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3.
BMC Pediatr ; 22(1): 549, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109730

RESUMO

BACKGROUND: Sickle cell disease (SCD) is associated with an increased risk of cardiovascular disease that may be due to a variety of possible risk factors, including abnormal blood pressure. Blood pressure (BP) of children and adolescents with SCD has been reported to be lower compared to the BP of the general pediatric population. METHODS: To confirm this prior observation, we compared reference BP values for children with SCD with reference BP values of the general pediatric population. We hypothesized that children with SCD do not have lower BPs than children without SCD. RESULTS: Systolic BP differed for both males and females, over the different age groups between pediatric subjects with and without SCD. Systolic BP was higher in children with SCD, in both obese and non-obese populations. Diastolic BP did not differ between the groups. CONCLUSIONS: Our analysis demonstrated that systolic BP values are indeed higher in children with SCD than in the general pediatric population. This finding is consistent with the most recent literature showing abnormal BP patterns in the SCD pediatric population utilizing 24-hour BP monitoring devices. This is an important step for recognizing abnormal BP as a risk factor for cardio- and neurovascular events in SCD.


Assuntos
Anemia Falciforme , Doenças Cardiovasculares , Adolescente , Anemia Falciforme/complicações , Pressão Sanguínea , Criança , Feminino , Humanos , Masculino , Obesidade/complicações , Fatores de Risco
4.
FASEB J ; 36(10): e22535, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36070139

RESUMO

Patients with sickle cell disease (SCD) display priapism. Clinical studies have shown a strong positive correlation between priapism and high levels of intravascular hemolysis in men with SCD. However, there are no experimental studies that show that intravascular hemolysis promotes alterations in erectile function. Therefore, we aimed to evaluate the corpus cavernosum smooth muscle relaxant function in a murine model that displays intravascular hemolysis induced by phenylhydrazine (PHZ), as well as the role of intravascular hemolysis in increasing the stress oxidative in the penis. Corpus cavernosum strips were dissected free and placed in organ baths. Acetylcholine and electrical field stimulation (EFS)-induced corpus cavernosum relaxations in vitro were obtained. Increased corpus cavernosum relaxant responses to acetylcholine and EFS were observed in the PHZ group. Protein expression of heme oxygenase-1 increased in the corpus cavernosum of the PHZ group, but PDE5 protein expression was not modified. Preincubation with the heme oxygenase inhibitor 1 J completely reversed the increased relaxant responses to acetylcholine and EFS in PHZ mice. Protein expression of NADPH oxidase subunit gp91phox, 3-nitrotyrosine, and 4-hydroxynonenal increased in the corpus cavernosum of the PHZ group, suggesting a state of oxidative stress. Basal cGMP production was lower in the PHZ group. Our results show that intravascular hemolysis promotes increased corpus cavernosum smooth muscle relaxation associated with increased HO-1 expression, as well as increased oxidative stress associated with upregulation of gp91phox expression. Moreover, our study supports clinical studies that point to a strong positive correlation between priapism and high levels of intravascular hemolysis in men with SCD.


Assuntos
Anemia Falciforme , Priapismo , Acetilcolina/farmacologia , Anemia Falciforme/complicações , Anemia Falciforme/metabolismo , Animais , Hemólise , Humanos , Masculino , Camundongos , Pênis , Priapismo/complicações
5.
Int J Clin Pract ; 2022: 9131423, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105789

RESUMO

Introduction: Sickle cell disease is characterized by the production of abnormal hemoglobin, which affects hemoglobin molecule stability during hypoxia and leads to the formation of sickle cells, resulting in increased hematic viscosity, hemolysis, and microvascular blockage. Vasoocclusion is assumed to be the primary cause of vision-threatening retinopathy in sickle cell disease. The aim of this study was to improve the early detection of sickle cell retinopathy (SCR) in children with sickle cell disease (SCD) and investigate the link between systemic and ocular symptoms. Methods: This cross-sectional study comprised children with SCD. The patient files provided a detailed medical history. The laboratory tests included a blood count, reticulocyte count, and Hb electrophoresis. The slit lamp, fundus, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were all part of the ophthalmological examination. Results: The study comprised 15 children with sickle cell disease who met the inclusion and exclusion criteria, with a mean age of 11.15 ± 1.29 years. Nine of the children were males (60%) and six were females (40%). 8 (53.3%) of the children had Hb SS, three (20%) had Hb SC, three (20%) had Hb SB+, and one (6.7%) had Hb SB0. Four children (26.7%) had poor visual acuity. A fundus examination revealed significant abnormal findings in 12 of the 7 children's eyes (40 percent). Macular thinning was detected by OCT in 10 eyes of 7 children (33.3%). Flow voids at the deep retinal capillary plexus were detected by OCTA in 10 eyes of 7 children (33.3%). Longer disease duration, higher reticulocytic percent, more painful crises, and noncompliance with hydroxyurea medication were all linked to the existence of eye abnormalities on fundus examination and OCT. Conclusion: OCTA can show early retinal damage in sickle cell patients with macular changes. Sickle cell retinopathy is usually associated with more severe disease.


