0000000000495718
AUTHOR
David Hervás
Resultados quirúrgicos estándar tras resección oncológica de colon. Creación de un nomograma para la autoevaluación
Resumen Introduccion Existe un gran interes en los ultimos anos en identificar estandares de calidad en las distintas enfermedades, entre ellas, el cancer de colon debido a su alta prevalencia. El objetivo del presente estudio es definir unos valores estandar de calidad en los resultados de la cirugia del cancer de colon. Metodos Se han utilizado los datos del estudio prospectivo multicentrico nacional «ANACO», que incluye pacientes con cancer de colon intervenidos en 52 hospitales espanoles (2011-2012). Para el presente analisis se han excluido los centros con menos de 30 pacientes y han quedado finalmente 42 hospitales (2.975 pacientes). Se presentan los valores de 4 indicadores de calida…
Risk Factors for Anastomotic Leak After Colon Resection for Cancer
To determine pre-/intraoperative risk factors for anastomotic leak after colon resection for cancer and to create a practical instrument for predicting anastomotic leak risk.Anastomotic leak is still the most dreaded complication in colorectal surgery. Many risk factors have been identified to date, but multicentric prospective studies on anastomotic leak after colon resection are lacking.Fifty-two hospitals participated in this prospective, observational study. Data of 3193 patients, operated for colon cancer with primary anastomosis without stoma, were included in a prospective online database (September 2011-September 2012). Forty-two pre-/intraoperative variables, related to patient, tu…
Clinical profile of motor neuron disease patients with lower urinary tract symptoms and neurogenic bladder
Introduction: Lower urinary tract symptoms (LUTS) are frequent in motor neuron disease (MND) patients, but clinical factors related to them are unknown. We describe differences in LUTS among MND phenotypes and their relationship with other clinical characteristics, including prognosis. Methods: For this study, we collected clinical data of a previously published cohort of patients diagnosed with classical amyotrophic lateral sclerosis (cALS), progressive muscular atrophy (PMA) or primary lateral sclerosis (PLS) with and without LUTS. Familial history was recorded and the C9ORF72 expansion was analysed in the entire cohort Patients were followed-up for survival until August 2016. Results: Fi…
miR‐200c and phospho‐AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis
Lung metastasis is the major cause of death in osteosarcoma patients. However, molecular mechanisms underlying this metastasis remain poorly understood. To identify key molecules related with pulmonary metastasis of pediatric osteosarcomas, we analyzed high-throughput miRNA expression in a cohort of 11 primary tumors and 15 lung metastases. Results were further validated with an independent cohort of 10 primary tumors and 6 metastases. In parallel, we performed immunohistochemical analysis of activated signaling pathways in 36 primary osteosarcomas. Only phospho-AKT associated with lower overall survival in primary tumors, supporting its role in osteosarcoma progression. CTNNB1 expression a…
Relaxant Effects of the Selective Estrogen Receptor Modulator, Bazedoxifene, and Estrogen Receptor Agonists in Isolated Rabbit Basilar Artery
We have previously shown that the selective estrogen receptor modulator, bazedoxifene, improves the consequences of ischemic stroke. Now we aimed to characterize the effects and mechanisms of action of bazedoxifene in cerebral arteries. Male rabbit isolated basilar arteries were used for isometric tension recording and quantitative polymerase chain reaction. Bazedoxifene relaxed cerebral arteries, as 17-β-estradiol, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol [estrogen receptor (ER) α agonist], and G1 [G protein-coupled ER (GPER) agonist] did it (4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol > bazedoxifene = G1 > 17-β-estradiol). 2,3-Bis(4-hydroxyphenyl)-propionitrile (E…
Altered antioxidant-oxidant status in the aqueous humor and peripheral blood of patients with retinitis pigmentosa.
