MIRIAM VERONICA FLOR PARK
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Changes in Gene Expression in Response to Red Blood Cell Transfusions in Chronically Transfused Sickle Cell Disease Patients(2019) KELLY, Shannon; DINARDO, Carla; DENG, Xutao; BELISARIO, Andre; PROIETTI, Anna Carneiro; LOUREIRO, Paula; MOTA, Rosimere Afonso; FLOR-PARK, Miriam V.; MAXIMO, Claudia; SABINO, Ester; CUSTER, Brian- The Sickle Cell Disease Ontology: enabling universal sickle cell-based knowledge representation(2019) ADEKILE, Adekunle; ANIE, Kofi A.; HAMDA, Cherif Ben; BROWN, Biobele; BUKINI, Daima; CAMPBELL, Andrew; CHAOUCH, Melek; CHIMUSA, Emile; CHUNDA-LIYOKA, Catherine; DENNIS-ANTWI, Jemima; DEREBAIL, Vimal K.; FLOR-PARK, Miriam; GEARD, Amy; GHEDIRA, Kais; HAENDEL, Melissa; HANCHARD, Neil A.; HOTCHKISS, Jade; JONAS, Mario; IBRAHIM, Muntaser; INGRAM, Clair; INUSA, Baba; JIMOH, Adijat Ozohu; JUPP, Simon; KAMGA, Karen; KASHIM, Zainab Abimbola; KNIGHT-MADDEN, Jennifer; LANDOURE, Guida; LOPEZ-SALL, Philomene; MAKANI, Julie; MALASA, Leonard; MASEKOAMENG, Tshepiso; MAZANDU, Gaston; MNIKA, Khuthala; MULDER, Nicola; MUNUNG, Nchangwi Syntia; MUNUBE, Deogratias; MWITA, Liberata; NEMBAWARE, Victoria; NNODU, Obiageli; OFORI-ACQUAH, Solomon; OHENE-FREMPONG, Kwaku; OSEI-AKOTO, Alex; PAINTSIL, Vivian; PANJI, Sumir; RAHIMY, Mohamed Cherif; ROYAL, Charmaine; SANGEDA, Raphael Z.; TAYO, Bamidele; TIOUIRI, Ines; TLUWAY, Furahini; TREADWELL, Marsha; TSHILOLO, Leon; VASILEVSKY, Nicole; WAISWA, Kasadhakawo Musa; WONKAM, AmbroiseSickle cell disease (SCD) is one of the most common monogenic diseases in humans with multiple phenotypic expressions that can manifest as both acute and chronic complications. Although described more than a century ago, challenges in comprehensive disease management and collaborative research on this disease are compounded by the complex molecular and clinical phenotypes of SCD, environmental and psychosocial factors, limited therapeutic options and ambiguous terminology. This ambiguous terminology has hampered the integration and interoperability of existing SCD knowledge, and SCD research translation. The SCD Ontology (SCDO), which is a community-driven integrative and universal knowledge representation system for SCD, overcomes this issue by providing a controlled vocabulary developed by a group of experts in both SCD and ontology design. SCDO is the first and most comprehensive standardized human- and machine-readable resource that unambiguously represents terminology and concepts about SCD for researchers, patients and clinicians. It is built around the central concept 'hemoglobinopathy', allowing inclusion of non-SCD haemoglobinopathies, such as thalassaemias, which may interfere with or influence SCD phenotypic manifestations. This collaboratively developed ontology constitutes a comprehensive knowledge management system and standardized terminology of various SCD-related factors. The SCDO will promote interoperability of different research datasets, facilitate seamless data sharing and collaborations, including meta-analyses within the SCD community, and support the development and curation of data-basing and clinical informatics in SCD. Availability: Ontology URL https://bioportal.bioontology.org/ontologies/SCDO.
