0.224)-but for delayed recall memory the mean change was statistically significant (improvement) + 0.44 (p = 0.001). Neither were there any differences in the three stratified subgroups according to lowest attained LDL-C level-0-54 mg/dL, 55-69 mg/dL and ≥ 70 mg/dL; p = 0.454-or between alirocumab and evolocumab arms. CONCLUSION: We did not find effect of monoclonal antibody PCSK9i on neurocognitive function over 24 months of treatment, either in global MoCA score or different cognitive domains. An improvement in delayed recall memory was shown. The study showed no differences in the cognitive function between the prespecified subgroups, even among patients who achieved very low levels of LDL-C. There were no differences between alirocumab and evolocumab. REGISTRATION: ClinicalTtrials.gov Identifier number NCT04319081.

Plastid 2-Cys peroxiredoxins are essential for embryogenesis in Arabidopsis.

The redox couple formed by NADPH-dependent thioredoxin reductase C (NTRC) and 2-Cys peroxiredoxins (Prxs) allows fine-tuning chloroplast performance in response to light intensity changes. Accordingly, the Arabidopsis 2cpab mutant lacking 2-Cys Prxs shows growth inhibition and sensitivity to light stress. However, this mutant also shows defective post-germinative growth, suggesting a relevant role of plastid redox systems in seed development, which is so far unknown. To address this issue, we first analyzed the pattern of expression of NTRC and 2-Cys Prxs in developing seeds. Transgenic lines expressing GFP fusions of these proteins showed their expression in developing embryos, which was low at the globular stage and increased at heart and torpedo stages, coincident with embryo chloroplast differentiation, and confirmed the plastid localization of these enzymes. The 2cpab mutant produced white and abortive seeds, which contained lower and altered composition of fatty acids, thus showing the relevance of 2-Cys Prxs in embryogenesis. Most embryos of white and abortive seeds of the 2cpab mutant were arrested at heart and torpedo stages of embryogenesis suggesting an essential function of 2-Cys Prxs in embryo chloroplast differentiation. This phenotype was not recovered by a mutant version of 2-Cys Prx A replacing the peroxidatic Cys by Ser. Neither the lack nor the overexpression of NTRC had any effect on seed development indicating that the function of 2-Cys Prxs at these early stages of development is independent of NTRC, in clear contrast with the operation of these regulatory redox systems in leaves chloroplasts.

Tolerancia a Entornos Virtuales Inmersivos multisensoriales y medida electrodermal Ratio como identificador de población TEA / Tolerance to Multisensory Immersive Virtual Environments and Electrodermal Ratio Measurement as an Identifier of ASD Population

Encontrar indicadores cuantificables para caracterizar a la población con Trastorno del Espectro Autista (TEA) es una prioridad para avanzar en el conocimiento de la afección. Por ello, medidas como la Actividad Electrodermal (EDA) en Entornos Virtuales Inmersivos (EVI) pueden reportar medidas objetivas obtenidas en contextos con la capacidad de obtener una respuesta similar a la de la realidad. El objetivo de este estudio fue estudiar la usabilidad de un EVI y una pulsera EDA y qué fases de la misma tienen capacidad de detectar a la población TEA en un contexto estimular multisensorial. Se llevó a cabo un diseño experimental mixto con un factor intersujetos y un factor intrasujetos. Para ello se contó con una muestra de 46 participantes TEA y 40 normotípicos. Los resultados mostraron una elevada adaptabilidad de uso del EVI y de la pulsera de medición EDA. Además, la componente electrodermal Ratio fue la que obtuvo la capacidad de diferenciar el comportamiento fisiológico entre grupos. Por ello dichos dispositivos son susceptibles en su generalización clínica, mientras que la medida Ratio apunta hacia una mayor percepción de los olores por parte de la población TEA, lo que puede estudiarse como un indicador de la afección. (AU)

