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1.
Clin Appl Thromb Hemost ; 26: 1076029620955240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32873056

RESUMO

The management of sickle cell disease (SCD) and its complications in the COVID-19 era is very challenging. The recurrent sickling process in SCD causes tissue hypoxemia and micro-infarcts, resulting in end organ damage. Since the outbreak of SARS-CoV-2 pandemic, little data has been published about SCD concerning clinical presentation with COVID-19 and management. Hydroxyurea has been the cornerstone of management in children and adults with SCD, with evidence of its effect on controlling end organ damage. There are several anti-sickling drugs that have been approved recently that might have an additive value toward the management of SCD and its complications. The role of simple and exchange transfusions is well established and should always be considered in the management of various complications. The value of convalescent plasma has been demonstrated in small case series, but large randomized controlled studies are still awaited. Immunomodulatory agents may play a role in reducing the damaging effects of cytokines storm that contributes to the morbidity and mortality in advanced cases. Prophylactic anticoagulation should be considered in every management protocol because SCD and COVID-19 are thrombogenic conditions. Management proposals of different presentations of patients with SCD and COVID-19 are outlined.


Assuntos
Anemia Falciforme/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Hidroxiureia/administração & dosagem , Controle de Infecções/métodos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Infecções por Coronavirus/prevenção & controle , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/terapia , Resultado do Tratamento
2.
Clin Appl Thromb Hemost ; 26: 1076029620955240, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-740342

RESUMO

The management of sickle cell disease (SCD) and its complications in the COVID-19 era is very challenging. The recurrent sickling process in SCD causes tissue hypoxemia and micro-infarcts, resulting in end organ damage. Since the outbreak of SARS-CoV-2 pandemic, little data has been published about SCD concerning clinical presentation with COVID-19 and management. Hydroxyurea has been the cornerstone of management in children and adults with SCD, with evidence of its effect on controlling end organ damage. There are several anti-sickling drugs that have been approved recently that might have an additive value toward the management of SCD and its complications. The role of simple and exchange transfusions is well established and should always be considered in the management of various complications. The value of convalescent plasma has been demonstrated in small case series, but large randomized controlled studies are still awaited. Immunomodulatory agents may play a role in reducing the damaging effects of cytokines storm that contributes to the morbidity and mortality in advanced cases. Prophylactic anticoagulation should be considered in every management protocol because SCD and COVID-19 are thrombogenic conditions. Management proposals of different presentations of patients with SCD and COVID-19 are outlined.


Assuntos
Anemia Falciforme/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Hidroxiureia/administração & dosagem , Controle de Infecções/métodos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Infecções por Coronavirus/prevenção & controle , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/terapia , Resultado do Tratamento
3.
Clin Ter ; 171(4): e291-e294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614360

RESUMO

The aim of this case report is to share with the forensic science community the experience of a rare complication of sickle cell anemia: acute chest syndrome. In October 2016, at the port of the city of Trapani (Sicily, Italy), the landing of an ONG "Médecins Sans Frontières" ship took place with 548 non-EU citizens and a corpse on board. The man, in the hours before his death, complained of severe chest pain and respiratory difficulties, and, despite of the therapeutic aids and resuscitation maneuvers, lastly died. The Public Prosecutor ordered that autopsy be executed on the corpse of the young Ghanaian, and it was to be supplemented by histological, toxicological, genetic investigations, and the dating of the biological age. The autoptic examination findings were indicative of bilateral bronchopneumonia, and were also confirmed by the histological findings, which identified a condition of massive adipose pulmonary embolism, due to the presence of extramedullary hematopoietic tissue, site of endovascular thrombosis secondary to hemolysis of sickle cells. The spleen appeared of small volume, with fibrotic phenomena. The predisposition to infections, thrombosis, extramedullary hematopoiesis are all complications of sickle cell anemia. The severe pulmonary condition characterized by vaso-occlusive findings and pulmonary inflammation with infiltrate, symptoms like fever, chest pain and severe systemic hypoxia allowed to ascribe the plausible cause of death as acute chest syndrome, a rare complication of sickle cell anemia. The peculiarity of this clinical case is also related to the methods of medical intervention (boat with non-governmental medical support for assistance to migrants).


