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2.
Front Pediatr ; 9: 648022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307247

RESUMO

Nuclear factor κappa-B (NFκB) is a family of transcription factors involved in regulating inflammation and immunity. Mutations in the NFκB1 pathway are associated with primary immune defects and underlie the most common monogenic etiology of common variable immunodeficiency (CVID). However, little is known about how NFκB1 defects or primary immunodeficiency (PID) complicate pregnancy. We present a previously healthy 34-year-old patient who suffered from poor wound healing and sterile sepsis during the post-partum period of each of her three pregnancies. She was otherwise asymptomatic, but her daughter developed Evans Syndrome (ES) with hypogammaglobulinemia prompting expanded genetic testing which revealed a novel monoallelic variant in NFκB1. This case highlights that pregnancy-related complications of PID can be difficult to recognize and may portend adverse patient outcomes. For these reasons, guidance regarding diagnosis and management of women of childbearing age with PID is warranted.

3.
JMIR Mhealth Uhealth ; 8(10): e19874, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107838

RESUMO

BACKGROUND: The use of location-based data in clinical settings is often limited to real-time monitoring. In this study, we aim to develop a proximity-based localization system and show how its longitudinal deployment can provide operational insights related to staff and patients' mobility and room occupancy in clinical settings. Such a streamlined data-driven approach can help in increasing the uptime of operating rooms and more broadly provide an improved understanding of facility utilization. OBJECTIVE: The aim of this study is to measure the accuracy of the system and algorithmically calculate measures of mobility and occupancy. METHODS: We developed a Bluetooth low energy, proximity-based localization system and deployed it in a hospital for 30 days. The system recorded the position of 75 people (17 patients and 55 staff) during this period. In addition, we collected ground-truth data and used them to validate system performance and accuracy. A number of analyses were conducted to estimate how people move in the hospital and where they spend their time. RESULTS: Using ground-truth data, we estimated the accuracy of our system to be 96%. Using mobility trace analysis, we generated occupancy rates for different rooms in the hospital occupied by both staff and patients. We were also able to measure how much time, on average, patients spend in different rooms of the hospital. Finally, using unsupervised hierarchical clustering, we showed that the system could differentiate between staff and patients without training. CONCLUSIONS: Analysis of longitudinal, location-based data can offer rich operational insights into hospital efficiency. In particular, they allow quick and consistent assessment of new strategies and protocols and provide a quantitative way to measure their effectiveness.


Assuntos
Ocupação de Leitos , Hospitais , Humanos
4.
AIDS ; 34(4): 529-537, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31764073

RESUMO

OBJECTIVES: To longitudinally measure LV diastolic function in HIV-exposed but uninfected (HEU) children perinatally exposed to ART. DESIGN: HEU children who were perinatally exposed to antiretroviral therapy (ART) may be at risk for adverse cardiac effects. We have previously reported that those children have decreased left ventricular (LV) mass, dimension, and septal thickness with increased contractility. METHODS: Serial echocardiograms were obtained at specific times from birth to 48 months from two groups of HIV-uninfected children: 148 HIV-negative children who were perinatally exposed to ART and 130 non-ART-exposed HIV-unexposed healthy controls. The following LV diastolic indices were obtained: mitral valve early and late diastolic velocity (E and A), tissue Doppler-derived LV-free wall and septal early diastolic velocity (LV e' and sep e'). RESULTS: All echocardiographic indices were significantly different in ART-exposed children compared with ART-unexposed healthy controls. Both E and A were overall lower at all ages by 8.28 cm/s (P = 0.0002) and 13.46 cm/s (P < 0.0001) respectively. E/A ratio was higher by 0.27, 0.46, and 0.28 units at birth, 1 year and 2 years of age, respectively (all P ≤ 0.01). Moreover, LV e' and sep e' were overall lower at all ages by 0.84 cm/s (P = 0.01) and 0.47 cm/s (P = 0.02), respectively. CONCLUSION: Children who were exposed to ART in utero have subclinical yet significant differences in specific LV diastolic indices. Follow-up with serial echocardiograms are recommended in this population to further assess the potential cardiac toxicity of perinatal exposure to ART.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Troca Materno-Fetal , Complicações Infecciosas na Gravidez/tratamento farmacológico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos , Pré-Escolar , Diástole , Ecocardiografia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez
6.
J Allergy Clin Immunol ; 144(1): 294-303.e13, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30735686

