Estibalitz Laresgoiti Servitje - Academia.edu (original) (raw)

Papers by Estibalitz Laresgoiti Servitje

Gastroenterology, 2015

Anastomotic leak (AL) is a devastating complication of colorectal surgery. It is associated with ... more Anastomotic leak (AL) is a devastating complication of colorectal surgery. It is associated with increased morbidity and mortality 1-3 , and higher risk of permanent ostomy and reoperation. 4-6 Loop diversion is a known alternative approach in the management of AL with similar or better outcomes than anastomotic revision. 1,4 We compared the efficacy of diverting stoma versus anastomotic revision in the management of colorectal leaks. Methods: Patients who developed colorectal AL at the Mount Sinai Hospital from 2003-2013 were identified retrospectively and were separated based on surgical approach: Loop diversion (LD) versus Anastomotic Revision (AR). AR was defined as anastomotic resection or revision and diversion with or without over-sewing of the distal stump (Hartmann's procedure). Diversion insufficiency was defined as reoperation, drainage, and creation or revision of an end stoma in either group. Patients were followed up to 30 days after they were initially operated on for AL. Results: 139 patients with colorectal AL managed operatively were identified. 87 (62.6%) in the LD and 52 (37.4%) in the AR group. 8 (9.2%) patients in the LD, and 6 (11.5%) patients in the AR group required reoperation and were insufficient (p= 0.772). Similarly, there was no difference in the rate of hospital days or SICU days between groups. Patients in the LD group were significantly younger (p = 0.003), and had a lower rate of diverticulosis (p = 0.03). [Table 1] Conclusions: There is no significant difference inreoperation rates, hospital stay, or SICU days between groups. This study shows that the creation of a diverting loop ileostomy is and effective treatment for AL and is equally efficacious as anastomotic revision and formation of an end stoma in the management of colorectal anastomotic leaks.

Endocrine Practice, 2021

OBJECTIVE To describe a third-degree polynomial function (hysteresis) of the effect size of age, ... more OBJECTIVE To describe a third-degree polynomial function (hysteresis) of the effect size of age, obesity, and insulin sensitivity over the carotid intima-media thickness (c-IMT), in children and adults groups. METHODS A quasi-experimental study with fixed factor analysis of age (children 8-to-12 years n=73 / adults 21-to-45 years old n=82) and obesity (yes n=76 /no n=79) was conducted to analyse the effect on c-IMT and Matsuda-ISI values. This quasi-experimental design was analysed with robust regression modelling. RESULTS The additive effect of obesity, independent of age, was evident in the case of c-IMT values. There was no interaction effect but a significant difference between subjects with normal weight and those with obesity was found (p < 0.0001). The difference between adults and children was also significant, but the effect size was smaller. A model was created based on age, Tanner stage, and obesity using the c-IMT and Matsuda-ISI values. A linear function fit as R2, and the cubic function estimated parameters like a polynomial model. CONCLUSION This practical study design showed children with obesity displayed the same levels of carotid-intima media abnormalities as adults with obesity. The polynomial shape of the model suggests potentially poor outcomes that resemble the hysteresis process and that may predict chronic cardiometabolic events during early adulthood.

Growth Hormone & IGF Research, 2020

Objective: Growth hormone (GH) deficiency has been associated with increased steatosis but the mo... more Objective: Growth hormone (GH) deficiency has been associated with increased steatosis but the molecular mechanism has not been fully elucidated. We investigated the effect of GH on lipid accumulation of HepG2 cells cultured on an in vitro steatosis model and examined the potential involvement of insulin-like growth factor 1 (IGF-1) as well as lipogenic and lipolytic molecules. Methods: Control and steatosis conditions were induced by culturing HepG2 cells with 5.5 or 25 mmol/l glucose for 24 h, respectively. Afterward, cells were exposed to 0, 5, 10 or 20 ng/ml GH for another 24 h. Lipid content was quantified as well as mRNA and protein levels of IGF-1, carbohydrate responsive element-binding protein (ChREBP), sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor alpha (PPAR-alpha) by qPCR and western blot, respectively. Data were analyzed by one-way ANOVA and the Games-Howell post-hoc test. Results: In the steatosis model, HepG2 hepatocytes showed a significant 2-fold increase in lipid amount as compared to control cells. IGF-1 mRNA and protein levels were significantly increased in control cells exposed to 10 ng/ml GH, whereas high glucose abolished this effect. High glucose also significantly increased both mRNA and protein of ChREBP and FAS without having effect on SREBP1c, CPT1A and PPAR-alpha. However, GH inhibited ChREBP and FAS production, even in HepG2 hepatocytes cultured under steatosis conditions. Conclusions: Growth hormone ameliorates high glucose-induced steatosis in HepG2 cells by suppressing de novo lipogenesis via ChREBP and FAS down-regulation.

