Maternal and fetal outcomes in multiparous women with Cystic Fibrosis.

BACKGROUND: Quality of life and survival in Cystic Fibrosis (CF) have improved dramatically, making family planning a feasible option. Maternal and perinatal outcomes in women with CF (wwCF) are similar to those seen in the general population. However, the effect of undergoing multiple pregnancies is unknown. METHODS: A multinational-multicenter retrospective cohort study. Data was obtained from 18 centers worldwide, anonymously, on wwCF 18-45 years old, including disease severity and outcome, as well as obstetric and newborn complications. Data were analyzed, within each individual patient to compare the outcomes of an initial pregnancy (1st or 2nd) with a multigravid pregnancy (≥3) as well as secondary analysis of grouped data to identify risk factors for disease progression or adverse neonatal outcomes. Three time periods were assessed - before, during, and after pregnancy. RESULTS: The study population included 141 wwCF of whom 41 (29%) had ≥3 pregnancies, "multiparous". Data were collected on 246 pregnancies, between 1973 and 2020, 69 (28%) were multiparous. A greater decline in ppFEV1 was seen in multiparous women, primarily in pancreatic insufficient (PI) wwCF and those with two severe (class I-III) mutations. Multigravid pregnancies were shorter, especially in wwCF over 30 years old, who had high rates of prematurity and newborn complications. There was no effect on pulmonary exacerbations or disease-related complications. CONCLUSIONS: Multiple pregnancies in wwCF are associated with accelerated respiratory deterioration and higher rates of preterm births. Therefore, strict follow-up by a multidisciplinary CF and obstetric team is needed in women who desire to carry multiple pregnancies.

Volumetric capnography and return of spontaneous circulation in an experimental model of pediatric asphyxial cardiac arrest.

A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbon dioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded. Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR.

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia.

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.

Early Enteral Nutrition and Gastrointestinal Complications in Pediatric Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: To assess the safety of enteral nutrition (EN) in children on extracorporeal membrane oxygenation (ECMO). To describe nutritional status and the characteristics of the nutritional support in this population. METHODS: A retrospective single-center analysis (2006-2016) including children <18 years on ECMO. Demographic data, nutritional status, characteristics of nutritional support, and development of gastrointestinal (GI) complications were recorded. RESULTS: One hundred children, with a median age of 9.7 months (interquartile range [IQR] 3.9-63.1) were enrolled. Undernutrition was prevalent among children on ECMO (33.3%) mainly in patients <2 years (P = 0.042). Most patients (64%) received EN at some point during ECMO therapy. EN was administered in the first 48 hours after ECMO initiation (48HEN) to 60.3% of the children.Mortality rate in the Pediatric Intensive Care Unit was lower in patients who received EN as the initial artificial nutrition support (ANS) (37.7 vs 51%, P = 0.005) and in children on 48HEN (34% vs 50%, P = 0.04). In the logistic regression analysis, duration of ECMO support and low cardiac output indication were the only factors associated with mortality.Although most patients on ECMO (45%) developed digestive complications, they were mostly mild, being constipation the most prevalent. In the logistic regression analysis, EN was not associated with an increase in GI complications (P = 0.09). Only three patients developed intestinal ischemia (one without EN and two on EN). CONCLUSIONS: Undernutrition is prevalent among children on ECMO, mainly in infants <2 years. EN is not associated with severe gastrointestinal complications or higher mortality in these children.

Curso e-learning "desafíos de la pandemia COVID-19 en pediatría": caracterización y relación con los resultados de aprendizaje y grado de satisfacción / E-learning course "challenges of the COVID-19 pandemic in pediatrics": characterization and association with learning results and grade of satisfaction