Retinitis Pigmentosa is a common form of hereditary retinal degeneration constituting the largest Mendelian genetic cause of blindness in the developed world. It has been widely suggested that oxidative stress possibly contributes to its pathogenesis. We measured the levels of total antioxidant capacity, free nitrotyrosine, thiobarbituric acid reactive substances (TBARS) formation, extracellular superoxide dismutase (SOD3) activity, protein, metabolites of the nitric oxide/cyclic GMP pathway, heme oxygenase-I and inducible nitric oxide synthase expression in aqueous humor or/and peripheral blood from fifty-six patients with retinitis pigmentosa and sixty subjects without systemic or ocular …
Obstetric and Neonatal Outcome of Pregnancies Fathered by Males on Immunosuppression After Solid Organ Transplantation
Immunosuppressive drugs may influence spermatogenesis, but little is known about outcome of pregnancies fathered by transplanted males. We estimated risk of adverse outcomes in pregnancies (with data after the first trimester) fathered by males that had undergone organ transplantation and were treated with immunosuppression. A population-based study, linking data from the Norwegian transplant registry and the Medical Birth Registry of Norway during 1967-2009 was designed. All Norwegian men undergoing solid organ transplantation were included. Odds ratios for major malformations, preeclampsia, preterm delivery (<37 weeks) and small-for-gestational-age were obtained using logistic regression.…
Trajectories of stress biomarkers and anxious-depressive symptoms from pregnancy to postpartum period in women with a trauma history
Background: Cross-sectional studies have found that a trauma history can be associated with anxious-depressive symptomatology and physiological stress dysregulation in pregnant women. Methods: This prospective study examines the trajectories of both anxiety and depressive symptoms and salivary cortisol and alpha-amylase biomarkers from women with (n = 42) and without (n = 59) a trauma history at (i) 38th week of gestation (T1), (ii) 48 hours after birth (T2), and (iii) three months after birth (T3). Results: The quantile regression model showed that trauma history was associated with higher cortisol levels at T1 and this difference was sustained along T2 and T3. Conversely, there were no si…
Combined resistance and endurance training at a moderate-to-high intensity improves physical condition and quality of life in liver transplant patients.
Background: Although currently, moderate and high intensity concurrent physical exercise is prescribed in populations with special needs due to its greater effect on physical condition and health-related quality of life (HRQOL), there are no data in the liver transplantation (LT) setting. Aim: To evaluate changes in maximal strength, aerobic capacity, body composition, liver function, and HRQOL in LT patients after a moderate to high intensity combined resistance-endurance training. Material and methods: 6 months after LT, 54 patients were randomized into two groups: intervention group (IG) and control group (CG). 50 patients completed the study with repeat testing at 6 and 12 months after …
Redox Status, Dose and Antioxidant Intake in Healthcare Workers Occupationally Exposed to Ionizing Radiation
The purpose of this study was to evaluate the relationship between blood redox status, dose and antioxidant dietary intake of different hospital staff groups exposed to low doses of ionizing radiation (LDIR) (Interventional Radiology and Cardiology, Radiation Oncology, and Nuclear Medicine) and non-exposed. Personal dose equivalent (from last year and cumulative), plasma antioxidant markers (total antioxidant capacity, extracellular superoxide dismutase activity, and glutathione/oxidized glutathione ratio), oxidative stress markers (nitrites and nitrates, and lipid peroxidation) and dietary intake (antioxidant capacity using ORAC values) were collected and analyzed from 28 non-exposed healt…
Emergent Uric Acid Treatment is Synergistic with Mechanical Recanalization in Improving Stroke Outcomes in Male and Female Rats.
Preclinical and clinical studies support a promising, albeit not definitive, neuroprotective effect of emergent uric acid (UA) administration in ischemic stroke. We assessed the effects of UA in an ischemic stroke model relevant to the current treatment paradigm of mechanical thrombectomy within the STAIR/RIGOR recommendations. A cohort of male and female Wistar rats was subjected to ischemic stroke with mechanical recanalization under physiological monitoring. The effects of transient middle cerebral artery occlusion (tMCAO) with adjunctive UA (IV, 16 mg/kg) or vehicle treatment were assessed at 24 h and 7 days. Outcomes included neurofunctional impairment, brain infarct (TTC staining, MRI…
Identification of Epigenetic Methylation Signatures With Clinical Value in Crohn's Disease.
