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2.
Medicine (Baltimore) ; 99(36): e21974, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899036

RESUMO

The present study attempted to analyze the clinical characteristics and pathogenesis of Kawasaki disease (KD) in children with hyperbilirubinemia.A total of 390 children with KD hospitalized in our hospital from September 2018 to July 2019 were selected and divided into control (270 cases) and hyperbilirubinemia (120 cases) groups based on the total, direct, and indirect bilirubin values after admission. Clinical data of the inflammatory index and fever process of the 2 groups were analyzed and compared.The difference in sex and age between the 2 groups was statistically nonsignificant (P > .05). In the hyperbilirubinemia group, the white blood cell count, C-reactive protein, hemoglobin, platelet count, erythrocyte sedimentation rate, alanine aminotransferase, aspartate aminotransferase, albumin, and routine urine leucocyte; and incidence of coronary artery expansion, heart injury, and unreactive gamma globulin treatment were higher than those in the control group and the differences were statistically significant (P < .05). In the hyperbilirubinemia group, the mean fever duration before admission was shorter than that in the control group, whereas the fever duration after gamma globulin treatment was longer than that in the control group; these differences were statistically significant (P < .05).Hyperbilirubinemia incidence in children with KD was approximately 30.77% (120 cases), of which increased direct bilirubin was observed in 70.83% (85 cases) and increased indirect bilirubin in 29.17% (35 cases). Children with KD combined with hyperbilirubinemia exhibited a strong inflammatory reaction, which may be due to liver damage or biliary block.


Assuntos
Hiperbilirrubinemia/complicações , Síndrome de Linfonodos Mucocutâneos/etiologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Masculino
3.
Medicine (Baltimore) ; 99(36): e22061, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899072

RESUMO

INTRODUCTION: Nilotinib is a selective inhibitor of the BCR-ABL tyrosine kinase receptor and is used in the management of chronic myelogenous leukemia (CML). Nilotinib therapy at high doses is associated with elevated serum bilirubin levels. If the serum bilirubin level exceeds 3 times the upper limit of normal, the recommendation is to either adjust nilotinib dosage or temporarily discontinue the treatment. However, it is unclear whether hyperbilirubinemia indicates obvious liver histology damage. PATIENT CONCERNS: A 24-year-old man with confirmed CML was treated with nilotinib therapy and developed hyperbilirubinemia after the treatment. Although the first remission of the hyperbilirubinemia was achieved after dose adjustment, the hematological parameters deteriorated. Thus, we initiated an antineoplastic therapy (at the standard dose) until complete remission of the CML was achieved. The pathogenic mechanism of hyperbilirubinemia may be related to the inhibition of uridine diphosphate-glucuronosyltransferase (UGT1A1) activity. Liver histological analysis revealed no significant liver damage. In addition, the patient had no family history of hyperbilirubinemia and liver disease. DIAGNOSIS: The patient was admitted to our hospital under the diagnosis of hyperbilirubinemia, and histopathology by liver biopsy showed no obvious damage. We also detected a UGT1A1 mutation [ex1 c.686C > A (p.Pro229Gln)] in the patient and his mother. INTERVENTIONS: When the nilotinib dose was decreased to 300 mg daily, the total bilirubin (TBIL) level decreased to 30 to 50 µmol/L for 1 month. However, because the Bcr-Abl/Abl ratio did not correspond to the major molecular response (MMR; <0.1%), the nilotinib dose was readjusted to 400 mg daily. One week later, the TBIL and indirect bilirubin levels increased to 89 and 79 µmol/L, respectively. The levels of alanine transaminase and other liver functional indicators were normal. OUTCOMES: A Naranjo Adverse Drug Reaction (ADR) Probability Scale score of 13 indicates that hyperbilirubinemia is attributed to ADR caused by nilotinib rather than by drug-induced liver injury. CONCLUSION: Although reducing the nilotinib dose can alleviate the occurrence of hyperbilirubinemia, the effect of MMR is also reduced. Treatment of CML without dose adjustment or discontinuation of nilotinib therapy may be more advantageous.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/diagnóstico , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , China/epidemiologia , Feminino , Glucuronosiltransferase/efeitos dos fármacos , Glucuronosiltransferase/genética , Humanos , Hiperbilirrubinemia/induzido quimicamente , Japão/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mães , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Indução de Remissão , Adulto Jovem
4.
Rev Assoc Med Bras (1992) ; 66(7): 1002-1008, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32844928