Assuntos
Anemia Falciforme/mortalidade , Emigrantes e Imigrantes , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Dor no Peito/etiologia , Dispneia/etiologia , Febre/etiologia , Gana/etnologia , Humanos , Masculino , Mar Mediterrâneo , Sicília
6.
Middle East Afr J Ophthalmol ; 27(1): 65-67, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32549729

RESUMO

Repeated vaso-occlusive crises (VOCs) are the hallmark of sickle cell disease (SCD). These repeated crises can lead to bone infarcts, necrosis, and, over time, degenerative changes in the bone marrow. Orbital complications in SCD patients are infrequent and usually present as orbital cellulitis. We report the appearance of orbital bone infarction intraoperatively in the case of an 18-year-old Saudi male patient who has been diagnosed with SCD and presented with severe headaches and generalized body aches. He was admitted with a case of SCD with acute VOC and started on the hospital sickle cell protocol. During the admission, the patient developed bilateral periorbital swelling and left inferior dystopia secondary to bilateral frontoparietal bone infarction, which was evident on the magnetic resonance imaging.


Assuntos
Anemia Falciforme/complicações , Osso Frontal/irrigação sanguínea , Infarto/diagnóstico , Celulite Orbitária/diagnóstico , Adolescente , Anemia Falciforme/diagnóstico , Diagnóstico Diferencial , Osso Frontal/diagnóstico por imagem , Humanos , Infarto/diagnóstico por imagem , Infarto/etiologia , Imagem por Ressonância Magnética , Masculino , Acuidade Visual/fisiologia
7.
Lancet Haematol ; 7(7): e534-e540, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32589979

RESUMO

BACKGROUND: Sickle cell disease is highly prevalent in sub-Saharan Africa, where it accounts for substantial morbidity and mortality. Newborn screening is paramount for early diagnosis and enrolment of affected children into a comprehensive care programme. Up to now, this strategy has been greatly impaired in resource-poor countries, because screening methods are technologically and financially intensive; affordable, reliable, and accurate methods are needed. We aimed to test the feasibility of implementing a sickle cell disease screening programme using innovative point-of-care test devices into existing immunisation programmes in primary health-care settings. METHODS: Building on a routine immunisation programme and using existing facilities and staff, we did a prospective feasibility study at five primary health-care centres within Gwagwalada Area Council, Abuja, Nigeria. We systematically screened for sickle cell disease consecutive newborn babies and infants younger than 9 months who presented to immunisation clinics at these five centres, using an ELISA-based point-of care test (HemoTypeSC). A subgroup of consecutive babies who presented to immunisation clinics at the primary health-care centres, whose mothers gave consent, were tested by the HemoTypeSC point-of-care test alongside a different immunoassay-based point-of-care test (SickleSCAN) and the gold standard test, high-performance liquid chromatography (HPLC). FINDINGS: Between July 14, 2017, and Sept 3, 2019, 3603 newborn babies and infants who presented for immunisation were screened for sickle cell disease at five primary health-care centres using the ELISA-based point-of-care test. We identified 51 (1%) children with sickle cell anaemia (HbSS), four (<1%) heterozygous for HbS and HbC (HbSC), 740 (21%) with sickle cell trait (HbAS), 34 (1%) heterozygous for HbA and HbC (HbAC), and 2774 (77%) with normal haemoglobin (HbAA). Of the 55 babies and infants with confirmed sickle cell disease, 41 (75%) were enrolled into a programme for free folic acid and penicillin, of whom 36 (88%) completed three visits over 9 months (median follow-up 226 days [IQR 198-357]). The head-to-head comparison between the two point-of-care tests and HPLC showed concordance between the three testing methods in screening 313 newborn babies, with a specificity of 100% with HemoTypeSC, 100% with SickleSCAN, and 100% by HPLC, and a sensitivity of 100% with HemoTypeSC, 100% with SickleSCAN, and 100% by HPLC. INTERPRETATION: Our pilot study shows that the integration of newborn screening into existing primary health-care immunisation programmes is feasible and can rapidly be implemented with limited resources. Point-of-care tests are reliable and accurate in newborn screening for sickle cell disease. This feasibility study bodes well for the care of patients with sickle cell disease in resource-poor countries. FUNDING: Doris Duke Charitable Foundation, Imperial College London Wellcome Trust Centre for Global Health Research, and Richard and Susan Kiphart Family Foundation.


