Inflammation and fatness in adolescents with and without Down syndrome: UP & DOWN study.

BACKGROUND: The main objective of this study was to describe the inflammatory status of adolescents with Down syndrome (DS) and their relationship with adiposity. METHODS: Ninety-five adolescents with DS (44.2% girls) and a control group of 113 adolescents (47.8% girls), aged between 11 and 18 years old, from the UP & DOWN study were included in this substudy. Serum C-reactive protein, C3 and C4 complement factors, total proteins, interleukin-6, tumour necrosis factor-α, insulin, cortisol, leptin, adiponectin, galactin-3 and visfatin were analysed; homeostatic model assessment index was calculated. In order to evaluate adiposity, we measured the following body fat variables: weight, height, waist circumference and skinfold thicknesses. Birth weight was obtained by questionnaire. In addition, body mass index, waist-to-height ratio (WHtR) and body fat percentage (BF%) were calculated. RESULTS: Down syndrome group showed higher levels of body mass index, WHtR, waist circumference, BF% and lower birth weight than controls (P < 0.001). In the general linear model in the total sample, WHtR was positively associated with C3 and C4 (P < 0.001) as well as with leptin levels (P = 0.015). BF% was positively associated with total proteins (P = 0.093) and leptin levels (P < 0.001). DS was positively associated with total proteins (P < 0.001), C3 (P = 0.047) and C4 (P = 0.019). Despite the higher levels of adiposity found in DS group, no direct association was found between BF% and leptin levels, comparing with the control group. CONCLUSIONS: These findings suggest that abdominal obesity should be controlled in adolescents because of its relationship with acute phase-inflammatory biomarkers but especially in DS adolescents who may show a peculiar metabolic status according to their relationship between adiposity and inflammatory biomarkers.

Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations.

Autism is a severe neurodevelopmental disorder, the aetiology of which remains mainly unknown. Family and twin studies provide strong evidence that genetic factors have a major role in the aetiology of this disease. Recently, whole exome sequencing (WES) efforts have focused mainly on rare de novo variants in singleton families. Although these studies have provided pioneering insights, de novo variants probably explain only a small proportion of the autism risk variance. In this study, we performed exome sequencing of 10 autism multiplex families with the aim of investigating the role of rare variants that are coinherited in the affected sibs. The pool of variants selected in our study is enriched with genes involved in neuronal functions or previously reported in psychiatric disorders, as shown by Gene Ontology analysis and by browsing the Neurocarta database. Our data suggest that rare truncating heterozygous variants have a predominant role in the aetiology of autism. Using a multiple linear regression model, we found that the burden of truncating mutations correlates with a lower non-verbal intelligence quotient (NVIQ). Also, the number of truncating mutations that were transmitted to the affected sibs was significantly higher (twofold) than those not transmitted. Protein-protein interaction analysis performed with our list of mutated genes revealed that the postsynaptic YWHAZ is the most interconnected node of the network. Among the genes found disrupted in our study, there is evidence suggesting that YWHAZ and also the X-linked DRP2 may be considered as novel autism candidate genes.

Effects of alcohol and polyphenols from beer on atherosclerotic biomarkers in high cardiovascular risk men: a randomized feeding trial.

BACKGROUND AND AIMS: Moderate alcohol consumption exerts a cardioprotective effect, but no studies have evaluated the alcohol-independent cardiovascular effects of the non-alcoholic components of beer. We aimed to evaluate the effects of ethanol and the phenolic compounds of beer on classical and novel cardiovascular risk factors. METHODS AND RESULTS: Thirty-three high risk male volunteers were included in a randomized, crossover feeding trial. After a washout period, all subjects received beer (30 g alcohol/d, 660 mL), the equivalent amount of polyphenols as non-alcoholic beer (990 mL), and gin (30 g alcohol/d, 100 mL) for 4 weeks. All outcomes were evaluated before and after each intervention period. Moderate alcohol consumption increased serum HDL-cholesterol (∼5%), ApoA-I (∼6%), ApoA-II (∼7%) and adiponectin (∼7%), and decreased serum fibrinogen (∼8%), and interleukin (IL)-5 (∼14%) concentrations, whereas the non-alcoholic fraction of beer (mainly polyphenols) increased the receptor antagonist of IL-1 (∼24%), and decreased lymphocyte expression of lymphocyte function-associated antigen-1 (∼11%), lymphocyte and monocyte expression of Sialil-Lewis X (∼16%) and monocyte expression of CCR2 (∼31%), and tumor necrosis factor (TNF)-ß (∼14%) and IL-15 (∼22%) plasma concentrations. No changes were observed in glucose metabolism parameters or in body weight and adiposity parameters. CONCLUSION: The phenolic content of beer reduces leukocyte adhesion molecules and inflammatory biomarkers, whereas alcohol mainly improves the lipid profile and reduces some plasma inflammatory biomarkers related to atherosclerosis.

