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1.
Clin Cancer Res ; 30(9): 1750-1757, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38393723

RESUMO

PURPOSE: Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas]. PATIENTS AND METHODS: Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor >3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily. End points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and linear growth rate (LGR) in all pancreatic lesions and pNETs per RECIST version 1.1 by independent review committee, and safety. RESULTS: All 61 enrolled patients (100%) had ≥1 pancreatic lesion and 22 (36%) had ≥1 pNET measurable at baseline. Median follow-up was 37.8 months (range, 36.1-46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs. Median DOR and median PFS were not reached in pancreatic lesions or pNETs. After starting treatment, median LGR for pNETs was -4.2 mm per year (range, -7.9 to -0.8). Eleven patients (18%) had ≥1 grade 3 treatment-related adverse event (AE). No grade 4 or 5 treatment-related AEs occurred. CONCLUSIONS: Belzutifan continued to show robust activity and manageable safety in VHL disease-associated pNETs.


Assuntos
Neoplasias Pancreáticas , Doença de von Hippel-Lindau , Humanos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/tratamento farmacológico , Doença de von Hippel-Lindau/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Idoso , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Adulto Jovem , Resultado do Tratamento , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Cistadenoma Seroso/tratamento farmacológico , Cistadenoma Seroso/patologia
2.
Emerg Infect Dis ; 25(12): 2264-2265, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31742511

RESUMO

We assessed IgM detection in Zika patients from the 2016 outbreak in Miami-Dade County, Florida, USA. Of those with positive or equivocal IgM after 12-19 months, 87% (26/30) had IgM 6 months later. In a survival analysis, ≈76% had IgM at 25 months. Zika virus IgM persists for years, complicating serologic diagnosis.


Assuntos
Anticorpos Antivirais/imunologia , Imunoglobulina M/imunologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Surtos de Doenças , Feminino , Florida/epidemiologia , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem , Zika virus/genética , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia
4.
Pediatrics ; 140(6)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29093135

RESUMO

BACKGROUND AND OBJECTIVE: In July 2016, local transmission of Zika virus (ZIKV) was announced in Miami-Dade County, Florida. In this report, we describe the epidemiology of pediatric ZIKV infections in locally acquired and travel-associated cases. METHODS: All children aged 1 to 17 years tested for ZIKV between October 1, 2015, and March 29, 2017, were included. SAS 9.4 was used to analyze age, sex, race and/or ethnicity, origin of exposure, onset date, affiliation with a household cluster, clinical symptoms, hospitalizations, viremia, viruria, and antibody detection in specimens. RESULTS: Among 478 confirmed ZIKV cases in Miami-Dade County, 33 (6.9%) occurred in children (1-17 years). Twenty-seven (82.3%) cases were travel-associated. The median age of a pediatric Zika case patient was 11 years. Seventeen (51.5%) case patients were boys, and 23 (69.9%) were Hispanic. Among 31 symptomatic cases, all reported having rash, 25 (80.6%) reported fever, 9 (29.0%) reported conjunctivitis, and 7 (22.6%) reported arthralgia. Sixteen (48.5%) cases reported 2 of 4 and 8 (24.2%) reported 3 of 4 main symptoms. CONCLUSIONS: This report found that the majority of children identified during the 2016 ZIKV outbreak only presented with 2 of the 4 main symptoms. In addition, pediatric ZIKV cases were frequently associated with symptomatic household members.


Assuntos
Surtos de Doenças , Etnicidade , Medição de Risco/métodos , Infecção por Zika virus/etnologia , Adolescente , Fatores Etários , Anticorpos Antivirais/análise , Criança , Pré-Escolar , DNA Viral/análise , Feminino , Florida/epidemiologia , Humanos , Lactente , Masculino , Morbidade/tendências , Estudos Retrospectivos , Fatores Sexuais , Zika virus/genética , Zika virus/imunologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia
5.
Clin Pharmacol Drug Dev ; 3(4): 270-5, 2014 07.
Artigo em Inglês | MEDLINE | ID: mdl-27128832