RESUMO

The increase in bilirubin levels in newborns can cause toxic effects on the auditory system, which can lead to hearing loss. This review aimed to verify the impact of hyperbilirubinemia in the hearing of newborns, relating audiological findings to serum levels of bilirubin. A literature review was conducted during October 2017, using the terms "hyperbilirubinemia", "jaundice", "infant", "newborn" and "hearing loss", on databases CAPES journals, MEDLINE and BIREME (SciELO, BBO). 827 studies were identified and 59 were selected for full-text reading, resulting in the selection of seven articles that met the inclusion criteria and were considered relevant to the sample of this study. All the reviewed studies performed brainstem auditory evoked potential as the main test for audiological evaluation. Changes in the audiological findings of neonates with hyperbilirubinemia were observed in all studies. There was no consensus on the serum bilirubin levels that may cause auditory changes; however, the relationship between hearing disorders and blood levels of bilirubin was positive. We identify the need to establish reference values for bilirubin levels considered critical for the occurrence of hearing disorders as well as the audiological follow-up of neonates with hyperbilirubinemia.


Assuntos
Perda Auditiva , Hiperbilirrubinemia , Audiometria , Bilirrubina , Potenciais Evocados Auditivos do Tronco Encefálico , Perda Auditiva/complicações , Humanos , Hiperbilirrubinemia/complicações , Recém-Nascido
5.
S Afr Med J ; 110(3): 249-254, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32657704

RESUMO

BACKGROUND: In South Africa (SA), healthy term newborns are usually discharged ˂72 hours after delivery. Discharged babies remain at risk for severe hyperbilirubinaemia if it is not identified early. Hyperbilirubinaemia is an important cause of readmission, and also leads to neonatal mortality and morbidity. Use of transcutaneous bilirubin (TcB) screening before hospital discharge has been controversial. OBJECTIVES: To test the clinical benefits of TcB screening of healthy newborns before discharge for the outcomes of readmission for jaundice and severe hyperbilirubinaemia in a randomised controlled trial (RCT). METHODS: This was a RCT. We compared predischarge TcB screening with visual assessment (alone) for jaundice in apparently healthy newborns at a public tertiary hospital in Cape Town, SA. Patients or study participants were not involved in the study design and implementation. RESULTS: Of the 1 858 infants, 63% were black, 35% of mixed race and 1% white. There was a significant reduction in the rate of readmission for jaundice (risk ratio (RR) 0.25; 95% confidence interval (CI) 0.14 - 0.46; p<0.0001) and in the incidence of severe hyperbilirubinaemia (RR 0.27; 95% CI 0.08 - 0.97; p=0.05) with the use of TcB screening compared with visual inspection. CONCLUSIONS: Predischarge TcB screening is superior in identifying newborns at risk of severe hyperbilirubinaemia compared with visual inspection. We recommend that every newborn, regardless of skin pigmentation, should receive objective bilirubin screening before hospital discharge. Universal bilirubin screening in newborns could potentially reduce hyperbilirubinaemia-related morbidity and mortality.


Assuntos
Bilirrubina/análise , Hiperbilirrubinemia/diagnóstico , Triagem Neonatal , Readmissão do Paciente/estatística & dados numéricos , Transfusão Total , Feminino , Humanos , Hiperbilirrubinemia/mortalidade , Hiperbilirrubinemia/terapia , Recém-Nascido , Tempo de Internação , Masculino , Fototerapia
6.
Ann Hematol ; 99(9): 2019-2026, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32676731