Frente a la pandemia del CoVID-19, resulta fundamental establecer estrategias manteniendo distanciamiento social, que permitan educar a profesionales de la salud sobre aspectos relacionados con SARS-CoV-2. La Sociedad Chilena de Neumología Pediátrica creó un E-learnig de contingencia de acceso libre. OBJETIVO: Describir las características del curso online "Desafíos de la pandemia CoVID-19 en Pediatría", y evaluar el grado de satisfacción de quienes lo cursaron. Estudio transversal. Todos los inscritos en el curso, entre mayo 2020 y julio 2020. Se grabaron 12 clases dictadas por especialistas con representación académica de Chile. Se realizó una prueba final y una encuesta de satisfacción, con puntaje de 1 a 7. Se realizó análisis descriptivo e inferencial, evaluando asociación entre clasificación final del curso, profesión y zona geográfica de los participantes con test de Kruskal Wallis, significancia estadística p<0,05. Aprobado por comité ética. Participaron 2541 alumnos, 73% mujeres. Mediana de edad 32,7 años. 90,7% de Chile, de estos 63,2% de regiones. De procedencia extranjera destacó Bolivia (2,9%) y Ecuador (2,5%). De los que realizaron la prueba, el 98,6% aprobó. Existió diferencia entre notas según profesión, Médicos-Kinesiólogos(p=0.025) y Médicos-Enfermeros(p=0.002); y según procedencia, Región Metropolitana (RM)-Otras regiones (p=0.041), RM-Internacional(p<0,001) y Otras regiones-Internacional(p<0,001). La evaluación de contenidos ponderó 6,6 y la accesibilidad 6,8. El 98% contestó que el curso cumplió sus expectativas. Concluimos que se inscribió un gran número de alumnos de Chile y Latinoamérica. Más del 98% aprobó la prueba final y refirió un alto nivel de satisfacción. Sugerimos emplear estrategias similares en situaciones de catástrofes sanitarias.

In the face of the CoVID-19 pandemic, it is essential to establish strategies, maintaining social distancing, that allow educating health professionals on aspects related to SARS-CoV-2. The Chilean Society of Pediatric Pulmonology created a free access contingency E-learning. OBJECTIVE: To describe the characteristics of the online course "Challenges of the CoVID-19 pandemic in Pediatrics", and to evaluate the grade of satisfaction of those who attended it.Transversal study. All those enrolled in the course, between May 2020 and July 2020. 12 classes taught by specialists with academic representation from Chile were recorded. A final test and a satisfaction survey were carried out, with a score from 1 to 7. A descriptive and inferential analysis was implemented, evaluating the association between the final classification of the course, profession and geographical area of the participants with the Kruskal Wallis test, statistical significance p< 0.05. Approved by ethics committee. 2541 students participated, 73% women. Median age 32.7 years. 90.7% from Chile, of these 63.2% from regions. Of foreign origin, Bolivia (2.9%) and Ecuador (2.5%) stand out. Of those who took the test, 98.6% were successful. There was a difference between grades according to profession, Physicians-Kinesiologists(p=0.025) and Physicians-Nurses(p=0.002); and according to origin, Metropolitan Region (RM)-Other regions (p=0.041), RM-International (p<0.001) and Other regions-International (p<0.001). The content evaluation pondered 6.6 and accessibility 6.8. 98% responded that the course met their expectations. CONCLUSION: A large number of students from Chile and Latin America were enrolled. More than 98% passed the final test and reported a high level of satisfaction. We suggest using similar strategies in situations of health catastrophes.

Effects of airway management and tidal volume feedback ventilation during pediatric resuscitation in piglets with asphyxial cardiac arrest.

To compare the effect on the recovery of spontaneous circulation (ROSC) of early endotracheal intubation (ETI) versus bag-mask ventilation (BMV), and expiratory real-time tidal volume (VTe) feedback (TVF) ventilation versus without feedback or standard ventilation (SV) in a pediatric animal model of asphyxial cardiac arrest. Piglets were randomized into five groups: 1: ETI and TVF ventilation (10 ml/kg); 2: ETI and TVF (7 ml/kg); 3: ETI and SV; 4: BMV and TVF (10 ml/kg) and 5: BMV and SV. Thirty breaths-per-minute guided by metronome were given. ROSC, pCO2, pO2, EtCO2 and VTe were compared among groups. Seventy-nine piglets (11.3 ± 1.2 kg) were included. Twenty-six (32.9%) achieved ROSC. Survival was non-significantly higher in ETI (40.4%) than BMV groups (21.9%), p = 0.08. No differences in ROSC were found between TVF and SV groups (30.0% versus 34.7%, p = 0.67). ETI groups presented lower pCO2, and higher pO2, EtCO2 and VTe than BMV groups (p < 0.05). VTe was lower in TVF than in SV groups and in BMV than in ETI groups (p < 0.05). Groups 1 and 3 showed higher pO2 and lower pCO2 over time, although with hyperventilation values (pCO2 < 35 mmHg). ETI groups had non significantly higher survival rate than BMV groups. Compared to BMV groups, ETI groups achieved better oxygenation and ventilation parameters. VTe was lower in both TVF and BMV groups. Hyperventilation was observed in intubated animals with SV and with 10 ml/kg VTF.