Validación de un cuestionario de conocimientos adquiridos por los pacientes tras un taller educativo de artroplastia de rodilla.

INTRODUCTION: Total knee arthroplasty (TKA) is a surgery that aims to restore function and relieve pain in advanced osteoarthritis. The Educational Workshop (EW) for TKA is given to patients in the pre-surgery period to inform them and facilitating their participation in their health process (empowerment). The aim of this study was developing and validating a self-administered questionnaire to evaluate the acquired knowledge after the EW by the patients who will undergo the TKA procedure. MATERIAL AND METHODS: It was a longitudinal and prospective observational study with a sample of TKA candidate patients. The phases for the construction and validation of this ad hoc questionnaire were: Phase 1: A panel of experts who agreed on a final questionnaire of 20 items; Phase 2: Pilot test administered to 47 patients; Phase 3: Final test of 11 items administered to 50 patients, before and after the EW; Phase 4: Re-test, after the EW and 2 weeks after, administered to 58 patients. RESULTS: One hundred and fifty five patients were included. The Cronbach's alpha coefficient for the item's internal consistency of the final questionnaire, 11 items, was 0.78. To reach the criterion validity, in pre-EW the mean number of hits was: 4.92 (SD=1.78) and in post-EW 10.68 (SD=0.55), a difference that had a statistical significance p<.0001, with no overlap in the 95% CI of the mean: 4.46-5.38/10.54-10.82. The test for stability and reliability, re-test, obtained a mean of right answers 10.87 (SD=0.33) and for the re-test of 10.70 (SD=0.59). The correlation of the interclass coefficient for the re-test was 0.99, which corresponds almost to a maximum concordance. CONCLUSIONS: The questionnaire developed in this study is a reliable and easy tool to evaluate the acquired knowledge in the EW for patients who will be TKA operated.

A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication.

Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD.

Analysis of the perfusion of the optic nerve using angio-OCT in glaucoma. / Análisis de la perfusión del nervio óptico mediante el uso de angio-OCT en glaucoma.

The introduction of optical coherence tomography angiography (OCT-A) has generated interest in evaluating vascular dysfunctions in the optic nerve head for the diagnosis and monitoring of glaucoma. The purpose of this study is to compare perfusion of the optic disc between normal subjects and subjects with glaucoma using OCT-A in order to detect changes in perfusion of the optic disc. Using the OCT-A AngioVue® system, an examination was performed on 40 eyes of 40 patients (20 with glaucoma and 20 healthy controls). Total radial peripapillary flow density (4.5×4.5mm) was measured at different levels of segmentation. The study demonstrated that the peripapillary vascular flow of OCT-A and exploration of the optic nerve head was better in the normal eyes compared to glaucoma patients. This review provides a comprehensive summary of the most important current and potential applications of OCT-A in glaucoma.

[Involvement of intestinal dysbiosis in the etiopathogenesis and treatment of autism spectrum disorder: a bibliographic review]. / Implicación de la disbiosis intestinal en la etiopatogenia y el tratamiento del trastorno del espectro autista: una revisión bibliográfica.

INTRODUCTION: Autism spectrum disorder is a neurodevelopmental disorder with phenotypic heterogeneity and variable symptomatic course of partly unknown etiology. The prevalence of gastrointestinal disorders in autism leads to investigate the role that intestinal microbiota may have as a causal factor and to propose specific therapeutic interventions. The role of microbiota in brain development and function, demonstrated in animal models, justifies its investigation in this neuropsychiatric disorder. OBJECTIVE: The aim was to investigate the relationship between altered microbiota composition and autism spectrum disorder, and to assess the therapeutic role of prebiotics, probiotics and fecal transplantation in this neurodevelopmental disorder. DEVELOPMENT: A literature review was conducted in PubMed, Cochrane Library and Google Scholar to select relevant articles related to the topic that were published between January 2012 and April 2020. Thirty-five relevant articles were selected. In 23 of them, significant differences were found in the composition and diversity of the microbiota in children with ASD, as well as in the biomolecules involved in certain metabolic pathways. The other 12 investigations reported gastrointestinal and behavioral improvements after therapeutic intervention. CONCLUSIONS: It is reasonable to state that there is enough evidence to support the existence of a relationship between intestinal microbiota and autism spectrum disorders. This fact should be explored in depth to assess the etiopathogenic burden of dysbiosis and the possible therapeutic tools.