Assuntos
Anemia Falciforme/diagnóstico , Prestação Integrada de Cuidados de Saúde/organização & administração , Triagem Neonatal , Testes Imediatos/organização & administração , Estudos de Viabilidade , Feminino , Humanos , Programas de Imunização/organização & administração , Recém-Nascido , Masculino , Triagem Neonatal/métodos , Triagem Neonatal/organização & administração , Nigéria , Projetos Piloto , Estudos Prospectivos
8.
Ann Hematol ; 99(6): 1225-1230, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32363415

RESUMO

Sickle cell anemia (SCA) is the most severe form of sickle cell disease caused by homozygosity of the ßS-gene (S/S or ßSßS) and has worldwide distribution. Six polymorphic sites in the ß-globin gene cluster were analyzed from a sample of 56 chromosomes of patients with SCA from the state of Maranhão, northeastern Brazil. PCR-RFLP showed that the CAR haplotype was predominant with a frequency of 64.28%, followed by the BEN haplotype (28.57%). Atypical haplotypes were identified at a frequency of 7.15%. Genotypes CAR/CAR, BEN/BEN, and CAR/BEN were present in 46.43%, 10.71%, and 35.71% of patients, respectively. ß-Globin haplotype determination is important not only for the monitoring and prognosis of patients with SCA, but it also serves to inform anthropological studies that contribute to elucidating any peculiarities associated with African influences that contributed to the ethnological, economic, cultural, and social formation of Brazil. The high frequency of the CAR/CAR and CAR/BEN haplotypes in this study, which are associated with low levels of fetal hemoglobin, may ultimately reflect a severe clinical course and poor prognosis in patients with SCA in Maranhão.


Assuntos
Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Haplótipos/genética , Adolescente , Adulto , Anemia Falciforme/diagnóstico , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Adulto Jovem
9.
Ann Hematol ; 99(6): 1217-1223, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32367178

RESUMO

While fluid replacement therapy is a primary treatment modality used in vaso-occlusive crises for sickle cell disease, data is limited on its safety, efficacy, and variability. We performed a retrospective analysis on 157 unique patient encounters from 49 sickle cell patients hospitalized with a vaso-occlusive episode at our institution from 2013 to 2017. The median length of hospital stay was 4 days (IQR 2-7). The mean total amount of intravenous fluid administered during the hospitalization was 7.4 L (Std 9.6). The mean total amount of fluid intake including intravenous fluids, blood transfusions, and oral fluids was 14.2 L (Std 18.2). Multivariate analyses revealed significant associations between the development of any adverse event (including a new oxygen requirement, acute chest syndrome, aspiration event, other hospital-acquired infection, acute kidney injury, and intensive care unit transfer) and the following variables: intravenous fluid administered in the first 24 h (p = 0.001, OR 1.899, 95% CI 1.319-2.733), total amount of intravenous fluid administered (p = 0.005, OR 1.081, 95% CI 1.023-1.141), and total amount of fluid intake including oral fluids, blood transfusions, and intravenous fluids (p = 0.009, OR 1.046, 95% CI 1.011-1.081). Other factors found to be significantly associated with any adverse event were dialysis dependence prior to admission (p < 0.001, OR 12.984, 95% CI 3.660-46.056) and admission to an inpatient service versus an emergency room or observation unit (p = 0.008, OR 3.201, 95% CI 1.346-7.612). While fluid administration may theoretically slow the sickling process, this data suggests that fluid administration during a vaso-occlusive episode, and especially total volume given in the first 24 h, may also lead to adverse events.


Assuntos
Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Hidratação/tendências , Manejo da Dor/tendências , Dor/epidemiologia , Administração Intravenosa , Adulto , Anemia Falciforme/diagnóstico , Feminino , Hidratação/métodos , Hospitalização/tendências , Humanos , Masculino , Dor/diagnóstico , Manejo da Dor/métodos , Estudos Retrospectivos , Resultado do Tratamento
11.
Ann Hematol ; 99(9): 2057-2064, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32458066