Finding quantifiable indicators to characterize the population with Autistic Disorder (ASD) is a priority to advance knowledge of the condition. For this reason, measures such as Electrodermal Activity (EDA) in Immersive Virtual Environments (EVI) can report objective measures obtained in contexts with the ability to obtain a response similar to that of reality. The objective of this study was to study the usability of an EVI and an EDA bracelet and which phases of it have the capacity to detect the ASD population in a multisensory stimulation context. A mixed experimental design was carried out with a between-subjects factor and a within-subjects factor. For this, there was a sample of 46 ASD participants and 40 normotypical. The results show a high adaptability of use of the EVI and the EDA measurement bracelet. In addition, the Ratio measure was the one that obtained the ability to differentiate the physiological behavior between groups. Therefore, these devices are susceptible in their clinical generalization, while the Ratio measure points to a greater perception of odors by the ASD population, which can be studied as an indicator of the condition. (AU)

Qualitative Analysis of Conversational Chatbots to Alleviate Loneliness in Older Adults as a Strategy for Emotional Health.

This article presents an exploration of conversational chatbots designed to alleviate loneliness among older adults. In addition to technical evaluation, it delves into effective communication between these systems and this demographic group, considering linguistic nuances, communicative preferences, and specific emotional needs. The intrinsic importance of chatbots as innovative solutions in combating loneliness is highlighted, emphasizing their ability to be understanding and empathetic allies, contributing to emotional well-being and socialization. The article explores how improved emotional well-being can positively impact the health and quality of life of older adults. The methodology, rooted in triangulation between a literature review and qualitative research through interviews and focus groups with older adults, provides a comprehensive insight into the findings. Ethical, technical, and design considerations such as privacy, autonomy, technology adaptation, and usability are also addressed. The article concludes with practical recommendations for developing user-friendly interfaces that encourage the active participation of older adults in chatbots. This holistic approach not only analyzes the technical effectiveness of chatbots in mitigating loneliness in older adults but delves into human, ethical, and practical aspects, enriching the understanding and implementation of these agents for social and emotional support.

Assessment of hyperactivity-impulsivity and attention deficit in adolescents by self-report and its association with psychopathology and academic performance.

The scientific literature highlights the risk of the appearance of internalizing and externalizing symptoms, together with difficulties in the academic area, linked to diagnosis of Attention Deficit Hyperactivity Disorder (ADHD). This is normally assessed by teachers and primary caregivers, disregarding the self-perception of the adolescents themselves, which limits detection of this disorder at an evolutionary stage. Our aim was to analyze the psychometric properties of a self-report for ADHD in adolescence and its relationship with psychopathology and academic performance. This study assessed an incidental sample of 267 students from secondary schools in the Region of Murcia, Spain, using the EDAH questionnaire adapted for self-report, in order to analyze its psychometric properties in assessing ADHD. The Youth Self-Report (YSR) and the Brief Self-Control Scale (BSCS) were also used to determine their association with psychopathological, self-control and academic performance variables. An ADHD prevalence of between 3.7 and 13.1% was observed depending on the established cut-off point. The adapted EDAH showed adequate reliability indices (α = 0.818; ω = 0.817) and explained a high variance percentage (50.655%). Adolescents with anxiety/depression difficulties, dissocial behavior, aggressiveness, and poor performance in mathematics showed a higher amount of ADHD symptoms. Moreover, self-control, dissocial behavior, age, and performance in Social Sciences acted as predictors of the disorder. The good psychometric properties of this questionnaire and its adequate correspondence with other variables of interest suggest it is an appropriate self-report instrument to assess ADHD in adolescence.

Impacto de la pandemia por COVID-19 en el control lipídico de pacientes que inician inhibidores de la PCSK9 / Impact of the COVID-19 pandemic in the lipid control of the patients that start PCSK9 inhibitors