TITLE: Implicación de la disbiosis intestinal en la etiopatogenia y el tratamiento del trastorno del espectro autista: una revisión bibliográfica.Introducción. El trastorno del espectro autista es un trastorno del neurodesarrollo con heterogeneidad fenotípica y curso sintomático variable de etiología parcialmente desconocida. La prevalencia de trastornos gastrointestinales en este perfil de pacientes invita a investigar el papel que la microbiota intestinal puede tener como factor causal y a plantear intervenciones terapéuticas específicas. El papel de la microbiota en el desarrollo y la función cerebral, demostrado en modelos animales, justifica su investigación en este trastorno neuropsiquiátrico. Objetivo. Investigar la relación entre la alteración en la composición de la microbiota y el trastorno del espectro autista, y evaluar el papel terapéutico de prebióticos, probióticos y trasplante fecal en este trastorno del neurodesarrollo. Desarrollo. Se realizó una revisión bibliográfica en PubMed, Cochrane Library y Google Scholar con el fin de seleccionar los artículos relevantes relacionados con el tema que se publicaron entre enero de 2012 y abril de 2020. Se seleccionaron 35 artículos relevantes. En 23 de ellos se encontraron diferencias significativas en la composición y la diversidad de la microbiota en niños con TEA, así como en biomoléculas involucradas en determinadas rutas metabólicas. Las otras 12 investigaciones describieron mejorías gastrointestinales y comportamentales tras la intervención terapéutica. Conclusiones. Resulta razonable afirmar que existe evidencia suficiente para apoyar la existencia de una relación entre la microbiota intestinal y los trastornos del espectro autista. Esta vinculación ha de ser explorada en profundidad para perfilar el peso etiopatogénico de la disbiosis y las posibles herramientas terapéuticas.

Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB.

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in which different genetic and environmental susceptibility factors are involved. Several lines of evidence support the view that at least 30% of ADHD patients diagnosed in childhood continue to suffer the disorder during adulthood and that genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. Genetic, biochemical and pharmacological studies support the idea that the serotonin system participates in the etiology of ADHD. Based on these data, we aimed to analyze single nucleotide polymorphisms across 19 genes involved in the serotoninergic neurotransmission in a clinical sample of 451 ADHD patients (188 adults and 263 children) and 400 controls using a population-based association study. Several significant associations were found after correcting for multiple testing: (1) the DDC gene was strongly associated with both adulthood (P=0.00053; odds ratio (OR)=2.17) and childhood ADHD (P=0.0017; OR=1.90); (2) the MAOB gene was found specifically associated in the adult ADHD sample (P=0.0029; OR=1.90) and (3) the 5HT2A gene showed evidence of association only with the combined ADHD subtype both in adults (P=0.0036; OR=1.63) and children (P=0.0084; OR=1.49). Our data support the contribution of the serotoninergic system in the genetic predisposition to ADHD, identifying common childhood and adulthood ADHD susceptibility factors, associations that are specific to ADHD subtypes and one variant potentially involved in the continuity of the disorder throughout lifespan.

Outcomes and prognostic factors in intermediate-risk prostate cancer: multi-institutional analysis of the Spanish RECAP database.

PURPOSE: To retrospectively assess outcomes and to identify prognostic factors in patients diagnosed with intermediate-risk (IR) prostate cancer (PCa) treated with primary external beam radiotherapy (EBRT). MATERIALS AND METHODS: Data were obtained from the multi-institutional Spanish RECAP database, a population-based prostate cancer registry in Spain. All IR patients (NCCN criteria) who underwent primary EBRT were included. The following variables were assessed: age; prostate-specific antigen (PSA); Gleason score; clinical T stage; percentage of positive biopsy cores (PPBC); androgen deprivation therapy (ADT); and radiotherapy dose. The patients were stratified into one of three risk subcategories: (1) favourable IR (FIR; GS 6, ≤ T2b or GS 3 + 4, ≤ T1c), (2) marginal IR (MIR; GS 3 + 4, T2a-b), and (3) unfavourable IR (UIR; GS 4 + 3 or T2c). Biochemical relapse-free survival (BRFS), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) were assessed. RESULTS: A total of 1754 patients from the RECAP database were included and stratified by risk group: FIR, n = 781 (44.5%); MIR, n = 252 (14.4%); and UIR, n = 721 (41.1%). Mean age was 71 years (range 47-86). Mean PSA was 10.4 ng/ml (range 6-20). The median radiotherapy dose was 74 Gy, with mean doses of 72.5 Gy (FIR), 73.4 Gy (MIR), and 72.8 Gy (UIR). Most patients (88%) received ADT for a median of 7.1 months. By risk group (FIR, MIR, UIR), ADT rates were, respectively, 88.9, 86.5, and 86.9%. Only patients with ≥ 24 months of follow-up post-EBRT were included in the survival analysis (n = 1294). At a median follow-up of 52 months (range 24-173), respective 5- and 10-year outcomes were: OS 93.6% and 79%; BRFS 88.9% and 71.4%; DFS 96.1% and 89%; CSS 98.9% and 94.6%. Complication rates (≥ grade 3) were: acute genitourinary (GU) 2%; late GU 1%; acute gastrointestinal (GI) 2%; late GI 1%. There was no significant association between risk group and BRFS or OS. However, patients with favourable-risk disease had significantly better 5- and 10-year DFS than patients with UIR: 98.7% vs. 92.4% and 92% vs. 85.8% (p = 0.0005). CSS was significantly higher (p = 0.0057) in the FIR group at 5 (99.7% vs. 97.3%) and 10 years (96.1% vs. 93.4%). On the multivariate analyses, the following were significant predictors of survival: ADT (BRFS and DFS); dose ≥ 74 Gy (BRFS); age (OS). CONCLUSIONS: This is the first nationwide study in Spain to report long-term outcomes of patients with intermediate-risk PCa treated with EBRT. Survival outcomes were good, with a low incidence of both acute and late toxicity. Patients with unfavourable risk characteristics had significantly lower 5- and 10-year disease-free survival rates. ADT and radiotherapy dose ≥ 74 Gy were both significant predictors of treatment outcomes.