Journal of Pediatric Endocrinology and Metabolism, 2019

Background Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disord... more Background Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disorder in the pediatric population and has grown along with the obesity pandemic in which we live today. Adipose tissue storage in the upper body segment has been positively correlated with visceral adiposity and metabolic disease, which suggests that neck circumference could represent an easily accessible and replicable anthropometric measurement to identify patients with a higher risk of developing NAFLD. The main purpose of this study is to determine if there is an association between neck circumference and NAFLD. The secondary objectives are to establish cutoff values based on gender and puberty staging. Methods We included a sample pediatric population of 112 patients diagnosed with obesity aged between 6 and 18 years. We performed anthropometric and metabolic measurements on every patient, and NAFLD diagnosis was determined with hepatic ultrasound. Results The neck circumference was la...

Annals of Hepatology, 2019

Introduction and Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common liver d... more Introduction and Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and it is more prevalent in Hispanic males. The gender differences can be explained by body fat distribution, lifestyle, or sex hormone metabolism. We evaluated anthropometric and metabolic differences by gender in children with and without NAFLD. Methods: We included 194 participants (eutrophic, overweight, and individuals with obesity). The presence of NAFLD was determined using ultrasonography, and we evaluated the association between this disease with metabolic and anthropometric variables by gender. Results: The mean age was 10.64 ± 2.54 years. The frequency of NAFLD in boys was 24.51% and in girls was 11.96% (OR = 2.39; 95%CI = 1.10-5.19; p = 0.025). For girls, NAFLD was significantly associated with triglycerides (p = 0.012), homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.048), and the visceral adiposity index (VAI) (p = 0.024). The variables related to NAFLD in a gender-specific manner were body mass index (BMI) (p = 0.001), waist circumference (WC) (p < 0.001), HDL cholesterol (p = 0.021), alanine aminotransferase (ALT) (p < 0.001), and aspartate aminotransferase (AST) (p = 0.002). Conclusions: In our study NAFLD is more frequent in boys, only ALT, and no other clinical or metabolic variables, were associated with NAFLD in these patients. HOMA-IR, VAI, triglyceride levels, and ALT were associated with NAFLD only in girls. The ALT cutoff points for the development of NAFLD in our study were 28.5 U/L in females and 27.5 U/L in males. Our findings showed that NAFLD should be intentionally screened in patients with obesity, particularly in boys.

Cellular Signalling, 2019

Isomers of conjugated linoleic acid induce insulin resistance through a mechanism involving activ... more Isomers of conjugated linoleic acid induce insulin resistance through a mechanism involving activation of protein kinase cε in liver cells. Cls (2018),

