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Behavioral economics has shown that single-item demand indicators are promising for capturing crucial aspects of nicotine reinforcement. It is suggested that brief breakpoint measures perform comparably to full-length demand indices in characterizing nicotine dependence; however, there have been no thorough assessments of their validity in clinical settings. This study aimed to assess the validity and accuracy of a single-item breakpoint in informing on tobacco demand. The sample consisted of 88 treatment-seeking smokers (% males = 70.5%) enrolled in substance use treatment. Participants provided data on smoking characteristics and completed the Fagerstrom Test for Nicotine Dependence, a single-item breakpoint measure and a 14-item cigarette purchase task (CPT). Hierarchical regressions were performed to compare the predictive capability of a single-item breakpoint and full-length tobacco demand indicators in determining nicotine addiction severity. The single-item breakpoint was significantly correlated with all indices stemmed from the CPT and both latent factors (all r values = .250–.368). Neither the brief breakpoint nor the full-length breakpoint significantly predicted nicotine dependence. After controlling for sex and smoking variables, factor 2 [β = .565, p

Silver Russell syndrome (SRS) is a congenital disorder characterised by intrauterine growth retardation (IUGR), feeding difficulties and postnatal growth retardation. In a small number of cases PLAG1 variants have been described (OMIM #618907). PLAG1 haploinsufficiency decreases IGF2 expression and produces a Silver Russell syndrome like phenotype. Here, we describe the phenotype and molecular features of a 26 months girl with clinical features of SRS and a de novo 2.1 Mb deletion encompassing PLAG1 is reported in association with clinical features suggestive of SRS. This manuscript has been published in "Clinical Dysmorphology". https://journals.lww.com/clindysmorphol/Abstract/2021/10000/Silver_Russell_syndrome_in_a_preterm_girl_with.7.aspxMust be cited as follows: Fernandez-Fructuoso JR, De la Torre-Sandoval C, Harbison MD, Chantot-Bastaraud S, Temple K, Lloreda-Garcia JM, Olmo-Sanchez M, Netchine I. Silver Russell syndrome in a preterm girl with 8q12.1 deletion encompassing PLAG1. Clin Dysmorphol. 2021 Oct 1;30(4):194-196. doi: 10.1097/MCD.0000000000000375. PMID: 34480472.

Early diagnosis of nicotine, ethanol and drug use during pregnancy is critical in order to provide adequate care. Current screening procedures show limitations in terms of reliability and short windows of detection.To investigate the prevalence and identify biomarkers of substance use and changes in substance use during pregnancy. To compare drug testing results in different types of biological samples (maternal hair, meconium, placenta, umbilical-cord) with self-reported data.Prospective cohort study using data from pregnant women and their newborns.Biological matrices were collected at birth and analyzed by liquid chromatography tandem mass spectrometry. A paper survey was provided to determine substance use habits.867 mother-newborn pairs were included. According to the analysis of biological samples, 29.1% cases were positive for one or more substances (13.6% nicotine, 8.4% ethanol, 8.3% cocaine, 6.4% cannabis, 5.7% opioids). The profile of the substance-using mother was a single woman,28 years-old, with no higher education and unemployed. Segmental maternal hair analysis showed a decrease in tobacco, cannabis and cocaine use throughout pregnancy (p 0.001). The level of concordance between results from interviews and from biological analyses was weak for opioids, cocaine, and cannabis (kappa coefficient0.40). Maternal hair detected the highest number of cases, followed by meconium and by placenta and/or umbilical-cord.Maternal survey was not a reliable screening technique. Analysis of maternal hair detected the highest number of cases with the broadest detection window (whole pregnancy).

Introduction Obesity-hypoventilation syndrome (OHS) is a risk factor for heart failure (HF). Some studies associate the use of non-invasive ventilation (NIV) with changes in hemodynamic parameters. Our objective was to describe the hemodynamic status of a group of patients with OHS and to study the effect of NIV. Patients and methods Patients with stable OHS treated with NIV were included in this cross-sectional repeated measurements study. Hemodynamics were measured by bioimpedance: 30 min at baseline and another 30 min on NIV. Cardiac output (CO), cardiac index, and systolic volume were measured. The CO calculated for each patient expressed as a percentage of the lower limit of normal (LLN) was taken as reference, and 2 groups were formed: patients without HF and normal CO (≥100% of LLN) and patients with HF and low CO ( Results The final sample comprised 36 patients, aged 66 (±8) years, 19 (52%) men. In 17 (46%) patients, HF was detected with a CO of 3.7 l/min (66%) compared to the group without HF, whose CO was 7 l/min (107%). After NIV, patients with HF showed improvement in CO 4.5 l/min (77%), P=.009, while the non-HF group remained unchanged, with CO 6.8 l/min (104%), P=.2. Conclusion A total of 46% of patients with stable OHS present HF; NIV improves hemodynamics and does not affect patients with normal CO.

Introducción: El tratamiento de la dermatitis atópica (DA) severa es una necesidad insatisfecha, dada la limitada eficacia y seguridad de los tratamientos sistémicos clásicos (TSC). Dupilumab es un anticuerpo monoclonal que bloquea la señalización de las interleuquinas mediadoras de la respuesta inflamatoria involucrada en la DA. Métodos: se analizó la respuesta clínica de un grupo de pacientes de Argentina con DA severa y respuesta insuficiente y/o toxicidad a los TSC que fueron tratados con dupilumab antes de su disponibilidad comercial. Se evaluaron las escalas EASI, SCORAD, DLQI y escalas visuales analógicas de prurito y sueño, durante una mediana de 189 días de seguimiento, así como la incidencia de eventos adversos. Resultados: Se incluyeron 20 pacientes (13 varones); mediana de edad: 37,5 años; mediana de evolución de la DA: 20 años; comorbilidad atópica: 70%. El 100% habían recibido corticoides sistémicos (complicaciones graves: 20%). Los principales motivos de suspensión de los TSC fueron falta de eficacia y aparición de eventos adversos. Los puntajes de todas las escalas se redujeron significativa y sostenidamente, con respuesta clínica evidente al segundo mes de tratamiento. Al final del seguimiento, solo 3 pacientes requerían tratamiento inmunosupresor sistémico concomitante. Dupilumab fue bien tolerado, con eventos adversos leves y controlables. Discusión: el dupilumab constituye el único agente biológico con elevada eficacia demostrada en estudios clínicos y observacionales. En esta casuística, se confirmó su efectividad en pacientes con DA severa de difícil tratamiento y respuesta inadecuada a los TSC. El perfil de seguridad resultó favorable y sostenido a mediano plazo.