Perceived diversity in software engineering: a systematic literature review.

We define perceived diversity as the diversity factors that individuals are born with. Perceived diversity in Software Engineering has been recognized as a high-value team property and companies are willing to increase their efforts to create more diverse work teams. The current diversity state-of-the-art shows that gender diversity studies have been growing during the past decade, and they have shown the benefits of including women in software teams. However, less is known about how other perceived diversity factors such as race, nationality, disability, and age of developers are related to Software Engineering. Through a systematic literature review, we aim to clarify the research area concerned with perceived diversity in Software Engineering. Our goal is to identify (1) what issues have been studied and what results have been reported; (2) what methods, tools, models, and processes have been proposed to help perceived diversity issues; and (3) what limitations have been reported when studying perceived diversity in Software Engineering. Furthermore, our ultimate goal is to identify gaps in the current literature and create a call for future action in perceived diversity in Software Engineering. Our results indicate that the individual studies have typically had a gender diversity perspective focusing on showing gender bias or gender differences instead of developing methods and tools to mitigate the gender diversity issues faced in SE. Moreover, perceived diversity aspects related to SE participants' race, age, and disability need to be further analyzed in Software Engineering research. From our systematic literature review, we conclude that researchers need to consider a wider set of perceived diversity aspects for future research.

Baseline Cystic fibrosis disease severity has an adverse impact on pregnancy and infant outcomes, but does not impact disease progression.

BACKGROUND: With increasing longevity and quality of life in adults with Cystic fibrosis (CF), growing maternity rates are reported. Women with severe CF are becoming pregnant, with unpredictable maternal and fetal outcomes. AIM: To determine how baseline disease severity, pancreatic insufficiency (PI) and Pseudomonas aeruginosa (PA) infection affect fertility, the pregnancy course, delivery, neonatal outcome, and subsequent disease progression. METHODS: A multicenter-retrospective cohort study. Data on patients that had been pregnant between 1986-2018 was collected from ten CF centers worldwide. Disease severity [mild or moderate-severe (mod-sev)] was defined according to forced expiratory volume % predicted in 1 second (FEV1) and body mass index (BMI). Three time periods were compared, 12 months prior to conception, the pregnancy itself and the 12 months thereafter. RESULTS: Data was available on 171 pregnancies in 128 patients aged 18-45 years; 55.1% with mod-sev disease, 43.1% with PI and 40.3% with PA. Women with mod-sev disease had more CF-related complications during and after pregnancy and delivered more preterm newborns. However, FEV1 and BMI decline were no different between the mild and mod-sev groups. A more rapid decline in FEV1 was observed during pregnancy in PI and PA infected patients, though stabilizing thereafter. PI was associated with increased risk for small for gestational age infants. CONCLUSION: Baseline disease severity, PA infection and PI have an adverse impact on infant outcomes, but do not impact significantly on disease progression during and after pregnancy. Consequently, pregnancies in severe CF patients can have a good prognosis.

Use of a Servo-Controlled Cooling Gel Pad System to Regulate Body Temperature in Critically Ill Children.

OBJECTIVES: To assess the efficacy and safety of a servo-controlled cooling pad system for target temperature management in critically ill pediatric patients. DESIGN: A prospective, single-center, observational study. SETTING: PICU of a tertiary hospital from September 2018 to September 2019. PATIENTS: Children from 28 days to 16 years old subjected to servo-controlled body temperature control. METHODS: The Arctic Sun 5000 system (Bard Medical, Covington, GA) and Arctic Gel Hydrogel pads were used for the purposes of the study. Data collected included demographics, indication of therapy, patient's body temperature, target temperature, time-to-target temperature, duration of therapy, and need to start or increase sedation and/or muscle relaxants. MEASUREMENTS AND MAIN RESULTS: A total of 16 patients were included, of whom 68.8% were male; mean age was 4.7 years. The most frequent indication was fever associated with hemodynamic instability (62.5%). The target temperature was normothermia (36 or 36.5°C) in 81% of cases. Mean baseline body temperature was 37.6°C (± 1.2°C), and 50% of patients had fever (> 38°C). The mean speed of cooling was 1.2°C/hr (± 1°C/hr). Mean time to target temperature was 118 minutes (± 98.8 min). Mean duration of therapy was 68.7 hours (± 58.3 hr). Two patients had fever related to device disconnection during the treatment. At the start of the therapy, 15 patients were receiving sedative and analgesic drugs, and four received muscle relaxants. A patient required increased sedation, whereas another patient needed to start muscle relaxants. One of the patients developed a skin lesion in the axilla, no other adverse events were registered. CONCLUSIONS: Despite the small sample size, the results of the study showed that target temperature management by the servo-controlled gel pad system in critically ill pediatric patients was effective in achieving satisfactory temperature control and it was well-tolerated.