[Conduct disorders in autism spectrum disorders]. / Alteraciones de conducta en los trastornos del espectro autista.

INTRODUCTION: Autism spectrum disorders (ASD) are neurodevelopmental disorders that affect social communication and present stereotypic behaviours. Comorbidity associated to conduct disorders is frequent, starts in infancy and, in general, continues into adulthood. It is sometimes associated with aggressiveness, negativism, self-harm and breaking social norms. It causes a high degree of dysfunctionality in persons with ASD, their family, professionals and those around them, and is the main cause of pharmacological treatment, hospitalisation and special education. Factors related to the symptoms of ASD, comorbidity and social factors are associated with an increased risk of conduct disorders. In many cases it would be necessary to perform a detailed examination that includes a functional analysis and a combination of psychoeducational, social and pharmacological interventions. AIM: To review the precipitating factors, causes, evaluation and treatment of the conduct disorders associated with ASD. DEVELOPMENT: The study outlines what is understood by conduct disorders in ASD, the different clinical and cognitive mechanisms associated with it, and the most effective strategies for intervention. CONCLUSIONS: Comorbid ASD with conduct disorders is frequent, begins in early infancy and continues throughout life. A detailed evaluation that includes a functional analysis of the behaviour to be eliminated and treatment with different psychological, social educational and pharmacological strategies are essential.

TITLE: Alteraciones de conducta en los trastornos del espectro autista.Introduccion. Los trastornos del espectro autista (TEA) son trastornos del neurodesarrollo que afectan la comunicacion social y presentan conductas estereotipadas. La comorbilidad asociada a trastornos de conducta es frecuente, comienza en la infancia y, en general, continua hasta la edad adulta. En ocasiones se asocia a agresividad, negativismo, autolesiones y ruptura de normas sociales. Origina gran disfuncionalidad a la persona con TEA, a la familia, a los profesionales y al entorno, y es causa principal de tratamiento farmacologico, hospitalizacion y educacion especial. Factores relacionados con los sintomas de TEA, comorbilidad y factores sociales se asocian a un incremento de riesgo de problemas conductuales. Sera necesaria una exploracion detallada que incluya un analisis funcional y una combinacion de intervenciones psicoeducativas, sociales y farmacologicas en muchos casos. Objetivo. Revisar los factores desencadenantes, causas, evaluacion y tratamiento de los problemas de conducta asociados a TEA. Desarrollo. Se expone que se entiende por problemas de conducta en TEA, los diferentes mecanismos clinicos y cognitivos asociados, y las estrategias mas efectivas para la intervencion. Conclusiones. El TEA comorbido con problemas de conducta es frecuente, comienza en la primera infancia y continua a lo largo de la vida. Una detallada evaluacion, que incluya un analisis funcional de la conducta a extinguir, y un tratamiento con diferentes estrategias psicologicas, educativas sociales y farmacologicas resultan esenciales.

Physical activity and frailty as indicators of cardiorespiratory reserve and predictors of surgical prognosis: General and digestive surgery population characterization. / Actividad física y fragilidad como indicadores de reserva cardiorrespiratoria y predictores del pronóstico quirúrgico: caracterización de la población quirúrgica en cirugía general y digestiva.