Resumen A pesar del consenso universal sobre la necesidad de administrar profilaxis para evitar la recurrencia de la hepatitis B despues del trasplante hepatico (TH), no existen hasta el momento unas recomendaciones nacionales sobre las pautas concretas para la profilaxis y el tratamiento de la infeccion por el virus de la hepatitis B (VHB) en el TH. El objetivo de la VII Reunion de consenso organizada por la Sociedad Espanola de Trasplante Hepatico (SETH) fue unificar criterios y protocolos clinicos entre todas unidades de TH en Espana, sobre como prevenir y tratar la reinfeccion por el VHB despues del TH. La evidencia y las recomendaciones de este documento se han llevado a cabo acuerdo con el sistema Grading of Recommendations Assessment Development and Evaluation (GRADE). En el presente documento se describen las recomendaciones y su grado de evidencia para: la definicion de la recurrencia del VHB post-TH y sus factores de riesgo, la monitorizacion y la profilaxis de la recurrencia del VHB tras el TH en sus diversas etapas, el tratamiento de la hepatitis B antes y despues del TH, y la profilaxis de la infeccion por VHB los receptores de TH con donantes anti-HBc positivo.

The collapsibility of the upper airway is a key factor in the pathogenesis of obstructive sleep apnea (OSA). The exact measurement of this parameter, typically performed by obtaining the critical pressure (Pcrit), has not been introduced into clinical practice. The techniques that are used to measure the upper airway resistance could provide information on its the collapsibility of the airway. The aim of this study was to associate resistance in the upper airway with the presence of OSA. Using a cross-sectional design with a control group, consecutive cases that were seen in the Chest Diseases Sleep Unit were recruited after undergoing nocturnal polysomnography. The upper airway collapsibility was determined based on the change in its resistance from the standing position to the supine position with a flow interruption (Rint) device by measuring the angle formed between the pressure/flow lines (PF angle) between the two positions. The PF angle was greater in the OSA group than in the controls: 7.5° (4) vs. 4° (2) (P

Simple Summary Melanoma still represents a major challenge for health systems around the world. A classical treatment for patients with a high tumor burden or rapidly recurrent in-transit metastases is isolated limb perfusion (ILP) therapy instead of locoregional surgical resection, or when the latter is no longer feasible. In this era of modern systemic treatments for melanoma, it still remains interesting to analyze the role of management approaches for locoregionally-advanced disease, such as isolated limb perfusion (ILP). With this purpose, we conducted a systematic review updating the available literature on ILP for malignant melanomas. The main objectives of this review were to focus on the effectiveness and safety of ILP. In conclusion, ILP, with its low incidence of regional and systemic toxicity, is a valuable palliative treatment not only for patients with disease confined to a limb, but also for patients with a metastatic melanoma with a bulky or symptomatic disease, in order to improve their quality of life. Abstract Background. Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP. Methods. PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000–2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures. Results. Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria. Discussion. ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era. Conclusions. ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies.

Hypoxic ischemic encephalopathy (HIE) is one of the main causes of morbidity and mortality during the neonatal period, despite treatment with hypothermia. There is evidence that oxidative damage plays an important role in the pathophysiology of hypoxic-ischemic (HI) brain injury. Our aim was to investigate whether postnatal allopurinol administration in combination with hypothermia would reduce oxidative stress (OS) biomarkers in an animal model of HIE. Postnatal 10-day rat pups underwent unilateral HI of moderate severity. Pups were randomized into: Sham operated, hypoxic-ischemic (HI), HI + allopurinol (HIA), HI + hypothermia (HIH), and HI + hypothermia + allopurinol (HIHA). Biomarkers of OS and antioxidants were evaluated: GSH/GSSG ratio and carbonyl groups were tested in plasma. Total antioxidant capacity (TAC) was analyzed in plasma and cerebrospinal fluid, and 8-iso-prostaglandin F2α was measured in brain tissue. Plasma 2,2′–azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) levels were preserved in those groups that received allopurinol and dual therapy. In cerebrospinal fluid, only the HIA group presented normal ferric reducing ability of plasma (FRAP) levels. Protein oxidation and lipid peroxidation were significantly reduced in all groups treated with hypothermia and allopurinol, thus enhancing neuroprotection in HIE.

Introduction: Congenital chylothorax (CC) is a rare and life-threating condition. Since its treatment is founded on the elimination of long-chain fatty acids from the diet, breastfeeding has been traditionally contraindicated. However, breast milk could be very beneficial due to its immunological and nutritional benefits. Only limited research has been published about the usage of modified-fat breast milk (MBM) in chylothorax treatment. Methods and Results: Systematic review methods were used by two independent reviewers. Only a few case report studies (quality assessment on the domains of the GRADE approach), two small controlled studies, a retrospective study, and some test-tube-based laboratory research met the inclusion criteria. Despite this, we have observed a widespread clinical adoption of this novel treatment in health institutions. Data suggest that modified-fat breast milk does facilitate the resolution of chylothoraces. Refrigerated centrifuge (2°C, 3,000 rpm for 15 minutes) and syringe fat removal methods were the most efficient options in terms of fat reduction. Conclusions: Feeding of human milk is advisable in CC and feasible by means of a simple milk defatting procedure. Open questions remain, related to length and degree of fat restriction and need for individualized fortification of defatted breast milk.