Characteristics and survival of hepatocellular carcinoma in non-cirrhotic liver.

INTRODUCTION: the characteristics, screening, and survival of hepatocellular carcinoma (HCC) for patients without cirrhosis have not been fully studied. METHODS: A retrospective cohort study was performed in non-cirrhotic patients with histological HCC, between January 2004 and October 2018. Their characteristics, treatment, follow-up and overall survival were described. RESULTS: 25 of the 332 patients with HCC met the inclusion criteria (7.5%), 76% were males and the median age was 69.9 years. The main etiology of liver disease was the hepatitis B virus (HBV) (32%), followed by non-alcoholic steatohepatitis (NASH) (20%). Liver fibrosis was mild (0-1) in 44% of cases. The nodule was diagnosed by ultrasonography in 32% of cases, 60% were found incidentally and 8% due to clinical symptoms. The Barcelona Clinic Liver Cancer (BCLC) staging was 0 in 4% of cases, A in 88%, B in 4% and C in 4%. The main initial treatment was surgical resection (76%) and 8% refused to be treated. Percutaneous ethanol injection, chemoembolization, sorafenib and palliative care were each performed in 4% of cases. There were some complications in 21% of patients treated with surgery, half of them were severe. The median follow-up was 22.2 (2.9-150.6) months and 56% were in remission and the median overall survival was 57.4 ± 29.8 months. The overall cumulative survival at 1, 3 and 5 years was 84%, 61.6% and 47.9%, respectively. CONCLUSION: 7.5% of HCC presented without cirrhosis and almost half of patients had mild fibrosis. HBV was the main cause of HCC, followed by NASH. The most frequent BCLC stage at diagnosis was early stage and surgery was the most common treatment. Overall cumulative survival at 5 years was almost 50%.

Diversity of Streptococcus equi subsp. zooepidemicus strains isolated from the Spanish sheep and goat population and the identification, function and prevalence of a novel arbutin utilisation system.

The zoonotic bacterium Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is a diverse, opportunistic pathogen that can cause mastitis in dairy sheep and goats. We used multilocus sequence typing (MLST) to define the genetic diversity of 60 isolates of S. zooepidemicus, which were recovered from sheep and goats in Spain between 2003 and 2010. We identify a novel clonal complex based on sequence type (ST), ST-236, which accounted for 39 of the 60 isolates. A representative ST-236 strain, S. zooepidemicus strain C7 (SzC7), was sequenced and interrogated for the presence of novel nutritional uptake or utilisation systems, the acquisition of which have previously been shown to be important for environmental adaptation in other streptococcal pathogens. A novel phosphoenolpyruvate sugar phosphotransferase system (PTS), which enabled the utilisation of arbutin, was identified. Functionality of the PTS was confirmed following deletion of the PTS from SzC7. Arbutin is found in multiple animal foodstuffs and we propose that the ability to utilise arbutin may have conferred a selective advantage to strains infecting animals, the diet of which contains this sugar.

TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients.

