325 research outputs found

    Diagnóstico precoce de neoplasia endócrina múltipla tipo 2B: um desafio para os médicos

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    BACKGROUND: The hereditary form of medullary thyroid carcinoma may occur isolated as a familial medullary thyroid carcinoma (FMTC) or as part of Multiple Endocrine Neoplasia 2A (MEN2A) and 2B (MEN2B). MEN2B is a rare syndrome, its phenotype may usually, but not always, be noted by the physician. In the infant none of the MEN2B characteristics are present, except by early gastrointestinal dysfunction caused by intestinal neuromas. When available, genetic analysis confirms the diagnosis and guides pre-operative evaluation and extent of surgery. Here we report four cases of MEN2B in which the late diagnosis had a significant impact in clinical evolution and, potentially, in overall survival. CASE REPORT: We report four cases, 2 men and 2 women, with differences in their phenotypes and with a late diagnosis. The first case has a history of severe gastrointestinal obstruction requiring a surgery intervention two days after his birth. The second told had nodules in the oral mucosa and constipation since childhood. The third case referred a history of constipation from birth until 5 months of life. The fourth has had a history of chronic constipation since childhood. DISCUSSION: New concepts have emerged since the RET oncogene was identified in 1993 as the responsible gene for hereditary medullary thyroid carcinoma. The majority of MEN2B individuals have M918T mutation in the exon 16 of RET, with a few cases having a mutation A883F or the association of V804M with E805K, Y806C or S904C mutations. The consensus classifies the RET mutation in codon 918 as of highest risk and recommends total thyroidectomy and central lymph node dissection until 6 months after birth. A fast and precise diagnosis is essential to reach these goals. The identification of early manifestations such as intestinal ganglioneuromatosis and oral mucosal neuromas should prompt the physician to initiate an investigation for multiple endocrine neoplasia type 2B. CONCLUSION: The diagnosis of MEN2B is very important to allow appropriate investigation of associated diseases and to allow counseling and appropriate screening of relatives for a RET mutation. Even patients with MEN2B, which often have typical physical features, may not be properly recognized and be followed as a sporadic case. Based on this, all suspicious cases of multiple endocrine neoplasia should undergo a molecular genetic test.A forma hereditária do carcinoma medular da tiróide pode ocorrer de modo isolado, o carcinoma medular da tiróide familiar (FMTC), ou como parte das neoplasias endócrinas múltiplas tipo 2A (MEN2A) e 2B (MEN2B). MEN2B é uma síndrome rara e seu fenótipo é usualmente, mas nem sempre, notado pelo médico. Na infância, nenhuma das características de MEN2B estão presentes, exceto pela disfunção gastrintestinal precoce, causada pelos neuromas intestinais. Quando disponível, a análise genética confirma o diagnóstico e orienta a avaliação pré-operatória e extensão da cirurgia. Neste artigo, apresentamos quatro casos de MEN2B, nos quais o diagnóstico tardio teve impacto significativo na evolução clínica e, potencialmente, na mortalidade em geral. APRESENTAÇÃO DOS CASOS: Apresentamos quatro casos, dois homens e duas mulheres, com diferenças em seus fenotipos e com diagnóstico tardio. O primeiro caso tem história de obstrução gastrintestinal importante em que foi necessária cirurgia dois dias após o nascimento. O segundo paciente apresentava nódulos na mucosa oral e constipação desde a infância. O terceiro referia história de constipação desde o nascimento até 5 meses de idade. O quarto tinha história de constipação intestinal desde a infância. DISCUSSÃO: Novos conceitos emergiram desde que o oncogene RET foi identificado, em 1993, como o gene responsável pelo carcinoma medular da tiróide hereditário. A maioria dos indivíduos apresenta a mutação M918T no éxon 16 do RET, enquanto poucos casos apresentam a mutação A883F ou a associação de V804M com E805K, Y806C ou S904C. O consenso recomenda a tiroidectomia total com dissecção dos linfonodos no compartimento central até os 6 meses após o nascimento. O diagnóstico rápido e preciso é essencial para o atingir os objetivos. CONCLUSÃO: O diagnóstico precoce de MEN2B é muito importante para propiciar a investigação apropriada de doenças associadas e para permitir aconselhamento e rastreamento dos parentes para uma mutação do RET. Pacientes com MEN2B, que apresentam frequentemente achados típicos ao exame físico, podem não ser reconhecidos e seguidos como casos esporádicos. Por causa disso, todos os casos de neoplasia endócrina múltipla devem ser avaliados pelo teste genético para mutações do RET.Federal University of São Paulo Department of Medicine Division of EndocrinologyFleury-Medicina e SaúdeUNIFESP, Department of Medicine Division of EndocrinologySciEL

    Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes

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    In this large clinical series of Brazilian children and adolescents, autoimmunehepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higherdisease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.sentation, laboratory findings, histological profile, treatments, and outcomes of children andadolescents with autoimmune hepatitis.Methods: The medical records of 828 children and adolescents with autoimmune hepatitiswere reviewed. A questionnaire was used to collect anonymous data on clinical presentation,biochemical and histological findings, and treatments.Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmunehepatitis-2. The female sex was predominant in both groups. The median age at symptomonset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher forautoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patientswith autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-foldhigher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were sig-nificantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels werelower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochem-ical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6%underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmunehepatitis-2: 2.4%).Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmunehepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higherdisease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.info:eu-repo/semantics/publishedVersio

    Prenatal ultrasound and postmortem histologic evaluation of tooth germs: an observational, transversal study

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    Introduction: Hypodontia is the most frequent developmental anomaly of the orofacial complex, and its detection in prenatal ultrasound may indicate the presence of congenital malformations, genetic syndromes and chromosomal abnormalities.To date, only a few studies have evaluated the histological relationship of human tooth germs identified by two-dimensional (2D) ultrasonography. In order to analyze whether two-dimensional ultrasonography of tooth germs may be successfully used for identifying genetic syndromes, prenatal ultrasound images of fetal tooth germs obtained from a Portuguese population sample were compared with histological images obtained from fetal autopsies.Methods: Observational, descriptive, transversal study. The study protocol followed the ethical principles outlined by the Helsinki Declaration and was approved by the Ethics Committee of the School of Dental Medicine, University of Porto (FMDUP, Porto, Portugal) and of the Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/EPE, Porto, Portugal) as well as by the CGC Genetics Embryofetal Pathology Laboratory. Eighty-five fetuses examined by prenatal ultrasound screening from May 2011 to August 2012 had an indication for autopsy following spontaneous fetal death or medical termination of pregnancy. Of the 85 fetuses, 37 (43.5%) were randomly selected for tooth germ evaluation by routine histopathological analysis. Fetuses who were up to 30 weeks of gestation, and whose histological pieces were not representative of all maxillary tooth germs was excluded. Twenty four fetus between the 13th and 30th weeks of gestation fulfilled the parameters to autopsy.Results: Twenty four fetuses were submitted to histological evaluation and were determined the exact number, morphology, and mineralization of their tooth germs. All tooth germs were identifiable with ultrasonography as early as the 13th week of gestation. Of the fetuses autopsied, 41.7% had hypodontia (29.1% maxillary hypodontia and 20.9% mandibular hypodontia).Conclusions: This results indicateinfo:eu-repo/semantics/publishedVersio

    Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections

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    Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin’s efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections

    Multicentre observational study on multisystem inflammatory syndrome related to COVID-19 in Argentina

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    Background: The impact of the pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in low- and middle-income countries remains poorly understood. Our aim was to understand the characteristics and outcomes of PIMS-TS in Argentina. Methods: This observational, prospective, and retrospective multicenter study enrolled patients younger than 18 years-old manifesting PIMS-TS, Kawasaki disease (KD) or Kawasaki shock syndrome (KSS) between March 2020 and May 2021. Patients were followed-up until hospital discharge or death (one case). The primary outcome was pediatric intensive care unit (PICU) admission. Multiple logistic regression was used to identify variables predicting PICU admission. Results: Eighty-one percent, 82%, and 14% of the 176 enrolled patients fulfilled the suspect case criteria for PIMS-TS, KD, and KSS, respectively. Temporal association with SARS-CoV-2 was confirmed in 85% of the patients and 38% were admitted to the PICU. The more common clinical manifestations were fever, abdominal pain, rash, and conjunctival injection. Lymphopenia was more common among PICU-admitted patients (87% vs. 51%, p < 0.0001), who also showed a lower platelet count and higher plasmatic levels of inflammatory and cardiac markers. Mitral valve insufficiency, left ventricular wall motion alterations, pericardial effusion, and coronary artery alterations were observed in 30%, 30%, 19.8%, and 18.6% of the patients, respectively. Days to initiation of treatment, rash, lymphopenia, and low platelet count were significant independent contributions to PICU admission. Conclusion: Rates of severe outcomes of PIMS-TS in the present study agreed with those observed in high-income countries. Together with other published studies, this work helps clinicians to better understand this novel clinical entity.Fil: Vainstein, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Baleani, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Urrutia, Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Affranchino, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ackerman, Judith. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Cazalas, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Goldsman, Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Sardella, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Tolin, Ana Laura. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Goldaracena, Pablo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Fabi, Mariana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Cosentino, Mariana. Hospital Británico de Buenos Aires; ArgentinaFil: Magliola, Ricardo. Hospital Británico de Buenos Aires; ArgentinaFil: Roggiero, Gustavo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Manso, Paula. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Triguy, Jésica. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Ballester, Celeste. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Cervetto, Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Vaccarello, María. Sanatorio de la Trinidad; ArgentinaFil: De Carli, Domingo Norberto. Clínica del Niño de Quilmes; ArgentinaFil: De Carli, Maria Estela. Clínica del Niño de Quilmes; ArgentinaFil: Ciotti, Ana Laura. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Sicurello, María Irene. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Rios Leiva, Cecilia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Villalba, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Hortas, María. Sanatorio de la Trinidad; ArgentinaFil: Peña, Sonia. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: González, Gabriela. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Zold, Camila Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Grippo, M.. No especifíca;Fil: Vázquez, H.. No especifíca;Fil: Morós, C.. No especifíca;Fil: Di Santo, M.. No especifíca;Fil: Villa, A.. No especifíca;Fil: Lazota, P.. No especifíca;Fil: Foti, M.. No especifíca;Fil: Napoli, N.. No especifíca;Fil: Katsikas, M. M.. No especifíca;Fil: Tonello, L.. No especifíca;Fil: Peña, J.. No especifíca;Fil: Etcheverry, M.. No especifíca;Fil: Iglesias, D.. No especifíca;Fil: Alcalde, A. L.. No especifíca;Fil: Bruera, M.J.. No especifíca;Fil: Bruzzo, V.. No especifíca;Fil: Giordano, P.. No especifíca;Fil: Pena Acero, F.. No especifíca;Fil: Netri Pelandi, G.. No especifíca;Fil: Pastaro, D.. No especifíca;Fil: Bleiz, J.. No especifíca;Fil: Rodríguez, M. F.. No especifíca;Fil: Laghezza, L.. No especifíca;Fil: Molina, M. B.. No especifíca;Fil: Patynok, N.. No especifíca;Fil: Chatelain, M. S.. No especifíca;Fil: Aguilar, M. J.. No especifíca;Fil: Gamboa, J.. No especifíca;Fil: Cervan, M.. No especifíca;Fil: Ruggeri, A.. No especifíca;Fil: Marinelli, I.. No especifíca;Fil: Checcacci, E.. No especifíca;Fil: Meregalli, C.. No especifíca;Fil: Damksy Barbosa, J.. No especifíca;Fil: Fernie, L.. No especifíca;Fil: Fernández, M. J.. No especifíca;Fil: Saenz Tejeira, M.M.. No especifíca;Fil: Cereigido, C.. No especifíca;Fil: Nunell, A.. No especifíca;Fil: Villar, D.. No especifíca;Fil: Mansilla, A. D.. No especifíca;Fil: Darduin, M. D.. No especifíca