Endocrine Practice, 2016

Objective: The accumulation of abdominal fat is associated with cardiometabolic abnormalities. Wa... more Objective: The accumulation of abdominal fat is associated with cardiometabolic abnormalities. Waist circumference (WC) measurements allow an indirect evaluation of abdominal adiposity. However, controversy exists over which WC reference values are the most suitable for identifying the pediatric population at risk. The aim of the study was to evaluate the ability of various WC indices to identify abdominal obesity as diagnostic tools for predicting cardiometabolic risk in Mexican children and adolescents. Methods: Anthropometric measurements were performed and biochemical profiles determined in a crosssectional study that included 366 children and adolescents. Four parameters were used to evaluate abdominal obesity in our study group: (1) WC >90th percentile, according to the Fernández reference in a Mexican-American population measured by the National Center for Health Statistics (NCHS) technique; (2) WC >90th percentile, according to the Klünder reference in a Mexican population (measured by the World Health Organization [WHO] technique); (3) waist-to-height ratio (WHtR) >0.5 according to WHO; and (4) WHtR >0.5 according to NCHS. The ability of each of the indices to discriminate cardiometabolic abnormalities (fasting plasma glucose, dyslipidemia, and hypertension) was assessed. Results: WHtR >0.5 according to WHO or NCHS references showed greater sensitivity to detect metabolic abnormalities compared to percentile reference parameters (74.3 to 100% vs. 59.0 to 88.9%; P<.05). However, the percentiles displayed more specificity to identify these alterations (46.2 to 62.2 vs. 21.3 to 46.9; P<.05). Area under the curve analysis showed that WHtR >0.5 can more readily detect hypertriglyceridemia (0.642), hypoalphalipoproteinemia (0.700), and a combination of two or more metabolic abnormalities (0.661), whereas WC >90th percentile, according to Klünder, better detected hyperglycemia (0.555). Conclusion: WHtR >0.5 is a sensitive measure to identify pediatric patients with cardiometabolic alterations, despite its low specificity, and is a useful diagnostic tool to detect populations at risk. Based on the results of this study, we recommend preferential use of the Klünder waist circumference references over the Fernández method in Mexican pediatric populations.

The Journal of Maternal-Fetal & Neonatal Medicine, 2019

Purpose: Neonatal sepsis is an important public health concern worldwide due to its immediate let... more Purpose: Neonatal sepsis is an important public health concern worldwide due to its immediate lethality and long-term morbidity rates, Clinical evaluation and laboratory analyses are indispensable for diagnosis of neonatal sepsis. However, assessing multiple biomarkers in neonates is difficult due to limited blood availability. The aim is to investigate if the neonatal sepsis in preterm could be identified by multiparameter analysis with flow cytometry. Materials and Methods: The expression of activation-related molecules was evaluated by flow cytometry in newborn with or without risk factors for sepsis. Results: Our analysis revealed that several markers could be useful for sepsis diagnosis, such as CD45RA, CD45RO, or CD71 on T cells; HLA-DR on NKT or classic monocytes, and TREM-1 on non-classic monocytes or neutrophils. However, ROC analysis shows that the expression of CD45RO on T lymphocytes is the only useful biomarker for diagnosis of neonatal late-onset sepsis. Also, decision tree analyses showed that CD45RO plus CD27 could help differentiate the preterm septic neonates from those with risk factors. Conclusions: Our study shows a complementary and practical strategy for biomarker assessment in neonatal sepsis.

International Journal of Environmental Research and Public Health, 2018

Intestinal perforation (IP) associated with necrotizing enterocolitis (NEC) is one of the leading... more Intestinal perforation (IP) associated with necrotizing enterocolitis (NEC) is one of the leading causes of mortality in premature neonates; with major nutritional and neurodevelopmental sequelae. Since predicting which neonates will develop perforation is still challenging; clinicians might benefit considerably with an early diagnosis tool and the identification of critical factors. The aim of this study was to forecast IP related to NEC and to investigate the predictive quality of variables; based on a machine learning-based technique. The Back-propagation neural network was used to train and test the models with a dataset constructed from medical records of the NICU; with birth and hospitalization maternal and neonatal clinical; feeding and laboratory parameters; as input variables. The outcome of the models was diagnosis: (1) IP associated with NEC; (2) NEC or (3) control (neither IP nor NEC). Models accurately estimated IP with good performances; the regression coefficients bet...

Children, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

The Journal of Clinical Endocrinology & Metabolism, 2016

Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascu... more Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascular disease and type 2 diabetes in children with obesity. Results of lifestyle modification programs have been discouraging, and the use of adjuvant strategies has been necessary. Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity. Design: A randomized, double-blinded, placebo-controlled clinical trial was conducted. Setting: Children with obesity were randomly assigned to receive metformin, CLA, or placebo. Results: Intervention had a positive effect in all groups. For insulin sensitivity Rd value (mg/kg/min), there was a statistically significant difference between the CLA vs placebo (6.53 ± 2.54 vs 5.05 ± 1.46, P = 0.035). Insulinemia and homeostatic model assessment of ins...