INTRODUCTION: DNA methylation is an epigenetic mechanism that regulates gene expression and represents an important link between genotype, environment, and disease. It is a reversible and inheritable mechanism that could offer treatment targets. We aimed to assess the methylation changes on specific genes previously associated with Crohn's disease (CD) and to study their possible associations with the pathology. METHODS: We included 103 participants and grouped them into 2 cohorts (a first [n = 31] and a second validation [n = 72] cohort), with active CD (aCD) and inactive CD (iCD) and healthy participants (CTR). DNA was obtained from the peripheral blood and analyzed by the Agena platform.…
Epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole for six Candida species as determined by the colorimetric Sensititre YeastOne method
ABSTRACT In the absence of clinical breakpoints (CBP), epidemiological cutoff values (ECVs) are useful to separate wild-type (WT) isolates (without mechanisms of resistance) from non-WT isolates (those that can harbor some resistance mechanisms), which is the goal of susceptibility tests. Sensititre YeastOne (SYO) is a widely used method to determine susceptibility of Candida spp. to antifungal agents. The CLSI CBP have been established, but not for the SYO method. The ECVs for four azoles, obtained using MIC distributions determined by the SYO method, were calculated via five methods (three statistical methods and based on the MIC 50 and modal MIC). Respectively, the median ECVs (in mg/lit…
Stem cell paracrine actions in tissue regeneration and its potential therapeutic effect in human endometrium: a retrospective study.
Objective: Determining genetic and paracrine mechanisms behind endometrial regeneration in Asherman's Syndrome and Endometrial Atrophy (AS/EA) patients after autologous CD133+ bone marrow-derived stem cells (CD133+BMDSCs) transplantation. Design: Retrospective study using human endometrial biopsies and mouse models. Setting: Fundación-IVI, IIS-La Fe, Valencia, Spain. Samples: Endometrial biopsies collected before and after CD133+BMDSCs therapy, from 8 women with AS/EA (NCT02144987). And uterus from 5 mice, with only left horns receiving CD133+BMDSCs therapy. Methods: In human samples, hematoxylin and eosin (H&E) staining, RNA arrays, PCR validation and neutrophil elastase (NE) immunohistoch…
Two independent epigenetic biomarkers predict survival in neuroblastoma.
Background Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with a highly variable clinical course, ranging from spontaneous regression to life-threatening disease. Survival rates for high-risk NB patients remain disappointingly low despite multimodal treatment. Thus, there is an urgent clinical need for additional biomarkers to improve risk stratification, treatment management, and survival rates in children with aggressive NB. Results Using gene promoter methylation analysis in 48 neuroblastoma tumors with microarray technology, we found a strong association between survival and gene promoter hypermethylation (P = 0.036). Hypermethylation of 70 genes significantly …
Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay
Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions…
A score model for the continuous grading of early allograft dysfunction severity
Early allograft dysfunction (EAD) dramatically influences graft and patient outcomes. A lack of consensus on an EAD definition hinders comparisons of liver transplant outcomes and management of recipients among and within centers. We sought to develop a model for the quantitative assessment of early allograft function [Model for Early Allograft Function Scoring (MEAF)] after transplantation. A retrospective study including 1026 consecutive liver transplants was performed for MEAF score development. Multivariate data analysis was used to select a small number of postoperative variables that adequately describe EAD. Then, the distribution of these variables was mathematically modeled to assig…
Cardiovascular Events During and After Bronchiectasis Exacerbations and Long-term Mortality.
ABSTRACT Background Population-based and retrospective studies have shown that risk for cardiovascular events such as arrythmias, ischemic episodes or heart failure, increase during and after bronchiectasis exacerbations. Research Question What are the risk factors for cardiovascular events (CVE) during and after bronchiectasis exacerbations and its impact on mortality? Study Design and Methods This was a post-hoc retrospective analysis of a prospective observational study of 250 patients with bronchiectasis at two tertiary care hospitals. Only the first exacerbation was considered for each patient, collecting demographic, comorbidity, and severity data. The main outcomes were the appearanc…
Short-term Neuropsychiatric Outcomes and Quality of Life in COVID-19 Survivors
ABSTRACTBackgroundThe general medical impacts of coronavirus (COVID-19) are increasingly appreciated. However, its impact on neurocognitive, psychiatric health and quality of life (QoL) in survivors after the acute phase is poorly understood. We aimed to evaluate neurocognitive function, psychiatric symptoms, and QoL in COVID-19 survivors shortly after hospital discharge.MethodsThis was a cross-sectional analysis of a prospective study of hospitalized COVID-19 survivors followed-up for 2 months after discharge. A battery of standardized instruments evaluating neurocognitive function, psychiatric morbidity, and QoL (mental and physical components) was administered by telephone.FindingsOf the…
Correlation between fecal calprotectin and inflammation in the surgical specimen of Crohn's disease
Background: An accurate assessment of the inflammatory activity is crucial to establish the most appropriate treatment in Crohn's disease (CD). The present study aimed to evaluate the utility of preoperative fecal calprotectin (FC) measurement in small bowel CD and its relationship with inflammatory activity in surgical pathology specimens. Methods: This was a prospective observational study including all the patients with small bowel CD operated on at our center between March 2011 and September 2013. Preoperative laboratory and stool tests were performed. A meticulous exploration of entire small bowel was performed during surgery, and the resected bowel (or a sample of whole intestinal wal…
Early Referral to an ALS Center Reduces Several Months the Diagnostic Delay: A Multicenter-Based Study.