Assuntos
Anemia Falciforme , Doenças Retinianas , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Criança , Estudos Transversais , Feminino , Angiofluoresceinografia/efeitos adversos , Angiofluoresceinografia/métodos , Humanos , Masculino , Doenças Retinianas/complicações , Doenças Retinianas/etiologia , Tomografia de Coerência Óptica/efeitos adversos , Tomografia de Coerência Óptica/métodos
7.
BMC Neurol ; 22(1): 335, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068544

RESUMO

BACKGROUND: Stroke is the second leading cause of death above the age of 60 years, and the fifth leading cause in people aged 15 to 59 years old as reported by the World Health Organization global burden of diseases. Stroke in the young is particularly tragic because of the potential to create long-term disability, burden on the victims, their families, and the community at large. Despite this, there is limited data on stroke in young adults, and its risk factors in Uganda. Therefore, we determined the frequency and risk factors for stroke among young adults at Mulago hospital. METHODS: A case control study was conducted among patients presenting consecutively to the general medical wards with stroke during the study period September 2015 to March 2016. A brain Computerized Tomography scan was performed to confirm stroke and classify the stroke subtype. Controls were patients that presented to the surgical outpatient clinic with minor surgical conditions, matched for age and sex. Social demographic, clinical and laboratory characteristics were assessed for both cases and controls. Descriptive statistics including frequencies, percentages, means, and standard deviation were used to describe the social demographics of case and controls as well as the stroke types for cases. To determine risk factors for stroke, a conditional logistic regression, which accounts for matching (e.g., age and sex), was applied. Odds ratio (with 95% confidence interval) was used as a measure for associations. RESULTS: Among 51 patients with stroke, 39(76.5%) had ischemic stroke and 12(23.5%) had hemorrhagic stroke. The mean age was 36.8 years (SD 7.4) for stroke patients (cases) and 36.8 years (SD 6.9) for controls. Female patients predominated in both groups 56.9% in cases and 52.9% in controls. Risk factors noted were HIV infection, OR 3.57 (95% CI 1.16-10.96), elevated waist to hip ratio, OR 11.59(95% CI 1.98-68.24) and sickle cell disease, OR 4.68 (95% CI 1.11-19.70). This study found a protective effect of oral contraceptive use for stroke OR 0.27 95% CI 0.08-0.87. There was no association between stroke and hypertension, diabetes, and hyperlipidemia. CONCLUSION: Among young adults with stroke, ischemic stroke predominated over hemorrhagic stroke. Risk factors for stroke were HIV infection, elevated waist to hip ratio and sickle cell disease.


Assuntos
Anemia Falciforme , Infecções por HIV , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Acidente Vascular Cerebral , Adolescente , Adulto , Anemia Falciforme/complicações , Estudos de Casos e Controles , Feminino , Infecções por HIV/complicações , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Adulto Jovem
8.
PLoS One ; 17(9): e0274254, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36084057

RESUMO

OBJECTIVE: To identify the prevalence of people with leg ulcers resulting from sickle cell disease, as well as to describe the clinical, social, economic, and demographic conditions of these people. METHOD: Descriptive study, carried out at the Minas Gerais Hematology and Hemotherapy Center Foundation. The study population consisted of individuals over the age of 18 with a diagnosis of sickle cell disease in the State of Minas Gerais, Brazil. Data collection was performed from August 2019 to April 2020 through interviews. For the prevalence calculation, a census was taken of 5,379 people over the age of 18 with sickle cell disease, 77 of whom had active leg ulcers. Descriptive data analysis was performed using SPSS software (version 20.0, Chicago, IL, USA). RESULTS: The prevalence of people with leg ulcers in Minas Gerais, Brazil was 1.4%. Of the 72 respondents, the average age was 39 years (range 18-64 years), 41.7% were single, 48.6% said they were black, 84.7% lived in their own house, 38.9% were retired, 61.1% had an income of one minimum wage. The median years of education was 10.5, 50% cited the church as a place for leisure activities, 79.2% denied smoking. Regarding pain, the median score was 3, the median baseline hemoglobin was 7.7 g/dL, and 91.7% had the HbSS genotype. The median age of the first ulcer was 18 years, 77.8% of active ulcers were recurrent, and 59.7% had only one active ulcer. The median time of existence of the ulcer was 3 years. The ulcer prevented 80.6% of people from doing some activity. Prejudice was experienced by 48.6% of the participants. CONCLUSION: The estimated prevalence of leg ulcers was lower than what it reported in the literature, however, the recurrence and the duration of ulcers were high. These findings bring reflection about the assistance to people with leg ulcer.