PURPOSE: In metastatic neuroblastoma (NB) patients, accurate risk stratification and disease monitoring would reduce relapse probabilities. This study aims to evaluate the independent prognostic significance of detecting tyrosine hydroxylase (TH) and doublecortin (DCX) mRNAs by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral blood (PB) and bone marrow (BM) samples from metastatic NB patients. PROCEDURES: RT-qPCR was performed on PB and BM samples from metastatic NB patients at diagnosis, post-induction therapy and at the end of treatment for TH and DCX mRNAs detection. RESULTS: High levels of TH and DCX mRNAs when detected in PB and BM at diagnosis independently predicted worse outcome in a cohort of 162 metastatic NB. In the subgroup of high-risk metastatic NB, TH mRNA detected in PB remained as independent predictor of EFS and OS at diagnosis. After the induction therapy, high levels of TH mRNA in PB and DCX mRNA in BM independently predicted poor EFS and OS. Furthermore TH mRNA when detected in BM predicted worse EFS. TH mRNA in PB samples at the end of treatment is an independent predictor of worse outcome. CONCLUSION: TH and DCX mRNAs levels in PB and BM assessed by RT-qPCR should be considered in new pre-treatment risk stratification strategies to reliable estimate outcome differences in metastatic NB patients. In those high-risk metastatic NB, TH and DCX mRNA quantification could be used for the assessment of response to treatment and for early detection of progressive disease or relapses.

[Validation of the eHealth Literacy Scale (eHEALS) in Spanish University Students]. / Validación de la escala eHealth Literacy (eHEALS) en población universitaria española.

BACKGROUND: One of the scales most used to measure quickly and easily eHealth Literacy is the eHealth Literacy Scale (eHEALS); however, there was no validation of this scale in Spanish. Therefore, the aim of this study was to adapt and validate the eHealth Literacy Scale (eHEALS) to the Spanish context. METHODS: Spanish translation of the scale eHEALS was administered along with other scales to measure some indicators of psychological well-being (self-esteem, subjective vitality and life satisfaction). A sample of 447 university students aged between 18 and 45 years was selected. An exploratory factor analysis, confirmatory factor analysis, analysis of invariance, reliability, temporal stability and bivariate correlations were performed. RESULTS: Exploratory factor analysis revealed a monofactorial structure that explained 52.55% of variance, with high factor loadings of the items. Reliability of 0.87 and test-retest correlation of 0.78 was obtained. The confirmatory factor analysis showed appropriate adjustments indices: χ2=66.60; p=0.00; χ2/ df=4.44; comparative fit index=0.97; incremental fit index=0.97; tucker lewis index=0.94; root mean square of approximattion =0.08; standardized root mean square residual=0.05. The questionnaire was invariant by gender. Regarding the criterion validity, a statistically significant and positive correlations between 0.12 and 0.16 with three indicators of psychological wellbeing was obtained (self-esteem, subjective vitality and life satisfaction). CONCLUSIONS: The spanish version of the eHEALS tested in this work has shown to be a valid and reliable scale to measure eHealth competence in university students.

Immunohistochemical, genetic and epigenetic profiles of hereditary and triple negative breast cancers. Relevance in personalized medicine.

This study aims to identify the profile of immunohistochemical (IHC) parameters, copy number aberrations (CNAs) and epigenetic alterations [promoter methylation (PM) and miR expression] related to hereditary (H) and triple negative (TN) breast cancer (BC). This profile could be of relevance for guiding tumor response to treatment with targeting therapy. The study comprises 278 formalin fixed paraffin-embedded BCs divided into two groups: H group, including 88 hereditary BC (HBC) and 190 non hereditary (NHBC), and TN group, containing 79 TNBC and 187 non TNBC (NTNBC). We assessed IHC parameters (Ki67, ER, PR, HER2, CK5/6, CK18 and Cadherin-E), CNA of 20 BC related genes, and PM of 24 tumor suppressor genes employing MLPA/MS-MLPA (MRC Holland, Amsterdam). MiR-4417, miR-423-3p, miR-590-5p and miR-187-3p expression was assessed by quantitative RT-PCR (Applied Biosystems). Binary logistic regression was applied to select the parameters that better differentiate the HBC or TN groups. For HBC we found that, ER expression, ERBB2 CNA and PM in RASSF1 and TIMP3 were associated with NHBC whereas; MYC and AURKA CNA were linked to HBC. For TNBC, we found that CDC6 CNA, GSTP1 and RASSF1 PM and miR-423-3p hyperexpression were characteristic of NTNBC, while MYC aberrations, BRCA1 hypermethylation and miR-590-5p and miR-4417 hyperexpression were more indicative of TNBC. The selected markers allow establishing BC subtypes, which are characterized by showing similar etiopathogenetic mechanisms, some of them being molecular targets for known drugs or possible molecular targets. These results could be the basis to implement a personalized therapy.