RESUMO

Hyperbilirubinemia and pigment gallstones are frequent complications in transfusion-dependent ß-thalassemia (TDßT) patients. Bilirubin production and clearance are determined by genetic as well as environmental variables like ineffective erythropoiesis, hemolysis, infection-induced hepatic injury, and drug- or iron-related toxicities. We studied the frequency of the Gilbert syndrome (GS), a common hereditary cause of hyperbilirubinemia in 102 TDßT patients aged 13-43 years (median 26 years). Total and unconjugated hyperbilirubinemia were frequent (81.4% and 84.3% patients respectively). Twenty (19.6%) patients showed total bilirubin > 3.0 mg/dL; 53 (51.9%) had an elevation of either alanine or aspartate aminotransferase, or alkaline phosphatase liver enzymes. Nineteen (18.6% of the 92 tested) were positive for hepatitis B or C, or HIV. The mean total and unconjugated bilirubin levels and AST, ALT, and ALP levels in patients positive for hepatitis B or C were not significantly different from negative cases. Eighteen patients (17.7%) had GS: homozygous (TA)7/7 UGT1A1 promoter motif (the *28/*28 genotype), 48 (47.1%) were heterozygous (TA)6/7. Total + unconjugated bilirubin rose significantly with the (TA)7 allele dose. Fourteen (13.7%) patients had gallstones. There was no significant difference in total/unconjugated bilirubin in patients with/without gallstones and no significant differences in frequencies of gallstones within the three UGT1A1 genotypes. This largest study in Indian TDßT patients suggests that GS should be excluded in TDßT cases where jaundice remains unexplained after treatable causes like infections, chelator toxicity, or transfusion-related hemolysis are excluded. GS was not associated with gallstones, possibly due to a lower incidence of cholelithiasis overall, a younger age cohort, or other environmental factors.


Assuntos
Grupo com Ancestrais do Continente Asiático , Colelitíase/epidemiologia , Doença de Gilbert/epidemiologia , Glucuronosiltransferase , Hiperbilirrubinemia/epidemiologia , Talassemia beta/epidemiologia , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Transfusão de Sangue/tendências , Colelitíase/genética , Feminino , Doença de Gilbert/genética , Glucuronosiltransferase/genética , Humanos , Hiperbilirrubinemia/genética , Índia/epidemiologia , Masculino , Estudos Prospectivos , Adulto Jovem , Talassemia beta/genética , Talassemia beta/terapia
8.
PLoS One ; 15(4): e0231264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294106

RESUMO

INTRODUCTION: Contrast-induced acute kidney injury (CI-AKI) is associated with high risks of morbidity and mortality. Hyperbilirubinemia might have some renal protection but with no clear cutoff value for protection. Related studies are typically on limited numbers of patients and only in conditions of vascular intervention. METHODS: We performed this study to elucidate CI-AKI in patients after contrast-enhanced computed tomography (CCT). The outcomes were CI-AKI, dialysis and mortality. Patients were divided to three groups based on their serum levels of total bilirubin: ≤1.2 mg/dl, 1.3-2.0 mg/dl, and >2.0 mg/dl. RESULTS: We enrolled a total of 9,496 patients who had received CCT. Patients with serum total bilirubin >2.0 mg/dl were associated with CI-AKI. Those undergoing dialysis had the highest incidence of PC-AKI (p<0.001). No difference was found between the two groups of total bilirubin ≤1.2 and 1.3-2.0 mg/dl. Patients with total bilirubin >2mg/dl were associated with CI-AKI (OR = 1.89, 1.53-2.33 of 95% CI), dialysis (OR = 1.40, 1.01-1.95 of 95% CI) and mortality (OR = 1.63, 1.38-1.93 of 95% CI) after adjusting for laboratory data and all comorbidities (i.e., cerebrovascular disease, coronary artery disease, peripheral arterial disease, and acute myocardial infarction, diabetes mellitus, hypertension, gastrointestinal bleeding, cirrhosis, peritonitis, ascites, hepatoma, shock lung and colon cancer). We concluded that total bilirubin level >2 mg/dl is an independent risk factor for CI-AKI, dialysis and mortality after CCT. These patients also had high risks for cirrhosis or hepatoma. CONCLUSION: This is the first study providing evidence that hyperbilirubinemia (total bilirubin >2.0 mg/dl) being an independent risk factor for CI-AKI, dialysis and mortality after receiving CCT. Most patients with total bilirubin >2.0mg/dl had cirrhosis or hepatoma.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Meios de Contraste/efeitos adversos , Hiperbilirrubinemia/complicações , Tomografia Computadorizada por Raios X , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/mortalidade , Idoso , Bilirrubina/sangue , Carcinoma Hepatocelular/metabolismo , Feminino , Fibrose/metabolismo , Humanos , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/diagnóstico por imagem , Incidência , Rim , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Diálise Renal , Fatores de Risco
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(3): 280-284, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32204767

RESUMO

Hyperbilirubinemia is a prevalent disease in neonates and is also a main reason for hospitalization within the first week after birth, and this disease is mainly caused by the imbalance between production and elimination of bilirubin. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), organic anion transporter polypeptide 2 (OATP2), heme oxygenase 1 (HO-1), and biliverdin reductase A (BLVRA) play crucial roles in the metabolism of bilirubin. More and more studies have revealed the association between the variation of the encoding genes for these enzymes and hyperbilirubinemia. This article reviews the research advances in the association between the gene polymorphisms of bilirubin metabolic enzymes and hyperbilirubinemia.


