GABRIELA NUNES LEAL
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Impact of ERT and follow-up of 17 patients from the same family with a mild form of MPS II(2022) STEPHAN, Bruno de Oliveira; QUAIO, Caio Robledo; SPOLADOR, Gustavo Marquezani; PAULA, Ana Carolina de; CURIATI, Marco Antonio; MARTINS, Ana Maria; LEAL, Gabriela Nunes; TENORIO, Artur; FINZI, Simone; CHIMELO, Flavia Teixeira; MATAS, Carla Gentile; HONJO, Rachel Sayuri; BERTOLA, Debora Romeo; KIM, Chong AeBackground: Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme Iduronate-2-Sulfatase (IDS), leading to progressive accumulation of Glycosaminoglycans (GAGs) in several organs. Over the years, Enzyme Replacement Therapy (ERT) has provided significant benefits for patients, retarding the natural progression of the disease. Results: The authors evaluated 17 patients from the same family with a mild form of MPS type II; the proband had developed acute decompensated heart failure refractory to clinical measurements at 23 years and needed a rather urgent heart transplant; however, he died from surgical complications shortly after the procedure. Nevertheless, subsequent to his tragic death, 16 affected male relatives were detected after biochemical tests identifying the low or absent activity of the IDS enzyme and confirmed by molecular analysis of the IDS gene. Following diagnosis, different options of treatment were chosen: 6 patients started ERT with Elaprase (R) (Idursulfase) soon after, while the other 10 remained without ERT. Eventually, 4 patients in the latter group began ERT with Hunterase (R) (Idursulfase Beta). None presented adverse effects to either form of the enzyme. Among the 6 individuals without any ERT, two died of natural causes, after reaching 70 years. Despite the variable phenotype within the same family (mainly heart dysfunctions and carpal tunnel syndrome), all 14 remaining patients were alive with an independent lifestyle. Conclusion: Here, the authors report the variable progress of the disease with and without ERT in a large Brazilian family with a slowly progressive form of MPS II, harboring the same missense variant in the IDS gene.
- Severe clinical spectrum with high mortality in pediatric patients with COVID-19 and multisystem inflammatory syndrome(2020) PEREIRA, Maria Fernanda Badue; LITVINOV, Nadia; FARHAT, Sylvia Costa Lima; EISENCRAFT, Adriana Pasmanik; GIBELLI, Maria Augusta Bento Cicaroni; CARVALHO, Werther Brunow de; FERNANDES, Vinicius Rodrigues; FINK, Thais de Toledo; FRAMIL, Juliana Valeria de Souza; GALLETI, Karine Vusberg; FANTE, Alice Lima; FONSECA, Maria Fernanda Mota; WATANABE, Andreia; PAULA, Camila Sanson Yoshino de; PALANDRI, Giovanna Gavros; LEAL, Gabriela Nunes; DINIZ, Maria de Fatima Rodrigues; PINHO, Joao Renato Rebello; SILVA, Clovis Artur; MARQUES, Heloisa Helena de SousaOBJECTIVES: To assess the outcomes of pediatric patients with laboratory-confirmed coronavirus disease (COVID-19) with or without multisystem inflammatory syndrome in children (MIS-C). METHODS: This cross-sectional study included 471 samples collected from 371 patients (age<18 years) suspected of having severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study group comprised 66/371 (18%) laboratory-confirmed pediatric COVID-19 patients: 61 (92.5%) patients tested positive on real-time reverse transcription-polymerase chain reaction tests for SARS-CoV-2, and 5 (7.5%) patients tested positive on serological tests. MIS-C was diagnosed according to the criteria of the Center for Disease Control. RESULTS: MIS-C was diagnosed in 6/66 (9%) patients. The frequencies of diarrhea, vomiting, and/or abdominal pain (67% vs. 22%, p=0.034); pediatric SARS (67% vs. 13%, p=0.008); hypoxemia (83% vs. 23%, p=0.006); and arterial hypotension (50% vs. 3%, p=0.004) were significantly higher in patients with MIS-C than in those without MIS-C. The frequencies of C-reactive protein levels >50 mg/L (83% vs. 25%, p=0.008) and D-dimer levels >1000 ng/mL (100% vs. 40%, p=0.007) and the median D-dimer, troponin T, and ferritin levels (p < 0.05) were significantly higher in patients with MIS-C. The frequencies of pediatric intensive care unit admission (100% vs. 60%, p=0.003), mechanical ventilation (83% vs. 7%, p < 0.001), vasoactive agent use (83% vs. 3%, p <0.001), shock (83% vs. 5%, p<0.001), cardiac abnormalities (100% vs. 2%, p <0.001), and death (67% vs. 3%, p < 0.001) were also significantly higher in patients with MIS-C. Similarly, the frequencies of oxygen therapy (100% vs. 33%, p=0.003), intravenous immunoglobulin therapy (67% vs. 2%, p < 0.001), aspirin therapy (50% vs. 0%, p < 0.001), and current acute renal replacement therapy (50% vs. 2%, p=0.002) were also significantly higher in patients with MIS-C. Logistic regression analysis showed that the presence of MIS-C was significantly associated with gastrointestinal manifestations [odds ratio (OR)=10.98; 95%CI (95% confidence interval)=1.20-100.86; p=0.034] and hypoxemia [OR=16.85; 95%CI=1.34-211.80; p=0.029]. Further univariate analysis showed a positive association between MIS-C and death [OR=58.00; 95%CI=6.39526.79; p <0 .0001]. CONCLUSIONS: Pediatric patients with laboratory-confirmed COVID-19 with MIS-C had a severe clinical spectrum with a high mortality rate. Our study emphasizes the importance of investigating MIS-C in pediatric patients with COVID-19 presenting with gastrointestinal involvement and hypoxemia.