RESUMO

BACKGROUND: Chronic HIV infection is known to trigger a population redistribution and alteration in the functional capacity of natural killer (NK) cells. Because of improved antiretroviral treatments, there are rising numbers of adolescents and young adults worldwide who are living with HIV infection since birth. OBJECTIVE: We sought to determine how NK-cell phenotypic and functional subsets are altered in treated pediatric patients. METHODS: NK cells were contrasted among 29 HIV-unexposed and uninfected controls (5-19 years), 23 HIV-exposed but uninfected patients (3-19 years), and 25 HIV-infected patients (3-19 years) using multiparametric flow cytometry. RESULTS: Although most NK-cell markers did not differ, activating receptors such as NKp46, DNAX accessory molecule-1, and NKG2C and stimulatory receptors such as CD2 and CD11c were expressed by a higher frequency of NK cells in HIV-infected patients than in controls. Interestingly, there were less differences between HIV-infected and HIV-exposed but uninfected children. There was an inverse relationship between CD4/CD8 T-cell ratio (as a marker of disease progression) and CD11c and NKG2C frequency and CD69 upregulation on stimulation among HIV-infected patients. CONCLUSIONS: A chronic NK-cell activation phenotype persists in HIV-infected children receiving antiretroviral therapy and is associated with declining CD4/CD8 T-cell ratios. A lower CD4/CD8 T-cell ratio was associated with higher baseline granzyme B (P = .0068; R2 = 0.29) and degranulation potential (P = .022; R2 = 0.22) in stimulated NK cells. Thus, NK cells in HIV-infected children receiving treatment have reduced functional potential and an activated phenotype that distinguishes them from uninfected children.


Assuntos
Infecções por HIV/imunologia , Células Matadoras Naturais/imunologia , Adolescente , Adulto , Relação CD4-CD8 , Criança , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Fenótipo , Adulto Jovem
8.
AIDS ; 32(16): 2337-2346, 2018 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-30102660

RESUMO

OBJECTIVE: To evaluate potential adverse associations of individual antiretroviral medications used in combination antiretroviral therapy regimens on cardiac structure and function in youth with perinatally-acquired HIV infection (PHIV). DESIGN: PHIV youth (N = 325) enrolled in a prospective multisite cohort study had a single echocardiogram at age 7-16 years to evaluate cardiac function and structure. METHODS: We applied several statistical approaches to evaluate associations between use of 18 individual antiretroviral medications with Z-scores for 11 measures of left ventricular function and structure. These included simultaneously evaluating all antiretroviral medications in adjusted linear regression models controlling for the false discovery rate (FDR), applying hierarchical models to estimate individual antiretroviral medication effects as deviations from drug class means, and evaluating latent measures of cardiac function and structure underlying multiple echocardiographic parameters. RESULTS: Youth taking combination regimens with a protease inhibitor (69%) had significantly better cardiac function than those on other regimens. After FDR control and adjustment for other antiretroviral medications, no individual antiretroviral medication was significantly associated with any measure of left ventricular function, but zidovudine was associated with higher adjusted mean Z-scores for one measure of left ventricular structure (end-systolic wall stress). Factor analysis identified three latent factors: heart function, heart size, and heart wall stress. Lopinavir was associated with better heart function scores, whereas zidovudine was associated with higher wall stress scores. Zidovudine and nevirapine were associated with higher heart size factor scores. CONCLUSIONS: Despite cardioprotective effects of combination regimens in PHIV youth, individual antiretroviral medications were associated with altered cardiac structure, which could progress to symptomatic cardiomyopathy in adulthood.