Objective: To analyze those factors contributing to the diagnostic delay in ALS.Methods: Consecutive ALS patients were categorized as those studied in departmental hospitals and those studied in a referral ALS center. Demographic and clinical variables, together with data of the diagnostic pathway were collected. Multivariable models were used to assess their effect in the time between symptoms onset and the first neurologist visit (time symptoms-neurologist), in the time between the first neurologist visit and the diagnosis (time neurologist-diagnosis) and in the diagnostic delay.Results: 166 ALS patients with a median diagnostic delay of 11.53 months (IQR: 6.68, 15.23) were included. The …
Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation.
Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc). The ABCB1 variant in rs1045642 was associated with significantly hig…
Predictive factors of immune tolerance treatment response in severe haemophilia A patients with inhibitors: A real‐world report from a single centre, mixed retrospective‐prospective long‐term study
Tomografía computarizada a nivel de C3 y dinamometría como técnicas de diagnóstico de sarcopenia en pacientes con cáncer de cabeza y cuello
Introducción: Estudio piloto que determina el diagnóstico de sarcopenia mediante tomografía computarizada (TC) a nivel de la tercera vértebra cervical (C3) y dinamometría en pacientes con cáncer de cabeza y cuello. Comparación de la masa magra (MM) determinada mediante TC con técnicas clásicas de antropometría y dinamometría.Material y métodos: Se analizó la MM y el tejido adiposo mediante TC a nivel de C3 en 37 pacientes oncológicos mediante Unidades Hounsfield (UH). Posteriormente, se calculó el índice musculoesquelético (IME) y se determinó la fuerza prensora de mano para la determinación de sarcopenia. Por último, se comparó el IME mediante técnicas de valoración antropométrica clásica …
Short‐term neuropsychiatric outcomes and quality of life in COVID‐19 survivors
BACKGROUND: The general medical impacts of coronavirus (COVID-19) are increasingly appreciated. However, its impact on neurocognitive, psychiatric health and quality of life (QoL) in survivors after the acute phase is poorly understood. We aimed to evaluate neurocognitive function, psychiatric symptoms, and QoL in COVID-19 survivors shortly after hospital discharge. METHODS: This was a cross-sectional analysis of a prospective study of hospitalised COVID-19 survivors followed-up for 2 months after discharge. A battery of standardised instruments evaluating neurocognitive function, psychiatric morbidity, and QoL (mental and physical components) was administered by telephone. RESULTS: Of the …
Analysis of the Possible Persistent Genotoxic Damage in Workers Linked to the Ardystil Syndrome
[EN] Background: A combination of several factors including a change in the paint application system; a lack of proper hygiene; and inadequate safety measures caused a severe health impact in the workers of some textile painting factories. This outbreak, mainly characterized by respiratory disorders, caused the death of six people and it has been classified as Ardystil syndrome. Materials and Methods: Fifty-two workers involved in the outbreak and 48 healthy subjects not known to have exposed to the potentially mutagenic agents participated in the study. The program evaluated possible genotoxic damage through the sister chromatid exchange (SCE) cytogenetic biomarker assay. We determined the…
Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy
ABSTRACTObjectiveTo assess in adult spinal muscular atrophy (SMA) patients the construct validity and responsiveness of several outcome measures.MethodsPatients older than 15 years and followed-up at least for 6 months, between October 2015 and August 2020, with one motor function scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM) in five referral centers were included. Bedside functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) were also collected when available. Correlations and regression models were performed to evaluate the construct validity. The monthly slopes of change were use…
Effect of uric acid in animal models of ischemic stroke: A systematic review and meta-analysis