    Improved Canine and Human Visceral Leishmaniasis Immunodiagnosis Using Combinations of Synthetic Peptides in Enzyme-Linked Immunosorbent Assay

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    Visceral leishmaniasis is endemic in many areas of tropical and subtropical America where it constitutes a significant public health problem. It is usually diagnosed by enzyme-linked immunosorbent assays (ELISA) using crude Leishmania antigens, but a variety of other immunological methods may also be applied. Although these approaches are useful, historically their sensitivity and specificity have often been compromised by the use of complex mixtures of antigens. In this context, the use of combinations of purified, well-characterized antigens appears preferable and may yield better results. In the present study, combinations of peptides derived from the previously described Leishmania diagnostic antigens A2, NH, LACK and K39 were used in ELISA against sera from 106 dogs and 44 human patients. Improved sensitivities and specificities, close to 100%, for both sera of patients and dogs was observed for ELISA using some combinations of the peptides, including the detection of VL in dogs with low anti-Leishmania antibody titers and asymptomatic infection. So, the use of combinations of B cell predicted synthetic peptides derived from antigens A2, NH, LACK and K39 may provide an alternative for improved sensitivities and specificities for immunodiagnostic assays of VL

    EpIG‐DB: A database of vascular epiphyte assemblages in the Neotropics

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    Vascular epiphytes are a diverse and conspicuous component of biodiversity in tropical and subtropical forests. Yet, the patterns and drivers of epiphyte assemblages are poorly studied in comparison with soil‐rooted plants. Current knowledge about diversity patterns of epiphytes mainly stems from local studies or floristic inventories, but this information has not yet been integrated to allow a better understanding of large‐scale distribution patterns. EpIG‐DB, the first database on epiphyte assemblages at the continental scale, resulted from an exhaustive compilation of published and unpublished inventory data from the Neotropics. The current version of EpIG‐DB consists of 463,196 individual epiphytes from 3,005 species, which were collected from a total of 18,148 relevés (host trees and ‘understory’ plots). EpIG‐DB reports the occurrence of ‘true’ epiphytes, hemiepiphytes and nomadic vines, including information on their cover, abundance, frequency and biomass. Most records (97%) correspond to sampled host trees, 76% of them aggregated in forest plots. The data is stored in a TURBOVEG database using the most up‐to‐date checklist of vascular epiphytes. A total of 18 additional fields were created for the standardization of associated data commonly used in epiphyte ecology (e.g. by considering different sampling methods). EpIG‐DB currently covers six major biomes across the whole latitudinal range of epiphytes in the Neotropics but welcomes data globally. This novel database provides, for the first time, unique biodiversity data on epiphytes for the Neotropics and unified guidelines for future collection of epiphyte data. EpIG‐DB will allow exploration of new ways to study the community ecology and biogeography of vascular epiphytes

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London
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