Assuntos
Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Adolescente , Criança , Ecocardiografia , Feminino , Humanos , Masculino , Estudos Prospectivos
10.
Biol Blood Marrow Transplant ; 24(8): 1643-1650, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29630926

RESUMO

There is a lack of consensus regarding the role and method of hematopoietic stem cell transplantation (HSCT) on patients with chronic granulomatous disease (CGD). Long-term follow-up after HSCT in these patient population is essential to know its potential complications and decide who will benefit the most from HSCT. We report the outcome of HSCT and long-term follow-up in 24 patients with CGD, transplanted in our center from either related (n = 6) or unrelated (n = 18) donors, over a 12-year period (2003 to 2015), using high-dose alemtuzumab in the preparative regimen. We evaluated the incidence and timing of adverse events and potential risk factors. We described in detailed the novel finding of increased autoimmunity after HSCT in patients with CGD. At a median follow-up of 1460 days, 22 patients were full donor chimeras, and 2 patients had stable mixed chimerism. All assessable patients showed normalization of their neutrophil oxidative burst test. None of the patients developed grades II to IV acute graft-versus-host disease, and no patient had chronic graft-versus-host disease. Twelve of 24 patients developed 17 autoimmune diseases (ADs). Severe ADs (cytopenia and neuropathy) occurred exclusively in the unrelated donor setting and mainly in the first year after HSCT, whereas thyroid AD occurred in the related donor setting as well and more than 3 years after HSCT. Two patients died due to infectious complications after developing autoimmune cytopenias. One additional patient suffered severe brain injury. The remaining 21 patients have long-term Lansky scores ≥ 80. The outcome of HSCT from unrelated donors is comparable with related donors but might carry an increased risk of developing severe AD. A lower dose of alemtuzumab may reduce this risk and should be tested in further studies.


Assuntos
Alemtuzumab/uso terapêutico , Doenças Autoimunes/etiologia , Doença Granulomatosa Crônica/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quimerismo , Seguimentos , Doença Granulomatosa Crônica/terapia , Síndrome de Guillain-Barré/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Pancitopenia/etiologia , Doadores não Relacionados
11.
AIDS ; 32(10): 1267-1277, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29596110

RESUMO

OBJECTIVES: To compare distributions of serum cardiac and inflammatory biomarkers between perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected (PHEU) children, to evaluate their associations with echocardiographic measures, and among PHIV youth, with antiretroviral therapy (ART) and HIV disease severity measures. DESIGN: Cross-sectional analysis of temporally paired serum samples for biomarkers and echocardiograms in a prospective multicenter cohort study of PHIV and PHEU youth. METHODS: Serum samples were analyzed among 402 youth in the PHACS Adolescent Master Protocol (AMP) for high-sensitivity cardiac troponin-T (hs-cTnT, a cardiomyocyte injury marker), N-terminal-pro-brain natriuretic peptide (NT-proBNP, a myocardial stress marker), and inflammatory markers [high-sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α (TNF-α), and soluble TNF receptor II (sTNF-RII)]. Echocardiograms were centrally measured and parameters converted to z cores to account for differences in age and body size. RESULTS: Compared with PHEU (N = 156), PHIV youth (N = 246) more often had detectable hs-cTnT and higher levels of sTNF-RII and IL-18. Higher inflammatory biomarkers were generally associated with higher left ventricular (LV) wall stress and lower LV function and LV mass in the two groups. Among PHIV youth, the biomarkers were more strongly associated with current rather than historical immunologic and virologic status. CONCLUSION: PHEU and PHIV have modest, significant differences in serum levels of specific inflammatory and active myocardial injury biomarkers. Higher biomarker levels were associated with lower LV mass and shifts in LV structure. Further study is warranted on the longitudinal role of cardiac and inflammatory biomarkers for targeting interventions among PHIV and PHEU youth.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Exposição Ambiental , Infecções por HIV/complicações , Voluntários Saudáveis , Inflamação/epidemiologia , Adolescente , Proteína C-Reativa/análise , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/patologia , Criança , Estudos Transversais , Citocinas/sangue , Ecocardiografia , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Inflamação/diagnóstico , Inflamação/patologia , Masculino , Peptídeo Natriurético Encefálico/sangue , Estudos Prospectivos , Precursores de Proteínas/sangue , Soro/química , Índice de Gravidade de Doença , Troponina T/sangue
12.
J Acquir Immune Defic Syndr ; 77(4): 417-426, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29303843

