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INVESTIGACIÓN - PUBLICACIONES
Publicaciones (WoS) con Abstract Académicos del Departamento de Pediatría y Cirugía Infantil Norte,
años 2018 - 2019
Gaete X., Vivanco M., Lopez P., Rocha A., Sepúlveda C., Codner E. Earlier puberty in boys with type 1 diabetes mellitus compared to a simultaneously recruited group of control adolescents. Pediatr Diabetes. 2019 Mar;20(2):197-201.
Abstract. Background: Recent studies have suggested that there is an earlier age of onset of puberty in healthy boys. However, no study has determined the age of pubertal development in boys with type 1 diabetes (T1D) and compared the results with a simultaneously recruited group of healthy children. Objective: The aim of this study was to evaluate the age of pubertal events in boys with TD1 and determine whether the duration of diabetes, metabolic control or insulin dose are associated with the age of puberty in boys with T1D. Methods: Boys aged 7 to 19 years with T1D (n = 148, age 12.9 ± 3.0 years) and healthy boys recruited from schools (n = 388 controls, age 12.8 ± 2.2 years) were studied. A pediatric endocrinologist evaluated pubertal development. Results: Boys at genital Tanner stage 2 and the final stages of puberty (genital Tanner 4 and 5) were younger than the control group (P = 0.005, P = 0.003, and P = 0.015, respectively). Both groups of boys had a similar age of pubic Tanner stage development. There were no cases of pubertal delay observed in the T1D cohort. There was no association observed between metabolic control with pubertal timing. T1D adolescents had lower height-SDS than the C group at the final stages of puberty. Conclusions: Boys with T1D who are treated with modern insulin therapy appear to have an earlier age of onset and an earlier age of final pubertal events than a simultaneously studied group of healthy children. These data suggest that pubertal delay is not a frequent problem for male T1D patients.
Ortega-García J. A. , Tellerías L., Ferrís-Tortajada J., Boldo E., Campillo-López F., van den Hazel P., Cortes-Arancibia S., Ramis R., Gaioli M., Monroy-Torres R., Farias-Guardia C., Borras M., Yohannessen K., García-Noriega-Fernández M., Cárceles-Álvarez A., Jaimes-Vega D. C., Cordero-Rizo M., López-Hernández F., Claudio L. Threats, challenges and opportunities for paediatric environmental health in Europe, Latin America and the Caribbean. An Pediatr (Barc). 2019 Feb;90(2):124.e1-124.e11.
Abstract. In a world that is increasingly technological and interconnected, but also more violent, overexploited and polluted, Paediatric Environmental Health (PEH) is one of the best contributions to improve global health. Few areas of the planet have a high affinity with common values and interests, such as the European Union (EU), Latin America and the Caribbean (LAC). The investments and actions of the PEH in pre- and postnatal periods during the first two decades of life will generate countless benefits in the health and well-being during the human life span. Detecting, reducing, or eliminating physical, chemical, biological and social pollutants is one of the main missions and actions of the PEH. In this special article, an update review is presented on the threats, challenges and cooperation opportunities in PEH among bio-health professionals and other social sectors involved, from the EU and LAC. New professional profiles, knowledge structures and architectures for engagement emerge. Courageous leaderships, new substantial resources, broad social changes, and the necessary collaboration between the two regions will be required to improve the health of present and future generations.
Lucero Y., O'Ryan M., Liparoti G., Huerta N., Mamani N., Ramani S., Lagomarcino A. J., Del Canto F., Quense J. Predominance of Rotavirus G8P[8] in a City in Chile, a Country Without Rotavirus Vaccination. J Pediatr. 2019 Jan;204:298-300.e1.
Abstract. Rotavirus G8P[8] infection has been common in Africa, but rare in the Americas. Among 23 rotavirus episodes observed during 18 months of surveillance of 100 families in Chile, 11 (48%) were identified as G8P[8]. Genotypes from these strains shared >99% identity with rotavirus sequences described in Asia, and may be misclassified as mixed G8/G12.
Yohannessen K., Pinto-Galleguillos D., Parra-Giordano D., Agost A., Valdés M., Smith L. M., Galen K., Arain A., Rojas F., Neitzel R. L., Ruiz-Rudolph P. Health Assessment of Electronic Waste Workers in Chile: Participant Characterization. Int J Environ Res Public Health. 2019 Jan 29;16(3). pii: E386.