INTRODUCTION: Frailty and low physical activity and cardiorespiratory reserve are related to higher perioperative morbimortality. The crucial step in improving the prognosis is to implement specific measures to optimize these aspects. It is critical to know the magnitude of the problem in order to implement preoperative optimization programmes. OBJECTIVE: To characterize surgical population in a university hospital. METHODS: All patients undergoing preoperative evaluation for abdominal surgery with admission were prospectively included during a 3-month period. Level of physical activity, functional capacity, frailty and emotional state were assessed using score tests. Additionally, physical condition was evaluated using 5 Times Sit-to-Stand Test. Demographic, clinical and surgical data were collected. RESULTS: One hundred and forty patients were included (60±15yr-old, 56% male, 25% ASA III or IV). Forty-nine percent of patients were proposed for oncologic surgery and 13% of which had received neoadjuvant treatment. Seventy percent of patients presented a low functional capacity and were sedentary. Eighteen percent of patients were considered frail and more than 50% completed the 5 Times Sit-to-Stand Test at a higher time than the reference values adjusted to age and sex. Advanced age, ASA III/IV, sedentarism, frailty and a high level of anxiety and depression were related to a lower functional capacity. CONCLUSIONS: The surgical population of our area has a low functional reserve and a high index of sedentary lifestyle and frailty, predictors of postoperative morbidity. It is mandatory to implement preoperative measures to identify population at risk and prehabilitation programmes, considered highly promising preventive interventions towards improving surgical outcome.

Adjuvant versus salvage radiotherapy in prostate cancer: multi-institutional retrospective analysis of the Spanish RECAP database.

PURPOSE: To compare adjuvant radiotherapy (ART) to salvage radiotherapy (SRT) after radical prostatectomy (RP) in a cohort of prostate cancer (PCa) patients. The primary aim was to comparatively assess 2- and 5-year biochemical relapse-free survival (BRFS). A secondary aim was to identify predictors of survival. PATIENTS AND METHODS: Data were acquired from the RECAP database, a population-based prostate cancer registry in Spain. Inclusion criteria included RP (with or without lymphadenectomy) followed by ART or SRT. A total of 702 patients were analyzed. Pre-RT PSA values (>0.5 vs. ≤0.5 ng/ml), pathological stage (T1-2 vs. T3-4), post-surgical Gleason score (≤7 vs. 8-10), margin status (positive vs. negative), hormonal treatment (yes vs. no), and RT dose (≤66 Gy vs. >66 Gy) were evaluated to assess their impact on BRFS. RESULTS: The mean patient age in the ART and SRT groups, respectively, was 64 years (range 42-82) and 64.8 years (range 42-82). Median follow-up after RT in the whole sample was 34 months (range 3-141). A total of 702 patients were included: 223 (31.8%) received ART and 479 (68.2%) SRT. BRFS rates (95% CI) in the ART and SRT groups at months 24 and 60 were, respectively: 98.1% (95.9-100.0%) vs. 91.2% (88.2-94.2%) and 84.5% (76.4-92.6%) vs. 74.0% (67.4-80.7%) (p = 0.004). No significant differences in OS were observed (p = 0.053). The following variables were significant predictors of biochemical recurrence in the SRT group: (1) positive surgical margin status (p = 0.049); (2) no hormonotherapy (p = 0.03); (3) total prostate dose ≤66 Gy (p = 0.004); and pre-RT PSA ≥0.5 ng/ml (p = 0.013). CONCLUSIONS: This is the first nationwide study in Spain to evaluate a large cohort of PCa patients treated with RP followed by postoperative RT. ART yielded better 2- and 5-year BRFS rates, although OS was equivalent. These findings are consistent with most other published studies and support ART in patients with adverse prognostic characteristics after radical prostatectomy. Prospective trials are needed to compare immediate ART to early SRT to better determine their relative benefits.

[Health related quality of life in patients with diabetes mellitus type 2]. / Calidad de vida relacionada con la salud en pacientes con diabetes mellitus tipo 2.

BACKGROUND: To evaluate the impact of diabetes mellitus type 2 on health related quality of life. METHODS: Cross-sectional study. Site: a basic health zone of the Foral Community of Navarre (12,200 inhabitants). Selection through simple random sampling (n=95) of the universe of patients diagnosed with diabetes mellitus type 2 of our basic health zone (n=655). Methods: Health Related Quality of Life evaluated with generic questionnaires SF-36 and EQ-5D; comparison of the general population samples carried out in Spain (SF-36), general population y>65 years of Navarre and Spanish diabetic population (EQ-5D). RESULTS: The diabetic patients have a tendency to show results lower than the general population in the following health concepts of the SF-36: "Physical Function" (76.6 +/- 27.2 SD), "Bodily Pain" (73.7 +/- 26.2 SD) , "General Health" (54.7 +/- 22.4 SD), "Social Function" (84.2 +/- 21.7 SD), "Role Emotional" (84.7 +/- 28.9 SD). Comparing the data with the general population >60 years, only two health concepts -"General Health" and "Role Emotional"- are equal to the reference values. With respect to the rates of respondents to some problem in the dimensions of the EQ-5D, the "Anxiety/Depression" dimension is outstanding with 43%. The value of the analogical visual scale in the diabetic patients is 64.6. CONCLUSIONS: This study increases the evidence that diabetes mellitus type 2 is related to a worse perception of quality of life related to health. The impact of certain diseases on the patients should not be measured only through the quantification of objective clinical parameters (such as morbidity or mortality).