Aim The aim of this study is to determine the most useful diagnostic tools to differentiate appendicitis from non-specific abdominal pain (NSAP) in pre-school children. Methods We prospectively evaluated all children aged 5 years or younger admitted for suspected appendicitis at a paediatric emergency department during 5 years. Cases of NSAP and appendicitis were enrolled according to inclusion and exclusion criteria. The different variables collected were assessed by statistic and diagnostic accuracy studies. Results A total of 82 patients were studied: 27 cases of NSAP and 55 cases of appendicitis. We found no symptoms or signs with a high power of discrimination between both processes. Complicated cases of appendicitis begin to appear when the duration of symptoms exceeds 12 h. Among laboratory tests, C-reactive protein (CRP) value >34 mg/L was the variable with a greater association to appendicitis (odds ratio 9.8). Abdominal ultrasound (US) had high sensitivity and specificity to differentiate appendicitis, significantly improving its diagnostic accuracy when the duration of symptoms exceeds 12 h. Conclusions A good history and physical examination are important in the diagnostic process, but reliable physical signs can be difficult to elicit in pre-school children. CRP and abdominal US are useful investigations that can improve diagnostic accuracy. According to our results, abdominal pain duration longer than 12 h or CRP value >34 mg/L should be an indication to perform an abdominal US in pre-school children with right lower quadrant tenderness.

Background: The clinical value of sentinel lymph node biopsy (SLNB) in patients with thick melanoma is uncertain. The purpose of this study was to investigate the correlations between survival and lymph node status in thick melanomas. Methods: Of a total of 736 melanoma patients registered between 2000 and 2016, 50 presented with thick melanomas (>= 4.0 mm) without distant metastatic disease. All patients were examined with a whole-body magnetic resonance imaging, or computed tomography, and positron emission tomography-computed tomography depending on the incorporation of the new technology in our medical institutions. They were studied according to the following procedure: 1) preoperative determination of regional lymph node along with the estimation and localization of sentinel lymph node (SLN) (dynamic isotope lymphography); 2) intraoperative localization and SLNB (lymphatic mapping); and 3) histopathology. Patient and tumor features were collected. Results: Mean follow-up was 40 months, and 37% had a follow-up >= 5 years. A positive SLN was identified in 28 patients (56%). No significant difference in melanoma-specific overall survival was observed in terms of the primary tumor site. Hazard ratios (HRs) were statistically significant for SLNB-positive group and mitotic rate (MR) > 3 mm 2 , but not for presence of ulceration. Mortality risk in the SLN-positive group was almost fourfold greater than that in the SLN-negative group at any time of follow-up. Conclusions: SLN status, along with MR, can provide valuable prognostic information in patients with thick primary cutaneous melanoma. World J Oncol. 2019;10(2):112-117 doi: https://doi.org/10.14740/wjon1181

Background and Objectives: Therapeutic interventions to improve the efficacy of whole-body cooling for hypoxic-ischemic encephalopathy (HIE) are desirable. Topiramate has been effective in reducing brain damage in experimental studies. However, in the clinical setting information is limited to a small number of feasibility trials. We launched a randomized controlled double-blinded topiramate/placebo multicenter trial with the primary objective being to reduce the antiepileptic activity in cooled neonates with HIE and assess if brain damage would be reduced as a consequence. Study Design: Neonates were randomly assigned to topiramate or placebo at the initiation of hypothermia. Topiramate was administered via a nasogastric tube. Brain electric activity was continuously monitored. Topiramate pharmacokinetics, energy-related and Krebs’ cycle intermediates, and lipid peroxidation biomarkers were determined using liquid chromatography-mass spectrometry and MRI for assessing brain damage. Results: Out of 180 eligible patients 110 were randomized, 57 (51.8%) to topiramate and 53 (48.2%) to placebo. No differences in the perinatal or postnatal variables were found. The topiramate group exhibited less seizure burden in the first 24 h of hypothermia (topiramate, n = 14 [25.9%] vs. placebo, n = 22 [42%]); needed less additional medication, and had lower mortality (topiramate, n = 5 [9.2%] vs. placebo, n = 10 [19.2%]); however, these results did not achieve statistical significance. Topiramate achieved a therapeutic range in 37.5 and 75.5% of the patients at 24 and 48 h, respectively. A significant association between serum topiramate levels and seizure activity (p < 0.016) was established. No differences for oxidative stress, energy-related metabolites, or MRI were found. Conclusions: Topiramate reduced seizures in patients achieving therapeutic levels in the first hours after treatment initiation; however, they represented only a part of the study population. Our results warrant further studies with higher loading and maintenance dosing of topiramate.

Background Dobutamine is particularly suited to treatment of haemodynamic insufficiency caused by increased peripheral vascular resistance and myocardial dysfunction in the preterm infant. Knowledge of the elimination half-life is essential to estimate the steady state when its efficacy/safety can be evaluated. Methods Analysis of pharmacokinetic data in ten preterm newborns treated with a new neonatal formulation of dobutamine (IMP) after screening for haemodynamic insufficiency within the first 72 h from birth. Blood samples were withdrawn at the end of IMP infusion and at a random time after the end of infusion (5 min, 15 min, 45 min, 2 h and 6 h). IMP concentration in each sample was measured by ultra-high performance liquid chromatography with electrochemical detection. Results Median duration of IMP infusion was 37.7 h (IQR 21.2). Calculated IMP half-life ranged between 3.06 and 36.1 min (median 10.6 min), leading to a time to reach the steady-state concentration between 15 min and >2 h. Adverse events were not related to IMP. Conclusions The wide variability in dobutamine metabolism in preterm infants requires awareness about the risk of under- or overtreatment. A delay of up to 3 h might be required before drawing blood samples to evaluate the effective dose. Impact Small trials suggest dobutamine as the optimal drug in the preterm infant with haemodynamic insufficiency after birth.Age-related differences in drug pharmacokinetics may result in suboptimal treatments.The lack of formal studies in preterms results in inadequate data on efficacy and safety.This study provides data on the variability of the elimination half-life of dobutamine in the very preterm infant during transitional circulation.There is a wide variation in the time to reach the plasma concentration corresponding to steady state, the moment when its efficacy/safety can be reliably evaluated.This information is crucial for planning future trials on cardiovascular support.