Assuntos
Hiperbilirrubinemia Neonatal , Polimorfismo Genético , Bilirrubina , Glucuronosiltransferase , Heme Oxigenase-1 , Humanos , Hiperbilirrubinemia , Hiperbilirrubinemia Neonatal/genética , Recém-Nascido , Transportador 1 de Ânion Orgânico Específico do Fígado
10.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32161111

RESUMO

The nutritional and immunologic properties of human milk, along with clear evidence of dose-dependent optimal health outcomes for both mothers and infants, provide a compelling rationale to support exclusive breastfeeding. US women increasingly intend to breastfeed exclusively for 6 months. Because establishing lactation can be challenging, exclusivity is often compromised in hopes of preventing feeding-related neonatal complications, potentially affecting the continuation and duration of breastfeeding. Risk factors for impaired lactogenesis are identifiable and common. Clinicians must be able to recognize normative patterns of exclusive breastfeeding in the first week while proactively identifying potential challenges. In this review, we provide new evidence from the past 10 years on the following topics relevant to exclusive breastfeeding: milk production and transfer, neonatal weight and output assessment, management of glucose and bilirubin, immune development and the microbiome, supplementation, and health system factors. We focus on the early days of exclusive breastfeeding in healthy newborns ≥35 weeks' gestation managed in the routine postpartum unit. With this evidence-based clinical review, we provide detailed guidance in identifying medical indications for early supplementation and can inform best practices for both birthing facilities and providers.


Assuntos
Aleitamento Materno/métodos , Prática Clínica Baseada em Evidências , Lactação/fisiologia , Leite Humano/fisiologia , Algoritmos , Peso ao Nascer , Glicemia/metabolismo , Peso Corporal/fisiologia , Extração de Leite/métodos , Colostro/fisiologia , Suplementos Nutricionais , Feminino , Glicogênio/metabolismo , Humanos , Hiperbilirrubinemia/terapia , Recém-Nascido , Método Canguru , Transtornos da Lactação/etiologia , Microbiota/fisiologia , Leite Humano/química , Leite Humano/imunologia , Mães , Fototerapia , Fatores de Risco , Fatores de Tempo
11.
Medicine (Baltimore) ; 99(9): e19364, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118780

RESUMO

To establish a clinical prediction rule for acute bilirubin encephalopathy (ABE) in term/near-term neonates with extreme hyperbilirubinemia.A retrospective cohort study was conducted between January 2015 and December 2018. Six hundred seventy-three out of 26,369 consecutive neonates with extreme hyperbilirubinemia were enrolled in this study. Data included demographic characteristics, total serum bilirubin (TSB), albumin, bilirubin/albumin ratio (B/A), direct antiglobulin test, glucose-6-phosphate deficiency, asphyxia, sepsis, acidosis. ABE was defined as a bilirubin induced neurological dysfunction score of 4 to 9. We used stepwise logistic regression to select predictors of ABE and devised a prediction score.Of the 673 eligible infants, 10.8% suffered from ABE. Our prediction score consisted of 3 variables: TSB (as a continuous variable; odds ratio [OR] 1.16; 95% confidence interval [CI], 1.02-1.31; logistic coefficient 0.15), B/A (as a continuous variable; OR 1.88; 95% CI, 1.19-2.97; logistic coefficient 0.67), and sepsis (OR 3.78; 95% CI, 1.40-10.21; logistic coefficient 1.19). Multiplying the logistic coefficients by 10 and subtracting 75, resulted in the following equation for the score: Score = 12 × (if sepsis) + 1.5 × (TSB) + 7 × (B/A) - 75. The model performed well with an area under the curve of 0.871.The risk of ABE can be quantified according to TSB, B/A, and sepsis in term/near-term neonates with extreme hyperbilirubinemia.