RESUMO

BACKGROUND: HIV-infected children with long-term nonprogressive (LTNP) disease eventually convert to a progressive disease type, yet the extent to which these children experience the cognitive and emotional symptoms observed in typical progressive HIV (Progressors) is unknown. METHODS: Eighty-eight LTNPs, 53 Progressors, and 323 healthy controls completed annual assessments of cognitive and emotional health as part of a prospective study. The 2 HIV-infected groups and the healthy controls were matched on age and sex distribution at enrollment. Plasma HIV RNA, T-cell counts/percentages, activated monocytes, perivascular monocytes, and markers of macrophage activation (sCD163 and sCD14) were compared by progression subtype. Cognitive and emotional outcomes were compared using cross-sectional linear regression analysis and longitudinal sensitivity models. RESULTS: LTNPs exhibited the same cognitive phenotype and emotional dysregulation as Progressors, with worse outcomes in both groups compared with controls. In addition, cognitive and emotional symptoms were evident before children reached the minimum age for LTNP designation (8 years). Baseline plasma HIV RNA, sCD163, activated monocytes, and perivascular monocytes were lower in LTNPs versus Progressors, with no difference in T-cell counts/percentages or sCD14 levels. Most LTNPs converted to a progressive disease subtype during the study, with similar cognitive and emotion profiles between these subgroups. CONCLUSIONS: Pediatric LTNPs experience cognitive and emotional difficulties that mirror symptoms of progressive disease. The abnormalities are present at young ages and persist independent of plasma T-cell counts. The findings highlight the neurodevelopmental risk of pediatric HIV, even in those with early innate disease control.


Assuntos
Infecções por HIV/patologia , Sobreviventes de Longo Prazo ao HIV , Transtornos Mentais/epidemiologia , Saúde Mental , Adolescente , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Criança , Pré-Escolar , Feminino , Infecções por HIV/complicações , Voluntários Saudáveis , Humanos , Lactente , Receptores de Lipopolissacarídeos/sangue , Estudos Longitudinais , Contagem de Linfócitos , Ativação de Macrófagos , Macrófagos/imunologia , Masculino , Transtornos Mentais/patologia , Monócitos/imunologia , Estudos Prospectivos , RNA Viral/sangue , Receptores de Superfície Celular/sangue , Linfócitos T/imunologia , Carga Viral
13.
Biol Blood Marrow Transplant ; 24(3): 537-541, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29196075

RESUMO

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Currently, hematopoietic stem cell transplantation (HSCT) is the most reliable curative treatment with excellent results for patients with HLA-matched family or unrelated donors. However, even after fully myeloablative preparative regimens, mixed donor chimerism is a potential concern. We performed a retrospective chart review of 12 children who underwent allogeneic HSCT for WAS to report our experience. The median age at transplant was 10.5 months (range, 3 to 39). The median nucleated cell dose from the marrow was 4.55 × 109/kg (range, .3 to 7.9). The median times to neutrophil and platelet engraftment were 19 days (range, 13 to 27) and 18.5 days (range, 12 to 31), respectively. The rate of overall survival was 92% with median follow-up of 67 months (range, 3 to 146). Two patients developed grade IV acute graft-versus-host disease, and 1 died on day +99. Five of 12 patient's (42%) had mixed donor chimerism (range, 12% to 85%) at day +180. None of the pretransplant patient parameters was predictive of mixed chimerism. Nonetheless, of these 5 patients, 2 had normalization of the platelet count despite the mixed chimerism, 2 had full donor chimerism after receiving a second transplant with the same donor, and 1 remains transfusion dependent awaiting a second transplant. Hence, even with a significant rate of mixed chimerism, HSCT provides substantial benefit to WAS patients, with excellent overall survival.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Síndrome de Wiskott-Aldrich , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Síndrome de Wiskott-Aldrich/sangue , Síndrome de Wiskott-Aldrich/mortalidade , Síndrome de Wiskott-Aldrich/terapia
14.
J Allergy Clin Immunol ; 141(3): 1036-1049.e5, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29241729

RESUMO

BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. METHODS: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. RESULTS: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. CONCLUSIONS: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.