Assuntos
Anemia Falciforme , Úlcera da Perna , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Brasil/epidemiologia , Humanos , Úlcera da Perna/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores Socioeconômicos , Úlcera , Adulto Jovem
10.
Sci Rep ; 12(1): 14976, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056104

RESUMO

The lakeshore site of La Marmotta is one of the most important Early Neolithic sites of Mediterranean Europe. The site is famous for the exceptional preservation of organic materials, including numerous wooden artefacts related to navigation, agriculture, textile production, and basketry. This article presents interdisciplinary research on three of the most complete and well-preserved sickles recovered from the site, yet unpublished. All the components of the tools are analysed: the stone inserts, the wooden haft and the adhesive substances used to fix the stones inside the haft. Our innovative methodology combines use-wear and microtexture analysis of stone tools through confocal microscopy, taxonomical and technological analysis of wood, gas chromatography-mass spectrometry analysis of the adhesive substances, and pollen, non-pollen palynomorphs, and phytolith analysis of the remains incorporated within the adhesive. This multiproxy approach provides a significant insight into the life of these tools, from their production to their use and abandonment, providing evidence of the species of harvested plants and the conditions of the field during the harvesting.


Assuntos
Anemia Falciforme , Tecnologia , Adesivos , Agricultura , Itália , Madeira
11.
West Afr J Med ; 39(8): 844-851, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36058006

RESUMO

BACKGROUND: Sickle cell anaemia (SCA) is associated with significant morbidity and mortality linked to multi-systemic complications. With recent improvements in healthcare globally, it is expected that SCA patients in Nigeria will live longer. The cardiovascular complications may thus become prevalent. SUBJECTS AND METHODS: Fifty-two patients with sickle cell anemia in steady state and 52 controls were recruited. The assessment included history, physical examination, 12-lead resting electrocardiography, 2D, M-Mode and Doppler echocardiography, six-minute walk test and NTerminal pro Brain Natriuretic Peptide (NT-pro BNP) assay. RESULTS: The mean age of the sickle cell patients was 28.87±7.89 years and most were post-secondary or tertiary institutions. They had faster pulse rates (84.69±9.48 vs75.48±10.35 beats/minute, p=0.000), lower blood pressure (Systolic 112.56 ±10.87 mmHg vs 115.42 ± 14.75mmHg; Diastolic 70.79±9.03mmHg vs 71.27±9.23 mmHg) and lower Body Mass Index (21.55±3.51 vs 24.94±4.56kg/m2; p=0.000). Mean left ventricular (LV) internal diameters in systole and diastole were (3.19 ±0.57cm vs 2.81±0.45 cm; p=0.000) and (4.99±0.69cm vs 4.29±0.56 cm; p=0.00) respectively. Left and right ventricular systolic functions were normal. None of the patients with SCA met the criteria for pulmonary hypertension while 88.89% of those screened using Natriuretic peptide were at risk of developing pulmonary hypertension (NT-proBNP levels ≥ 160pg/ml). Functional status assessed by sixminute walk test was normal (373.00 ±60.40m vs 403.83±72.87 m; but significantly lower than in controls (p= 0.021). CONCLUSION: The cardiovascular system is adversely affected in persons with sickle cell anaemia especially as they grow older. Despite the presence of left ventricular remodeling, the patients with SCA in this study maintained good functional status. Regular cardiovascular assessment is advised.