- How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians(2020) NUNES, Kelly; AGUIAR, Vitor R. C.; SILVA, Marcio; SENA, Alexandre C.; OLIVEIRA, Danielli C. M. de; DINARDO, Carla L.; KEHDY, Fernanda S. G.; TARAZONA-SANTOS, Eduardo; ROCHA, Vanderson G.; CARNEIRO-PROIETTI, Anna Barbara F.; LOUREIRO, Paula; FLOR-PARK, Miriam V.; MAXIMO, Claudia; KELLY, Shannon; CUSTER, Brian; WEIR, Bruce S.; SABINO, Ester C.; PORTO, Luis Cristovao; MEYER, DiogoA match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of multilocus HLA genotypes. Further, HLA variability is not homogeneously distributed throughout the world: African populations on average have greater variability than non-Africans, reducing the chances that two unrelated African individuals are HLA identical. Here, we explore how self-identification (often equated with ""ethnicity"" or ""race"") and genetic ancestry are related to the chances of finding HLA compatible donors in a large sample from Brazil, a highly admixed country. We query REDOME, Brazil's Bone Marrow Registry, and investigate how different criteria for identifying ancestry influence the chances of finding a match. We find that individuals who self-identify as ""Black"" and ""Mixed"" on average have lower chances of finding matches than those who self-identify as ""White"" (up to 57% reduction). We next show that an individual's African genetic ancestry, estimated using molecular markers and quantified as the proportion of an individual's genome that traces its ancestry to Africa, is strongly associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary.
- Prevalence of serologic markers of transfusion and sexually transmitted infections and their correlation with clinical features in a large cohort of Brazilian patients with sickle cell disease(2020) BLATYTA, Paula F.; KELLY, Shannon; SABINO, Ester; PREISS, Liliana; MENDES, Franciane; CARNEIRO-PROIETTI, Anna B.; RODRIGUES, Daniela de Oliveira Werneck; MOTA, Rosimere; LOUREIRO, Paula; MAXIMO, Claudia; PARK, Miriam; MENDRONE-JR, Alfredo; GONCALEZ, Thelma T.; ALMEIDA NETO, Cesar de; CUSTER, BrianBACKGROUND: Patients with sickle cell disease (SCD) often require red blood cell (RBC) transfusion for clinical complications, so may be exposed to transfusion-transmitted infections (TTIs). The prevalence of markers for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and B (HBV), human T-cell lymphotropic virus (HTLV-1/2), Chagas disease, and syphilis in an SCD cohort in Brazil were studied. STUDY DESIGN AND METHODS: Clinical history, interview data, blood samples, and medical chart review data were collected during cohort enrollment from November 2013 to May 2015. Serologic markers of infection were assessed. Standard measures of statistical association were calculated, and multivariable models were developed for the most prevalent infections to identify associated factors. RESULTS: Infectionmarkers were evident in 5.2% (144/2779) of the enrolled cohort. Anti-HCV was detected in 69 (2.5%), syphilis antibodies in 34 (1.2%), anti-HTLV-1/2 in 17 (0.6%), HBV surface antigen in 13 (0.5%), Chagas disease antibodies in 13 (0.5%), and anti-HIV in 8 (0.3%) of participants. Factors associated with increased odds of being anti-HCV reactive were older age, illegal drug use, increasing number of RBCs, more than three pain crises in the previous year, and geographic location. Syphilis was associated with older age, females, and smoking history. CONCLUSION: HCV infection was more common in older patients who may have received RBCs before testing was performed on donations, suggesting possible historic transfusion transmission. The cohort showed decreasing rates of infections and a reduction in transfusion transmission markers in younger patients compared to historical literature except for syphilis, indicating contemporary reduced risk of TTI.
- Identification and Characterization of Hematopoietic Stem Cell Transplant Candidates in a Sickle Cell Disease Cohort(2019) V, Miriam Flor-Park; KELLY, Shannon; PREISS, Liliana; CUSTER, Brian; CARNEIRO-PROIETTI, Anna B. F.; ARAUJO, Aderson S.; LOUREIRO, Paula; MAXIMO, Claudia; RODRIGUES, Daniela O. W.; MOTA, Rosimere A.; SABINO, Ester C.; ROCHA, VandersonSickle cell disease (SCD) is associated with significant morbidity, and allogeneic hematopoietic stem cell transplantation (HSCT) remains the primary curative treatment. Recently, the Brazilian Ministry of Health released a regulation that required the publically funded healthcare system to pay for HSCT for SCD patients with defined indications. We used an existing 2794-member SCD cohort established during 2013 to 2015 to characterize candidates for HSCT and estimate the number of possible donors. Of 2064 patients with SC anemia (SCA), 152 of 974 children (16%) and 279 of 1090 adults (26%) had at least 1 HSCT indication. The most common indication for transplant was stroke (n = 239) followed by avascular necrosis (n = 96), priapism (n = 82), cerebrovascular disease (n = 55), >2 vaso-occlusive episodes (n = 38), alloantibodies and chronic transfusion therapy (n = 18), and >2 acute chest syndrome episodes (n = 11). Increasing age, number of transfusions, abnormal transcranial Doppler, retinopathy, dactylitis, and use of hydroxyurea were more frequent in the 152 children with an indication for HSCT compared with 822 without (P < .001). Of 152 children and 279 adults meeting the eligibility definition, 77 (50%) and 204 (73%), respectively, had at least 1 non-SCD full sibling who could potentially serve as a donor. In conclusion, in a large cohort of SCA patients, 16% of children and 26% of adults had at least 1 indication for HSCT; these indications were associated with the severity of the disease. This study provides clinical data necessary for estimating the costs and infrastructure that would be required to implement HSCT in a public healthcare system. (C) 2019 American Society for Transplantation and Cellular Therapy.