[Percutaneous ablation of hepatocellular carcinoma in older patients in clinical practice]. / Tratamiento percutáneo del carcinoma hepatocelular en pacientes con edad avanzada en la práctica clínica.

INTRODUCTION: A high percentage of older patients with early-stage hepatocellular carcinoma (HCC) are potential candidates for percutaneous ablation. MATERIAL AND METHODS: We prospectively assessed data from patients older than 70 years with HCC. We determined their demographic and clinical characteristics, the treatment provided and the response, complications and survival among those treated with radiofrequency ablation (RFA) and/or percutaneous ethanol injection (PEI). RESULTS: Of 194 patients with HCC, 84 were older than 70 years (43.3%). The mean age was 76.8 ± 4.5 years. Seventy-five percent were male and 91.7% had cirrhosis. Cancer was initially identified by a surveillance program in 61.9%. According to the Barcelona Clinic Liver Cancer staging system, 60.7% were classified as having early stage cancer (0-A), 19% as stage B, 12% as stage C, and 8.3% as stage D. Potentially curative initial treatment was provided in 38.2% (surgical resection in 4.8%, PEI in 22.6%, RFA in 4.8%, PEI+RFA in 6%), transarterial chemoembolization in 20.2%, and sorafenib in 3.6%. Twenty-five percent of patients were not treatment candidates and 13% refused the recommended treatment. The median follow-up after percutaneous ablation was 23 months (IQR 14.2-40.6). The mean number of sessions was 3.5 ± 2.2 for PEI and 1.8 ± 1.6 for RFA. The complications rate per session was 4%. Remission was achieved in 35.7%. The overall median survival was 45.7 months (95% CI 20.8-70.6). CONCLUSIONS: Almost half of the patients with HCC in our sample were elderly and more than half were diagnosed at an early stage. Percutaneous ablation was performed in one-third of the sample, achieving remission in 37.5%. There were few complications. Therefore, these patients should be assessed for percutaneous ablation.

The evaluation of hyaluronic acid, with and without lidocaine, in the filling of nasolabial folds as measured by ultrastructural changes and pain management.

BACKGROUND: Pain management is an important objective in procedures involving dermal fillers composed of hyaluronic acid (HA). OBJECTIVE: To compare the 1-year clinical results of filling the nasolabial fold with 2 types of filler: large-gel particle HA and large-gel particle HA plus 0.3% lidocaine (HA+L). We compared the level of pain during treatment and 10 minutes after treatment and assessed the safety and efficacy profile, satisfaction, and histological findings (using reflectance confocal microscopy [RCM]). MATERIALS AND METHODS: We performed a comparative, parallel-group, double-blind trial with an external observer (blinded to the type of treatment administered). The filler was applied to the nasolabial fold in 119 patients (HA in 62 patients and HA+L in 57). Patients were followed at months 3, 9, and 12. Pain was evaluated using a visual analog scale. Efficacy and satisfaction were evaluated using the Wrinkle Severity Rating Scale and the Global Aesthetic Improvement Scale. RCM images (n=32) were taken at baseline and at months 3 and 12. RESULTS: Pain: The severity of pain was decreased in patients treated with HA+L on application (P <.001) and 10 minutes later ( P=.008). Efficacy and satisfaction: No significant differences existed between the 2 groups at months 3, 9, and 12. RCM: Skin rejuvenation occurred with a 32% increase in the height of the dermoepidermal junction at month 12 (P <.001), which was similar in both groups. Adverse events: At month 3, the most common adverse events (AEs) were erythema (68%) and hematoma (11%). No AEs were recorded at months 9 or 12. CONCLUSION: The use of HA+L provides pain relief without affecting efficacy, satisfaction, safety, or the duration of results. RCM showed that the changes in the dermoepidermal junction represented a histological improvement in the skin with similar results in both groups.

CXCL12-mediated murine neural progenitor cell movement requires PI3Kß activation.