CONTEXTE: La drépanocytose (SCA) est associée à une morbidité et une mortalité importantes liées à des complications multisystémiques. Avec les récentes améliorations des soins de santé dans le monde, on s'attend à ce que les patients atteints d'ACS au Nigeria vivent plus longtemps. Les complications cardiovasculaires pourraient donc devenir prévalentes. SUJETS ET MÉTHODES: Cinquante-deux patients atteints de drépanocytose à l'état d'équilibre et 52 témoins ont été recrutés. L'éva lua tion c om prena it l'histoire, l'exa m en physique, l'électrocardiographie de repos à 12 dérivations, l'échocardiographie 2D, M-Mode et Doppler, un test de marche de six minutes et un test d'apnée du sommeil. le dosage du NTerminal pro Brain Natriuretic Peptide (NT-pro BNP). RÉSULTATS: L'âge moyen des patients drépanocytaires était de 28,87±7,89 ans et la plupart étaient issus d'établissements post-secondaires ou tertiaires. Ils avaient un pouls plus rapides (84,69±9,48 vs75,48±10,35 battements/minute, p=0,000), une pression artérielle plus basse (Systolique 112,56 ±10,87 mmHg vs 115,42 ± 14,75 mmHg ; diastolique 70,79±9,03 mmHg vs 71,27±9,23 mmHg) et un indice de masse corporelle plus faible (21,55±3,51 vs 24,94±4,56kg/m2 ; p=0,000). Les diamètres internes moyens du ventricule gauche (VG) en systole et en diastole étaient de (3,19 ±0,57 cm vs 2,81±0,45 cm ; p=0,000) et (4,99±0,69 cm vs 4,29±0,56 cm ; p=0,00) respectivement. Les fonctions systoliques des ventricules gauche et droit étaient normales. Aucun des patients atteints d'ACS ne répondait aux critères d'hypertension pulmonaire, tandis que 88,89 % des patients dépistés à l'aide du peptide natriurétique étaient à risque de développer une hypertension pulmonaire(taux de NT-proBNP ≥160pg/ml). L'état fonctionnel évalué par le test de marche de six minutes était normal (373,00 ±60,40 m vs 403,83±72,87 m ; mais significativement plus faible que chez les témoins (p= 0,021). CONCLUSION: Le système cardiovasculaire est affecté de manière négative chez personnes atteintes de drépanocytose, en particulier lorsqu'elles vieillissent. Malgré la présence d'un remodelage ventriculaire gauche, les patients atteints d'ACS dans cette étude ont conservé un bon état fonctionnel. Une évaluation cardiovasculaire régulière est conseillée. MOTS CLÉS: Fonction ventriculaire, Drépanocytaires adultes, État d'équilibre, Hypertension pulmonaire.


Assuntos
Anemia Falciforme , Hipertensão Pulmonar , Adulto , Anemia Falciforme/complicações , Eletrocardiografia , Humanos , Hipertensão Pulmonar/complicações , Nigéria/epidemiologia , Sístole , Adulto Jovem
12.
Dtsch Med Wochenschr ; 147(19): 1259-1266, 2022 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-36126924

RESUMO

Sickle cell disease has come to Germany from the Mediterranean region, Africa and the Middle East since the 1950 s and initially mainly concerned paediatricians. Since the 1970 s, the life expectancy of those affected has risen significantly, and about 95 % now live to adulthood. Therefore, general practitioners and internists should be familiar with the different forms of sickle cell disease, especially HbSC disease (approx. 20 %).A precise diagnosis of sickle cell disease (exact phenotype) is essential; the term "sickle cell anaemia" must be avoided. In patients of African origin with microcytosis, slightly elevated reticulocytes and pain symptomatology, the possibility of HbSC disease should be considered - even with age-appropriate haemoglobin values. Annual retinoscopy is recommended for HbSC patients from the age of 7, and for all other sickle cell patients from the age of 10. If a hearing loss occurs in an HbSC patient, phlebotomy should be performed immediately. In all sickle cell patients with dizziness or pain and an Hb > 10 g/dl, phlebotomy is indicated.


Assuntos
Anemia Falciforme , Doença da Hemoglobina SC , África , Anemia Falciforme/diagnóstico , Anemia Falciforme/terapia , Hemoglobinas/análise , Humanos , Dor
13.
West Afr J Med ; 39(9): 958-963, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36128750

RESUMO

BACKGROUND: Information on the causes and outcome of treatment of vitreous hemorrhage (VH) in sub-Saharan Africa is limited. OBJECTIVES: To determine the causes and postoperative vision after vitrectomy for VH. DESIGN: A retrospective review of records from consecutive eyes, with VH greater than one-month duration, who had vitrectomy and adjunctive treatment in a retina unit in Nigeria. METHODS: We assessed the change between preoperative and postoperative visual acuity, bio data, cause of VH, duration of follow up, and additional treatment. Data was analyzed using SPSS statistical package 17.0 to determine the significance of the change in visual acuity for each cause of VH. A p value <0.05 was considered statistically significant. RESULTS: Of the 221 eyes of 219 patients, the common causes of VH were trauma 43 eyes, (19.7%), proliferative diabetic retinopathy, 37 eyes (17.0%) and proliferative sickle cell retinopathy, 30 eyes (13.8%). There was no association between cause and the presenting preoperative visual acuity. There was a statistically significant association between cause of VH and postoperative visual outcome. Postoperative visual improvement was significant for branch retinal vein occlusion, central retinal vein occlusion, proliferative diabetic retinopathy with VH only, proliferative sickle cell retinopathy, and trauma with VH only, p value = 0.000, 0.002, 0.001, 0.039, and 0.000 respectively. Postoperative visual change was not significant in age-related macular degeneration and polypoidal choroidal vasculopathy (p value = 0.155, 0.428 respectively). CONCLUSION: Significant improvements in visual acuity can be achieved with active treatment of VH in the majority of cases in Nigeria. This information is useful for discussions on prognosis and agrees with previous studies.