Objetivos: El estudio MEMOGAL (NCT04319081) está dirigido a evaluar cambios en la función cognitiva en pacientes tratados con inhibidores de la PCSK9 (iPCSK9). Se realiza primer análisis: 1) discutir el papel de los farmacéuticos hospitalarios durante de la pandemia, así como evaluar el impacto de la misma en el control lipídico; 2) análisis descriptivo; 3) eficacia en reducción de colesterol-LDL (c-LDL) de alirocumab y evolocumab; y 4) reportar seguridad de los iPCSK9. Material y métodos: Se trata de un análisis prospectivo en vida real de pacientes tratados por primera vez con iPCSK9 en la práctica clínica habitual e incluidos en su primera dispensación en las consultas de farmacia de 12 hospitales de Galicia desde mayo de 2020-abril de 2021. Los valores basales de c-LDL son los previos al inicio del tratamiento con iPCSK9 y como seguimiento los valores a los 6 meses. Resultados: Se incluyeron 89 pacientes. El 86,5% con enfermedad cardiovascular y un 53,9% intolerancia a las estatinas. Un 78,8% de los pacientes fueron tratados con estatinas de alta intensidad. Las estatinas más usadas fueron rosuvastatina (34,1%) y atorvastatina (20,5%). El nivel basal de c-LDL fue 148mg/dl y de 71mg/dl al seguimiento. Los pacientes tratados con alirocumab (n=43) presentaban valores basales de 144mg/dl y de 73mg/dl al seguimiento y con evolocumab (n=46) de 151mg/dl basal y 69mg/dl al seguimiento. La reducción de c-LDL fue para evolocumab 51,21% y alirocumab 51,05%. El 43,1% presentaba a los 6 meses valores>70mg/dl, el 19,4% entre 55 y 69mg/dl y el 37,5%<55mg/dl. Los pacientes que obtuvieron una reducción>50% de c-LDL fueron el 58,3%. Los eventos adversos presentados fueron: reacción en el lugar de inyección (n=2), mialgias (n=1), síntomas pseudogripales (n=1) y deterioro neurocognitivo (n=1).(AU)

Objectives: MEMOGAL study (NCT04319081) is aimed at evaluating changes in cognitive function in patients treated with PCSK9 inhibitors (PCSK9i). This is the first analysis: (1) discussion about the role of the Hospital Pharmacists during the pandemic, and also the assessment of the impact of COVID-19 in the lipid control; (2) descriptive analysis; (3) effectiveness in LDL cholesterol (LDL-c) reduction of alirocumab and evolocumab; (4) communicate PCSK9i safety. Material and methods: It is a prospective Real-World Evidence analysis of patients that take PCSK9i for the first time in the usual clinical practice, and they are included after the first dispensation in the public pharmacy consultations of 12 Hospitals in Galicia from May 2020 to April 2021. Baseline values of LDL-c are the previous values before taking PCSK9 and the follow-up values are in 6 months time. Results: 89 patients were included. 86.5% with cardiovascular disease and 53.9% with statin intolerances. 78.8% of the patients were treated with high intensity statins. Statins most used were rosuvastatin (34.1%) and atorvastatin (20.5%). Baseline value of LDL-c was 148mg/dL and the follow-up value was 71mg/dL. The baseline value of patients treated with alirocumab (N=43) was 144mg/dL and 73mg/dL in the follow-up. With evolocumab (N=46) was 151mg/dL in basaline and 69mg/dL in follow-up. The LDLc- reduction was 51.21% with evolocumab and 51.05% with alirocumab. 43.1% of the patients showed values >70mg/dL in six month time; 19.4% between 69mg/dl and 55mg/dL and 37.5% <55mg/dL. 58.3% of the patients achieved a reduction >50% of LDL-c. The adverse events were: injection point reaction (N=2), myalgias (N=1), flu-like symptoms (N=1) and neurocognitive worsening (N=1).(AU)

Experience of the Spanish Group for Hematopoietic Transplantation (GETMON-GETH) in allogenic Hematopoietic stem cell Transplantation in Philadelphia acute lymphoblastic leukemia.

INTRODUCTION: Outcomes in patients diagnosed of acute lymphoblastic leukemia with Philadelphia chromosome (Ph-ALL) remains unfavourable compared to other subtypes of acute lymphoblastic leukemia despite improvements in drug treatments as well as advances in hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: The role of allogeneic HSCT in Ph-ALL patients has been analysed through a multicentric study where data belonging to 70 patients diagnosed of this entity in different centers that received HSCT between years 1998 and 2014, were reported by the Grupo Español de Trasplante Hematopoyético (GETH). RESULTS: The performance of HSCT from year 2004, in first complete remission (CR) status with thymoglobulin (ATG) based conditioning had a favorable impact on overall survival (OS). HSTC performance from year 2004, in first CR with ATG-based conditioning in addition to acute graft versus host disease (aGvHD) development, increased event free survival (EFS). Treatment with imatinib as well as undetectable minimal residual disease (MRD) prior to HSCT, combined with aGvHD, reduced risk of relapse (RR). Patient age less than 10 years when HSCT, first CR and ATG-based conditioning were associated to a lower transplant related mortality (TRM). CONCLUSIONS: Patients that could achieve first CR that also received ATG-based conditioning had a better OS and EFS, so HSCT should be considered for this group of patients.