[EN] Artificial intelligence and its application in medicine change the premises of the doctor-patient relationship as we know it. The creation of medical robots and the existence of computer applications in which the new information and communication technologies are the main axis of their action determine that the relationship between the machine and the patient is reviewed. To address these contents, we will reflect on robotics, and the scarce applicable community regulations to provide some clues about the so-called electronic personality, and civil liability for damages caused by robots in the medical field., [ES] La inteligencia artificial y su aplicación en la medicina cambia las premisas de la relación médico-paciente como la conocemos. La creación de robots médicos y la existencia de aplicaciones informáticas en las que las nuevas tecnologías de la informa-ción y comunicación son el eje principal de su actuación determinan que se revise la relación entre la máquina y el paciente. Para abordar estos contenidos, reflexionaremos sobre robótica y la escasa normativa comunitaria aplicable, para aportar algunas claves sobre la denominada personalidad electrónica, además de la responsabilidad civil por daños causados por los robots en el ámbito médico, Trabajo elaborado en el marco del Proyecto I+D+i «Retos investigación» del Programa estatal de I+D+i orientado a los Retos de la Sociedad del Ministerio de Ciencia, Innovación y Universidades: «Contratos, transparencia y protección de datos en el mercado digital», RTI 2018-097354-B-100 (2019-2022). Sus investigadores principales son el doctor Javier Plaza Penadés, catedrático de Derecho Civil, y la doctora Luz M. Martínez Velencoso, catedrática de Derecho Civil, ambos de la Universitat de València. Proyecto de I+D+i Retos MICINN PID2019-108710RB-I00 (2020-2022): «Derechos y garantías frente a las decisiones automatizadas en entornos de inteligencia artificial, IoT, big data y robótica». Su investigador principal es el doctor Lorenzo Cotino Hueso, catedrático de Derecho Constitucional de la Universitat de València

[EN] Artificial intelligence and its application in medicine change the premises of the doctor-patient relationship as we know it. The creation of medical robots and the existence of computer applications in which the new information and communication technologies are the main axis of their action determine that the relationship between the machine and the patient is reviewed. To address these contents, we will reflect on robotics, and the scarce applicable community regulations to provide some clues about the so-called electronic personality, and civil liability for damages caused by robots in the medical field. [ES] La inteligencia artificial y su aplicación en la medicina cambia las premisas de la relación médico-paciente como la conocemos. La creación de robots médicos y la existencia de aplicaciones informáticas en las que las nuevas tecnologías de la informa-ción y comunicación son el eje principal de su actuación determinan que se revise la relación entre la máquina y el paciente. Para abordar estos contenidos, reflexionaremos sobre robótica y la escasa normativa comunitaria aplicable, para aportar algunas claves sobre la denominada personalidad electrónica, además de la responsabilidad civil por daños causados por los robots en el ámbito médico Trabajo elaborado en el marco del Proyecto I+D+i «Retos investigación» del Programa estatal de I+D+i orientado a los Retos de la Sociedad del Ministerio de Ciencia, Innovación y Universidades: «Contratos, transparencia y protección de datos en el mercado digital», RTI 2018-097354-B-100 (2019-2022). Sus investigadores principales son el doctor Javier Plaza Penadés, catedrático de Derecho Civil, y la doctora Luz M. Martínez Velencoso, catedrática de Derecho Civil, ambos de la Universitat de València. Proyecto de I+D+i Retos MICINN PID2019-108710RB-I00 (2020-2022): «Derechos y garantías frente a las decisiones automatizadas en entornos de inteligencia artificial, IoT, big data y robótica». Su investigador principal es el doctor Lorenzo Cotino Hueso, catedrático de Derecho Constitucional de la Universitat de València

IntroductionPneumonia is a frequent and costly cause of emergency department (ED) visits and hospitalisations in children. There are no evidence-based, validated tools to assist physicians in management and disposition decisions for children presenting to the ED with community-acquired pneumonia (CAP). The objective of this study is to develop a clinical prediction model to accurately stratify children with CAP who are at risk for low, moderate and severe disease across a global network of EDs.Methods and analysisThis study is a prospective cohort study enrolling up to 4700 children with CAP at EDs at ~80 member sites of the Pediatric Emergency Research Networks (PERN; https://pern-global.com/). We will include children aged 3 months to Ethics and disseminationThis study will result in a clinical prediction model to accurately identify risk of severe disease on presentation to the ED. Ethics approval was obtained for all sites included in the study. Cincinnati Children’s Hospital Institutional Review Board (IRB) serves as the central IRB for most US sites. Informed consent will be obtained from all participants. Results will be disseminated through international conferences and peer-reviewed publications. This study overcomes limitations of prior pneumonia severity scores by allowing for broad generalisability of findings, which can be actively implemented after model development and validation.