CONTEXTE: Les informations sur les causes et les résultats du traitement de l'hémorragie vitréenne (HV) en Afrique subsaharienne sont limitées. OBJECTIFS: Déterminer les causes et la vision postopératoire après une vitrectomie pour une HV. CONCEPTION: Une revue rétrospective des dossiers d'yeux consécutifs, avec une HV de plus d'un mois, qui ont subi une vitrectomie et un traitement d'appoint dans une unité de rétine au Nigeria. MÉTHODES: Nous avons évalué la variation entre l'acuité visuelle préopératoire et postopératoire, les données biologiques, la cause de l'HV, la durée du suivi et le traitement complémentaire. Les données ont été analysées à l'aide du progiciel statistique SPSS 17.0 afin de déterminer la signification du changement d'acuité visuelle pour chaque cause de HV. Une valeur p <0,05 a été considérée comme statistiquement significative. RÉSULTATS: Sur les 221 yeux de 219 patients, les causes les plus fréquentes de l'HV étaient les suivantes : traumatisme, 43 yeux (19,7%), rétinopathie diabétique proliférante, 37 yeux (17,0 %) et rétinopathie drépanocytaire proliférante, 30 yeux (13,8 %). Il n'y avait pas d'association entre la cause et l'acuité visuelle préopératoire. Il y avait une association statistiquement significative entre la cause de l'HV et le résultat visuel postopératoire. L'amélioration visuelle postopératoire était significative pour l'occlusion de la veine rétinienne de branche, l'occlusion de la veine rétinienne centrale, la rétinopathie diabétique proliférante avec HV uniquement, la rétinopathie drépanocytaire proliférante et le traumatisme avec HV uniquement, valeur p = 0,000, 0,002, 0,001, 0,039 et 0,000 respectivement. Le changement visuel postopératoire n'était pas significatif dans la dégénérescence maculaire liée à l'âge et la vasculopathie choroïdienne polypoïde (valeur p = 0,155,0,428 respectivement). CONCLUSION: Des améliorations significatives de l'acuité visuelle peuvent être obtenues avec un traitement actif de l'HV dans la majorité des cas au Nigeria. Cette information est utile pour les discussions sur le pronostic et concorde avec les études précédentes. Mots clés: Rétinopathie diabétique, traumatisme oculaire, rétinopathie diabétique proliférante, rétinopathie drépanocytaire, Afrique subsaharienne, hémorragie vitrée, vitrectomie, acuité visuelle.


Assuntos
Anemia Falciforme , Retinopatia Diabética , Doenças Retinianas , Anemia Falciforme/complicações , Retinopatia Diabética/complicações , Retinopatia Diabética/cirurgia , Humanos , Doenças Retinianas/complicações , Doenças Retinianas/cirurgia , Vitrectomia/efeitos adversos , Hemorragia Vítrea/etiologia , Hemorragia Vítrea/cirurgia
14.
J Trop Pediatr ; 68(5)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-36130307

RESUMO

Hemoglobin S is caused by a nucleotide change in HBB gene (HBB:c.20A>T, p.Glu6Val), is presented in diverse forms: simple carriers (HbSA), homozygotes (HbSS) also known as sickle cell anemia, and compound heterozygotes with other ß-hemoglobinopathies. It is worldwide distributed, in Mexico, is frequently observed in the southern states Guerrero, Oaxaca and Chiapas. Elevated fetal hemoglobin (HbF) is associated with mild phenotype; single-nucleotide variants (SNVs) in modifier genes, such as BCL11A, HBG2, HBBP1 pseudogene and HBS1L-MYB intergenic region, upregulate HbF synthesis. The aim of this study was to identify HbF regulating genetic variants in HbSS and HbSA Mexican subjects. We studied 39 individuals (HbSS = 24, 61%, HbSA = 15, 39%) from Chiapas (67%) and Guerrero (33%), peripheral blood was collected in ethylenediamine tetraacetic acid (EDTA) for molecular and hematological studies, DNA was isolated by salting-out technic and genotyping was performed through allelic discrimination by real time polymerase chain reaction (RT-PCR) using Taqman® probes for 15 SNV (in BCL11A: rs6706648, rs7557939, rs4671393, rs11886868, rs766432, rs7599488, rs1427407; HBS1L-MYB: rs28384513, rs7776054, rs9399137, rs4895441, rs9402686, rs1320963; HBG2: rs7482144; and HBBP1: rs10128556). The obtained data were analyzed using IMB SPSS v.22.0 software. All minor alleles were observed in frequencies over 0.05, the most frequent was rs9402686 (0.82), while the less frequent was rs101028556 (0.08). In HbSS group, the mean fetal hemoglobin was 11.9 ± 5.9% and was significantly elevated in BCL11A rs11886868 wildtype homozygotes and in carriers of HBS1L-MYB intergenic region rs7776054 (p = 0.04 and p = 0.03, respectively). In conclusion, in HbSS Mexican patients, two SNVs were observed related to increased HbF; BCL11A rs11886868 and HBS1L-MYB rs7776054.