[Emotional dysregulation and autism spectrum disorders]. / Desregulacion emocional y trastornos del espectro autista.

INTRODUCTION: Autism spectrum disorders (ASD) are neurodevelopmental disorders that affect social communication and present stereotyped behaviours. They exhibit a wide range of phenotypic variability related with the capacity to use language for expression, cognitive skills and psychiatric comorbidities, among others. Psychiatric comorbidity is very frequent in ASD and in many cases it is multiple. Emotional dysregulation is related with ASD and with other psychiatric and neurodevelopmental disorders. Multiple comorbidity associated with ASD is the group that presents a high degree of functional inability, multiple pharmacology and hospital admissions. Emotional dysregulation could be the basis of the multiple comorbidity that exists in ASD and will require its own particular considerations in the diagnostic evaluation and treatment. AIMS: To review emotional dysregulation, the currently held concept of it and its relationship with ASD. DEVELOPMENT: This work offers a review of the different definitions of emotional dysregulation, the associated cognitive and neurobiological mechanisms, the clinical presentation when associated to ASD, its role in psychiatric comorbidity and further considerations regarding psychological and pharmacological interventions. CONCLUSIONS: Emotional dysregulation could be associated to the multiple comorbidity present in persons with ASD, as well as being related with high rates of morbidity, hospital admissions and use of psychopharmaceuticals. Failure to identify and diagnose emotional dysregulation could be linked with low effectiveness and a large number of side effects in the case of comorbidity associated to ASD.

TITLE: Desregulacion emocional y trastornos del espectro autista.Introduccion. Los trastornos del espectro autista (TEA) son trastornos del neurodesarrollo que afectan la comunicacion social y presentan conductas estereotipadas. Muestran una gran variabilidad fenotipica relacionada con la capacidad expresiva del lenguaje, habilidades cognitivas y comorbilidades psiquiatricas, entre otras. La comorbilidad psiquiatrica resulta muy frecuente en TEA y en muchos casos es multiple. La desregulacion emocional se relaciona con TEA y con otros trastornos psiquiatricos y del neurodesarrollo. La comorbilidad multiple asociada a TEA es el grupo que presenta gran incapacidad funcional, multiple farmacologia e ingresos hospitalarios. La desregulacion emocional podria ser la base de la comorbilidad multiple existente en TEA y requerira consideraciones propias en la valoracion diagnostica y tratamiento. Objetivo. Revisar la desregulacion emocional, el concepto actual y su relacion con TEA. Desarrollo. Se exponen las diferentes definiciones de desregulacion emocional, los mecanismos cognitivos y neurobiologicos asociados, la presentacion clinica cuando se asocia a TEA, su papel en la comorbilidad psiquiatrica y consideraciones en las intervenciones psicologicas y farmacologicas. Conclusiones. La desregulacion emocional podria asociarse a la comorbilidad multiple presente en personas con TEA, relacionandose con alta morbilidad, ingresos hospitalarios y uso de psicofarmacos. La falta de identificacion y diagnostico de la desregulacion emocional podria relacionarse con poca efectividad y un elevado numero de efectos secundarios cuando se trata la comorbilidad asociada a TEA.

Intermittent versus continuous androgen deprivation therapy to biochemical recurrence after external beam radiotherapy: a phase 3 GICOR study.

PURPOSE: We compared biochemical control and quality of life with intermittent (6 months) versus continuous (36 months) androgen deprivation therapy (ADT) in a non-inferiority randomized phase 3 trial in patients with biochemical failure (BF) after external beam radical radiotherapy (EBRT). MATERIALS AND METHODS: Patients were stratified according to the Gleason score (GS) and were classified as low risk with a GS < 6 and 7 (3 + 4) and high risk with a GS of 7 (4 + 3) and >7. Patients were followed with PSA determinations and quality-of-life assessments (QLQ C-30 and QLQ PR-25) every 6 months for a period of 3 years. BF after radiation was defined as a PSA level of nadir +2 ng/ml. Disease progression (DP) after ADT was defined as PSA ≥4 ng/ml (BF) and/or metastases. RESULTS: Seventy-seven patients were included in this multicenter phase 3 trial from 2005 to 2009. Thirty-eight and 39 patients were included in the intermittent and continuous groups, respectively. The median follow-up for both groups was 48 months (40-68). DP after ADT in the intermittent group was seen in three patients (distant metastases in one patient) versus 0 in the continuous group. The QLQ-C30 and QLQ PR-25 scores did not show any statistically difference between the two ADT groups. CONCLUSIONS: No significant differences were seen in DP and QLQ between intermittent (6 months) and continuous (36 months) ADT in patients with BF after EBRT.