Abstract. Little research has been done to evaluate the occupational health of electronic waste (e-waste) recycling workers in Latin America. The objective of this study was to complete comprehensive health evaluations on e-waste recycling workers in Chile and to compare those that work in informal (i.e., independent) to those that work in formal (i.e., established company) settings. A cross-sectional study in the summer of 2017 recruited 78 informal recycling workers from two cities and 15 formal e-waste recycling workers from a single recycling facility to assess exposures and health outcomes. Participants completed a health questionnaire and underwent a full health assessment. Herein, only health questionnaire data are reported. Participants were primarily male, middle-aged, married with children, and had worked in e-waste recycling for an average of 12 years. Participants generally reported good health status, and their prevalence of chronic diseases was comparable to national rates. Workers frequently reported exposures to several occupational stressors, including noise and insufficient income, as well as other mental health stressors. Occupational injuries were commonly reported and use of safety equipment was low. Only a few significant differences, generally of a rather small magnitude, were found between informal and formal workers. In conclusion, from survey data, we did not identify major risks to health among e-waste workers, and only minor differences between workers in informal and formal settings.
Herrera A. M., Brand P ., Cavada G., Koppmann A., Rivas M., Mackenney J., Sepúlveda H., et al. Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study. Allergol Immunopathol (Madr). 2018 Dec 27. pii: S0301-0546(18)30159-9.
Abstract. Objective: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. Methods: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. Results: 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16-0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010-0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. Conclusions: Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.
Palomino M. A., Castiglioni C. Respiratory care in spinal muscular atrophy in the new therapeutic era. Rev Chil Pediatr. 2018 Dec;89(6):685-693.
Abstract. Spinal muscular atrophy (SMA) is the first inherited cause of mortality in infants, with four subtypes: SMA0 prenatal onset, SMA1 babies less than 3 months non sitters, SMA2 sitters and SMA3 walkers. Pneumonia and respiratory insufficiency are the most severe complications. Informed parental decisions are relevant. Respiratory management includes cough assistance, prevention of lung under development due to chest deformity, prompt treatment of respiratory infections, hypoventilation, swallow problems, gastro esophageal reflux and malnutrition. In view of the FDA and EMA approval of the nonsense oligonucleotides nusinersen, the first specific treatment for SMA and the future with gene therapy and others under development, we need to optimize preventive respiratory manage ment with the new standard of care.
Biondi A., Gandemer V., De Lorenzo P., Cario G., Campbell M., Castor A., Pieters R., Baruchel A., Vora A., Leoni V., Stary J., Escherich G., Li C. K., Cazzaniga G., Cavé H., Bradtke J., Conter V., Saha V., Schrappe M., Grazia Valsecchi M. Imatinib treatment of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (EsPhALL2010): a prospective, intergroup, open-label, single-arm clinical trial. Lancet Haematol. 2018 Dec;5(12):e641-e652.
Abstract. Background: The EsPhALL2004 randomised trial showed a 10% advantage in disease-free survival for short, discontinuous use of imatinib after induction compared with no use of imatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia receiving Berlin-Frankfurt-Münster chemotherapy and haemopoietic stem-cell transplantation (HSCT). Other contemporary studies showed an advantage from continuous protracted exposure to imatinib, challenging the indications to transplant. The EsPhALL2010 study was designed to assess whether imatinib given from day 15 of induction and continuously throughout chemotherapy led to a different outcome to that obtained in EsPhALL2004, despite decreasing the number of patients having HSCT. Methods: This prospective, intergroup, open-label, single-arm clinical trial (EsPhALL2010) was done at 11 study groups across Europe, Chile, and Hong Kong. Patients aged 1-17 years with the translocation t(9;22)(q34;q11) who were recruited into national front-line trials for acute lymphoblastic leukaemia were eligible for this trial. Patients with abnormal renal or hepatic function or an active systemic infection were ineligible. Patients received imatinib 300 mg/m2 continuously from day 15 of induction during chemotherapy. Eligibility to HSCT depended on early morphological response and minimal residual disease. Imatinib was recommended throughout the first year after transplant. The co-primary endpoints were event-free survival and overall survival. All analyses were done in the intention-to-treat population. The trial is registered with the European Clinical Trials Database (EudraCT 2004-001647-30) and with ClinicalTrials.gov (NCT00287105) and is completed. Findings: 158 patients were screened for eligibility, of whom 155 were enrolled between Jan 1, 2010, and Dec 31, 2014. 151 (97%) patients achieved first complete remission after induction and four after the consolidation phase, with 102 (66%) patients categorised as good risk and 53 (34%) as poor risk according to EsPhALL risk stratification criteria. 59 (38%) patients had HSCT during their first complete remission. 40 (26%) patients relapsed and 41 (26%) patients died during the study (25 [61%] during complete continuous remission, and 16 [39%] after relapse). The 5-year event-free survival was 57·0% (95% CI 48·5-64·6) and 5-year overall survival was 71·8% (63·5-78·5). 154 serious adverse events were reported in 80 (52%) of 155 patients. The most common toxicity was infection (61 [39%] patients, mostly bacterial); gastrointestinal disorders occurred in ten (6%) patients and osteonecrosis in eight (5%). Serious adverse events occurred mainly during high-risk blocks and delayed intensifications, including 14 fatal events (one in the consolidation phase, six in high-risk blocks, six in first delayed intensification, and one in second delayed intensification). Interpretation: Although HSCT was done in a smaller proportion of patients in EsPhALL2010 than in EsPhALL2004, event-free and overall survival were similar between the two studies. Our data suggest that imatinib given early and continuously with intensive chemotherapy might increase toxicity. Funding: Projet Hospitalier de Recherche Clinique-Cancer and Novartis France; Bloodwise and Cancer Research UK; Ministry of Health, Czech Republic.