- An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C(2021) DUARTE-NETO, Amaro Nunes; CALDINI, Elia Garcia; GOMES-GOUVEA, Michele Soares; KANAMURA, Cristina Takami; MONTEIRO, Renata Aparecida de Almeida; FERRANTI, Juliana Ferreira; VENTURA, Andrea Maria Cordeiro; REGALIO, Fabiane Aliotti; FIORENZANO, Daniela Matos; GIBELLI, Maria Augusta Bento Cicaroni; CARVALHO, Werther Brunow de; LEAL, Gabriela Nunes; PINHO, Joao Renato Rebello; DELGADO, Artur Figueiredo; CARNEIRO-SAMPAIO, Magda; MAUAD, Thais; SILVA, Luiz Fernando Ferraz da; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, MarisaBackground: COVID-19 in children is usually mild or asymptomatic, but severe and fatal paediatric cases have been described. The pathology of COVID-19 in children is not known; the proposed pathogenesis for severe cases includes immune-mediated mechanisms or the direct effect of SARS-CoV-2 on tissues. We describe the autopsy findings in five cases of paediatric COVID-19 and provide mechanistic insight into the mechanisms involved in the pathogenesis of the disease. Methods: Children and adolescents who died with COVID-19 between March 18 and August 15, 2020 were autopsied with a minimally invasive method. Tissue samples from all vital organs were analysed by histology, electron microscopy (EM), reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Findings: Five patients were included, one male and four female, aged 7 months to 15 years. Two patients had severe diseases before SARS-CoV-2 infection: adrenal carcinoma and Edwards syndrome. Three patients were previously healthy and had multisystem inflammatory syndrome in children (MIS-C) with distinct clinical presentations: myocarditis, colitis, and acute encephalopathy with status epilepticus. Autopsy findings varied amongst patients and included mild to severe COVID-19 pneumonia, pulmonary microthrombosis, cerebral oedema with reactive gliosis, myocarditis, intestinal inflammation, and haemophagocytosis. SARSCoV-2 was detected in all patients in lungs, heart and kidneys by at least one method (RT-PCR, IHC or EM), and in endothelial cells from heart and brain in two patients with MIS-C (IHC). In addition, we show for the first time the presence of SARS-CoV-2 in the brain tissue of a child with MIS-C with acute encephalopathy, and in the intestinal tissue of a child with acute colitis. Interpretation: SARS-CoV-2 can infect several cell and tissue types in paediatric patients, and the target organ for the clinical manifestation varies amongst individuals. Two major patterns of severe COVID-19 were observed: a primarily pulmonary disease, with severe acute respiratory disease and diffuse alveolar damage, or a multisystem inflammatory syndrome with the involvement of several organs. The presence of SARS-CoV-2 in several organs, associated with cellular ultrastructural changes, reinforces the hypothesis that a direct effect of SARS-CoV-2 on tissues is involved in the pathogenesis of MIS-C. (c) 2021 The Author(s).
- What are the benefits of two-dimensional speckle tracking echocardiography for diagnosis and treatment follow-up of childhood-onset systemic lupus erythematosus myocarditis?(2016) LEAL, Gabriela Nunes; DINIZ, Maria De Fatima; BRUNELLI, Juliana; LIANZA, Alessandro C.; SALLUM, Adriana M. E.; SILVA, Clovis A.