RESUMO

Sleep disturbance is common among children with sickle cell disease (SCD) and is related to neurocognitive difficulties. However, research on sleep disturbances and related variables among adults with SCD is extremely limited. The present study examined the relationship between sleep, executive functioning, and emotional functioning among 62 adults (29 females; M age = 32 years, SD = 7.79) with SCD preparing to undergo a stem cell transplant. Participants were administered a neurocognitive evaluation that included objective and subjective measures of executive functioning, and they completed PROMIS self-report measures of anxiety, depression, and pain intensity. Results showed that about 17% of participants endorsed clinically significant sleep disruptions, while 16.1% and 8% endorsed clinically significant symptoms of anxiety and depression, respectively. Sleep disturbance in these adults was not significantly correlated with objective or subjective measures of executive functioning. Moreover, anxiety, but not depression, was a significant mediator between self-reported sleep difficulties and both objective and subjective measures of executive functioning while controlling for pain intensity. Future research on sleep interventions will be essential for ameliorating the effects of sleep disturbance on executive functioning and anxiety among adults with SCD.


Assuntos
Anemia Falciforme/psicologia , Emoções/fisiologia , Função Executiva/fisiologia , Transtornos do Sono-Vigília/psicologia , Adulto , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Feminino , Transplante de Células-Tronco Hematopoéticas/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , Adulto Jovem
12.
J Stroke Cerebrovasc Dis ; 29(7): 104864, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32402717

RESUMO

PURPOSE: The purpose of this study was to determine the additional information provided by Magnetic Resonance Angiography (MRA) in pediatric sickle cell disease (SCD) patients with normal Transcranial Doppler imaging (TCDI) examinations. METHODS: This cohort study included all pediatric SCD patients over an 18-year period who had no history of stroke and had normal TCDI examinations and subsequently underwent MRA. Routine TCDI inclusive of time-averaged mean of maximum velocities (TAMMV) were assesses and compared with tortuosity on MRA and silent infarct on MRI. RESULTS: 86 children (52.3% female; mean age 8.7 ± 3.5years) were included. There were 77 patients (89.5%) with Hb-SS disease and 9(10.4%) with HB-S beta-thalassemia. All patients had normal TAMMV (<170 cm/s) on TCDI. 76/86 (88.3%) patients also had one or more velocity readings <70 cm/s, albeit none in the middle cerebral arteries. Posterior cerebral arteries had the lowest velocities, <70 cm/s in 51.7% (right) and 60.9% (left). Silent MRI infarcts were seen in 27/86 (31.4%) patients. No new lesions were identified on follow-up MRI. Although mild vascular tortuosity was appreciated in 31/86 (36.0%) of the patients, there were no steno-occlusive lesions in the circle of Willis. CONCLUSIONS: TCDI and MRA are routinely performed for non-invasively evaluating intracranial vascular abnormalities in children with SCD. In SCD children with no history of TIA or stroke, MRA following a normal TCDI examination is unlikely to show vascular abnormality. However, almost a third of these patients show silent infarcts on MRI, unassociated with MRA changes.


Assuntos
Anemia Falciforme/complicações , Isquemia Encefálica/diagnóstico por imagem , Angiografia Cerebral/métodos , Angiografia por Ressonância Magnética , Acidente Vascular Cerebral/diagnóstico por imagem , Adolescente , Fatores Etários , Anemia Falciforme/diagnóstico , Doenças Assintomáticas , Isquemia Encefálica/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Ultrassonografia Doppler Transcraniana
13.
Ann Hematol ; 99(9): 2073-2079, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32377816

RESUMO

Vasculopathy is a hallmark of sickle cell disease ultimately resulting in chronic end organ damage. Leg ulcer is one of its sequelae, occurring in ~ 5-10% of adult sickle cell patients. The majority of leg ulcer publications to date have emanated from single center cohort studies. As such, there are limited studies on the geographic distribution of leg ulcers and associated risk factors worldwide. The Consortium for the Advancement of Sickle Cell Research (CASiRe) was formed to improve the understanding of the different phenotypes of sickle cell disease patients living in different geographic locations around the world (USA, UK, Italy, Ghana). This cross-sectional cohort sub-study of 659 sickle cell patients aimed to determine the geographic distribution and risk factors associated with leg ulcers. The prevalence of leg ulcers was 10.3% and was associated with older age, SS genotype, male gender, and Ghanaian origin. In fact, the highest prevalence (18.6%) was observed in Ghana. Albuminuria, proteinuria, increased markers of hemolysis (lower hemoglobin, higher total bilirubin), lower oxygen saturation, and lower body mass index were also associated with leg ulceration. Overall, our study identified a predominance of leg ulcers within male hemoglobin SS patients living in sub-Saharan Africa with renal dysfunction and increased hemolysis.