Experiencia del Grupo Español de Trasplante Hematopoyético (GETMON-GETH) en el trasplante alogénico de progenitores hematopoyéticos en leucemia aguda linfoblástica Philadelphia / Experience of the Spanish Group for Hematopoietic Transplantation (GETMON-GETH) in allogenic hematopoietic stem cell transplantation in Philadelphia acute lymphoblastic leukemia

Introducción: Los resultados de los pacientes con diagnóstico de leucemia linfoblástica aguda con cromosoma de Philadelphia (LLA-Ph) continúan siendo desfavorables comparados con los otros tipos de leucemias linfoblásticas agudas, pese a las mejoras en los tratamientos farmacológicos y los avances del trasplante de progenitores hematopoyéticos (TPH).Pacientes y métodos: Se ha analizado el papel del TPH alogénico en pacientes diagnosticados de LLA-Ph mediante un estudio multicéntrico donde se recogen datos pertenecientes a 70 pacientes reportados por el Grupo Español de Trasplante Hematopoyético (GETH), diagnosticados de esta enfermedad trasplantados en distintos hospitales españoles entre los años 1998 y 2014.Resultados: La realización del TPH a partir del año 2004, en primera remisión completa (RC) y con el empleo de timoglobulina (ATG) como parte del acondicionamiento, impactó favorablemente en la supervivencia global (SG). El TPH a partir del año 2004 en primera RC, así como el tratamiento con ATG y el desarrollo de enfermedad de injerto contra receptor aguda (EICRa), aumentaron la supervivencia libre de eventos (SLE). La administración de imatinib, así como la ausencia de enfermedad mínima residual previas al TPH, junto con la EICRa redujeron la probabilidad de recaída. La edad del paciente inferior a 10 años, el estado de primera RC y el empleo de ATG en el acondicionamiento disminuyeron la mortalidad relacionada con el TPH.Conclusiones: Los pacientes en primera RC que han recibido ATG durante el acondicionamiento presentan mayores SG y SLE. La indicación de TPH debería considerarse en estas situaciones. (AU)

Introduction: Outcomes in patients diagnosed of acute lymphoblastic leukemia with Philadelphia chromosome (Ph-ALL) remains unfavourable compared to other subtypes of acute lymphoblastic leukemia despite improvements in drug treatments as well as advances in hematopoietic stem cell transplantation (HSCT).Patients and methods: The role of allogeneic HSCT in Ph-ALL patients has been analysed through a multicentric study where data belonging to 70 patients diagnosed of this entity in different center that received HSCT between years 1998 and 2014, were reported by the Grupo Español de Trasplante Hematopoyético (GETH).Results: The performance of HSCT from year 2004, in first complete remission (CR) status with thymoglobulin (ATG) based conditioning had a favorable impact on overall survival (OS). HSTC performance from year 2004, in first CR with ATG-based conditioning in addition to acute graft versus host disease (aGvHD) development, increased event free survival (EFS). Treatment with imatinib as well as undetectable minimal residual disease (MRD) prior to HSCT, combined with aGvHD, reduced risk of relapse (RR). Patient age less than 10 years when HSCT, first CR and ATG-based conditioning were associated to a lower transplant related mortality (TRM).Conclusions: Patients that could achieve first CR that also received ATG-based conditioning had a better OS and EFS, so HSCT should be considered for this group of patients. (AU)

Impact of the COVID-19 pandemic in the lipid control of the patients that start PCSK9 inhibitors. / Impacto de la pandemia por COVID-19 en el control lipídico de pacientes que inician inhibidores de la PCSK9.