Assuntos
Regras de Decisão Clínica , Hiperbilirrubinemia/complicações , Kernicterus/etiologia , Bilirrubina/análise , Bilirrubina/sangue , China/epidemiologia , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Hiperbilirrubinemia/diagnóstico , Hiperbilirrubinemia/epidemiologia , Recém-Nascido , Kernicterus/diagnóstico , Kernicterus/epidemiologia , Masculino , Estudos Retrospectivos
12.
Lancet Haematol ; 7(4): e309-e319, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32145771

RESUMO

BACKGROUND: Mutations in isocitrate dehydrogenase-2 (IDH2) occur in around 5% of patients with myelodysplastic syndromes. Neomorphic activity of mutant IDH2 proteins results in hypermethylation of DNA and histones, leading to blocked haemopoietic differentiation. Enasidenib, an inhibitor of mutated IDH2 proteins, induces responses in patients with IDH2-mutated, relapsed or refractory acute myeloid leukaemia. We aimed to establish the clinical outcomes of enasidenib monotherapy in a subgroup of patients with myelodysplastic syndromes harbouring mutations in IDH2 from the AG221-C-001 trial. METHODS: The multicentre, open-label, phase 1-2 AG221-C-001 trial enrolled patients with advanced haematological malignancies (2008 WHO criteria) harbouring an IDH2 mutation. The present study is a subgroup analysis of patients with IDH2-mutated myelodysplastic syndromes in the phase 1 dose-escalation and expansion portions of the trial. Patients with myelodysplastic syndromes were aged 18 years or older with an ECOG performance status score of 2 or lower, and were relapsed or refractory to, or ineligible for, standard treatments. Patients received oral doses of enasidenib at 60-300 mg per day in repeated 28-day treatment cycles. In this subgroup analysis, we focused on the safety and activity of enasidenib as main outcomes. Overall response rate, duration of response, and overall and event-free survival analyses were by intention-to-treat. Safety was assessed in all participants who received at least one dose of study drug in terms of treatment-emergent adverse events. The AG221-C-001 trial is registered on ClinicalTrials.gov, NCT01915498, status ongoing but closed to recruitment. FINDINGS: 17 patients with myelodysplastic syndromes harbouring an IDH2 mutation (median age, 67·0 years [IQR 60·5-73·0]) were enrolled between Feb 18, 2014, and Sept 1, 2015. At data cutoff (Oct 1, 2018), after a median follow-up of 11·0 months (IQR 6·8-23·0), all patients had discontinued enasidenib, with a median of 3 treatment cycles (2-15) for all patients (five [29%] received ≥12 cycles). At entry, three (18%) patients had relapsed after allogeneic stem-cell transplants, 13 (76%) had previously received therapy with hypomethylating agents, and ten (59%) had received at least two previous therapies. No dose-limiting toxicities were reported. The most common treatment-emergent adverse events were diarrhoea and nausea (in nine [53%] patients each). Most common grade 3-4 treatment-emergent adverse events were indirect hyperbilirubinaemia (in six [35%] patients), pneumonia (in five [29%] patients), and thrombocytopaenia (in four [24%] patients). Serious treatment-emergent adverse events in more than one patient were pneumonia (in five [29% patients); tumor lysis syndrome (in three [18%] patients); and sepsis, atrial flutter, indirect hyperbilirubinaemia, cerebral hemorrhage, and mental status change (in two [12%] patients each). No treatment-related deaths occurred. An overall response was achieved in 9 patients (53% [95% CI 28-77]), with a median duration of response of 9·2 months (95% CI 1·0-not reached). Six (46%) of 13 patients previously treated with hypomethylating agents responded. Median overall survival was 16·9 months (95% CI 1·5-32·3), and median event-free survival was 11·0 months (1·5-16·7). INTERPRETATION: Enasidenib is generally well tolerated and can induce responses in patients with mutant IDH2 myelodysplastic syndromes, including in those who have had previous therapy with hypomethylating agents. Testing for IDH2 mutations in myelodysplastic syndromes is essential for identifying patients who might benefit from enasidenib therapy, including those patients in whom conventional treatments have been unsuccessful. FUNDING: Celgene and Agios Pharmaceuticals.