- Post-natal prognostic factors in CDH: experience of 11 years in a referral center in Brazil(2023) NAM, Camila Pinho Brasileiro Martins; CAMPOS, Carolina Vieira; LEAL, Gabriela Nunes; TANNURI, Uenis; CECCON, Maria Esther Jurfest Rivero; CARVALHO, Werther Brunow deObjective: To describe post-natal risk factors associated with death in Newborns (NB) with Congenital Diaphragmatic Hernia (CDH) in a Brazilian reference center.Methods: In this retrospective cohort study, post-natal clinical factors of all NB diagnosed with CDH were reviewed in an 11-year period (2007-2018). The primary outcome was death. Secondary outcomes included clinical features, prognostic indexes, type of mechanical ventilation, complications during hospitalization and surgical repair.Results: After applying the exclusion criteria, the authors analyzed 137 charts. Overall mortality was 59% (81/ 137), and the highest rates were observed for low-birth-weight NB (87%), syndromic phenotype (92%), and those with major malformations (100%). Prognostic indexes such as Apgar, SNAPPE-II and 24hOI (best oxygenation index in 24 hours) were all associated with poor evolution. In a multivariate analysis, only birth weight and 24hOI were statistically significant risk factors for mortality, with a reduction in mortality risk of 17.1% (OR = 0.829, 95% IC 0.72-0.955, p = 0.009) for each additional 100g at birth and an increase by 26.5% (OR = 1.265, 95% IC 1.113-1.436, p = 0.0003) for each unitary increase at the 24hOI.Conclusion: Prognostic indexes are an important tool for predicting outcomes and improving resource allocation. Post-natal risk factors may be more suitable for settings where antenatal diagnosis is not universal. Classical risk factors, such as prematurity, low birth weight, higher need for supportive care, and poorer prognostic indexes were associated with mortality in our CDH population.
- Diagnosis and management of systemic hypertension due to renovascular and aortic stenosis in patients with Williams-Beuren syndrome(2018) FURUSAWA, Erika Arai; ESPOSITO, Camila Sanches Lanetzki; HONJO, Rachel Sayuri; SUZUKI, Lisa; LEAL, Gabriela Nunes; KIM, Chong Ae; SCHVARTSMAN, Benito Galassi SoaresAIM: To describe the incidence, diagnosis, and management of systemic arterial hypertension related to renal artery stenosis in patients with Williams-Beuren syndrome. METHODS: Sixty-five patients with Williams-Beuren syndrome were evaluated for hypertension. Enrolled patients underwent Doppler sonography of the renal arteries and Doppler echocardiography. Those with Doppler sonography-detected lesions or with normal Doppler sonography but severe hypertension underwent computed tomography or gadolinium-enhanced magnetic resonance angiography of the aorta and renal vessels. Patients needing vascular therapeutic intervention underwent conventional angiography. RESULTS: Systemic arterial hypertension was diagnosed in 21/65 patients with Williams-Beuren syndrome (32%; 13 male) with a mean age of 13.9 years (5mo-20yrs). In 8/21 patients renovascular hypertension was detected. Angioplasty was unsuccessful in five patients with renal artery stenosis, requiring additional treatment. Doppler echocardiography showed cardiac abnormalities in 16/21 (76%) hypertensive patients. CONCLUSION: Cardiac abnormalities and hypertension in patients with Williams-Beuren syndrome are common. Thus, thorough evaluation and follow-up are necessary to reduce cardiovascular risks and mortality of these patients.
- Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital(2021) FINK, Thais T.; MARQUES, Heloisa H. S.; GUALANO, Bruno; LINDOSO, Livia; BAIN, Vera; ASTLEY, Camilla; MARTINS, Fernanda; MATHEUS, Denise; MATSUO, Olivia M.; SUGUITA, Priscila; TRINDADE, Vitor; PAULA, Camila S. Y.; FARHAT, Sylvia C. L.; PALMEIRA, Patricia; LEAL, Gabriela N.; SUZUKI, Lisa; ODONE FILHO, Vicente; CARNEIRO-SAMPAIO, Magda; DUARTE, Alberto Jose S.; ANTONANGELO, Leila; BATISTTELLA, Linamara R.; V, Guilherme Polanczyk; PEREIRA, Rosa Maria R.; CARVALHO, Carlos Roberto R.; BUCHPIGUEL, Carlos A.; XAVIER, Ana Claudia L.; SEELAENDER, Marilia; SILVA, Clovis Artur; PEREIRA, Maria Fernanda B.OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.
- Cardiac manifestations in pediatric COVID-19(2021) CAPUCHO, Ana Carolina Marques do Vale; RESENDE, Paola Laureza Silva; MASCARENHAS, Daniel Alves; SILVA, Camila Lino Martins Rodrigues da; SAWAMURA, Karen Saori Shiraishi; MENEZES, Carolina da Rocha Brito; DINIZ, Maria de Fatima Rodrigues; LIANZA, Alessandro Cavalcanti; CARVALHO, Werther Brunow de; SILVA, Clovis Artur Almeida da; LEAL, Gabriela Nunes