Viruses, 2021

BMJ open, Jan 17, 2018

To define and compare the reference interval of B-type natriuretic peptide (BNP) in healthy newbo... more To define and compare the reference interval of B-type natriuretic peptide (BNP) in healthy newborns (HN) from healthy mothers and with severe pre-eclampsia. Prospective, multicentre, cross-sectional study. Four obstetric wards of second-level academic hospitals. 167 HN, from 146 healthy and 21 severe pre-eclamptic women. We included newborns from healthy mothers with full-term pregnancies (38 to 42 gestational weeks), who received adequate prenatal care and who had Apgar scores ≥7 at 0 and 5 min. Newborns with chromosomopathies identified during prenatal consultations, those with respiratory distress and those with cardiac or pulmonary disease detected in the first paediatric evaluation were excluded from this study. In the group of pre-eclamptic women, we considered the same inclusion criteria, but the patients also had to meet the diagnostic criteria for pre-eclampsia with severity features, according to the American College of Obstetricians and Gynaecologists guidelines. The sam...

PLOS ONE, 2016

Furthermore, arterial cord blood TAC and IL-1β and IL1-RA levels positively predicted newborn iri... more Furthermore, arterial cord blood TAC and IL-1β and IL1-RA levels positively predicted newborn irisin concentrations. Multiple regression analyses showed that maternal IL-13 negatively predicted offspring irisin levels (p = 0.03) and that maternal IL-1β positively predicted newborn irisin concentrations (p = 0.046). Conclusion No evidence was found that serum irisin concentrations in mothers at pregnancy termination or those of their newborns correlated with maternal body mass index, the presence of diabetes mellitus, or free fatty acid levels. However, the results of this study indicated that cytokines might predict irisin concentration in mothers and their offspring, although interactions between irisin levels during pregnancy and the newborn have not yet been fully elucidated. and analysis, decision to publish, or preparation of the manuscript.

Immunology and Cell Biology, 2012

Human Reproduction Update, 2010

† Introduction † Search method † The role of the immune system in the origin of pre-eclampsia † T... more † Introduction † Search method † The role of the immune system in the origin of pre-eclampsia † The role of NK cells in pre-eclampsia † The expression and role of MHC molecules on the trophoblast † ILT receptors † The role of IFN-g and other cytokines † The Th1/Th2 paradigm and its relationship with pre-eclampsia † The role of regulatory T lymphocytes † Do Th17 lymphocytes participate in pre-eclampsia? † Negative co-regulatory molecules: their participation in immune control in pregnancy † Immune system modulation by DCs and their relationship with pre-eclampsia † The role of indoleamine 2,3-dioxygenase † Could damage-and pathogen-associated molecular patterns participate in the origins of pre-eclampsia? † Conclusions background: Pre-eclampsia is a syndrome of heterogeneous origin characterized by deficient placentation due to the inability of the cytotrophoblast to acquire an invasive phenotype and to remodel the uterine spiral arteries. One of the main problems observed early in pre-eclampsia is an altered regulation of the immune system, where the shift toward a Th2 cytokine profile observed in normal pregnancies, does not occur. In pre-eclampsia, high interferon (IFN)-g concentrations are present, along with transforming growth factor-b cytokines, which retard migration of cytotrophoblasts. methods: A review of the scientific literature was performed on the immunological factors associated with the origins of pre-eclampsia. The various components of the immune system that may be participating in the aberrant immune activation that pathologically affect early pregnancy events and inhibit cytotrophoblast invasion were identified. results and conclusions: Cells and their signaling and regulatory molecules have been implicated in the immunological alterations found in the placental microenvironment of patients who develop pre-eclampsia. One of the main differences found in pre-eclampsia is a shift toward Th1 responses and the production of IFN-g. The origin of IFN-g is not clearly identified and could be the uterine natural killer cells, the placental dendritic cells modulating Th responses, alterations in synthesis of or response to regulatory molecules, or changes in the function of regulatory T cells in pregnancy. Aberrant immune responses promoting pre-eclampsia may also be due to an altered fetal allorecognition or to inflammatory triggers. Understanding the immunological basis for pre-eclampsia will expand knowledge regarding other adverse pregnancy outcomes.