OBJECTIVES: MEMOGAL study (NCT04319081) is aimed at evaluating changes in cognitive function in patients treated with PCSK9 inhibitors (PCSK9i). This is the first analysis: (1) discussion about the role of the Hospital Pharmacists during the pandemic, and also the assessment of the impact of COVID-19 in the lipid control; (2) descriptive analysis; (3) effectiveness in LDL cholesterol (LDL-c) reduction of alirocumab and evolocumab; (4) communicate PCSK9i safety. MATERIAL AND METHODS: It is a prospective Real-World Evidence analysis of patients that take PCSK9i for the first time in the usual clinical practice, and they are included after the first dispensation in the public pharmacy consultations of 12 Hospitals in Galicia from May 2020 to April 2021. Baseline values of LDL-c are the previous values before taking PCSK9 and the follow-up values are in 6 months time. RESULTS: 89 patients were included. 86.5% with cardiovascular disease and 53.9% with statin intolerances. 78.8% of the patients were treated with high intensity statins. Statins most used were rosuvastatin (34.1%) and atorvastatin (20.5%). Baseline value of LDL-c was 148mg/dL and the follow-up value was 71mg/dL. The baseline value of patients treated with alirocumab (N=43) was 144mg/dL and 73mg/dL in the follow-up. With evolocumab (N=46) was 151mg/dL in basaline and 69mg/dL in follow-up. The LDLc- reduction was 51.21% with evolocumab and 51.05% with alirocumab. 43.1% of the patients showed values >70mg/dL in six month time; 19.4% between 69mg/dl and 55mg/dL and 37.5% <55mg/dL. 58.3% of the patients achieved a reduction >50% of LDL-c. The adverse events were: injection point reaction (N=2), myalgias (N=1), flu-like symptoms (N=1) and neurocognitive worsening (N=1). CONCLUSIONS: (1) Despite the number of prescriptions was reduced because of the pandemic, the lipid control was not affected. (2) Half of the patients treated with PSCK9i is due to statins intolerance and the 86% is for secondary prevention. (2) The reduction results were similar to pivotal clinical trials. Despite this, 39% of the total of the patients and 60% of patients with dual teraphy did not reach the goal of ESC/EAS guidelines (<55mg/dL and/or reduction>50%). There were not significant differences between evolocumab and alirocumab: 51.21% vs 51.05% (P=.972). (3) There were not any adverse events of special interest. The possible neurocognitive worsening will be studied as the primary endpoint once the MEMOGAL study has been completed.

Outcome of patients with acute heart failure secondary to acute myocardial infarction treated with noninvasive mechanical ventilation.

INTRODUCTION AND OBJECTIVES: Noninvasive ventilation (NIV) has been shown to reduce the rate of endotracheal intubation and mortality in patients with acute heart failure (AHF). However, patients with AHF secondary to acute coronary syndrome/acute myocardial infarction (ACS-AMI) have been excluded from many clinical trials. The purpose of this study was to compare the effectiveness of NIV between patients with AHF triggered by ACS-AMI and by other etiologies. METHODS: Prospective cohort study of all patients with AHF treated with NIV admitted to the intensive care unit for a period of 20 years. Patients were divided according to whether they had ACS-AMI as the cause of the AHF episode. NIV failure was defined as the need for endotracheal intubation or death. RESULTS: A total of 1009 patients were analyzed, 403 (40%) showed ACS-AMI and 606 (60%) other etiologies. NIV failure occurred in 61 (15.1%) in the ACS-AMI group and in 64 (10.6%) in the other group (P=.031), without differences in in-hospital mortality (16.6% and 14.9%, respectively; P=.478). CONCLUSIONS: The presence of ACS-AMI as the triggering cause of AHF did not influence patients with acute respiratory failure requiring noninvasive respiratory support.

[Experience of the Spanish Group for Hematopoietic Transplantation (GETMON-GETH) in allogenic hematopoietic stem cell transplantation in Philadelphia acute lymphoblastic leukemia]. / Experiencia del Grupo Español de Trasplante Hematopoyético (GETMON-GETH) en el trasplante alogénico de progenitores hematopoyéticos en leucemia aguda linfoblástica Philadelphia.