Addition of uric acid (UA) to thrombolytic therapy, although safe, showed limited efficacy in improving patients’ stroke outcome, despite alleged neuroprotective effects of UA in preclinical research. This systematic review assessed the effects of UA on brain structural and functional outcomes in animal models of ischemic stroke. We searched Medline, Embase and Web of Science to identify 16 and 14 eligible rodent studies for qualitative and quantitative synthesis, respectively. Range of evidence met 10 of a possible 13 STAIR criteria. Median (Q1, Q3) quality score was 7.5 (6, 10) on the CAMARADES 15-item checklist. For each outcome, we used standardised mean difference (SMD) as effect size…
Sister chromatid exchange, (SCE), High-Frequency Cells (HFCs) and SCE distribution patterns in peripheral blood lymphocytes of Spanish adult smokers compared to non-smokers
According to the International Agency for Research on Cancer, smoking tobacco is a major cause of cancer in humans. It causes about half of all male cancer deaths and an ever increasing number of cancer deaths in females. The aim of this study was to establish whether cigarette smoking increases sister chromatid exchanges (SCEs) in peripheral blood lymphocytes in two Spanish population groups; light and heavy smokers. The mean number of High-Frequency Cells (HFCs) was determined and, the SCE distribution pattern among the chromosomes was analysed represented by a ratio described below. A local sample of 101 adult smokers (n = 48) and non-smokers (n = 53), aged from 18 to 49 years, was studi…
Can stress biomarkers predict preterm birth in women with threatened preterm labor?
Background: Preterm birth is a major paediatric challenge difficult to prevent and with major adverse outcomes. Prenatal stress plays an important role on preterm birth; however, there are few stress-related models to predict preterm birth in women with Threatened Preterm Labor (TPL). Objective: The aim of this work is to study the influence of stress biomarkers on time until birth in TPL women. Methods: Eligible participants were pregnant women between 24 and 31 gestational weeks admitted to the hospital with TPL diagnosis (n = 166). Stress-related biomarkers (a-amylase and cortisol) were determined in saliva samples after TPL diagnosis. Participants were followed-up until labor. A paramet…
Development and electronic validation of the revised Cystic Fibrosis Questionnaire (CFQ-R Teen/Adult)
Abstract Background The Cystic Fibrosis Questionnaire-Revised (CFQ-R+14) is a disease-specific, health-related quality of life instrument for cystic fibrosis (CF) patients ≥14years. We have developed a Spanish electronic version of the CFQ-R (e-CFQ-R+14 Spain). Our aim was to compare the paper and electronic versions and to validate the electronic version. Methods Fifty CF patients completed the study. All answered the paper and electronic versions on day 1 and repeated the e-CFQR version 15days later. Results Concordance between the electronic and paper copy versions was high, with correlations above 0.9 in all domains. Test-retest reliability of the e-CFQ-R results was strong, with coeffi…
A preliminary study to assess the impact of maternal age on stress-related variables in healthy nulliparous women
Purpose: Childbearing age has progressively increased in industrialized countries. The impact of this delay on motherhood, however, requires further research. Methods: The study sample included a prospective cohort of healthy nulliparous pregnant women aged between 18 and 40 years (n = 148) assessed at 38 weeks gestation (Time#1, T1), 48 h after birth (Time#2, T2), and 3 months after birth (Time#3, T3). The effect of age on psychological, biological, and social variables was evaluated. Maternal psychological symptoms in terms of depression and anxiety were assessed at T1-T3; and parenting stress at T3. Stress biomarkers (cortisol, alpha-amylase) were determined in mothers at T1-T3. Question…
Silencing of Foxp3 enhances the antitumor efficacy of GM-CSF genetically modified tumor cell vaccine against B16 melanoma
Antonio Miguel,1 Luis Sendra,1 Ver&oacute;nica No&eacute;,2 Carles J Ciudad,2 Francisco Das&iacute;,3,4 David Hervas,5 Mar&iacute;a Jos&eacute; Herrero,1,6 Salvador F Ali&ntilde;o17 1Department of Pharmacology, Faculty of Medicine, University of Valencia, 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, 3Research University Hospital of Valencia, INCLIVA Health Research Institute, 4Department of Physiology, Faculty of Medicine, University of Valencia Foundation, 5Biostatistics Unit, 6Pharmacogenetics Unit, Instituto de Investigaci&oacute;n Sanitaria La Fe (IIS La Fe), 7Clinical Pharmacology Unit, ACM Hospital Univers…
Anastomotic leakage after colon cancer resection: does the individual surgeon matter?