The migratory route of neural progenitor/precursor cells (NPC) has a central role in central nervous system development. Although the role of the chemokine CXCL12 in NPC migration has been described, the intracellular signaling cascade involved remains largely unclear. Here we studied the molecular mechanisms that promote murine NPC migration in response to CXCL12, in vitro and ex vivo. Migration was highly dependent on signaling by the CXCL12 receptor, CXCR4. Although the JAK/STAT pathway was activated following CXCL12 stimulation of NPC, JAK activity was not necessary for NPC migration in vitro. Whereas CXCL12 activated the PI3K catalytic subunits p110α and p110ß in NPC, only p110ß participated in CXCL12-mediated NPC migration. Ex vivo experiments using organotypic slice cultures showed that p110ß blockade impaired NPC exit from the medial ganglionic eminence. In vivo experiments using in utero electroporation nonetheless showed that p110ß is dispensable for radial migration of pyramidal neurons. We conclude that PI3K p110ß is activated in NPC in response to CXCL12, and its activity is necessary for immature interneuron migration to the cerebral cortex.

[Characteristics of patients with chronic hepatitis B virus infection. analysis of a series of 474 patients]. / Características de los pacientes con infección crónica por el virus de la hepatitis B. Análisis de una serie de 474 pacientes.

OBJECTIVE: To determine the clinical, laboratory, serological and histologic characteristics of chronic hepatitis B virus carriers in our environment. MATERIAL AND METHODS: A retrospective cohort study was performed that included chronic AgHBs carriers aged more than 13 years attending our service since January 2000. RESULTS: A total of 474 patients were included. At diagnosis, 55.49% were men, with a mean age of 41.05±13.93 years. Alanine aminotransferase (ALT) levels were within the normal range in 57.17% of the patients, and 87.76% were AgHBe(-). Hepatitis C and D virus coinfection was found in 3.62% and 1.86%, respectively. Liver biopsy was performed in 31.22%; varying grades of inflammation-fibrosis were found in 63.51% and cirrhosis was found in 12.84%. Compared with AgHBe(-) patients, those who were AgHBe(+) were younger and had greater disease activity. This difference was statistically significant. Patients in the immunotolerant phase were the least numerous (5.26%), while AgHBe(-) patients with chronic HBV infection were the most numerous (48.32%). Patients in the immunoreactive phase showed greater histological involvement (16.67% cirrhosis). A familial history of chronic HBV was found in 21.52%. The percentage of non-Spanish patients increased in the last few years and accounted for 18.78%. CONCLUSION: Chronic HBV infection in our environment occurs mainly in middle-aged persons. GPT values are normal in more than 50%, most are AgHBe(-), and approximately half are inactive carriers. The incidence of chronic infection has increased in the non-Spanish population in recent years.

The value of the Barcelona Clinic Liver Cancer and alpha-fetoprotein in the prognosis of hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: presently, the reference staging system to evaluate the prognosis of hepatocellular carcinoma (HCC) patients is "The Barcelona Clinic Liver Cancer" (BCLC) system. The value of alpha-fetoprotein (AFP) has not been properly defined. The aim of this study was to evaluate the BCLC classification in our clinical practice and to know what the prognostic value of AFP is. MATERIAL AND METHODS: 136 consecutive HCC patients were prospectively included in this study. The diagnosis of HCC was based on the recommendation of international guidelines. The patients were studied and managed according to usual clinical practice. Survival curves were estimated using the Kaplan-Meier method and predictors of survival were identified using the Cox model. RESULTS: 110 patients (80.9%) were male. The mean age of the patients was 66.62 + or - 11.68 years. Liver cirrhosis was present in 91.2%. The most frequent cause of liver disease was hepatitis C infection (38.97%). Serum AFP was - or = 20 ng/mL in the 57%, > 20-200 ng/mL in the 20%, and > 200 ng/mL in 23%. According to the BCLC staging system, 79 patients were classified as stage A (58.09%), 29 (21.32%) stage B, 17 (12.50%) stage C and 11 patients (8.09%) as stage D. The overall median survival time was 26.52 months (95% CI 16.7-36.3). The median survival according to BCLC system was: BCLC A 62.27, BCLC B 12.72, BCLC C 4.83, and BCLC D 0.62 months (p < 0.0001); and according to serum AFP was: AFP - or = 20: 62.27 months, > 20-200: 22.08 months, and > 200 ng/mL: 5.39 months (p < 0.0001). Multivariate analysis showed that AFP, BCLC classification and treatment were independent prognostic factors. CONCLUSIONS: our results confirm that the BCLC is a good prognostic system. The AFP has prognosis value in HCC patients. The addition of AFP could improve the BCLC system. Future studies are needed to confirm our results and also the best way to combine BCLC and AFP properly.