Assuntos
Diabetes Mellitus Tipo 1/congênito , Diarreia , Fatores de Transcrição Forkhead , Doenças Genéticas Ligadas ao Cromossomo X , Transplante de Células-Tronco Hematopoéticas , Doenças do Sistema Imunitário/congênito , Terapia de Imunossupressão , Mutação , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/terapia , Diarreia/genética , Diarreia/imunologia , Diarreia/mortalidade , Diarreia/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/mortalidade , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/mortalidade , Doenças do Sistema Imunitário/terapia , Lactente , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
15.
Pediatrics ; 140(5)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29084832

RESUMO

This policy statement is intended to provide information to guide pediatricians, obstetricians, and other medical specialists and health care providers in responding to parents' questions about cord blood donation and banking as well as the types (public versus private) and quality of cord blood banks. Cord blood is an excellent source of stem cells for hematopoietic stem cell transplantation in children with some fatal diseases. Cord blood transplantation offers another method of definitive therapy for infants, children, and adults with certain hematologic malignancies, hemoglobinopathies, severe forms of T-lymphocyte and other immunodeficiencies, and metabolic diseases. The development of universal screening for severe immunodeficiency assay in a growing number of states is likely to increase the number of cord blood transplants. Both public and private cord blood banks worldwide hold hundreds of thousands of cord blood units designated for the treatment of fatal or debilitating illnesses. The procurement, characterization, and cryopreservation of cord blood is free for families who choose public banking. However, the family cost for private banking is significant and not covered by insurance, and the unit may never be used. Quality-assessment reviews by several national and international accrediting bodies show private cord blood banks to be underused for treatment, less regulated for quality control, and more expensive for the family than public cord blood banks. There is an unquestionable need to study the use of cord blood banking to make new and important alternative means of reconstituting the hematopoietic blood system in patients with malignancies and blood disorders and possibly regenerating tissue systems in the future. Recommendations regarding appropriate ethical and operational standards (including informed consent policies, financial disclosures, and conflict-of-interest policies) are provided for physicians, institutions, and organizations that operate or have a relationship with cord blood banking programs. The information on all aspects of cord blood banking gathered in this policy statement will facilitate parental choice for public or private cord blood banking.


Assuntos
Academias e Institutos/normas , Bancos de Sangue/normas , Transplante de Células-Tronco de Sangue do Cordão Umbilical/normas , Sangue Fetal/transplante , Pediatria/normas , Academias e Institutos/economia , Bancos de Sangue/economia , Bancos de Sangue/tendências , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/economia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/tendências , Política de Saúde/tendências , Doenças Hematológicas/economia , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/terapia , Humanos , Pediatria/economia , Estados Unidos/epidemiologia
16.
J Am Coll Cardiol ; 70(18): 2240-2247, 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29073951