Herrera A. M., Brand P., Cavada G., Koppmann A., Rivas M., Mackenney J., Sepúlveda H., et al. Hospitalizations for asthma exacerbation in Chilean children: A multicenter observational study. Allergol Immunopathol (Madr). 2018 Nov - Dec;46(6):533-538.
Abstract. Background: Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this. Objective: Describe clinical characteristics of children hospitalized for asthma exacerbation. Methods: Observational prospective cohort study in 14 hospitals. Over a one-year period, children five years of age or older hospitalized with asthma exacerbation were eligible for inclusion. Parents completed an online questionnaire with questions on demographic information, about asthma, indoor environmental contaminant exposure, comorbidities and beliefs about disease and treatment. Disease control was assessed by the Asthma Control Test. Inhalation technique was observed using a checklist. Results: 396 patients were enrolled. 168 children did not have an established diagnosis of asthma. Only 188 used at least one controller treatment at the time of hospitalization. 208 parents said they believed their child had asthma only when they had an exacerbation and 97 correctly identified inhaled corticosteroids as anti-inflammatory treatment. 342 patients used the wrong spacer and 73 correctly performed all steps of the checklist. Conclusions: Almost half of the patients were not diagnosed with asthma at the time of hospitalization despite having a medical history suggestive of the disease. In the remaining patients with an established diagnosis of asthma potentially modifiable factors like bad adherence to treatment and poor inhalation technique were found. Implementing a nationwide asthma program including continued medical education for the correct diagnosis and follow up of these patients and asthma education for patients and caregivers is needed to reduce asthma hospitalization rates in Chilean children.
Lucero Y., George S., O'Ryan M. Indications for Helicobacter pylori Eradication: Do We Need to Consider to Screen and Treat Asymptomatic Children? J Pediatr Gastroenterol Nutr. 2018 Oct;67(4):e86-e87.
Excerpt. To the Editor: Helicobacter pylori treatment of asymptomatic adults in areas with high gastric cancer prevalence can reduce cancer rates and has been recommended in recent guidelines (1,2). The “screen and treat” strategy is currently not recommended for children as its clinical benefit is considered unclear (3). H pylori is acquired largely during the first years of life, and although mostly asymptomatic, persistent infection is associated with serologic and genetic expression modifications which could, in a subset, derive in future disease (4–6). A screening program using non-invasive tests in 3251 Japanese high school students detected H pylori in 4.2%. Upper endoscopy and biopsies revealed that all infected adolescents had inflammatory cell infiltration and focal atrophic changes; two individuals had intestinal metaplasia, a preneoplastic condition. They estimated that a nation-wide “screen and treat” program in Japanese adolescents would prevent 6071 gastric cancers in adulthood (7). H pylori infection is associated with modifications in expression level of a number of genes related with cancer in both symptomatic (8,9) and asymptomatic children (5,10). Taken together these findings suggest that the oncogenic process triggered by H pylori infection begins early in life and that reducing the age of “screen and treat” in an area with high gastric cancer rates could further reduce this cancer prevalence. Potential downsides to consider are reinfection rates, induction of antimicrobial resistance, and modifying potential beneficial effects of H pylori in allergic/atopic disease during childhood. Pinpointing child populations that could benefit from a “screen and treat” approach and pilot studies addressing the above issues should be in the horizon.
