Three-Year Clinical Follow-Up of Children Intrauterine Exposed to Zika Virus

Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up

Avaliação do refluxo gastroesofagico na morbidade de lactentes chiadores atopicos e não-atopicos

Orientador: Jose Dirceu RibeiroObservação: Faltam as páginas 113 a 132Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Este estudo tem como objetivos caracterizar e avaliar o papel do refluxo gastroesofágico no quadro clínico de crianças, atópicas e nào-atópicas, portadoras da síndrome do ladente chiador. Adicionalmente, verificou-se a influência dos seguintes fatores de risco para doença respiratória: aleitamento materno, fumo passivo e permanência em creche. Estudou-se prospectivamente uma COOl'te de 80 crianças com síndrome do lactente chiador definida como a ocorrência de sibilância recorrente (três ou mais crises, ou uma crise com duração igualou maior de 30 dias), em crianças de até 2 anos de idade. As crianças forarn classificadas, quanto a atopia, utilizando-se o índice de AKASAKA modificado, que considera os seguintes parámetros: idade da 1a crise de sibiláncia, resposta a broncodilatador, nível sérico de IGE elevado, antecedente familiar de atopia., estigmas pessoais de atopia. Encontrou-se 60% ATÓPICAS (A), e 40% NÃO-ATÓPICAS (NA). Estas crianças apresentavam refluxo gastroesofágico diagnostica.do antes ou durante a investigaçào para SLC, comprovado por pelo menos dois exames positivos dentre os seguintes: seriografia esôfago-gastro-duodenal, cintilografia, esôfago-gástrica, ultrasonografia abdominal superior, endoscopia e biópsia esofágicas, e caracterizado, ainda, com estudo do esvaziamento gástrico e pesquisa de aspiração pulmonar. O RGE foi classificado quanto à gravidade, em GRAVE (63,3%) e NÃO-GRAVE (33,8%), utilizando-se a lógica booleana. para combinar os resultados de três métodos de estudo da. função esofágica: RxEED, endoscopia e biópsia esofágicas, cujos conceitos foram previamente determinados como MAJOR, MINOR ou NEGATIVO. As crianças foram agrupadas quanto a atopia: 48 A e 32 NA, e quanto a gravidade do RGE: 53 G e 27 NG. Combinando ambas as classificações obtivemos 4 grupos: A-G (31 crianças),A-NG (17 crianças), NA-G (22 crianças) e NA-NG (10 crianças). Determinou-se a. MORBILIDADE referida e diagnosticada das crianças à. época da admissão no estudo através de protocolo de investigação clínica: anamnese, exame físico, teste com broncodilatador e avaliaçào de 16 parâmetros laboratoriais, perfazendo 48 variáveis objetos de análise estatística para os grupos isolados (A/NA e G/NG), e combinados quanto a atopia e RGE (A-G, A-NG, NA-G, NA-NG) . Adicionalmente, investigou-se a influência de três fatores de risco sobre as variáveis pertinentes. Continua...Abstract: The aims of this study were to characterize and then to evaluate the role of gastroesophageal reflux in the clinical picture of infants and small children, atopic and non-atopic, who presented recurrent wheeze. Additionally, we verified the influence of some risk factors to respiratory disease in infancy such as: breastfeeding, passive smoking and staying in daycare centers. The recurrent wheezy illness of infants and preschool children is known as wheezy or asthmatoid bronchitis, wheezy baby syndrome, etc. The literature, at last instance, reflects the hesitation of authors to diagnose as asthma the wheezing disorders of early childhood - which is proving to be a correct posture, in the face of solid epidemiological evidence from research such as the Tucson Children's Respiratory Study. We studied prospectively 80 children below the age of three years, who presented the wheezy baby syndrome (WBS) defined as: at least three wheezing attacks or an episode that lasted more than 30 days, which occurred before the age of two. To determine the atopic state of the children, we used the modified AKASAKA score which consists of major criteria: family history of major allergies, high serum 19E leveI; and minor criteria: age of onset after six months, family history of minor allergies, eosinophilia in the nasal smear, other personal allergic signs, remarkable improvement with bronchodilator nebulization. 1nfants having two majors or one major and three or more minor cri teria were diagnosed as atopic - 60% were atopic (group A) and 40% nonatopic (group NA). These children also presented gastroesophageal reflux diagnosed before or during the clinical investigation to elucidate the wheezing illness, and proved by two positive tests among the following: upper gastrointestinal series, gastric scintiscanning, abdominal ultrasonography, esophageal endoscopy and biopsy. Reflux was further characterized by gastric emptying isotopic study and aspiration searching by means of barium swallow and pulmonary scintiscan. \i\Te created a criterium to classify the severity of gastroesophageal reflux using boolean logic to combine the results of three esophageal function tests, namely barium esophagography, esophagoscopy and esophageal biopsy, previously determined as major, minor or negative. We found 63,3% of severe reflux (group G) and 33,8% of non-severe reflux (group NG). The sample could then be divided into four combined groups, in relation to atopy and reflux: A-G (31 cases), A-NG (17 cases), NA-G (22 cases) and NA-NG (10 cases). Children's morbidity was determined by means of a clinical protocol: anamnesis, physical examination, bronchodilator testing ando sixteen laboratorial exams, in a total of 48 variables. The variables were statistically analized to atopy and reflux, and also to the selected risk factors: duration of breastfeeding, passive smoke and daycare staying. Continue...DoutoradoMedicina InternaDoutor em Medicin

Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas

Background: Esophageal squamous cell carcinoma (ESCC) shows a 5-year survival rate below 10%, demonstrating the urgency in improving its treatment. Alterations in epidermal growth factor receptors are closely related to malignancy transformation in a number of tumors and recent successful targeted therapies have been directed to these molecules. Therefore, in this study, we analyzed the expression of EGFR and HER2 and evaluated EGFR mutation profile as well as the presence of mutations in hotspots of KRAS and BRAF in ESCC patients. Methods: We performed RT-qPCR, immunohistochemistry and Fluorescent in situ hybridization to determine EGFR and HER2 expression in ESCC patients, and direct sequencing and PCR-RFLP for mutations and polymorphism analysis. Results: Our results showed an increased EGFR mRNA expression in tumors compared to surrounding tissue (p <0.05), with 11% of the cases presenting at least a four-fold difference between tumor and paired adjacent mucosa. EGFR protein overexpression was present only in 4% of the cases. The median expression of HER2 mRNA was not different between tumors and adjacent mucosa. Still, 7% of the tumors presented at least a 25-fold higher expression of this gene when compared to its paired counterpart. Immunohistochemical analysis revealed that 21% of the tumors were positive for HER2 (scores 2+ and 3+), although only 3+ tumors presented amplification of this gene. Mutation analysis for EGFR (exons 18-21), KRAS (codons 12 and 13) and BRAF (V600E) showed no mutations in any of the hotspots of these genes in almost 100 patients analyzed. EGFR presented synonymous polymorphisms at codon 836 (C>T) in 2.1% of the patients, and at codon 787 (G>A) in 79.2% of the cases. This last polymorphism was also evaluated in 304 healthy controls, which presented a similar frequency (73.7%) in comparison with ESCC patients. The absence of mutations of EGFR, KRAS and BRAF as well as the overexpression of EGFR and HER2 in less than 10% of the patients suggest that this signaling pathway is altered in only a small proportion of patients with ESCC. Conclusion: HER receptors target therapies may have the potential to be effective in only a minor fraction of patients with ESCC