Assuntos
Aminopiridinas/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Isocitrato Desidrogenase/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Triazinas/uso terapêutico , Idoso , Aminopiridinas/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Hiperbilirrubinemia/etiologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Polimorfismo de Nucleotídeo Único , Taxa de Sobrevida , Resultado do Tratamento , Triazinas/efeitos adversos
13.
Medicine (Baltimore) ; 99(7): e19109, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049823

RESUMO

BACKGROUND: Mild hemolysis is difficult to determinate by traditional methods, and its role in Gilbert's syndrome (GS) is unclear. The main aims were to inspect the erythrocyte (RBC) survival in GS by using Levitt's carbon monoxide (CO) breath test and to assess its contribution to unconjugated hyperbilirubinemia. METHODS: Fifty subjects with GS and 1 with type-II Crigler-Najjar syndrome (CN2) received RBC lifespan measurement with Levitt's CO breath test. Mean RBC lifespan was compared with normal referral value. Correlations of serum total bilirubin (TB) with RBC lifespan, blood panel data, demographic factors, and uridine diphosphate glucuronosyltransferase (UGT1A1) mutation load were calculated by Spearman analysis. Susceptibility factors for mild hemolysis were analyzed by multivariate regression analysis. RESULTS: The mean RBC lifespan of the GS subjects was significantly shorter than the normal reference value (95.4 ±â€Š28.9 days vs 126 days; t = -7.504, P < .01), with 30.0% below the lower limit of the normal reference range (75 days). The RBC lifespan of the participant with CN2 was 82 days. Serum TB correlated positively with UGT1A1 mutation load (γ = 0.281, P = .048), hemoglobin (γ = .359, P = .010) and hematocrit (γ = 0.365, P = .010), but negatively with RBC lifespan (γ = -0.336, P = .017). No significant susceptibility factors for mild hemolysis were found. CONCLUSIONS: The results indicate that mild hemolysis indeed, exists in a portion of patients with GS and might serve as an important contributor to unconjugated hyperbilirubinemia in addition to UGT1A1 polymorphism. Further studies on the mechanism and the potential risks in various medical treatments might be wanted.


Assuntos
Monóxido de Carbono/análise , Doença de Gilbert/complicações , Hemólise , Hiperbilirrubinemia/etiologia , Adulto , Testes Respiratórios/instrumentação , Eritrócitos/fisiologia , Feminino , Humanos , Hiperbilirrubinemia/sangue , Masculino , Pessoa de Meia-Idade
16.
Arch Dis Child ; 105(7): 625-630, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31959596

RESUMO

OBJECTIVE: There are few studies on cerebral palsy (CP) in African children and our study aimed to describe the aetiology, characteristics and severity of CP in children from Nigeria. DESIGN: A population-based study using key informant methodology (KIM) was conducted as part of a clinical research trial. Children aged 4-15 years were clinically assessed for CP. RESULTS: The estimated prevalence of CP using KIM was 2.3/1000 children (95% CI 2.0 to 2.5/1000). 388 children were diagnosed with CP, with Gross Motor Function Classification System level 1 in 70 (18.1%), II in 156 (40.2%), III in 54 (13.9%), IV in 54 (13.9%), V in 54 (13.9%). 300/388 (77.3%) had Manual Ability Classification Scale of level 1-3 and 88 (22.7%) of level 4-5. CP types were spastic in 271 (70%), with 60% of these bilateral and 40% unilateral, ataxic 38 (9.8%), dystonic 18 (4.6%), choreoathetoid 29 (7.5%) and unclassifiable 32 (8.3%). Postneonatal risk factors for CP were seen in 140 (36.1%) children including malaria with seizures 101/140 (72.1%), malaria with coma 21/140 (15.0%), meningitis 12/140 (8.6%), tuberculosis 2/140 (1.4%), sickle cell disease 3/140 (2.2%), HIV 1/221 (0.7%). Prenatal/perinatal risk factors were seen in 248 (63.9%%), birth asphyxia 118 (47.6%) and clinical congenital rubella syndrome 8 (3.3%) and hyperbilirubinaemia 59 (23.8%) were identified as preventable risk factors for CP. CONCLUSION: The profile of CP in this population is similar to that found in other low-income and middle-income countries (LMIC). Some risk factors identified were preventable. Prevention and management strategies for CP designed for LMIC are needed.