Sickle cell anemia (SCA) is one of the most common types of hemoglobinopathies in people of African ancestry, it is caused by homozygosity of HbS mutation (HBB:c.20A>T). It is known that fetal hemoglobin plays a key role in decreasing HbS polymerization which damages the erythrocyte structure and is responsible for the characteristic hemolytic crises endured by these patients. Single-nucleotide variant (SNV) in genes that regulate fetal hemoglobin (HbF) after birth have been associated with its increment, thus ameliorating the hematologic phenotype of this pathology and other ß-hemoglobinopathies. Therefore, in this study, we identified, for the first time in Mexican patients with SCA (HbSS) and HbS carriers (HbSA), the presence of 15 SNVs on BCL11A, HBS1L-MYB and HBG2; all HbSS patients had anemia and elevated HbF; 2 variants were related to increased HbF rs11688888C of BCL11A and rs7776054G of HBSIL-MYB; and finally, all minor alleles were found at a frequency higher than 0.05.


Assuntos
Anemia Falciforme , Hemoglobina Fetal , DNA Intergênico , Ácido Edético , Hemoglobina Fetal/genética , Hemoglobina Falciforme/genética , Heterozigoto , Homozigoto , Humanos , México , Nucleotídeos , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética
15.
Hemoglobin ; 46(2): 114-117, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36069257

RESUMO

Red blood cell (RBC) transfusions have been established as one of the primary therapies in treating sickle cell anemia. However, they are not free of side effects, with overloading the body with iron being one of the most important. Iron chelation therapy greatly reduces the iron load of the body. In addition, hydroxyurea (HU), an oral chemotherapeutic drug also has a significant role in the treatment of the disease with beneficial effects on many of the clinical problems that arise, mainly in reducing painful crises. The aim of this study was to investigate the effect of synergistic transfusion therapy and HU on the response to deferasirox (DFX) chelation therapy. Eighteen patients with sickle cell disease were divided into two groups based on their treatment, either with simple transfusions and DFX or with a combination of transfusion therapy, DFX and HU, and were evaluated with magnetic resonance imaging (MRI) for liver iron concentration (LIC) and biochemistry. All patients completed the study. The results of the study showed improvement in serum ferritin (FER) levels and LIC after 12 months of therapy in both groups, especially in the group receiving the combination therapy with HU. In addition, there was a noteworthy improvement in serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH) levels with serum creatinine (Cr) levels remaining stable during the study in both groups. Hydroxyurea, when combined with iron chelators such as DFX, provides an additional benefit of iron chelation in patients receiving chronic transfusion therapy.


Assuntos
Anemia Falciforme , Sobrecarga de Ferro , Alanina Transaminase/uso terapêutico , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Aspartato Aminotransferases/uso terapêutico , Benzoatos/efeitos adversos , Benzoatos/uso terapêutico , Terapia por Quelação , Creatinina/uso terapêutico , Deferasirox/uso terapêutico , Ferritinas , Humanos , Hidroxiureia/uso terapêutico , Ferro , Quelantes de Ferro , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Lactato Desidrogenases
16.
Cochrane Database Syst Rev ; 9: CD002202, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047926