Here we describe phenotype and molecular features of a preterm girl diagnosed of Silver-Russell syndrome (SRS), resulting of a de novo heterozygous 8q12.1 deletion encompassing PLAG1 gene. The proband was a 32 weeks preterm girl born asymmetric small for gestational age, after a pregnancy complicated by severe intrauterine growth restriction (IUGR). SRS was clinically diagnosed, but molecular genetic testing for methylation analysis of 11p15.5 and maternal UPD7 yielded normal results. A 60k microarray CGH was also performed simultaneously, showing a 2.1 Mb de novo deletion of 8q12.1 involving PLAG1 gene. To our knowledge, this is the first time a deletion involving PLAG1 is reported as causative of SRS. This finding could further support the previously reported dominant expression of PLAG1 mutations associated to SRS and could contribute to more accurate diagnosis of affected patients.

Altres ajuts: This work was partially supported by grants from La Marató TV3 (20142910, 2014/U/477); FIS (PI14/02058, PI15/00962); CIBERNED. Introduction: Memory alterations are common in Parkinson's disease (PD) patients but the mechanisms involved in these deficits remain poorly understood. The study aims to explore the profile of episodic memory deficits in non-demented early PD patients. Methods: We obtained neurological, cognitive and behavioral data from 114 PD patients and 41 healthy controls (HC). PD participants were grouped as normal cognition (PD-NC) and mild cognitive impairment (PD-MCI) according to the Level II criteria of the Movement Disorders Society Task Force (MDS-TF). We evaluate the performance amongst groups on an episodic memory task using the Free and Cued Selective Reminding Test (FCSRT). Additionally, gray matter volume (GMV) voxel based morphometry, and mean diffusivity (MD) analyses were conducted in a subset of patients to explore the structural brain correlates of FCSRT performance. Results: Performance on all subscores of the FCSRT was significantly worse in PD-MCI than in PD-NC and HC. Delayed total recall (DTR) subscore was the best at differentiating PD-NC from PD-MCI. Using crosstabulation, DTR allowed identification of PD-MCI patients with an accuracy of 80%. Delayed free and cued recall was associated with decreased GMV and increased MD in multiple fronto-temporal and parietal areas. Conclusion: Encoding and retrieval deficits are a main characteristic of PD-MCI and are associated with structural damage in temporal, parietal and prefrontal areas.

Background and purpose Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson's disease, it has been associated with the expression of impulse control disorders, a highly prevalent non-motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test choice has not been addressed. The aim was to evaluate whether different impulsivity measures in Parkinson's disease share substantial inter-scale and anatomical correlations or rather mirror different underlying phenomena. Methods In a consecutive sample of 89 Parkinson's disease patients without impulse control disorders, four common tests were evaluated assessing different aspects of impulsivity: impulsiveness trait, decisions under implicit risk with and without losses, and delay discounting. Correlations among test scores were analysed and each score was used as a regressor in a set of grey matter volume (GMV) voxel-based morphometry analyses to explore their brain structural correlates. Results No significant correlations were found between the different impulsivity tests. Furthermore, their structural brain correlates were divergent. Impulsiveness trait appeared to be associated with lower GMV in dorsal-lateral prefrontal cortices, implicit risk (with losses) with higher GMV in the left nucleus accumbens and lower left insular GMV, implicit risk (without losses) with higher GMV in the left lingual gyrus and lower GMV in the gyri recti and delay discounting with higher GMV in the left nucleus accumbens. Conclusions In Parkinson's disease, different impulsivity measures reflect very dissimilar behavioural and brain structural correlates. Our results suggest that parkinsonian impulsivity is not a unitary phenomenon but rather a heterogeneous entity.

Background Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with a high global prevalence. The main scientific societies dedicated to the management of this disease have published clinical practice guidelines for quality practice. However, at present, there are important weaknesses in COPD diagnosis criteria that often lead to underdiagnosis or misdiagnosis. Objective We sought to develop a new support system for COPD diagnosis. The system was designed to overcome the weaknesses detected in current guidelines with the goals of enabling early diagnosis, and improving the diagnostic accuracy and quality of care provided. Methods We first analyzed the main clinical guidelines for COPD to detect weaknesses that exist in the current diagnostic process, and then proposed a redesign based on a business process management (BPM) strategy for its optimization. The BPM system acts as a backbone throughout the process of COPD diagnosis in this proposed approach. The newly developed support system was integrated into a health information system for validation of its use in a hospital environment. The system was qualitatively evaluated by experts (n=12) and patients (n=36). Results Among the 12 experts, 10 (83%) positively evaluated our system with respect to increasing the speed for making the diagnosis, helping in interpreting results, and encouraging opportunistic diagnosis. With an overall rating of 4.29 on a 5-point scale, 27/36 (75%) of patients considered that the system was very useful in providing a warning about possible cases of COPD. The overall assessment of the system was 4.53 on a 5-point Likert scale with agreement to extend its use to all primary care centers. Conclusions The proposed system provides a functional method to overcome the weaknesses detected in the current diagnostic process for COPD, which can help foster early diagnosis, while improving the diagnostic accuracy and quality of care provided.

Objective Chronic obstructive pulmonary disease (COPD) is a disease that causes airflow limitation to the lungs and has a high morbidity around the world. The objective of this study was to evaluate how artificial intelligence (AI) is being applied for the management of the disease, analyzing the objectives that are raised, the algorithms that are used and what results they offer. Methods We conducted a scoping review following the Arksey and O'Malley (2005) and Levac et al. (2010) guidelines. Two reviewers independently searched, analyzed and extracted data from papers of five databases: Web of Science, PubMed, Scopus, Cinahl and Cochrane. To be included, the studies had to apply some AI techniques for the management of at least one stage of the COPD clinical process. In the event of any discrepancy between both reviewers, the criterion of a third reviewer prevailed. Results 380 papers were identified through database searches. After applying the exclusion criteria, 67 papers were included in the study. The studies were of a different nature and pursued a wide range of objectives, highlighting mainly those focused on the identification, classification and prevention of the disease. Neural nets, support vector machines and decision trees were the AI algorithms most commonly used. The mean and median values of all the performance metrics evaluated were between 80% and 90%. Conclusions The results obtained show a growing interest in the development of medical applications that manage the different phases of the COPD clinical process, especially predictive models. According to the performance shown, these models could be a useful complementary tool in the decision-making by health specialists, although more high-quality ML studies are needed to endorse the findings of this study.

