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Garcia A.,Center for Medical Education and Clinical Research
Applied Immunohistochemistry and Molecular Morphology | Year: 2017

Lung carcinoma is the main cause of cancer death worldwide. Adenocarcinoma molecular biomarkers have been discovered, and targeted therapies have been developed with encouraging results. The epidermal growth factor receptor gene is one of these biomarkers. Exons 18 to 21 should be studied in patients with advanced adenocarcinoma, who are candidates for treatment with tyrosine kinase inhibitors. The objective was to compare the performance of the determination in large and small samples in daily practice conditions, trying to adjust to published consensus guidelines. A retrospective observational study of 141 cases was carried out, with exons 19 and 21 sequencing. Sample size (small vs. large), including number of satisfactory polymerase chain reaction (PCR), sequencing, deletions, and mutations, were evaluated. In small biopsies, sample type, fragment number, and percentage of tumor per sample were analyzed. The results shown 114/141 (80.8) cases that met selection criteria; 60/114 (53%) were large (surgical) and 54/114 (47%) were small samples (19/54 endoscopic, 17/54 fine needle aspiration clots, 4/54 lymph nodes, 14/54 core and other). All large samples were satisfactory PCR, 56/60 (93%) satisfactory sequencing, and 12/56 (21%) had deletions in exon 19. Small samples were satisfactory PCRs in 50/54 (93%) cases, and satisfactory sequencing in 35/50 (65%), 8/35 (23%) showed alterations in exon 19, and 1/35 (3%) in exon 21. In conclusion, the proportion of samples unfit for the study of the epidermal growth factor receptor gene mutational status increased from 7% in large samples to 35% in small ones. Nineteen small samples were inconclusive, with cell blocks predominating, 10/19 (53%). Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.


PubMed | University of Colorado at Denver, ECLAMC Latin American Collaborative Study of Congenital Malformations at INAGEMP National Institute of Population Medical Genetics, University of Pittsburgh, Center for Medical Education and Clinical Research and 5 more.
Type: | Journal: Human genetics | Year: 2017

Nonsyndromic orofacial clefts (OFCs) are a heterogeneous group of common craniofacial birth defects with complex etiologies that include genetic and environmental risk factors. OFCs are commonly categorized as cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which have historically been analyzed as distinct entities. Genes for both CL/P and CP have been identified via multiple genome-wide linkage and association studies (GWAS); however, altogether, known variants account for a minority of the estimated heritability in risk to these craniofacial birth defects. We performed genome-wide meta-analyses of CL/P, CP, and all OFCs across two large, multiethnic studies. We then performed population-specific meta-analyses in sub-samples of Asian and European ancestry. In addition to observing associations with known variants, we identified a novel genome-wide significant association between SNPs located in an intronic TP63 enhancer and CL/P (p=1.1610


PubMed | Hospital Infantil Universitario Nino Jesus, Istanbul University, Obafemi Awolowo University, University of Dundee and 26 more.
Type: Journal Article | Journal: Human molecular genetics | Year: 2016

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case-parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 10


D'Antonio F.,St George's, University of London | Iacovella C.,St George's, University of London | Palacios-Jaraquemada J.,Center for Medical Education and Clinical Research | Bruno C.H.,South Scientific Foundation | And 2 more authors.
Ultrasound in Obstetrics and Gynecology | Year: 2014

Objective To assess systematically the performance of prenatal magnetic resonance imaging (MRI) in diagnosing the presence, degree and topography of disorders of invasive placentation and to explore the role of the different MRI signs in predicting these disorders. The diagnostic accuracy of ultrasound and MRI in the detection of invasive placentation was also compared. Methods MEDLINE, EMBASE, CINAHL and The Cochrane Library, including The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and The Cochrane Central Register of Controlled Trials, were searched electronically utilizing combinations of the relevant medical subject heading terms, keywords and word variants for 'invasive placentation' and 'magnetic resonance imaging'. Only prospective studies reporting a diagnosis of invasive placentation at the time of MRI and retrospective studies in which the radiologist was blinded to the final results were included in the analysis. The MRI signs explored were: uterine bulging, heterogeneous signal intensity, dark intraplacental bands on T2 weighted sequences, focal interruption of the myometrium and tenting of the bladder. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-) and diagnostic odds ratio (DOR) were based, depending on the number of studies, upon DerSimonian-Laird random-effect or hierarchical summary receiver-operating characteristics models. Results A total of 18 studies involving 1010 pregnancies at risk for invasive placentation were included. The overall diagnostic accuracy of MRI in detecting the presence of invasive placentation was: sensitivity, 94.4% (95% CI, 86.0-97.9%); specificity, 84.0% (95% CI, 76.0-89.8%); LR+, 5.91 (95% CI, 3.73-9.39); LR-, 0.07 (95% CI, 0.02-0.18); DOR, 89.0 (95% CI, 22.8-348.1). MRI had a high predictive accuracy in assessing both the depth and topography of placental invasion. All five MRI signs showed good predictive accuracy in the diagnosis of disorders of invasive placentation. There was no difference in either the sensitivity (P = 0.24) or the specificity (P = 0.91) between ultrasound and MRI for the detection of invasive placentation. Conclusions Prenatal MRI is highly accurate in diagnosing disorders of invasive placentation. Ultrasound and MRI have comparable predictive accuracy. Large population-based studies are needed in order to assess whether ultrasound can predict the depth and topography of placental invasion as reliably as can MRI. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.


Palacios-Jaraquemada J.M.,Center for Medical Education and Clinical Research | Palacios-Jaraquemada J.M.,Scientific South Foundation | Palacios-Jaraquemada J.M.,University of Buenos Aires
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2013

In the past decade, the incidence of placenta praevia and placenta accreta has increased and seems to be associated with induced labour, termination of pregnancy, caesarean section and pregnancy at older age. These factors imply some degree of tissue damage, which can modify the decidualisation process, and produce excessive vascular remodelling. Placenta praevia and accreta are mainly located in the lower segment, a place that predisposes to persistent uterine bleeding because of the development of new vessels and because it is a poorly contractile area of the uterus. The complexity, determined by tissue destruction, newly formed vessels, and vascular invasion of surrounding tissues, warrants multi-disciplinary management. When resective procedures are undertaken, a suitable plan to tackle surgical problems allows better control of bleeding and avoids unnecessary hysterectomies. In cases of placenta accrete, and especially when skills or institutional resources are not available, leaving the placenta in situ may be the best option until definitive treatment is undertaken. © 2012 Elsevier Ltd. All rights reserved.

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