RESUMO

BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising foetal haemoglobin (HbF). This is an update of a previously published Cochrane Review. OBJECTIVES: The aims of this review are to determine through a review of randomised or quasi-randomised studies whether the use of hydroxyurea in people with SCD alters the pattern of acute events, including pain; prevents, delays or reverses organ dysfunction; alters mortality and quality of life; or is associated with adverse effects. In addition, we hoped to assess whether the response to hydroxyurea in SCD varies with the type of SCD, age of the individual, duration and dose of treatment, and healthcare setting. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. The date of the most recent search was 17 February 2022. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials (RCTs and quasi-RCTs), of one month or longer, comparing hydroxyurea with placebo or standard therapy in people  with SCD. DATA COLLECTION AND ANALYSIS: Authors independently assessed studies for inclusion, carried out data extraction, assessed the risk of bias and assessed the quality of the evidence using GRADE. MAIN RESULTS: We included nine RCTs recruiting 1104 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sߺthalassaemia (HbSߺthal) genotypes). Studies lasted from six to 30 months. We judged the quality of the evidence for the first two comparisons below as moderate to low as the studies contributing to these comparisons were mostly large and well-designed (and at low risk of bias); however, the evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events, and the results are applicable only to individuals with HbSS and HbSߺthal genotypes. We judged the quality of the evidence for the third and fourth comparisons to be very low due to the limited number of participants, the lack of statistical power (both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes. Hydroxyurea versus placebo Five studies (784 adults and children with HbSS or HbSߺthal) compared hydroxyurea to placebo; four recruited individuals with only severe disease and one recruited individuals with all disease severities. Hydroxyurea probably improves pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use) and life-threatening illness, but we found no difference in death rates (10 deaths occurred during the studies, but the rates did not differ by treatment group) (all moderate-quality evidence). Hydroxyurea may improve measures of HbF (low-quality evidence) and probably decreases neutrophil counts (moderate-quality evidence). There were no consistent differences in terms of quality of life and adverse events (including serious or life-threatening events) (low-quality evidence). There were fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups.  Hydroxyurea and phlebotomy versus transfusion and chelation Two studies (254 children with HbSS or HbSߺthal also with risk of primary or secondary stroke) contributed to this comparison. There were no consistent differences in terms of pain alteration, death or adverse events (low-quality evidence) or life-threatening illness (moderate-quality evidence). Hydroxyurea with phlebotomy probably increased HbF and decreased neutrophil counts (moderate-quality evidence), but there were more occurrences of acute chest syndrome and infections. Quality of life was not reported. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early.  Hydroxyurea versus observation One study (22 children with HbSS or HbSߺthal also at risk of stoke) compared hydroxyurea to observation. Pain alteration and quality of life were not reported. There were no differences in life-threatening illness, death (no deaths reported in either group) or adverse events (very low-quality evidence). We are uncertain if hydroxyurea improves HbF or decreases neutrophil counts (very low-quality evidence). Treatment regimens with and without hydroxyurea One study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea. Pain alteration, life-threatening illness and quality of life were not reported. There were no differences in death rates (no deaths reported in either group), adverse events or neutrophil levels (very low-quality evidence). We are uncertain if hydroxyurea improves HbF (very low-quality evidence). AUTHORS' CONCLUSIONS: There is evidence to suggest that hydroxyurea may be effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSߺthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial Doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly with regard to preventing chronic complications of SCD, or recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with the HbSC genotype. Future studies should be designed to address such uncertainties.


Assuntos
Síndrome Torácica Aguda , Anemia Falciforme , Acidente Vascular Cerebral , Síndrome Torácica Aguda/induzido quimicamente , Síndrome Torácica Aguda/complicações , Síndrome Torácica Aguda/tratamento farmacológico , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/efeitos adversos , Criança , Hemoglobina Falciforme/uso terapêutico , Humanos , Hidroxiureia/efeitos adversos , Dor/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle
17.
PLoS One ; 17(9): e0274762, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36129958

RESUMO

Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity.


Assuntos
Anemia Falciforme , Doença da Hemoglobina SC , Anemia Falciforme/complicações , Anemia Falciforme/genética , Epigênese Genética , Feminino , Doença da Hemoglobina SC/genética , Hemoglobina Falciforme/genética , Humanos , Recém-Nascido , Placenta/metabolismo , Gravidez , Proteoglicanas/metabolismo
18.
J Int Med Res ; 50(9): 3000605221125050, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36134571

RESUMO

OBJECTIVE: The purpose of this study was to perform hematological and molecular analyses of the HbS allele of the hemoglobin subunit beta gene in the Sudanese population. METHODS: This was a descriptive cross-sectional study. Hematological parameters and fetal hemoglobin (HbF) levels were assessed in all participants. Data were gathered through the use of questionnaires and laboratory investigations. The ßS-globin haplotypes, S allele distributions, and hematological parameters with HbF levels were investigated using PCR-restriction fragment length polymorphism, gel electrophoresis, and a Sysmex hematology analyzer, respectively. RESULTS: According to our findings, the Bantu (BA) haplotype was found in 10.8% of participants with homozygous uncontested haplotypes, followed by Benin (BA) and Sudan (SU), each in 9.8% of participants. This Sudanese group from Northern Kordofan lacked the Arab-Indian haplotype. Two heterozygous versions of undisputed haplotypes were found in 17.3% of participants: SU/BA in 10.8% and CA/BE in 6.5%. CONCLUSION: As a result of sickle cell anemia, this investigation found changes in hematological parameters. In the Sudanese population, a new haplotype of the S gene was discovered.