- Estimated glomerular filtration rate in Brazilian adults with sickle cell disease: results from the REDS-III multicenter cohort study(2023) BELISARIO, Andre Rolim; SILVA, Ana Cristina Simoes e; MOURA, Isabel Cristina Gomes; CARNEIRO-PROIETTI, Anna Barbara; SABINO, Ester Cerdeira; LOUREIRO, Paula; MAXIMO, Claudia; FLOR-PARK, Miriam V.; RODRIGUES, Daniela de Oliveira Werneck; OZAHATA, Mina Cintho; MOTA, Rosimere Afonso; DINARDO, Carla Luana; KELLY, Shannon; CUSTER, BrianChronic kidney disease (CKD) has a significant impact on sickle cell disease (SCD) morbidity and mortality. Early identification of individuals at highest risk of developing CKD may allow therapeutic intervention to prevent worse outcomes. This study aimed to evaluate the prevalence and risk factors for reduced estimated glomerular filtration rate (eGFR) among adults with SCD in Brazil. Participants in the REDS-III multicenter SCD cohort with more severe genotypes aged >= 18 years with at least two serum creatinine values were analyzed. The eGFR was calculated using the Jamaica Sickle Cell Cohort Study GFR equation. The eGFR categories were defined according to the K/DOQI. Participants with eGFR >= 90 were compared to those with those with eGFR < 90. Among the 870 participants, 647 (74.4%) had eGFR >= 90, 211 (24.3%) had eGFR 60 to 89, six (0.7%) had eGFR 30 to 59, and six (0.7%) had ESRD. Male sex (OR: 37.3; 95%CI: 22.4-65.1), higher age (OR: 1.04; 95%CI: 1.02-1.06), higher diastolic blood pressure (OR: 1.03; 95%CI: 1.009-1.06), lower Hb (OR: 0.80; 95%CI: 0.68-0.93), and lower reticulocytes (OR: 0.94; 95%CI: 0.89-0.99) levels were independently associated with eGFR < 90. There was a trend towards higher odds of death in participants with eGFR < 90 (OR: 1.8; 95%CI: 0.95-3.32; p = 0.065). In turn, participants with eGFR < 60 had a 12.2 (95%CI: 2.1-96.9) times higher odds for death when compared to those with eGFR >= 60. In this study, eGFR < 90 was observed in one-quarter of adults. Older age, male sex, higher diastolic blood pressure, lower hemoglobin, and lower reticulocyte levels were associated with occurrence of eGFR < 90. Estimated GFR < 60 increased the risk of mortality.