Gajardo A. I., von Dessauer B., Molina V., Vera S., Libuy M., Rodrigo R. Plasma Antioxidant Potential at Admission is Associated with Length of ICU Stay in Child with Sepsis: A Pilot Study. Fetal Pediatr Pathol. 2018 Oct;37(5):348-358.
Abstract. Objective: To assess the relationship between biomarkers of oxidative stress (OS) and the length of stay in intensive care units (LSICU) in septic children. Methods: Clinical parameters and biomarkers of OS were measured in 16 children admitted for sepsis in an intensive care unit. The associations between biomarkers of OS and the LSICU were assessed by linear correlation. Multiple linear regression models were constructed to adjust other variables. Results: The mean of LSICU was 7.13 ± 4.17 days. LSICU was associated with the catalase activity (rho =0.56, p-value =0.024) and the ferric reducing ability of plasma (FRAP, r = 0.73, p-value =0.001). However, only FRAP at ICU admission was independently associated with LSICU, which rose 0.21 days for each 10 µmol/l of increase in the FRAP level. Conclusion: We conclude for first time that FRAP level at ICU admission is independently associated with LSICU in pediatric patients.
Santolaya M. E., Álvarez A. M., Acuña M., Avilés C. L., Salgado C., Tordecilla J., Varas M., Venegas M., Zubieta M., Farfán M., de la Maza V., Valenzuela R., Torres J. P. Efficacy of pre-emptive versus empirical antifungal therapy in children with cancer and high-risk febrile neutropenia: a randomized clinical trial. J Antimicrob Chemother, 2018 Oct 1;73(10): 2860-2866.
Abstract. Objective: To compare the efficacy of pre-emptive versus empirical antifungal therapy in children with cancer, fever and neutropenia. Methods: This was a prospective, multicentre, randomized clinical trial. Children presenting with persistent high-risk febrile neutropenia at five hospitals in Santiago, Chile, were randomized to empirical or pre-emptive antifungal therapy. The pre-emptive group received antifungal therapy only if the persistent high-risk febrile neutropenia was accompanied by clinical, laboratory, imaging or microbiological pre-defined criteria. The primary endpoint was overall mortality at day 30 of follow-up. Secondary endpoints included invasive fungal disease (IFD)-related mortality, number of days of fever, days of hospitalization and use of antifungal drugs, percentage of children developing IFD, requiring modification of initial treatment strategy and need for ICU. The trial was registered with Registro Brasileiro de Ensaios Clínicos (ReBEC) under trial number RBR-3m9d74. Results: A total of 149 children were randomized, 73 to empirical therapy and 76 to pre-emptive therapy. Thirty-two out of 76 (42%) children in the pre-emptive group received antifungal therapy. The median duration of antifungal therapy was 11 days in the empirical arm and 6 days in the pre-emptive arm (P < 0.001), with similar overall mortality (8% in the empirical arm and 5% in the pre-emptive arm, P = 0.47). IFD-related mortality was the same in both groups (3%, P = 0.97), as were the percentage of children with IFD (12%, P = 0.92) and the number of days of fever (9, P = 0.76). The number of days of hospitalization was 19 in the empirical arm and 17 in the pre-emptive arm (P = 0.15) and the need for ICU was 25% in the empirical arm and 20% in the pre-emptive arm (P = 0.47). Conclusions: Pre-emptive antifungal therapy was as effective as empirical antifungal therapy in children with cancer, fever and neutropenia, significantly reducing the use of antifungal drugs.
Giugliano C., Reculé F., Guler K., Gantz J. T., Hasbún T. Persistent Nasal Infantile Hemangioma: A Surgical Treatment Algorithm. J Craniofac Surg. 2018 Sep;29(6):1509-1513.