Assuntos
Anemia Falciforme , Hemoglobina Fetal , Alelos , Anemia Falciforme/genética , Estudos Transversais , Hemoglobina Fetal/análise , Hemoglobina Fetal/genética , Haplótipos/genética , Humanos , Globinas beta/genética
19.
Clin J Pain ; 38(10): 601-611, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35997659

RESUMO

OBJECTIVES: Youth with sickle cell disease (SCD) and chronic pain, defined in this study as pain on most days for 3 months, experience variability in daily pain and physical and psychosocial functioning. This study aimed to (1) empirically derive chronic pain subgroups based on pain characteristics among youth with chronic SCD pain; and (2) investigate derived subgroups for differences in sociodemographics, clinical characteristics, and psychosocial and functional outcomes. MATERIALS AND METHODS: Youth with chronic SCD pain (n=62, Mage =13.9, SD=2.5, 10 to 18 y; 58% female, 60% HbSS) completed a battery of questionnaires. Clinical characteristics (eg, medications, treatments) and health care utilization were abstracted from electronic medical records. Hierarchical cluster analysis informed the number of clusters at the patient level. k-means cluster analysis used multidimensional pain assessment to identify and assign patients to clusters. RESULTS: Cluster 1 (n=35; Moderate Frequency, Moderate Pain) demonstrated significantly lower worst pain intensity, number of pain days per month, number of body sites affected by pain, and pain quality ratings. Cluster 2 (n=27; Almost Daily, High Pain) reported high ratings of worst pain intensity, almost daily to daily pain, greater number of body sites affected by pain, and higher ratings of pain quality (all P 's <0.05). There were no differences between subgroups by sociodemographics, clinical characteristics, or health care utilization. The Almost Daily, High Pain subgroup reported significantly higher pain interference, depressive symptoms, and pain catastrophizing than the Moderate Frequency, Moderate Pain subgroup. DISCUSSION: Identifying chronic SCD pain subgroups may inform tailored assessment and intervention to mitigate poor pain and functional outcomes.


Assuntos
Anemia Falciforme , Dor Crônica , Adolescente , Catastrofização/psicologia , Criança , Dor Crônica/psicologia , Feminino , Humanos , Masculino , Medição da Dor/métodos , Inquéritos e Questionários
20.
Artigo em Inglês | MEDLINE | ID: mdl-36018254

RESUMO

OBJECTIVES: Sickle-cell disease (SCD) patients are considered to be at high risk from open-heart surgery. This study assessed the role of a simple sickling-prevention protocol. METHODS: Perioperative non-specific and SCD-specific morbidity and 30-day mortality are investigated in a retrospective cohort study on patients undergoing isolated mitral valve surgery. Patients with and without SCD were compared. In the SCD cohort, a bundle of interventions was applied to limit the risk of sickling: 'on-demand' transfusions to keep haemoglobin levels of around 7-8 g/dl, cardiopulmonary bypass (CPB) with higher blood flow and perfusion temperature, close monitoring of acid-base balance and oxygenation. RESULTS: Twenty patients with and 40 patients without SCD were included. At baseline, only preoperative haemoglobin levels differed between cohorts (8.1 vs 11.8 g/dl, P < 0.001). Solely SCD patients received preoperative transfusions (45.0%). Intraoperative transfusions were significantly larger in SCD patients during CPB (priming: 300 vs 200 ml; entire length: 600 vs 300 ml and 20 vs 10 ml/kg). SCD patients had higher perfusion temperatures during CPB (34.7 vs 33.0°C, P = 0.01) with consequently higher pharyngeal temperature, both during cooling (34.1 vs 32.3°C, P = 0.02) and rewarming (36.5 vs 36.2°C, P = 0.02). No mortality occurred, and non-SCD-specific complications were comparable between groups, but one SCD patient suffered from perioperative cerebrovascular accident with seizures, and another had evident haemolysis. CONCLUSIONS: SCD patients may undergo open-heart surgery for mitral valve procedures with an acceptable risk profile. Simple but thoughtful perioperative management, embracing 'on-demand' transfusions and less-aggressive CPB cooling is feasible and probably efficacious.


Assuntos
Anemia Falciforme , Procedimentos Cirúrgicos Cardíacos , Anemia Falciforme/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Protocolos Clínicos , Hemoglobinas , Humanos , Valva Mitral/cirurgia , Estudos Retrospectivos
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