Although impulsivity and sensation seeking have been consistently associated with substance use, few studies have analyzed the relationship between changes in these variables and substance use in early adolescents. The aim of this study was to identify trajectories of impulsivity and sensation seeking and explore their relationship with substance use and heavy drinking. A total of 1342 non-user adolescents (53.6% males; mean age = 12.98, SD = 0.50) annually completed the Barratt Impulsiveness Scale, the Zuckerman's Impulsive Sensation Seeking scale and a delay discounting task, over a total period of three years. Past alcohol, tobacco and cannabis use, drunkenness episodes (DE) and problem drinking were also assessed. Impulsivity trajectories were explored using latent class mixed modelling. To study their predictive power binary logistic regressions were used. Two trajectories of impulsivity were found in males and five were found in females. Males with an increasing impulsivity trajectory were more likely to report tobacco [odds ratio (OR) = 1.84] and cannabis (OR = 3.01) use, DE (OR = 2.44) and problem drinking (OR = 3.12). The early increasing trajectory in females predicted tobacco use (OR = 3.71), cannabis use (OR = 5.87) and DE (OR = 3.64). Lack of premeditation and delay discounting were the most relevant facets in high-risk trajectories. Selective intervention and more intense and tailored treatment might help these adolescents to reduce early increases in impulsivity and prevent escalation of substance use.

Resumen Introduccion En la patogenia del sindrome de obesidad-hipoventilacion (SOH) se ha postulado una disfuncion del centro respiratorio, que muchas veces precisa la utilizacion de ventilacion no invasiva (VNI) en domicilio para el tratamiento. Nuestro objetivo fue medir el efecto de la VNI en la funcion del CR en pacientes con SOH y los factores que lo determinan. Metodos Con un diseno prospectivo de mediciones repetidas se estudio la respuesta a la hipercapnia (RHC) midiendo la pendiente de la relacion p01/pEtCO2 en situacion basal y tras 6 meses de tratamiento con VNI en un grupo de pacientes con SOH. Previamente en un grupo control se establecio un umbral en 0,22 cmH2O/mmHg para diferenciar la respuesta optima (RO) de la respuesta suboptima (RSO) del CR. Resultados Se incluyeron 36 casos, 19 varones (52%), de 65 (DE: 9) anos de edad; un 63% de ellos tenian un p01/pEtCO2 por debajo del valor de referencia. El valor basal de p01/pEtCO2 fue de 0,17 (DE: 0,14) cmH2O/mmHg y tras 6 meses de VNI fue de 0,30 (DE: 0,22) cmH2O/mmHg (p = 0,011). Tras 6 meses de tratamiento con VNI, 12 casos (33%) mantienen una funcion deprimida de su CR. Conclusion Un 63% de los pacientes con SOH mostraron disfuncion de su CR. La aplicacion de VNI mejora la funcion del CR, aunque no en todos los casos.

Resumen: Introducción: La displasia del desarrollo de la cadera (DDC) engloba un espectro de anomalías que afecta a la maduración y desarrollo de la cadera. La presentación podálica es uno de los factores de riesgo asociado a esta patología y puede ser modificada en las últimas semanas de gestación mediante la versión cefálica externa (VCE). El objetivo de nuestro trabajo es determinar la incidencia de DDC en pacientes sometidos a una VCE exitosa, así como valorar la necesidad de incluir a estos niños (podálicos durante gran parte de la gestación) en el protocolo de cribado de DDC. Material y métodos: Estudio de cohortes prospectivo realizado en el Hospital Universitario de Vigo entre el 1 de enero y el 31 de diciembre del 2015. Participaron niños sometidos a VCE y niños podálicos no sometidos a VCE. A todos ellos se les realizó una ecografía de cadera para estudiar la incidencia de DDC en ambos grupos. Resultados: Se incluyeron un total de 122 pacientes. Se intentó realizar VCE en 67 (54,9%) siendo exitosa en 35 (52,2%). De los 122 niños: 14 fueron diagnosticados de DDC mediante ecografía. Tres (8,5%) de los niños con DDC nacieron en presentación cefálica tras VCE exitosa con exploración física de caderas normal al nacimiento. Conclusiones: La VCE reduce el riesgo de DDC con respecto a la presentación podálica pero de no incluir a los niños versionados con éxito en el protocolo de cribado de DDC, corremos el riesgo de no detectar precozmente esta patología. Abstract: Introduction: Developmental dysplasia of the hip (DDH) refers to the spectrum of abnormalities of maturation and development of the hip. Breech presentation is associated with DDH. This risk factor can be modified by external cephalic version (ECV). The aim of this study is to evaluate the incidence of DDH in patients who successfully underwent ECV, as well as to evaluate need for these children (breech for a period during gestation) to be included in the DDH screening protocol. Material and methods: A prospective cohort study was conducted in the Hospital Universitario de Vigo from January 1, 2015 to December 31, 2015. It included children born in cephalic presentation after a successful ECV, as well as children born in breech presentation. They all were screened for DDH by ultrasound examination of the hip. Results: Out of a total of 122 newborns included in the study, ECV was attempted on 67 (54.9%), of which 35 (52.2%) were successful. Out of the 14 children diagnosed with DDH, 3 of those born in cephalic presentation after a successful ECV were found to be normal on physical examination. Conclusions: Successful ECV is associated with a lower incidence of DDH as regards breech presentation. However, these patients should be included in the DDH screening protocol for the early detection of this disorder.