Abstract. Treatment of infantile hemangioma is usually medical. The nose is one of the most important aesthetic and functional units of the face; therefore, surgical management is preferred in persistent lesions (fibro-fatty tissue component) that do not respond to medical treatment. Herein, the authors analyze the results of surgical nasal hemangioma treatment in their center, a literature review and propose an algorithm for surgical management. A retrospective analysis of 23 persistent nasal hemangioma operated between 1996 and 2014 at our institution was made. The authors recollected the following demographic and clinical data: hemangioma subtype, phase of evolution, affected aesthetic nasal subunit, previous treatment, surgery type, complications and follow-up period. The Strasser scale was chosen for assessment of postoperative photographic results. Surgical treatment was performed. Age average was 6.8 years old (range 2-19). Mixed hemangioma was the most common subtype (83%). Surgery was mainly performed in the involution phase (87%). The most affected aesthetic subunit was nasal tip (44%). All lesions received previous medical treatment. The most common surgical technique was open rhinoplasty approach. Follow-up was an average of 26.6 months. Aesthetic results according to the Strasser method included: 3 excellent scores, 15 good, 5 regular, and none poor. Surgery was performed on patients in order to correct nasal persistent hemangiomas sequel. The nose has serious psychosocial impact and mixed infantile hemangiomas appear to have a higher rate of persistent hemangioma requiring surgery, but further studies are needed. Aesthetic outcome with surgical procedures chosen were acceptable and no complications were reported.
Garone C., Taylor R. W., Nascimento A., Poulton J., Fratter C., Domínguez-González C., Evans J. C., Loos M., Isohanni P., Suomalainen A., Ram D., Hughes M. I., McFarland R., Barca E1,15, Lopez Gomez C., Jayawant S., Thomas N. D., Manzur A. Y., Kleinsteuber K., et al. Retrospective natural history of thymidine kinase 2 deficiency. J Med Genet. 2018 Aug;55(8):515-521.
Abstract. Background: Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine and deoxycytidine. Autosomal recessive TK2 mutations cause a spectrum of disease from infantile onset to adult onset manifesting primarily as myopathy. Objective: To perform a retrospective natural history study of a large cohort of patients with TK2 deficiency. Methods: The study was conducted by 42 investigators across 31 academic medical centres. Results: We identified 92 patients with genetically confirmed diagnoses of TK2 deficiency: 67 from literature review and 25 unreported cases. Based on clinical and molecular genetics findings, we recognised three phenotypes with divergent survival: (1) infantile-onset myopathy (42.4%) with severe mitochondrial DNA (mtDNA) depletion, frequent neurological involvement and rapid progression to early mortality (median post-onset survival (POS) 1.00, CI 0.58 to 2.33 years); (2) childhood-onset myopathy (40.2%) with mtDNA depletion, moderate-to-severe progression of generalised weakness and median POS at least 13 years; and (3) late-onset myopathy (17.4%) with mild limb weakness at onset and slow progression to respiratory insufficiency with median POS of 23 years. Ophthalmoparesis and facial weakness are frequent in adults. Muscle biopsies show multiple mtDNA deletions often with mtDNA depletion. Conclusions: In TK2 deficiency, age at onset, rate of weakness progression and POS are important variables that define three clinical subtypes. Nervous system involvement often complicates the clinical course of the infantile-onset form while extraocular muscle and facial involvement are characteristic of the late-onset form. Our observations provide essential information for planning future clinical trials in this disorder.
Lucero Y., Vidal R., O'Ryan M. Norovirus vaccines under development. Vaccine. 2018 Aug;36(36):5435-5441.
Abstract. Noroviruses (NoVs) are one of the leading causes of acute gastroenteritis, including both outbreaks and endemic infections. The development of preventive strategies, including vaccines, for the most susceptible groups (children <5 years of age, the elderly and individuals suffering crowding, such as military personnel and travelers) is desirable. However, NoV vaccine development has faced many difficulties, including genetic/antigenic diversity, limited knowledge on NoV immunology and viral cycle, lack of a permissive cell line for cultivation and lack of a widely available and successful animal model. Vaccine candidates rely on inoculation of virus-like particles (VLPs) formed by the main capsid protein VP1, subviral particles made from the protruding domain of VP1 (P-particles) or viral vectors with a NoV capsid gene insert produced by bioengineering technologies. Polivalent vaccines including multiple NoV genotypes and/or other viruses acquired by the enteric route have been developed. A VLP vaccine candidate has reached phase II clinical trials and several others are in pre-clinical stages of development. In this article we discuss the main challenges facing the development of a NoV vaccine and the current status of prevailing candidates
Hrusak O., de Haas V., Stancikova J., Vakrmanova B., Janotova I., Mejstrikova E., Capek V., Trka J., Zaliova M., Luks A., Bleckmann K., Möricke A., Irving J., Konatkowska B., Alexander T. B., Inaba H., Schmiegelow K., Stokley S., Zemanova Z., Moorman A. V., Rossi J. G., Felice M. S., Dalla-Pozza L., Morales J., Dworzak M., Buldini B., Basso G., Campbell M., Cabrera M. E., Marinov N., Elitzur S., et al. International cooperative study identifies strategy in childhood ambiguous lineage leukemia. Blood, 2018 Jul 19:132(3): 264-276.