Assuntos
Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Internacionalidade , Úlcera da Perna/diagnóstico , Úlcera da Perna/epidemiologia , Adolescente , Adulto , Idoso , Anemia Falciforme/sangue , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Gana/epidemiologia , Humanos , Lactente , Itália/epidemiologia , Úlcera da Perna/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
15.
Ann Hematol ; 99(7): 1453-1463, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32447424

RESUMO

Fetal hemoglobin (HbF) ameliorates clinical severity of sickle cell anemia (SCA). The major loci regulating HbF levels are HBB cluster, BCL11A, and HMIP-2 (HBS1L-MYB). However, the impact of noncoding single-nucleotide polymorphisms (SNPs) in these loci on clinical outcomes and their functional role on regulating HbF levels should be better elucidated. Therefore, we performed comprehensive association analyses of 14 noncoding SNPs in five loci with HbF levels and with clinical outcomes in a cohort of 250 children with SCA from Southeastern Brazil, and further performed functional annotation of these SNPs. We found SNPs independently associated with HbF levels: rs4671393 in BCL11A (ß-coefficient = 0.28), rs9399137 in HMIP-2A (ß-coefficient = 0.16), and rs4895441 in HMIP-2B (ß-coefficient = 0.15). Patients carrying minor (HbF-boosting) alleles for rs1427407, rs93979137, rs4895441, rs9402686, and rs9494145 showed reduced count of reticulocytes (p < 0.01), while those carrying the T allele of rs9494145 showed lower white blood cell count (p = 0.002). Carriers of the minor allele for rs9402686 showed higher peripheral saturation of oxygen (p = 0.002). Patients carrying minor alleles in BCL11A showed lower risk of transfusion incidence rate ratio (IRR ≥ 1.3; p < 0.0001). This effect was independent of HbF effect (p = 0.005). Carriers of minor alleles for rs9399137 and rs9402686 showed lower risk of acute chest syndrome (IRR > 1.3; p ≤ 0.01). Carriers of the reference allele for rs4671393 showed lower risk of infections (IRR = 1.16; p = 0.01). In conclusion, patients carrying HbF-boosting alleles of BCL11A and HMIP-2 were associated with milder clinical phenotypes. Higher HbF concentration may underlie this effect.


Assuntos
Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Hemoglobina Fetal/metabolismo , Proteínas de Ligação ao GTP/genética , Genes myb , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Alelos , Anemia Falciforme/sangue , Anemia Falciforme/epidemiologia , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hemoglobina Fetal/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos
16.
Ann Hematol ; 99(7): 1465-1474, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32451712

RESUMO

Sickle cell disease (SCD) describes a set of chronic inherited anemias characterized by hemolysis, episodes of vaso-occlusion, and high infectious risk, with high morbidity and mortality. Newborn screening (NBS) for SCD allows family health education and early start of infectious prophylaxis. In the Community of Madrid, a pilot universal NBS study found that the SCA birth prevalence was 1/5851 in newborns, higher than expected, confirming the need to include early detection in the NBS program. The aim of the present prospective single-center study is to analyze the results of newborn SCD screening in Madrid in terms of epidemiological data and its inclusion in a comprehensive care program during the last 15 years, between 1st of May 2003 and 1st of May 2018. During the study period, 1,048,222 dried bloodspots were analyzed. One hundred ninety-seven patients were diagnosed with possible SCD (HPLC phenotype of FS, FSA, FSC, FSE, FSDPunjab, FSOArab), with 187 patients finally confirmed (birth prevalence 1/5552 newborns, 0.18 per 1000 live births), and 1 out of 213 infants carried Hb S. All of them were seen by a specialist clinician; median age at the first visit consultation was 35 days and median age at the beginning of penicillin treatment was 66 days. The Madrid SCD NBS program achieved high rates of sensitivity and specificity and good quality of care assistance. Establishing a good relationship with the family, a strong education program, and a multidisciplinary team that includes social workers and a psychologist are needed to ensure the success of early intervention.


Assuntos
Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Triagem Neonatal , Europa (Continente)/epidemiologia , Feminino , História do Século XXI , Humanos , Recém-Nascido , Masculino , Triagem Neonatal/história , Triagem Neonatal/tendências , Prevalência , Estudos Prospectivos , Espanha/epidemiologia
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