Resumen: Introducción: El dolor abdominal agudo inespecífico es el principal proceso que requiere diagnóstico diferencial con la apendicitis en la práctica clínica. El objetivo de este estudio es evaluar la utilidad del Pediatric Appendicitis Score (Regla de predicción clínica de apendicitis pediátrica) para diferenciar estas 2 entidades. Material y métodos: Se evaluó prospectivamente a los pacientes atendidos por sospecha de apendicitis en nuestro centro durante 2 años, incorporando al estudio casos de dolor abdominal agudo inespecífico y apendicitis. Se recogieron diferentes variables, incluyendo las que conforman el Score y la proteína C reactiva, que se analizaron estadísticamente de manera descriptiva, univariante y multivariante, y mediante pruebas de rendimiento diagnóstico (curvas ROC). Resultados: Se estudiaron 275 casos; 143 casos de dolor abdominal agudo inespecífico y 132 casos de apendicitis. La temperatura y el dolor a palpación en fosa iliaca derecha fueron las únicas variables que no mostraron diferencias significativas entre los grupos, careciendo de poder de discriminación. El dolor con la tos, el salto y/o la percusión fue la variable con mayor asociación a apendicitis. El Score estratificó correctamente a los pacientes en grupos de riesgo. La sustitución de la temperatura por la proteína C reactiva en el Score aumentaba su rendimiento diagnóstico, aunque sin diferencias significativas. Conclusiones: El Pediatric Appendicitis Score ayuda en el diagnóstico diferencial entre apendicitis y dolor abdominal agudo inespecífico. Sería recomendable la sustitución de la temperatura en el Score, pues carece de poder de discriminación entre estos grupos. La proteína C reactiva, categorizada en el valor 25,5 mg/L, podría ser utilizada en su lugar. Abstract: Introduction: Non-specific acute abdominal pain is the most common process requiring differential diagnosis with appendicitis in clinical practice. The aim of this study was to assess the Paediatric Appendicitis Score in differentiating between these two entities. Material and methods: All patients admitted due to suspicion of appendicitis were prospectively evaluated in our hospital over a two-year period. Cases of non-specific acute abdominal pain and appendicitis were enrolled in the study. Several variables were collected, including Score variables and C-reactive protein levels. Descriptive, univariate and multivariate analyses and diagnostic accuracy studies (ROC curves) were performed. Results: A total of 275 patients were studied, in which there were 143 cases of non-specific acute abdominal pain and 132 cases of appendicitis. Temperature and right iliac fossa tenderness on palpation were the variables without statistically significant differences, and with no discrimination power between groups. Pain on coughing, hopping, and/or percussion tenderness in the right lower quadrant was the variable with greater association with appendicitis. The Score correctly stratified the patients into risk groups. Substitution of temperature for C-reactive protein in the Score increased diagnostic accuracy, although with no statistically significant differences. Conclusions: The Paediatric Appendicitis Score helps in differential diagnosis between appendicitis and non-specific acute abdominal pain. It would be advisable to replace the temperature in the Score, since it has no discrimination power between these groups. C-reactive protein at a cut-off value of 25.5 mg/L value could be used instead.

Therapeutic hypothermia (TH) initiated within 6 h from birth is the most effective therapeutic approach for moderate to severe hypoxic-ischemic encephalopathy (HIE). However, underlying mechanisms and effects on the human metabolism are not yet fully understood. This work aims at studying the evolution of several energy related key metabolites in newborns with HIE undergoing TH employing gas chromatography - mass spectrometry. The method was validated following stringent FDA requirements and applied to 194 samples from a subgroup of newborns with HIE (N = 61) enrolled in a multicenter clinical trial (HYPOTOP) for the determination of lactate, pyruvate, ketone bodies and several Krebs cycle metabolites at different sampling time points. The analysis of plasma samples from newborns with HIE revealed a decrease of lactate, pyruvate and β-hydroxybutyrate concentrations, whereas rising malate concentrations were observed. In healthy control newborns (N = 19) significantly lower levels of pyruvate and lactate were found in comparison to age-matched newborns with HIE undergoing TH, whereas acetoacetate and β-hydroxybutyrate levels were clearly increased. Access to a validated analytical method and a controlled cohort of newborns with HIE undergoing hypothermia treatment for the first time allowed the in-depth study of the evolution of key metabolites of metabolic junctions in this special population., MV acknowledges the EC11-244 grant from the Instituto Carlos III. ANR acknowledges a research contract by the Spanish Maternal, Neonatal and Developmental Network SAMID RETICS funded by the PN 2018–2011 (Spain), ISCIII-Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (FEDER), reference RD12/0026. JK, MCe and ASI are grateful for their personal grants from the Instituto Carlos III (grant numbers CP16/00034, JR16/00038 and FI16/00380, respectively). APL acknowledges her personal grant from the Health Research Institute La Fe (CPR2015/0371)

OBJECTIVES: Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. METHODS: Retrospective analysis of hepatitis C virus (HCV) patients aged >= 65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). RESULTS: Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged >= 80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin = 75 years (2.59 (1.16-5.83); P = 0.02) and albumin = 75 years) or those with advanced liver disease (albumin

Asbestos is the term used for a set of mineral silicates that tend to break up into fibers. Its use has been associated with numerous diseases affecting the lung and pleura in particular, all of which are characterized by their long period of latency. Asbestos, moreover, has been recognized by the WHO as a Group IA carcinogen since 1987 and its use was banned in Spain in 2002. The publication in 2013 of the 3rd edition of the specific asbestos health monitoring protocol, together with the development of new diagnostic techniques, prompted the SEPAR EROM group to sponsor publication of guidelines, which review the clinical, radiological and functional aspects of the different asbestos-related diseases. Recommendations have also been made for the diagnosis and follow-up of exposed patients. These recommendations were drawn up in accordance with the GRADE classification system.