Abstract. Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Münster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80% ± 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% ± 7.2% and 50% ± 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD19+ leukemia was 83% ± 5.3% on ALL-type primary treatment compared with 0% ± 0% and 28% ± 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19+ ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19- and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with ≥5% blasts after remission induction. The results provide a basis for a prospective trial.
Bravo M. P., Balboa P., Torrejón C., Bozzo R., Boza M. L. , Contreras I., Jorquera P., Astorga L., Weisstaub G. Bone mineral density, lung function, vitamin D and body composition in children and adolescents with cystic fibrosis: a multicenter study. Nutr Hosp. 2018 Jun 28;35(4):789-795.
Abstract. Background: cystic fibrosis (CF) is the most common inherited disease in Caucasian population. Nowadays, long survival has led to the emergence of new complications, such as CF bone disease (CFBD), which is characterized by increased fracture risk. Objectives: evaluate the association of bone mineral density (BMD) with lung function and BMD with 25-hydroxivitamin D (25OHD) plasmatic levels in children/adolescents with CF. Methods: we conducted a multicenter, cross-sectional study with clinically stable CF patients between five and 18 years. Weight, height, pubertal development, BMD and body composition (DXA), pulmonary function (FEV1 and FEF25-75) and 25OHD plasmatic levels were measured. Patients answered food intake and physical activity surveys. p values under 0.05 were considered as statistically significant. Results: thirty-seven patients were enrolled, 51% with normal respiratory function. Mean BMD Z-score in lumbar spine and in total body less head were -0.4 and -0.5 respectively. Twenty seven percent had a fat free mass index below the third percentile, 89% had 25OHD levels lower than 30 ng/ml and 78.4% had a low calcium intake. We did not find any correlations between BMD Z-scores, lung function or 25OHD levels. Patients with fat free mass (FFM) below the third percentile had BMD Z-score lower than -1 more frequently, in both locations (p < 0.006 and p < 0.001, respectively). Conclusions: although most assessed patients had normal BMD and normal lung function, a high proportion had low: FFM, calcium intake and 25OHD levels. The association between low FFM and low BMD highlights the importance of improving body composition in CF patients, in order to prevent future CFBD.
Ossa J. C., Yáñez D., Valenzuela R., Gallardo P., Lucero Y., Farfán M.J. Intestinal Inflammation in Chilean Infants Fed With Bovine Formula vs. Breast Milk and Its Association With Their Gut Microbiota. Front Cell Infect Microbiol. 2018 Jun 21;8:190.
Abstract. Introduction: Compared to bovine formula (BF), breast milk (BM) has unique properties. In the newborn intestine, there is a homeostatic balance between the counterparts of the immune system, which allows a physiological inflammation, modulated by the gut microbiota. Many studies have attempted to understand the effect of BF vs. BM, and the changes in the gut microbiota, but few also focus on intestinal inflammation. Methods: We conducted a cohort study of newborn infants during their first 3 months. In stool samples taken at 1 and 3 months (timepoints T1 and T3), we quantified calprotectin, IL-8 and α1-antitrypsin by ELISA and we evaluated the expression of IL8 and IL1β genes by RT-qPCR. To determine the microbiota composition, the 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs). Results: In total 15 BM and 10 BF infants were enrolled. In the BM group, we found calprotectin and α1-antitrypsin levels were significantly elevated at T3 compared to T1; no differences were found between T1 and T3 in the BF group. A comparison between the BM and BF groups showed that calprotectin levels at T1 were lower in the BM than the BF group; this difference was not observed at T3. For IL-8 levels, we found no differences between groups. A gene expression analysis of the IL8 and IL1β genes showed that infants from the BF group at T1 have a significantly increased expression of these markers compared to the BM group. Gut microbiota analyses revealed that the phylum Bacteroidetes was higher in BM than BF, whereas Firmicutes were higher in BF. A redundancy analysis and ANOVA showed BM has a community structure statistically different to BF at T1 but not at T3. Compared to BF, BM at T1 showed a higher representation of Enterococcus, Streptococcus, Enterobacter, Lactococcus, and Propionibacterium. Conclusions: We found a basal state of inflammation in the infants' intestine based on inflammation markers. One month after birth, infants receiving BF exhibited higher levels of inflammation compared to BM.