Aim Anastomotic leakage is one of the most feared complications after colonic resection. Many risk factors for anastomotic leakage have been reported, but the impact of an individual surgeon as a risk factor has scarcely been reported. The aim of this study was to assess if the individual surgeon is an independent risk factor for anastomotic leakage in colonic cancer surgery. Method This was a retrospective analysis of prospectively collected data from patients who underwent elective resection for colon cancer with anastomosis at a specialized colorectal unit from January 1993 to December 2010. Anastomotic leaks were diagnosed according to standardized criteria. Patient and tumour character…
Synergistic activation of AMPK prevents from polyglutamine-inducedtoxicity inCaenorhabditis elegans
11 páginas, 4 figuras. Supplementary material related to this article can be found, in the online version, at doi: https://doi.org/10.1016/j.phrs.2020.105105.
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Circulating miRNAs as diagnostic biomarkers for adolescent idiopathic scoliosis
AbstractThe aetiology of adolescent idiopathic scoliosis (AIS) has been linked to many factors, such as asymmetric growth, neuromuscular condition, bone strength and genetic background. Recently, epigenetic factors have been proposed as contributors of AIS physiopathology, but information about the molecular mechanisms and pathways involved is scarce. Regarding epigenetic factors, microRNAs (miRNAs) are molecules that contribute to gene expression modulation by regulating important cellular pathways. We herein used Next-Generation Sequencing to discover a series of circulating miRNAs detected in the blood samples of AIS patients, which yielded a unique miRNA biomarker signature that diagnos…
Inflammatory bowel disease in patients over the age of 70y. Does the disease duration influence its behavior?
Introduction: The fastest growing segment of our population is that of people above 70 years of age. Elderly patients with IBD exhibit several specific problems. Our objective was to evaluate the clinical course, the side effects of the treatments and the need for surgery of elderly patients, regardless of the age of onset.Materials and Methods: This was a cross-sectional study wherein retrospective data were collected from multiple centers from seven hospitals within the Valencia metropolitan area. Data were collected on patients older than 70y with inflammatory bowel disease.Results: We identified a total of 331 patients older than 70 years of age (5.3% of patients monitored at our center…
P051 DNA methylation signatures associated with pathogenesis Crohn's disease-related genes
Nusinersen in adult patients with 5q spinal muscular atrophy: a multicenter observational cohorts’ study
ABSTRACTObjectiveTo assess safety and efficacy of nusinersen in adult 5q spinal muscular atrophy (SMA) patients.MethodsPatients older than 15 years and followed at least for 6 months with one motor scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM) in five referral centers were included. Clinical and patients’ global impression of change (CGI-C and PGI-C) were recorded in treated patients at the last visit. Functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) and the percent-predicted forced vital capacity were collected when available.ResultsSeventy-nine SMA patients (39 treated with n…
Anxiety and depressive symptoms, and stress biomarkers in pregnant women after in vitro fertilization: a prospective cohort study.