Biology of Reproduction, 2012

Pre-eclampsia is a syndrome characterized by inadequate placentation, which is due to deficient t... more Pre-eclampsia is a syndrome characterized by inadequate placentation, which is due to deficient trophoblastic invasion of the uterine spiral arteries. This deficiency can lead to placental hypoxia, secretion of proinflammatory cytokines, and release of angiogenic and antiangiogenic factors. Hypoxic conditions in the placenta can promote oxidative stress and the production of angiogenic factors that are antagonized by soluble receptors, which are also elevated in this syndrome. In addition to these factors, the development of hypertension in women with preeclampsia may be associated with the renin-angiotensin system and endothelial dysfunction. The presence of antiangiotensin II type 1 receptor autoantibodies is relevant in pre-eclampsia because it has been related to the secretion of antiangiogenic factors through cytokine pathways, indicating that autoimmune mechanisms may participate in the pathophysiology of this syndrome.

Biology of Reproduction, 2010

Several studies indicate that at the choriodecidual interface, where maternal and fetal tissues m... more Several studies indicate that at the choriodecidual interface, where maternal and fetal tissues make contact, a network of signals is established during labor that includes infiltration of leukocytes and secretion of pro-inflammatory cytokines. In this review, we provide an overview of the inflammatory milieu present in the choriodecidua during membrane rupture, describe the recruitment and homing of leukocytes to the reproductive tissues, and detail specific actions of the key chemokines released by the choriodecidual cells. These data lend further support to the hypothesis that labor is an inflammatory response, wherein the infiltrated leukocytes in the choriodecidua interface could be contributing to the creation of a microenvironment leading to collagenolysis, which would promote the rupture of these tissues during labor. In addition to the available information describing biological actions of chemokines during various pathological conditions such as infection, preterm labor and preterm rupture of membranes suggest that these compounds play important roles in other gestational events such as cervical dilation and myometrial contractions. Even though we do not know the totality of biochemical signals that integrate the molecular dialogue between leukocytes and the various gestational tissues, it is becoming increasingly evident that this microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the fetal membranes. Therefore, chemokines should be considered as important regulatory molecules with the ability to initiate the events that characterize normal and pathological labor.

Journal of Leukocyte Biology, 2013

Preeclampsia syndrome is characterized by inadequate placentation, because of deficient trophobla... more Preeclampsia syndrome is characterized by inadequate placentation, because of deficient trophoblastic invasion of the uterine spiral arteries, leading to placental hypoxia, secretion of proinflammatory cytokines, the release of angiogenic and antiangiogenic factors and miRNAs. Although immune-system alterations are associated with the origin of preeclampsia, other factors, including proinflammatory cytokines, neutrophil activation, and endothelial dysfunction, are also related to the pathophysiology of this syndrome. The pathophysiology of preeclampsia may involve several factors, including persistent hypoxia at the placental level and the release of high amounts of STBMs. DAMP molecules released under hypoxic conditions and STBMs, which bind TLRs, may activate monocytes, DCs, NK cells, and neutrophils, promoting persistent inflammatory conditions in this syndrome. The development of hypertension in preeclamptic women is also associated with endothelial dysfunction, which may be mediated by various mechanisms, including neutrophil activation and NET formation. Furthermore, preeclamptic women have higher levels of nonclassic and intermediate monocytes and lower levels of lymphoid BDCA-2 ϩ DCs. The cytokines secreted by these cells may contribute to the inflammatory process and to changes in adaptive-immune system cells, which are also modulated in preeclampsia. The changes in T cell subsets that may be seen in preeclampsia include low Treg activity, a shift toward Th1 responses, and the presence of Th17 lymphocytes. B cells can participate in the pathophysiology of preeclampsia by producing autoantibodies against adrenoreceptors and au-toantibodies that bind the AT1-R.