Araya M., Díaz J., Oyarzun A., Lucero Y., Alarcon T., González M., Canales P., Fierro L., Pérez-Bravo F. Avoiding Small Intestinal Biopsies for Diagnosis of Celiac Disease in Children: A Reliable Strategy for All Patients? J Pediatr Gastroenterol Nutr. 2018 May;66(5):785-788.
Abstract. Background: Current reports applying ESPGHAN exception criteria (EEC) to diagnose celiac disease (CD) without duodenal biopsies indicate that a high percentage of patients with CD may be identified when applied correctly in specialized settings. Application of the EEC, however, in "daily life conditions" at the different levels of medical services is not clear. Methods: EEC was applied to 130 pediatric patients evaluated for CD at 5 public hospitals in Santiago, Chile, during 2010 to 2015. Clinical presentation, serum anti-tissue transglutaminase 2 and anti-endomysium antibodies (EMA), genotyping, and small intestinal histology were obtained from clinical charts. Results: A total of 78 of 130 patients reviewed had some of the data required for analysis, but EMA was determined in 54% and genotyping in 2.3% of patients, limiting the study. After offering free genotyping, only 12 of 78 (15%) had all data required for EEC application. In this small group, 10 of 12 (83.3%) patients could avoid duodenal biopsies and 2 (16.7%) with potential CD were misdiagnosed. Main reasons for not doing EMA and genotyping were that they are expensive, unavailable in the local health care center, and considered "not necessary" for diagnosis. Conclusion: Limited resources in clinical settings reduce availability of EMA and genotyping, making application of EEC criteria difficult and only possible only in 15% of our patients. Within this subgroup, biopsies could be avoided in 83.3%, and 16.7% of patients with potential CD were misdiagnosed. Insufficient studies and incorrect interpretation of EEC contributed to incomplete assessment in 52 of 130 (40%) patients. The Chilean public health system is likely representative of several others present in developing and developed countries.
Schilling K. W., Yohannessen K., Araya M. Perception of following gluten-free diet and adherence to treatment in pediatric patients with celiac disease. Rev Chil Pediatr. 2018 Apr;89(2):216-223.
Abstract. Introduction: Celiac disease (CD) is a chronic immune-mediated enteropathy present in ~1% of population. Gluten-free diet (GFD) is the only treatment for this condition and the main limitation of its efficacy is the lack of adherence. Objective: To assess factors influencing adherence to GFD in pediatric patients and measure the concordance between serological results and a nutritional adherence questionnaire. Patients and methods: celiac patients younger than 18 years of age, diagnosed CD following ESPGHAN criteria, on GFD for at least 6 months and consulting at Hospital Roberto del Río, Santiago, in 2008-2016, were assessed. Clinical presentation, nutritional evaluation and fac tors related to adherence to treatment (diet) were registered. A subsample answered Biaggi's nutritional questionnaire. Results: Of 65 evaluated patients, 44% and 30,1% adhered to GFD according to blood autoantibodies (TTG and EMA) and the adherence questionnaire, respectively. "Age at debut" (p = 0.049), "perception of following GFD correctly" (p = 0.002) and "behavior in social events" (p = 0.005) were significantly associated with adherence to GFD. There was concordance between serological test and Biagi's questionnaire (p = 0.0001). Discussion: Adherence to GFD was lower than reported in literature. Intervention of some of the identified variables associated with adherence may help improving follow-up of celiac patients, especially those that due to diverse situations cannot measure their antibodies periodically.
Maldonado M. E., Acuña M., Álvarez A. M., Avilés C. L., de la Maza V., Salgado C., Tordecilla J., Varas M., Venegas M., Villarroel M., Zubieta M., Santolaya M. E. Microorganisms isolated from blood cultures in children with cancer and high-risk febrile neutropenia from five hospitals in Santiago, Chile, 2012-2015. Rev Chilena Infectol. 2018 Apr;35(2):140-146.