- Is Severity Score Associated With Indication for Hematopoietic Stem Cell Transplantation in Individuals With Sickle Cell Anemia?(2022) V, Miriam Flor-Park; OZAHATA, Mina Cintho; MOURA, Isabel Cristina Gomes; BLATYTA, Paula; KELLY, Shannon; OLIVEIRA, Claudia di Lorenzo; CAPUANI, Ligia; BELISARIO, Andre Rolim; CARNEIRO-PROIETTI, Anna B. F.; ARAUJO, Aderson S.; LOUREIRO, Paula; MAXIMO, Claudia; RODRIGUES, Daniela O. W.; MOTA, Rosimere A.; SABINO, Ester; CUSTER, Brian; ROCHA, VandersonManifestations of sickle cell disease (SCD) begin early in childhood and cause morbidity and decreased life expectancy. Hematopoietic stem cell transplantation (HSCT) is curative but associated with risk of mortality attributable to the transplant. This risk should be counterbalanced with SCD morbidity and mortality. A severity score using a Bayesian network model was previously validated to predict the risk of death in adult individuals with SCD. The objective of this study is to calculate the severity scores of participants in a multicenter cohort of Brazilians with SCD, using a previously published Bayesian network-derived score, associated with risk of death and then compare the severity scores between participants with and without an indication for HSCT as defined by the Brazilian Ministry of Health (MoH) criteria. This is an observational, retrospective study. We analyzed 2063 individuals with sickle cell anemia from the Recipient Epidemiology and Donor Evaluation Study-Ill Brazil SCD cohort and applied a Bayesian network-derived score to compare candidates and non-candidates for HSCT according to the Brazilian MoH transplant criteria. Classical statistical methods were used to analyze data and make comparisons. We compared severity scores between cohort members with (n = 431) and without (n = 1632) HSCT indications according to Brazilian MoH. Scores were not different in adult participants with >= 1 HSCT indication when compared to those with no indication (mean 0.342 versus 0.292; median 0.194 versus 0.183, P = .354) and receiver operating characteristic curves did not demonstrate an obvious threshold to differentiate participants with or without HSCT indications. Severity score may predict risk of death but does not differentiate HSCT candidates. Current indications should be evaluated to ensure that patients with more severe disease who might benefit from HSCT are appropriately identified.
- The Sickle Cell Disease Ontology: Enabling Collaborative Research and Co-Designing of New Planetary Health Applications(2020) NEMBAWARE, Victoria; MAZANDU, Gaston K.; HOTCHKISS, Jade; SERUFURI, Jean-Michel Safari; KENT, Jill; KENGNE, Andre Pascal; ANIE, Kofi; MUNUNG, Nchangwi Syntia; BUKINI, Daima; BITOUNGUI, Valentina Josiane Ngo; MUNUBE, Deogratias; CHIRWA, Uzima; CHUNDA-LIYOKA, Catherine; JONATHAN, Agnes; FLOR-PARK, Miriam V.; ESOH, Kevin Kum; JONAS, Mario; MNIKA, Khuthala; OOSTERWYK, Chandre; MASAMU, Upendo; MORRICE, Jack; UWINEZA, Annette; NGUWENEZA, Arthemon; BANDA, Kambe; NYANOR, Isaac; ADJEI, David Nana; SIEBU, Nathan Edward; NKANYEMKA, Malula; KUONA, Patience; TAYO, Bamidele O.; CAMPBELL, Andrew; ORON, Assaf P.; NNODU, Obiageli E.; PAINSTIL, Vivian; MAKANI, Julie; MULDER, Nicola; WONKAM, AmbroiseSickle cell disease (SCD) is one of the most common blood disorders impacting planetary health. Over 300,000 newborns are diagnosed with SCD each year globally, with an increasing trend. The sickle cell disease ontology (SCDO) is the most comprehensive multidisciplinary SCD knowledge portal. The SCDO was collaboratively developed by the SCDO working group, which includes experts in SCD and data standards from across the globe. This expert review presents highlights and lessons learned from the fourth SCDO workshop that marked the beginning of applications toward planetary health impact, and with an eye to empower and cultivate multisite SCD collaborative research. The workshop was organized by the Sickle Africa Data Coordinating Center (SADaCC) and attended by 44 participants from 14 countries, with 2 participants connecting remotely. Notably, from the standpoint of democratizing and innovating scientific meeting design, an SCD patient advocate also presented at the workshop, giving a broader real-life perspective on patients' aspirations, needs, and challenges. A major component of the workshop was new approaches to harness SCDO to harmonize data elements used by different studies. This was facilitated by a web-based platform onto which participants uploaded data elements from previous or ongoing SCD-relevant research studies before the workshop, making multisite collaborative research studies based on existing SCD data possible, including multisite cohort, SCD global clinical trials, and SCD community engagement approaches. Trainees presented proposals for systematic literature reviews in key SCD research areas. This expert review emphasizes potential and prospects of SCDO-enabled data standards and harmonization to facilitate large-scale global SCD collaborative initiatives. As the fields of public and global health continue to broaden toward planetary health, the SCDO is well poised to play a prominent role to decipher SCD pathophysiology further, and co-design diagnostics and therapeutics innovation in the field.