Objectives: An evaluation is made of the impact of a series of five interventions on the incidence of hospital-related infections in a level iii neonatal unit. Material and methods: Quasi-experimental, pre-post intervention study, which included preterm infants weighing 1500 g at birth or delivered at

Fabry disease is an X-linked lysosomal storage disorder caused by the impairment of α-galactosidase A. Enzyme replacement therapy is available to treat patients, who often experience delayed diagnosis. A newborn screening for Fabry disease was performed to study the prevalence of the pathology and to evaluate the possibility to implement the test in systematic screenings. We collected 14,600 dried blood spot samples (7575 males and 7025 females) and carried out a diagnostic study by fluorometric measurement of α-galactosidase A enzymatic activity and GLA gene sequencing. We detected one patient with a mutation in GLA associated with classical Fabry Disease (M290I), ten subjects carrying genetic variants of uncertain diagnosis (S126G, R118C, A143T), and a girl with the non-characterized variant F18Y, which was not previously described. Additional 25 samples presented nucleotide substitutions described as polymorphisms (D313Y, rs2071225, and rs2071397). The estimated prevalence for Fabry disease in north-western Spanish males is of 0.013%. Conclusion: These results confirm that the prevalence of Fabry disease is underestimated and systematic screening is feasible; however, further characterization of variants of uncertain clinical significance is necessary to establish protocols of patients’ management. What is Known: • Fabry disease is a rare disease of delayed diagnosis, whose prevalence is underestimated. However, early diagnosis is important for better efficiency of the current available treatment. What is New: • This newborn screening for Fabry disease performed on Spanish population reveals a prevalence of genetic alterations in GLA of 0.1% in males (0.013% with classic Fabry disease) and also characterizes these modifications in order to discriminate between pathogenic mutations and genetic variants of unknown significance.

Background: Most theoretical models of self-determination suggest that both environmental and personal factors influence the development of self-determination. The design and implementation of inte...

We present the first longitudinal study reporting the natural history of human papillomavirus (HPV) infection in sun-exposed skin of healthy individuals living in a geographical area in which solar UV radiation is influenced by the ozone content of the atmosphere. During three climatic seasons, skin swab samples were obtained from 78 healthy individuals and the prevalence of cutaneous HPVs was assessed with broad-spectrum FAP and CUT primers and determined at 54, 45 and 47 % in spring, summer and winter, respectively. Frequencies of mixed HPV infections were significantly higher in spring with respect to summer and winter (P=0.02). Seventy-one different HPV types/putative types were identified. While 62 volunteers were HPV-infected in at least one season, 23 had persistent infections. β-PVs (β-1) were the most prevalent and persistent. Age was associated with both the infection status (P=0.01) and the type of HPV infection (no infection, indeterminate/ transient, persistent P=0.02). The molecular/phylogenetic analysis of the newly identified β-PV, officially designated as HPV209, showed that the virus has a typical genomic organization of cutaneous HPVs with five early (E6, E7, E1, E2 and E4) and two late genes (L2 and L1), which clusters to the species β-2. This provides useful data on cutaneous HPV infections in high UV-exposed regions. Fil: Bolatti, Elisa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Chouhy, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Hošnjak, Lea. University of Ljubljana; Eslovenia Fil: Casal, Pablo E.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Kocjan, Boštjan J.. University of Ljubljana; Eslovenia Fil: Bottai, Hebe. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Stella, Emma Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Sanchez, Adriana. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Bussy, Ramón Fernandez. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Poljak, Mario. University of Ljubljana; Eslovenia Fil: Giri, Adriana Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina

Resumen: Introducción: La administración prenatal de MgSO4 ha mostrado su eficacia en reducir la parálisis cerebral y la disfunción motora severa a los 2 años de edad.El objetivo de este trabajo es estudiar la evolución clínica inicial de los neonatos menores de 29 semanas, que han recibido prenatalmente MgS04 con indicación neuroprotectora y dilucidar la asociación entre la dosis de magnesio administrada a la madre y las concentraciones de magnesio en suero neonatal. Material y métodos: Estudio prospectivo de cohortes en el que se incluyó a los neonatos menores de 29 semanas ingresados en la Unidad de Cuidados Intensivos Neonatales del Hospital Universitario de Vigo desde diciembre del 2012 hasta julio del 2015. Análisis comparativo de resultados perinatales, de morbimortalidad neonatal y magnesemia entre el grupo expuesto prenatalmente al sulfato de magnesio y un grupo control. Resultados: Se incluyó a un total de 42 recién nacidos, en 28 de los cuales sus madres habían recibido MgSO4.Se encontró significación estadística en la variable mortalidad. No hubo diferencias significativas en el resto de las variables estudiadas. Se obtuvo una correlación significativa entre la dosis total de MgSO4 recibida por la madre y los niveles de magnesio del recién nacido en las primeras 24 h de vida (r2 0,436; p

We present a case of iliopsoas abscess secondary to inflammatory bowel disease associated to glycogen storage disease 1b in a 12-year-old boy. To the best of our knowledge, a similar case has not been reported in medical literature.

We report six cases of female patients who, after the application by mesotherapy with platelet-rich plasma, as well as of an intradermal filler material of unknown origin, developed infection at the injection sites associated to Mycobacterium massiliense, as well as granuloma with reaction to foreign body. Although the cultures were negative, the identification of the microorganism was achieved by extraction of soft tissue DNA obtained by biopsy and sequencing the obtained product, with which the therapy was redirected against the particular species. Due to the great similarity in the culture between M. massiliense with the related species M. abscessus, to the required time for its growth, and to the different therapeutic response of each strain, molecular diagnostic techniques are a real option to consider to administer in an early way the appropriate treatment against the pathogen and prevent infection progression.