RESUMO

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), cardiac mortality and morbidity were common in HIV-infected children. OBJECTIVES: This study sought to identify long-term cardiovascular effects of HAART in HIV-infected children. METHODS: The CHAART-2 (HAART-Associated Cardiotoxicity in HIV-Infected Children) study prospectively compared 148 echocardiograms from 74 HAART-exposed children to 860 echocardiograms from 140 HAART-unexposed but HIV-infected children from the Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) study. Both studies used similar protocol, centralized echocardiographic interpretation, and measures expressed as z-scores referenced to healthy controls. Associations between HAART exposure and echocardiographic measures were evaluated using generalized estimating equations. RESULTS: Comparing the HAART-exposed and HAART-unexposed groups, any HAART exposure was positively associated with left ventricular (LV) fractional shortening (z-score for difference = 1.07; p = 0.02) and HAART exposure duration (z-score difference per year = 0.17; p = 0.003. LV mass was negatively associated with any HAART exposure (z-score difference = -0.64; p = 0.01) as was septal thickness (z-score difference = -0.93; p = 0.001). Duration of HAART exposure was negatively associated with LV end-systolic dimension and heart rate (z-score difference per year= -0.11; p = 0.05; and z-score difference per year = -0.10; p = 0.002, respectively). During 11 years of follow-up, in the HAART-exposed group, LV mass and LV end-diastolic septal thickness were lower whereas LV contractility and LV fractional shortening were higher when compared to the HAART-unexposed group. CONCLUSIONS: Cardiac structure and function were better in perinatally HIV-infected children exposed to HAART than in those of similar children from the pre-HAART era but did decline over time. Evidence-based strategies for cardiovascular monitoring are needed to inform treatment decisions to improve long-term cardiovascular health.


Assuntos
Terapia Antirretroviral de Alta Atividade/tendências , Cardiotoxinas/administração & dosagem , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/tratamento farmacológico , Assistência Perinatal/tendências , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Cardiotoxinas/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Humanos , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/prevenção & controle , Estudos Longitudinais , Masculino , Assistência Perinatal/métodos , Gravidez , Estudos Prospectivos , Método Simples-Cego , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/prevenção & controle
17.
Blood ; 130(25): 2718-2727, 2017 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-29021228

RESUMO

The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patients with typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history. The 2-year overall survival was 90%, but was 95% for those who were infection-free at HCT vs 81% for those with active infection (P = .009). Other factors, including the diagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, use of preparative chemotherapy, or the type of donor used, did not impact survival. Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day +100 post-HCT revealed that CD3 < 300 cells/µL, CD8 < 50 cells/µL, CD45RA < 10%, or a restricted Vß T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free. The trial was registered at www.clinicaltrials.gov as #NCT01186913.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Reconstituição Imune , Imunodeficiência Combinada Severa/terapia , Pré-Escolar , Feminino , Genótipo , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Reconstituição Imune/genética , Lactente , Recém-Nascido , Infecções/etiologia , Masculino , Triagem Neonatal , Estudos Prospectivos , Fatores de Risco , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/mortalidade , Análise de Sobrevida , Doadores de Tecidos
19.
PLoS One ; 12(8): e0181134, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28767726

RESUMO

Natural killer (NK) cells are critical in immune defense against infected, stressed or transformed cells. Their function is regulated by the heterogeneous expression of a wide array of surface receptors that shape its phenotypic diversity. Although NK cells develop in the bone marrow and secondary lymphoid tissues, substantive differentiation is apparent in the peripheral blood including known age-related variation. In order to gain greater insight into phenotypic and functional variation within peripheral blood NK cells across age groups, we used multi-parametric, polyfunctional flow cytometry to interrogate the NK cell variability in 20 healthy adults and 15 5-10, 11-15 and 16-20 year-old children. We found that the normative ranges in both adults and children displayed great inter-individual variation for most markers. While the expression of several receptors did not differ, among those that did, the majority of the differences existed between adults and the three pediatric groups, rather than among children of different ages. Interestingly, we also identified variation in the individual expression of some markers by sex and ethnicity. Combinatorial analysis of NK cell receptors revealed intermediate subsets between the CD56bright and CD56dim NK cells. Furthermore, on examining the NK cell diversity by age, adults were discovered to have the lowest developmental diversity. Thus, our findings identify previously unappreciated NK cell subsets potentially distinguishing children from adults and suggest functional correlates that may have relevance in age-specific host defense.


Assuntos
Imunofenotipagem , Células Matadoras Naturais/metabolismo , Adolescente , Adulto , Fatores Etários , Antígeno CD56/metabolismo , Criança , Análise por Conglomerados , Feminino , Citometria de Fluxo , Humanos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/citologia , Pessoa de Meia-Idade , Receptores de Células Matadoras Naturais/metabolismo , Adulto Jovem
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