- Proceedings of a Sickle Cell Disease Ontology workshop - Towards the first comprehensive ontology for Sickle Cell Disease(2016) MULDER, Nicola; NEMBAWARE, Victoria; ADEKILE, Adekunle; ANIE, Kofi A.; INUSA, Baba; BROWN, Biobele; CAMPBELL, Andrew; CHINENERE, Furahini; CHUNDA-LIYOKA, Catherine; DEREBAIL, Vimal K.; GEARD, Amy; GHEDIRA, Kais; HAMILTON, Carol M.; HANCHARDN, Neil A.; HAENDEL, Melissa; HUGGINS, Wayne; IBRAHIM, Muntaser; JUPP, Simon; KAMGA, Karen Kengne; KNIGHT-MADDEN, Jennifer; LOPEZ-SALL, Philomene; MBIYAVANGA, Mamana; MUNUBE, Deogratias; NIRENBERG, Damian; NNODU, Obiageli; OFORI-ACQUAH, Solomon Fiifi; OHENE-FREMPONG, Kwaku; OPAP, Kenneth Babu; PANJI, Sumir; PARK, Miriam; PULE, Gift; ROYAL, Charmaine; SANGEDA, Raphael; TAYO, Bamidele; TREADWELL, Marsha; TSHILOLO, Leon; WONKAM, AmbroiseSickle cell disease (SCD) is a debilitating single gene disorder caused by a single point mutation that results in physical deformation (i.e. sickling) of erythrocytes at reduced oxygen tensions. Up to 75% of SCD in newborns world-wide occurs in sub-Saharan Africa, where neonatal and childhood mortality from sickle cell related complications is high. While SCD research across the globe is tackling the disease on multiple fronts, advances have yet to significantly impact on the health and quality of life of SCD patients, due to lack of coordination of these disparate efforts. Ensuring data across studies is directly comparable through standardization is a necessary step towards realizing this goal. Such a standardization requires the development and implementation of a disease-specific ontology for SCD that is applicable globally. Ontology development is best achieved by bringing together experts in the domain to contribute their knowledge. The SCD community and H3ABioNet members joined forces at a recent SCD Ontology workshop to develop an ontology covering aspects of SCD under the classes: phenotype, diagnostics, therapeutics, quality of life, disease modifiers and disease stage. The aim of the workshop was for participants to contribute their expertise to development of the structure and contents of the SCD ontology. Here we describe the proceedings of the Sickle Cell Disease Ontology Workshop held in Cape Town South Africa in February 2016 and its outcomes. The objective of the workshop was to bring together experts in SCD from around the world to contribute their expertise to the development of various aspects of the SCD ontology. (C) 2016 The Authors.
- Clinical and genetic ancestry profile of a large multi-centre sickle cell disease cohort in Brazil(2018) CARNEIRO-PROIETTI, Anna B. F.; KELLY, Shannon; TEIXEIRA, Carolina Miranda; SABINO, Ester C.; ALENCAR, Cecilia S.; CAPUANI, Ligia; SILVA, Tassila P. Salomon; ARAUJO, Aderson; LOUREIRO, Paula; MAXIMO, Claudia; LOBO, Clarisse; FLOR-PARK, Miriam V.; RODRIGUES, Daniela O. W.; MOTA, Rosimere A.; GONCALEZ, Thelma T.; HOPPE, Carolyn; FERREIRA, Joao E.; OZAHATA, Mina; PAGE, Grier P.; GUO, Yuelong; PREISS, Liliana R.; BRAMBILLA, Donald; BUSCH, Michael P.; CUSTER, BrianApproximately 3500 children with sickle cell disease (SCD) are born in Brazil each year, but the burden of SCD morbidity is not fully characterised. A large, multi-centre cohort was established to characterise clinical outcomes in the Brazilian SCD population and create the infrastructure to perform genotype-phenotype association studies. Eligible patients were randomly selected from participating sites and recruited at routine visits. A biorepository of blood samples was created and comprehensive demographic and clinical outcome data were entered in a centralized electronic database. Peripheral blood genome-wide single nucleotide polymorphism (SNP) genotyping was performed using a customized Transfusion Medicine (TM) Array. A total of 2795 participants at six Brazilian sites were enrolled between 2013 and 2015. The cohort included slight predominance of children <18 years (55.9%) and females (53.0%). Haemoglobin (Hb) SS was the most common SCD genotype (70.7%), followed by HbSC (23%), S beta 0 (3.0%) and S beta+ (2.9%). SNP data from the TM Array were analysed to evaluate the genetic ancestry of the cohort and revealed significant admixture among the population. Demographics and clinical complications, stratified by age and SCD genotype, are summarized and future studies in this cohort are discussed.