STUDY QUESTION Does in vitro fertilization (IVF) affect the course of anxiety and depressive symptoms as well as physiological stress from pregnancy to postpartum period? SUMMARY ANSWER IVF mothers have more anxiety symptoms and higher stress biomarker levels but fewer depression symptoms than natural conception mothers at the third trimester of pregnancy, but these differences are negligible during postpartum period. WHAT IS KNOWN ALREADY Cross-sectional studies have found an association between IVF and high stress levels during the prenatal period. There is, however, no follow-up study about the IVF effect on the mental health status from pregnancy to postpartum, adopting simultaneous mea…
Impact of maternal age on infants' emotional regulation and psychomotor development
AbstractBackgroundMaternal age has progressively increased in industrialized countries. Most studies focus on the consequences of delayed motherhood for women's physical and mental health, but little is known about potential effects on infants' neurodevelopment. This prospective study examines the association between maternal age and offspring neurodevelopment in terms of both psychomotor development (Ages & Stages Questionnaires-3) and emotional competences (Early Childhood Behavior Questionnaire).MethodsWe evaluated a cohort of healthy pregnant women aged 20–41 years and their offspring, assessed at 38 weeks gestation (n= 131) and 24 months after birth (n= 101). Potential age-related …
Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis
Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membra…
MTHFR and VDR Polymorphisms Improve the Prognostic Value of MYCN Status on Overall Survival in Neuroblastoma Patients
Single nucleotide polymorphisms (SNPs) in Pharmacogenetics can play an important role in the outcomes of the chemotherapy treatment in Neuroblastoma, helping doctors maximize efficacy and minimize toxicity. Employing AgenaBioscience MassArray, 96 SNPs were genotyped in 95 patients looking for associations of SNP with response to induction therapy (RIT) and grade 3&ndash
Moral reasoning and moral conflict in patients of the amyotrophic lateral sclerosis – Frontotemporal dementia spectrum
The aim of this study was to investigate the moral reasoning and moral conflict in patients of the amyotrophic lateral sclerosis – frontotemporal dementia (ALSFTD) spectrum. Ten ALS patients without cognitive impairment, 10 ALS patients with cognitive or behavioral impairment, 10 ALSFTD patients and 23 controls were examined with neuropsychological and behavioral tests as well as with a set of eight well -designed moral dilemmas. The responses to the moral dilemmas were used as proxies to evaluate interpersonal moral reasoning. Reactivity to change, reaction time and arousal were used as markers of moral conflict. ALSFTD patients showed more “utilitarian” responses and less moral conflict t…
Standard Outcome Indicators After Colon Cancer Resection. Creation of a Nomogram for Autoevaluation
Abstract Introduction Lately there has been an increasing interest in identifying quality standards in different pathologies, among them colon cancer due to its great prevalence. The main goal of this study is to define the quality standards of colon cancer surgery based on a large prospective national study dataset. Methods Data from the prospective national study ANACO were used. This study included a consecutive series of patients operated on for colon cancer in 52 Spanish hospitals (2011–2012). Centers with less than 30 patients were excluded. The present analysis finally included 42 centers (2975 patients). Based on the results obtained in 4 main indicators from each hospital (anastomo…
Impact ofABCsingle nucleotide polymorphisms upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia
Anthracycline uptake could be affected by efflux pumps of the ABC family. The influence of 7 SNPs of ABC genes was evaluated in 225 adult de novo acute myeloid leukemia (AML) patients. After multivariate logistic regression there were no significant differences in complete remission, though induction death was associated to ABCB1 triple variant haplotype (p = .020). The ABCB1 triple variant haplotype was related to higher nephrotoxicity (p = .016), as well as this haplotype and the variant allele of ABCB1 rs1128503, rs2032582 to hepatotoxicity (p = .001; p = .049; p .001). Furthermore, the variant allele of ABCC1 rs4148350 was related to severe hepatotoxicity (p = .044), and the variant al…
Immunosuppressive profiles in liquid biopsy at diagnosis predict response to neoadjuvant chemotherapy in triple-negative breast cancer.
Background: Triple-negative breast cancer (TNBC) is characterised by high pathological complete response to neoadjuvant chemotherapy (NAC). However, refractory and poor NAC responders still face very poor outcome, emphasising the urgent need for tools that facilitate identification of these patients, so that surgery or alternatives to NAC are considered early in the treatment protocol. Materials and methods: We combined metabolomics, exosome circulating miRNAs and flow cytometry experimental approaches in TNBC patients at diagnosis with immunohistochemistry in needle biopsy tumours to generate NAC-response predictive models. We also co-cultured and studied crosstalk between isolated patient…
Trajectories of stress biomarkers and anxious-depressive symptoms from pregnancy to postpartum period in women with a trauma history
Background: Cross-sectional studies have found that a trauma history can be associated with anxious-depressive symptomatology and physiological stress dysregulation in pregnant women. Methods: This prospective study examines the trajectories of both anxiety and depressive symptoms and salivary cortisol and α-amylase biomarkers from women with (n = 42) and without (n = 59) a trauma history at (i) 38th week of gestation (T1), (ii) 48 hours after birth (T2), and (iii) three months after birth (T3). Results: The quantile regression model showed that trauma history was associated with higher cortisol levels at T1 and this difference was sustained along T2 and T3. Conversely, there were no signif…