INTRODUCTION: Outcomes in patients diagnosed of acute lymphoblastic leukemia with Philadelphia chromosome (Ph-ALL) remains unfavourable compared to other subtypes of acute lymphoblastic leukemia despite improvements in drug treatments as well as advances in hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: The role of allogeneic HSCT in Ph-ALL patients has been analysed through a multicentric study where data belonging to 70 patients diagnosed of this entity in different center that received HSCT between years 1998 and 2014, were reported by the Grupo Español de Trasplante Hematopoyético (GETH). RESULTS: The performance of HSCT from year 2004, in first complete remission (CR) status with thymoglobulin (ATG) based conditioning had a favorable impact on overall survival (OS). HSTC performance from year 2004, in first CR with ATG-based conditioning in addition to acute graft versus host disease (aGvHD) development, increased event free survival (EFS). Treatment with imatinib as well as undetectable minimal residual disease (MRD) prior to HSCT, combined with aGvHD, reduced risk of relapse (RR). Patient age less than 10 years when HSCT, first CR and ATG-based conditioning were associated to a lower transplant related mortality (TRM). CONCLUSIONS: Patients that could achieve first CR that also received ATG-based conditioning had a better OS and EFS, so HSCT should be considered for this group of patients.

Phase 2 Clinical Trial of Infusing Haploidentical K562-mb15-41BBL-Activated and Expanded Natural Killer Cells as Consolidation Therapy for Pediatric Acute Myeloblastic Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) accounts for approximately 20% of pediatric leukemia cases; 30% of these patients experience relapse. The antileukemia properties of natural killer (NK) cells and their safety profile have been reported in AML therapy. We proposed a phase 2, open, prospective, multicenter, nonrandomized clinical trial for the adoptive infusion of haploidentical K562-mb15-41BBL-activated and expanded NK (NKAE) cells as a consolidation strategy for children with favorable and intermediate risk AML in first complete remission after chemotherapy (NCT02763475). PATIENTS AND METHODS: Before the NKAE cell infusion, patients underwent a lymphodepleting regimen. After the NKAE cell infusion, patients were administered low doses (1 × 106/IU/m2) of subcutaneous interleukin-2. The primary study endpoint was AML relapse-free survival. We needed to include 35 patients to demonstrate a 50% reduction in relapses. RESULTS: Seven patients (median age, 7.4 years; range, 0.78-15.98 years) were administered 13 infusions of NKAE cells, with a median of 36.44 × 106 cells/kg (range, 6.92 × 106 to 193.2 × 106 cells/kg). We observed chimerism in 4 patients (median chimerism, 0.065%; range, 0.05-0.27%). After a median follow-up of 33 months, the disease of 6 patients (85.7%) remained in complete remission. The 3-year overall survival was 83.3% (95% confidence interval, 68.1-98.5), and the cumulative 3-year relapse rate was 28.6% (95% confidence interval, 11.5-45.7). The study was terminated early because of low patient recruitment. CONCLUSION: This study emphasizes the difficulties in recruiting patients for cell therapy trials, though NKAE cell infusion is safe and feasible. However, we cannot draw any conclusions regarding efficacy because of the small number of included patients and insufficient biological markers.

Study protocol for a phase II, multicentre, prospective, non-randomised clinical trial to assess the safety and efficacy of infusing allogeneic activated and expanded natural killer cells as consolidation therapy for paediatric acute myeloblastic leukaemia.

INTRODUCTION: Acute myeloblastic leukaemia (AML) constitutes the second most common haematological malignancy in the paediatric population. Current treatment regimens are based on the administration of polychemotherapy, combining high doses of cytarabine with anthracyclines and topoisomerase inhibitors. Allogeneic haematopoietic stem cell transplantation (HSCT) is an option for high-risk patients with AML (and for intermediate-risk patients if a sibling donor is available). With this strategy, AML survival has increased substantially; however, it has remained stagnant at approximately 60%, with relapse being the principal culprit. The predominant role of the immune system and natural killer (NK) cells in controlling paediatric AML has gained importance within the context of HSCT. In this protocol, we propose incorporating this cell therapy as an adjuvant treatment through the infusion of activated and expanded haploidentical NK (NKAE) cells in paediatric patients with AML who are in cytological remission after completing consolidation therapy, and with no indication for HSCT. METHODS AND ANALYSIS: Patients up to 30 years of age, diagnosed with AML, in their first cytological remission, who have completed both the induction and the consolidation phases of chemotherapy and do not meet the criteria for allogeneic HSCT are eligible. The patients will receive two doses of NKAE cells once a week, using a GMP K562-mbIL15-41BBL stimulus from a haploidentical donor and interleukin 2 subcutaneously. The patients will then be followed up for 36 months to assess the primary endpoint, which is the probability of relapse after NK cell infusion. ETHICS AND DISSEMINATION: This clinical trial was approved by the Clinical Research Ethics Committee of La Paz University Hospital and The Spanish Agency of Medicines and Medical Devices. Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. TRIAL REGISTRATION NUMBER: EudraCT code: 2015-001901-15, ClinicalTrials.gov Identifier: NCT02763475.