Assuntos
Paralisia Cerebral/epidemiologia , Paralisia Cerebral/etiologia , Países em Desenvolvimento/estatística & dados numéricos , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Traumatismos do Nascimento/complicações , Traumatismos do Nascimento/epidemiologia , Paralisia Cerebral/classificação , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Hiperbilirrubinemia/complicações , Hiperbilirrubinemia/epidemiologia , Malária/complicações , Malária/epidemiologia , Masculino , Meningite/complicações , Meningite/epidemiologia , Nigéria/epidemiologia , Razão de Chances , Prevalência , Síndrome da Rubéola Congênita/complicações , Síndrome da Rubéola Congênita/epidemiologia , Índice de Gravidade de Doença , Tuberculose/complicações , Tuberculose/epidemiologia
17.
Am J Physiol Gastrointest Liver Physiol ; 318(1): G41-G52, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31604032

RESUMO

Infants receiving long-term parenteral nutrition (PN) develop PN-associated liver disease (PNALD). We previously (Ng K et al. JPEN J Parenter Enteral Nutr 40: 656-671, 2016. doi:10.1177/0148607114567900.) showed that PN containing soy-based lipid supplemented with vitamin E (α-tocopherol) prevents the development of PNALD. We hypothesize that this occurs via vitamin E activation of pregnane X receptor (PXR)-mediated pathways involved in bile acid metabolism. Neonatal piglets received PN for 14 days containing Intralipid (IL; soy-based lipid emulsion), IL supplemented with 12.6 mg·kg-1·day-1 vitamin E (VITE), or IL with 10 mg·kg-1·day-1 Rifadin IV (RIF), a PXR agonist. Pigs treated with IL and VITE, but not RIF, developed cholestasis and hyperbilirubinemia, markers of liver disease. The hepatic PXR target genes CYP3A29 and UGT1A6 increased during RIF treatment. RIF also modestly increased metabolism of chenodeoxycholic acid to the more hydrophilic bile acid hyocholic acid. Serum fibroblast growth factor (FGF)-19, a key regulator in suppressing hepatic bile acid synthesis, significantly increased in the RIF group. We conclude rifampicin modified markers of PNALD development by increased metabolism of bile acids and potentially suppressed bile acid synthesis. Vitamin E was ineffective at high lipid doses in preventing PNALD.NEW & NOTEWORTHY Intravenous vitamin E and rifampicin were administered to neonatal piglets receiving parenteral nutrition to determine their efficacy in reducing the progression of parenteral nutrition-associated liver disease (PNALD). Rifampicin increased serum FGF-19 concentrations and synthesis of the bile acid hyocholic acid which led to a reduction of PNALD parameters at 2 wk of administration. This result has potential clinical implications for the use of rifampicin as a safe and inexpensive treatment for short-term development of PNALD.


Assuntos
Ácidos e Sais Biliares/metabolismo , Emulsões Gordurosas Intravenosas , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Nutrição Parenteral , Fosfolipídeos , Receptor de Pregnano X/agonistas , Rifampina/farmacologia , Óleo de Soja , Vitamina E/farmacologia , Animais , Animais Recém-Nascidos , Ácidos e Sais Biliares/biossíntese , Colestase/etiologia , Colestase/metabolismo , Colestase/prevenção & controle , Citocromo P-450 CYP3A/metabolismo , Modelos Animais de Doenças , Emulsões , Glucuronosiltransferase/metabolismo , Hiperbilirrubinemia/etiologia , Hiperbilirrubinemia/metabolismo , Hiperbilirrubinemia/prevenção & controle , Fígado/metabolismo , Fígado/patologia , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Receptor de Pregnano X/metabolismo , Transdução de Sinais , Sus scrofa
18.
Lab Med ; 51(1): 50-55, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31150549

RESUMO

OBJECTIVE: To evaluate how clinical practice was affected by the change in direct antiglobulin testing (DAT) methodologies and subsequent stronger reported DAT results at our large academic medical center. METHOD: We retrospectively reviewed DAT results of umbilical cord blood from infants with blood type A or B born to mothers with antibody-negative type O blood, based on records kept at the University of Alabama at Birmingham (UAB) Hospital, a 1400-bed academic medical center. RESULTS: We randomly chose 50 neonates with positive DAT results who had been tested using the tube method and 50 whose testing had used the gel method. Although 86% of results with the tube method were positive microscopically, 52% and 40% of the DAT results with the gel method were 1+ and 2+ positive, respectively. Further, we observed an increase in the number of neonates treated with phototherapy who had been tested using the gel method. CONCLUSION: We report that DATs performed using the gel method had increased DAT strength compared with tube testing, which led to increased use of phototherapy by our clinical colleagues.