[Efficacy and safety of two dosing regimens with Tadalafil in Spanish men with erectile dysfunction: results from the SURE study in 14 European countries]. / Eficacia y seguridad de Tadalafilo en dos regímenes de dosificación diferentes en pacientes españoles con disfunción eréctil: resultados procedentes del estudio SURE realizado en 14 países europeos.

OBJECTIVE: [corrected] To compare the efficacy and safety of tadalafil 20 mg administered 3 times/week (SCH) vs. on demand (OD) in a cohort of Spanish men with erectile dysfunction (ED), since Tadalafil period of responsiveness lasts up to 36 hours post-dosing. MATERIAL AND METHODS: The 418 Spanish patients participating in the European multicenter, crossover, open-label SURE clinical trial (comprising 4262 men) were randomly assigned to one of the treatment sequences: tadalafil 20 mg SCH for 5-6 weeks followed by tadalafil 20 mg OD for 5-6 weeks, or the inverse sequence. At completion, patients were asked to select the regimen they preferred to receive in an extension phase. RESULTS: In both regimens, tadalafil led to a similar improvement in erectile function compared to baseline. However, the SCH regimen showed statistically significant higher scores for several IIEF questions (i.e. sexual desire domain). Normal erectile function (IIEF EF domain score > or = 26) was achieved by 69.3% of patients on SCH and 64.3 % on OD, with a sexual intercourse success rate (SEP3) of 75.6% and 72.2% respectively (p<0.05). Nevertheless, more patients preferred to receive tadalafil OD for the extension phase (55.9% vs 44.1%, p<0.05). Tadalafil was well tolerated in both regimens. The most common TEAEs (> or = 5%) were headache, dyspepsia and back pain. There were no clinically significant differences in the incidence of TEAEs between regimens. CONCLUSIONS: Tadalafil 20 mg is efficacious and well tolerated for the treatment of ED, regardless the regimen of administration (OD or SCH). Patients can choose the pattern of administration that fits better with their expectations.

[One autism, several autisms. Phenotypical variability in autism spectrum disorders]. / Un autismo, varios autismos. Variabilidad fenotipica en los trastornos del espectro autista.

INTRODUCTION: Autism spectrum disorders (ASD) are a heterogeneous group of disorders that begin in the early months of life and follow a chronic progression. They have a biological origin, with complex aetiological factors that involve different genetic, epigenetic and environmental mechanisms that interact with one another. AIM: To review the main factors that vary the presentation of autism taking into account the most recent scientific evidence. DEVELOPMENT: Aspects related with the development of symptoms, gender, comorbidity, age and aetiology determine the variability in the clinical presentation of ASD. CONCLUSIONS: Autism is highly heterogeneous and is phenotypically related, at least in part, with a wide range of causations, which researchers have begun to unravel but which are still largely unknown. Aetiological research, especially in the area of genetics, will make it possible to identify different homogeneous subgroups with their corresponding phenotypes, while also opening up the way to possible therapeutic alternatives in the future.

TITLE: Un autismo, varios autismos. Variabilidad fenotipica en los trastornos del espectro autista.Introduccion. Los trastornos del espectro autista comprenden un grupo heterogeneo de trastornos que se inician en los primeros meses de la vida y que siguen una evolucion cronica. Su origen es biologico, con factores etiologicos complejos que implican diferentes mecanismos geneticos, epigeneticos y ambientales, que interactuan. Objetivo. Revisar los principales factores que varian la presentacion del autismo considerando la evidencia cientifica actual. Desarrollo. Aspectos relacionados con el desarrollo de sintomas, el sexo, la comorbilidad, la edad y la etiologia determinan la variabilidad en la presentacion clinica de los trastornos del espectro autista. Conclusiones. El autismo es altamente heterogeneo y se relaciona fenotipicamente, en parte, con una gran heterogeneidad etiologica, que comienza a descifrarse, pero que todavia permanece desconocida en gran parte. La investigacion etiologica, especialmente en el area de la genetica, permitira identificar diferentes subgrupos homogeneos con sus correspondientes fenotipos y abrir la posibilidad de alternativas terapeuticas futuras.