Comparative in Mechanical Behavior of 6061 Aluminum Alloy Welded by Pulsed GMAW with Different Filler Metals and Heat Treatments.

Precipitation hardening aluminum alloys are used in many industries due to their excellent mechanical properties, including good weldability. During a welding process, the tensile strength of the joint is critical to appropriately exploit the original properties of the material. The welding processes are still under study, and gas metal arc welding (GMAW) in pulsed metal-transfer configuration is one of the best choices to join these alloys. In this study, the welding of 6061 aluminum alloy by pulsed GMAW was performed under two heat treatment conditions and by using two filler metals, namely: ER 4043 (AlSi5) and ER 4553 (AlMg5Cr). A solubilization heat treatment T4 was used to dissolve the precipitates of ß"- phase into the aluminum matrix from the original T6 heat treatment, leading in the formation of ß-phase precipitates instead, which contributes to higher mechanical resistance. As a result, the T4 heat treatment improves the quality of the weld joint and increases the tensile strength in comparison to the T6 condition. The filler metal also plays an important role, and our results indicate that the use of ER 4043 produces stronger joints than ER 4553, but only under specific processing conditions, which include a moderate heat net flux. The latter is explained because Mg, Si and Cu are reported as precursors of the production of ß"- phase due to heat input from the welding process and the redistribution of both: ß" and ß precipitates, causes a ductile intergranular fracture near the heat affected zone of the weld joint.

Central Venous Sinus Thrombosis in a Boy With Acute Severe Ulcerative Colitis.

Cerebral venous sinus thrombosis (CVST) in childhood is uncommon. Certain diseases predispose patients to CVST, such as inflammatory bowel disease (IBD), which is considered a risk factor for developing thrombosis, which in turn is considered an extraintestinal manifestation of IBD. The use of prophylaxis in certain patients is a controversial topic. We present the case of a 5-years-old child with ulcerative colitis, who presented with transverse sinus thrombosis immediately after colectomy. Considering the recent recommendations on prophylaxis in this disease, our patient and probably many others would benefit from establishing treatment with low-molecular-weight heparin. We believe that these recommendations should be known, with our case serving as an example, given that we are heading in a direction that has so far been controversial.

Myocardial infarction associated with infective endocarditis: a case series.

INTRODUCTION: Embolic myocardial infarction is an uncommon but increasingly recognized complication of infective endocarditis (IE). Its incidence ranges between 1% and 10%, but it has a high mortality rate. A high index of suspicion is required to diagnose it. Only case reports and small studies on this condition have been published; thus, it is unknown what the ideal treatment is. We review the challenges to diagnosing this disease and the most effective treatments for it. CASE PRESENTATION: We report a case series of three patients with acute coronary syndrome (ACS) in IE. The first patient presented with non-ST-elevation ACS. He underwent a stent placement for late-diagnosed embolic myocardial infarction, after which he was treated conservatively without valve replacement, with good results. The second patient with ST-elevation presented with ACS, for which conventional balloon angioplasty and successful double valve replacement were performed. ST-elevation ACS was also observed in the last patient, who experienced periannular complications, which necessitated surgery. DISCUSSION: Acute coronary syndrome is a rare complication of IE but is associated with an increased risk of heart failure and high mortality rate. Its management is complicated and cannot be standardized. Because each situation is unique, a multidisciplinary discussion is required to choose the best treatment.