Assuntos
Teste de Coombs/normas , Hiperbilirrubinemia/sangue , Fototerapia/estatística & dados numéricos , Sistema ABO de Grupos Sanguíneos/imunologia , Centros Médicos Acadêmicos/estatística & dados numéricos , Automação Laboratorial/métodos , Automação Laboratorial/normas , Teste de Coombs/métodos , Feminino , Humanos , Hiperbilirrubinemia/diagnóstico , Hiperbilirrubinemia/terapia , Recém-Nascido , Masculino , Distribuição Aleatória
19.
Xenobiotica ; 50(1): 64-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31092094

RESUMO

The role that the phase-II reaction, glucuronidation, plays in the biotransformation of endo and xenobiotics is discussed with particular emphasis given to the UGT1A1 isoenzyme. This individual isoenzyme is responsible for both the mono and di-glucuronidation of bilirubin together with the glucuronidation of a number of xenobiotics of clinical interest (irinotecan, belinostat, atazanavir, pegvisomant).The review then discusses the roles that the various allelic variants of the UGT1A1 gene play in bilirubin metabolism and in particular how these allelic variants are involved in the clinical manifestation of the diseases of GS, CN1 and CN2.The review concludes with the roles that the UGT1A1*28 and UGT1A1*6 alleles play in adverse drug reactions (decreased glucuronidation of irinotecan, belinostat, atazanavir, pegvisomant) leading to increased exposure, reduced clearance and neutropenia (irinotecan, belinostat), increased risk for jaundice and hyperbilirubinaemia (atazanavir) and liver toxicity (pegvisomant) before discussing the future role of UGT1A1 in personalised medicine.


Assuntos
Glucuronosiltransferase/genética , Alelos , Bilirrubina , Genótipo , Glucuronosiltransferase/metabolismo , Humanos , Ácidos Hidroxâmicos/metabolismo , Hiperbilirrubinemia/metabolismo , Irinotecano/metabolismo , Sulfonamidas/metabolismo
20.
J Pediatr Surg ; 55(1): 153-157, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672409

RESUMO

PURPOSE: Cholestasis is problematic for infants with intestinal failure (IF). The soy-based lipid Intralipid® (IL) has been implicated. An alternative, Smoflipid® (SMOF), is increasingly used. However, its role in cholestasis prevention is unclear. This study compares the incidence and degree of cholestasis between infants with IF receiving SMOF or IL. METHODS: Infants with IF receiving SMOF or IL during the first 8 weeks of parenteral nutrition (PN) support between 2014 and 2017 were reviewed. Clinical characteristics, cholestasis incidence (conjugated bilirubin (Cbili) >2 mg/dL for >2 weeks), and nutritional parameters were compared using Welch's t-test. RESULTS: 91% (21/23) of IL and 76% (16/21) of SMOF babies became cholestatic (p = 0.18). There was no significant difference in median peak Cbili, but SMOF babies normalized more quickly (p = 0.04). Median z-scores for weight were similar throughout the study. SMOF patients getting full PN had a lower incidence of cholestasis compared to IL patients (78% vs. 92%, p = 0.057), but those with cholestasis had similar peak Cbili, time to resolution, and growth. CONCLUSION: Early use of Smoflipid® did not reduce the incidence of cholestasis compared to Intralipid® in infants with IF, but hyperbilirubinemia did resolve more quickly. SMOF may be most beneficial for infants tolerating no enteral nutrition. LEVEL OF EVIDENCE: Level III Retrospective Comparative Treatment Study. TYPE OF STUDY: Retrospective Review.


Assuntos
Colestase/prevenção & controle , Emulsões Gordurosas Intravenosas/uso terapêutico , Enteropatias/terapia , Lipídeos/uso terapêutico , Nutrição Parenteral Total , Fosfolipídeos/uso terapêutico , Óleo de Soja/uso terapêutico , Bilirrubina/sangue , Colestase/sangue , Colestase/etiologia , Emulsões/uso terapêutico , Nutrição Enteral/efeitos adversos , Feminino , Óleos de Peixe , Humanos , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/etiologia , Lactente , Recém-Nascido , Enteropatias/complicações , Masculino , Apoio Nutricional , Azeite de Oliva , Estudos Retrospectivos , Triglicerídeos
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