Abstract. Background: Microorganisms isolated from blood cultures (BC) in patients with febrile neutropenia (NF) vary over time, requiring systematic monitoring to guide appropriate empirical therapy. Aim: To identify microorganisms isolated from BC and their antimicrobial resistance profile in children with cancer and high risk NF. Method: Prospective, multicenter study. The analysis included episodes of high-risk FN with positive BC in children under 18 years of age treated in five hospitals in Santiago, Chile, 2012-2015. Results: A total of 206 microorganisms were analyzed in 185 episodes of high-risk FN. The main isolates were Gram negative bacilli (46.6%) and Gram positive cocci (45.1%) and the most frequent microorganisms were Escherichia coli (22.8%), coagulase negative Staphylococcus (18.0%) and Klebsiella spp. (16.5%). Escherichia coli and Klebsiella spp showed 4.2% and 67.6% resistance to third generation cephalosporins (cefotaxime/ceftriaxone), 10.6% and 40.6% resistance to fluoroquinolones (ciprofloxacin) and 2.1% and 26.5% to amikacin, respectively. Coagulase negative Staphylococcus and Staphylococcus aureus had 86.4% and 22.2% resistance to oxacillin, Streptococcus viridans group had 71% resistance to penicillin. Discussion: This study updates the etiology and resistance profile of microorganisms isolated in BC from children with cancer and high-risk FN, an essential tool for the adequate management of these patients.
Castiglioni C., Fattori F., Udd B., De Los Angeles Avaria M., Suarez B., D'Amico A., Malandrini A., Carrozzo R., Verrigni D., Bertini E., Tasca G. Neuromyopathy with congenital cataracts and glaucoma: A distinct syndrome caused by POLG variants /692/308 /692/699 article. Eur J Hum Genet 2018 Mar; 26(3): 367-372.
Abstract. We identified three non-related patients manifesting a childhood-onset progressive neuromyopathy with congenital cataracts, delayed walking, distal weakness and wasting, glaucoma and swallowing difficulties. Electrophysiology and nerve biopsies showed a mixed axonal and demyelinating neuropathy, while muscle biopsy disclosed both neurogenic and myopathic changes with ragged red fibers, and muscle MRI showed consistent features across patients, with a peculiar concentric disto-proximal gradient of fatty replacement. We used targeted next generation sequencing and candidate gene approach to study these families. Compound biallelic heterozygous variants, p.[(Pro648Arg)]; [(His932Tyr)] and p.[(Thr251Ile),(Pro587Leu)]; [(Arg943Cys)], were found in the three patients causing this homogeneous phenotype. Our report on a subset of unrelated patients, that showed a distinct autosomal recessive childhood-onset neuromyopathy with congenital cataracts and glaucoma, expands the clinical spectrum of POLG-related disorders. It also confirms the association between cataracts and neuropathy with variants in POLG. Early onset cataract is otherwise rare in POLG-related disorders and so far reported only in a few patients with the clinical pattern of distal myopathy or neuromyopathy.
Rostion, C. Reply to letter to the editor. J Pediatr Surg. 2018 Feb;53(2):373.
Ríos G., Rodríguez L., Lucero Y., Miquel I., Arancibia M. E., Alliende F. Endoscopic Findings Associated With Button Battery Ingestion in Children: Do We Need to Change the Protocol for Managing Gastric Location? Pediatr Emerg Care. 2018 Jan 23.
Abstract. Background: Ingested button batteries (BB) can cause corrosive damage of digestive mucosa within minutes. Immediate endoscopic removal of esophageal BB has been clearly established, but the management of BB located in the stomach is still controversial. AIM: To describe demographic, clinical, radiologic, and endoscopic characteristics of a series of pediatric patients evaluated for BB ingestion. Methods: Retrospective analysis of clinical charts belonging to children younger than 15 years, who underwent endoscopic removal of BB at Clínica Alemana of Santiago, between November 2007 and November 2011. Results: Twenty-five patients subjected to upper endoscopy were analyzed; median age, 31 months; 15 were male (60%), and 11 patients (46%) were symptomatic after ingestion. The BB ingestion was confirmed by radiograph. Endoscopy revealed 10 patients with BB in the esophagus, 12 patients in the stomach and 3 distal to duodenum. Range time between ingestion and endoscopy was 2 to 10 hours for esophageal BB and 2 hours to 3 days for gastric BB. Eight of the 22 BBs removed had a diameter of 20 mm or greater, 6 of them were located in the esophagus and 2 in stomach. The BB color changes were observed in 14 of the 22 BBs. Breakage of battery edges was present in 11 of the 22 batteries. All patients with esophageal BB and 6 of those 12 with gastric BB presented mucosal damage. Conclusion: Esophageal BB cause damage within hours. The BB located in the stomach may also cause damage early. Extraction of gastric BB before 48 hours should be considered.