Implicación de la disbiosis intestinal en la etiopatogenia y el tratamiento del trastorno del espectro autista: una revisión bibliográfica / Involvement of intestinal dysbiosis in the etiopathogenesis and treatment of autism spectrum disorder: a bibliographic review

Introducción: El trastorno del espectro autista es un trastorno del neurodesarrollo con heterogeneidad fenotípica y curso sintomático variable de etiología parcialmente desconocida. La prevalencia de trastornos gastrointestinales en este perfil de pacientes invita a investigar el papel que la microbiota intestinal puede tener como factor causal y a plantear intervenciones terapéuticas específicas. El papel de la microbiota en el desarrollo y la función cerebral, demostrado en modelos animales, justifica su investigación en este trastorno neuropsiquiátrico. Objetivo: Investigar la relación entre la alteración en la composición de la microbiota y el trastorno del espectro autista, y evaluar el papel terapéutico de prebióticos, probióticos y trasplante fecal en este trastorno del neurodesarrollo. Desarrollo: Se realizó una revisión bibliográfica en PubMed, Cochrane Library y Google Scholar con el fin de seleccionar los artículos relevantes relacionados con el tema que se publicaron entre enero de 2012 y abril de 2020. Se seleccionaron 35 artículos relevantes. En 23 de ellos se encontraron diferencias significativas en la composición y la diversidad de la microbiota en niños con TEA, así como en biomoléculas involucradas en determinadas rutas metabólicas. Las otras 12 investigaciones describieron mejorías gastrointestinales y comportamentales tras la intervención terapéutica. Conclusiones:Resulta razonable afirmar que existe evidencia suficiente para apoyar la existencia de una relación entre la microbiota intestinal y los trastornos del espectro autista. Esta vinculación ha de ser explorada en profundidad para perfilar el peso etiopatogénico de la disbiosis y las posibles herramientas terapéuticas.(AU)

Introduction: Autism spectrum disorder is a neurodevelopmental disorder with phenotypic heterogeneity and variable symptomatic course of partly unknown etiology. The prevalence of gastrointestinal disorders in autism leads to investigate the role that intestinal microbiota may have as a causal factor and to propose specific therapeutic interventions. The role of microbiota in brain development and function, demonstrated in animal models, justifies its investigation in this neuropsychiatric disorder. Objective: The aim was to investigate the relationship between altered microbiota composition and autism spectrum disorder, and to assess the therapeutic role of prebiotics, probiotics and fecal transplantation in this neurodevelopmental disorder. Development: A literature review was conducted in PubMed, Cochrane Library and Google Scholar to select relevant articles related to the topic that were published between January 2012 and April 2020. Thirty-five relevant articles were selected. In 23 of them, significant differences were found in the composition and diversity of the microbiota in children with ASD, as well as in the biomolecules involved in certain metabolic pathways. The other 12 investigations reported gastrointestinal and behavioral improvements after therapeutic intervention. Conclusions: It is reasonable to state that there is enough evidence to support the existence of a relationship between intestinal microbiota and autism spectrum disorders. This fact should be explored in depth to assess the etiopathogenic burden of dysbiosis and the possible therapeutic tools.(AU)

The number of risk factors is the strongest predictor of prostate cancer mortality: multi-institutional outcomes of an extreme-risk prostate cancer cohort.

PURPOSE: To report treatment outcomes in a cohort of extreme-risk prostate cancer patients and identify a subgroup of patients with worse prognosis. MATERIALS AND METHODS: Extreme-risk prostate cancer patients were defined as patients with at least one extreme-risk factor: stage cT3b-cT4, Gleason score 9-10 or PSA > 50 ng/ml; or patients with 2 or more high-risk factors: stage cT2c-cT3a, Gleason 8 and PSA > 20 ng/ml. Overall survival (OS), cause-specific survival (CSS), clinical-free survival (CFS), and biochemical non-evidence of disease (bNED) survival are the four outcomes of interest in a population of 1341 patients. RESULTS: With a median follow-up of 71.5 months, 5- and 10-year bNED survival, CFS, CSS and OS for the entire cohort were 77.1 % and 57.0, 89.2 and 78.9 %, 97.4 and 93.6 %, and 92.0 and 71.3 %, respectively. On multivariate analysis, PSA and clinical stage were associated with bNED survival. PSA and Gleason score predicted for CFS, whereas only Gleason score predicted for OS. When a simplified model was performed using the "number of risk factors" variable, this model provided the best distinction between patients with ≥2 extreme-risk factors and patients with 2 high-risk factors, showing a hazard ratio (HR) of 1.737 (p = 0.0003) for bNED survival, HR 1.743 (p = 0.0448) for OS and an HR of 3.963 (p = 0.0039) for the CSS endpoint. CONCLUSIONS: Patients presenting at diagnosis with two extreme-risk criteria have almost fourfold higher risk for prostate cancer mortality. Such patients should be considered for more aggressive multimodal treatments.