Mother's IPV, Child Maltreatment Type and the Presence of PTSD in Children and Adolescents.

This correlational cross-sectional study was designed to investigate whether the intimate partner violence (IPV) suffered by mothers (physical and psychological maltreatment), child eyewitness of psychological and physical maltreatment suffered by the mother, the neglect suffered by children, and the maltreatment (physical and psychological) directly suffered by children are statistically associated to post-traumatic stress disorder (PTSD) symptoms exhibited by the child. In addition, the prevalence of child PTSD was estimated, as well as the concordance between the PTSD symptoms assessed by the Child PTSD Symptom Scale (CPSS) and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for child PTSD. The sample consisted of 152 Spanish children aged 8 to 17 and their mothers, who were recruited from Centers of Specialized Assistance for Women Victims of IPV. PTSD prevalence was 20.4%. The results of a canonical correlation analysis showed that the two types of maltreatment with the largest contribution to the canonical variable were physical maltreatment directly suffered by the child, and child eyewitness of physical maltreatment suffered by the mother. The potential developmental pathway of PTSD when both children and mothers suffer severe maltreatment needs to be examined, and this will contribute to the choice of the most effective type of specialized intervention.

[Quality and compliance with Clinical Practice Guidelines of Chronic Noncommunicable Diseases in primary care]. / Calidad y cumplimiento de guías de práctica clínica de enfermedades crónicas no transmisibles en el primer nivel.

OBJECTIVE:: To assess the quality and compliance of clinical practice guidelines (CPG) applicable to chronic non-communicable diseases (CNCD) in primary healthcare (CS), and views of staff on the barriers, facilitators and their use. MATERIALS AND METHODS:: 18 valued CPG with AGREEII, 3 are selected to develop indicators and assess compliance using lot quality acceptance sample (LQAS, standard 75 / 95% threshold 40 / 75% respectively, α:0. 05, ß:0. 10) on 5 CS. 70 professionals surveyed about knowledge and use of CPG. RESULTS:: Average quality of the CPG was 57.2%; low rating in domains: "Applicability" (<25%), "Stakeholder involvement" (43.5%) and "Rigour of development" (55.0%). Compliance in CS ranges from 39 to 53.4%. Professionals show uneven knowledge of CPG; 44 to 45% (according to CPG), they declare that they are not used, they identify as main barriers the lack of training, and their difficult accessibility and management. CONCLUSIONS:: The quality and implementation of evaluated CPG is deficient constituting an opportunity of improvement in health services.

Amiloidosis cardiaca senil y estenosis aórtica degenerativa: 2 enfermedades interrelacionadas en el anciano / Wild-type transthyretin-related cardiac amyloidosis and degenerative aortic stenosis: two inter-related pathologies in the elderly

La variedad senil de la amiloidosis por transtiretina (ATTRwt) presenta algunas características clínicas que se superponen con las de la estenosis aórtica (EA) degenerativa. Recientemente se ha planteado la posibilidad de que algunas de las complicaciones que pueden tener lugar durante y tras el implante percutáneo de prótesis valvular aórtica (TAVI), puedan deberse a una ATTRwt coexistente, puesto que se ha encontrado amiloidosis hasta en un tercio de las autopsias de pacientes sometidos a implante de TAVI. A continuación describimos 2 casos de ATTRwt en pacientes con EA que iban dirigidos a implante de TAVI. Dado que se ha visto que la ATTRwt tiene un curso clínico lento, habría que replantear las decisiones sobre la actitud terapéutica en estos pacientes (AU)

Wild-type transthyretin-related cardiac amyloidosis (ATTRwt) and degenerative aortic stenosis share a common demographic and clinical profile. It was recently suggested that some of the complications arising during and after transcatheter aortic valve replacement (TAVR) could be due to a co-existing cardiac amyloidosis. In a series of autopsies of patients who had undergone TAVR, researchers found ATTR amyloidosis in one third of the cases. A report is presented on two patients with aortic stenosis who were diagnosed with ATTRwt when they were about to undergo a TAVI. ATTRwt is a slowly progressing disease so we need to review the decisions on the therapeutic approach in these patients (AU)