RESUMO

The pharmacokinetics (PK) and pharmacodynamics of two leuprolide acetate (LA) 45 mg 6-month depot formulations were characterized in prostate cancer patients. Subjects (planned N = 150 in each cohort) received two intramuscular injections of LA Formulation-A or Formulation-B administered 24 weeks apart. Samples were collected for the measurement of testosterone, LH (all subjects) and leuprolide (in a subset of subjects approximately N = 24 in each cohort) at the same time points. Leuprolide PK profile showed an initial peak followed by a rapid decline over the first week post-dose, with mean leuprolide concentrations staying relatively constant through the end of 24-week period. Mean testosterone and LH serum concentrations showed initial increases above baseline values after the first dose and then decreased to 16.0 ng/dL and 0.6 mIU/mL by Week 4 for Formulation-A and were maintained at ≤14.3 ng/dL and 0.4 mIU/mL, thereafter, with negligible mean increases after the second dose. Formulation-A showed a lower initial peak and higher leuprolide concentration during the sustained release phase which may explain higher testosterone suppression rates for Formulation-A compared to Formulation-B. Differences in PK between LA depot formulations were reflected in pharmacodynamic responses, with a higher rate of testosterone suppression and less escapes and acute-on-chronic responses for Formulation-A.


Assuntos
Antineoplásicos Hormonais/farmacocinética , Leuprolida/farmacocinética , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Preparações de Ação Retardada , Composição de Medicamentos , Humanos , Injeções Intramusculares , Leuprolida/administração & dosagem , Leuprolida/efeitos adversos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Testosterona/sangue , Resultado do Tratamento , Estados Unidos
6.
Pain Med ; 14(7): 1088-100, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23590428

RESUMO

OBJECTIVE: Examine response patterns to low-dose intravenous (IV) ketamine continuous infusions on multiple pain outcomes, and demonstrate effectiveness, safety, and tolerability of ketamine administration on general wards. DESIGN: Retrospective case series of consecutive patients given low-dose IV ketamine continuous infusions. SETTING: Walter Reed Army Medical Center, Washington, DC. PATIENTS: Nineteen eligible inpatients with neuropathic pain from major limb injuries sustained in combat with inadequate pain control from multimodal analgesia. INTERVENTIONS: A 3-day IV infusion of ketamine at doses ≤ 120 µg/kg/h. OUTCOME MEASURES: Daily present (PPI), average (API), and worst (WPI) pain intensity (0-10), global pain relief (GPR) (1 "no relief" to 5 "complete relief"), daily assessments of adverse events, and daily opioid requirements measured during therapy. RESULTS: A significant reduction in PPI (P < 0.001) and improvement in GPR (P = 0.031) was noted over time. Higher baseline WPI (≥ 7; N = 4) was associated with a significant decrease in WPI (P = 0.0388), but lower baseline WPI (N = 5) was not. Significant mean percent decreases in PPI with higher baseline PPI (N = 8; P = 0.0078) and WPI with no phantom limb pain (PLP) (N = 10; P = 0.0436) were observed. Mean percent increase in overall GPR was better for those reporting GPR scores ≤ 3 (N = 13) in the first 24 hours of therapy (P = 0.0153). While not significant, mean opioid requirement (IV morphine equivalents) decreased from 129.9 mgs ± 137.3 on day 1 to 112.14 ± 86.3 24 hours after therapy. CONCLUSIONS: Low-dose ketamine infusions for complex combat injury pain were safe and effective, and demonstrated response patterns over time and by baseline pain score stratification and presence or absence of PLP.


Assuntos
Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Extremidades/lesões , Ketamina/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Guerra , Ferimentos e Lesões/complicações , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Humanos , Infusões Intravenosas , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Medição da Dor , Estudos Retrospectivos , Resultado do Tratamento , Ferimentos por Arma de Fogo , Adulto Jovem
7.
J Clin Endocrinol Metab ; 97(5): 1572-80, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22344198

RESUMO

CONTEXT: GnRH agonist (GnRHa) monthly injections are frequently used in the treatment of central precocious puberty (CPP). The 3-month leuprolide depot 11.25- and 30-mg formulations are newly approved treatment options. OBJECTIVE: The aim of the study was to investigate the safety and efficacy of leuprolide acetate 3-month depot formulations for the treatment of CPP in children. DESIGN: This was a phase III, randomized, open-label, dose-ranging 6-month study. SETTING: Twenty-two U.S. medical centers (including Puerto Rico) participated. PATIENTS: Children diagnosed with CPP (n = 84), who were either treatment naive or previously treated with GnRHa, were recruited. Chronological age at onset of pubertal signs was less than 8 yr in girls and less than 9 yr in boys, and bone age was advanced over chronological age at least 1 yr. INTERVENTION: Leuprolide acetate depot (11.25 or 30 mg) was administered im every 3 months. MAIN OUTCOME MEASURES: Biochemical [peak-stimulated LH, estradiol (girls), and testosterone (boys)] and anthropometric (growth rate, bone age acceleration, pubertal progression) parameters and safety were assessed. RESULTS: Peak-stimulated LH was suppressed in the 11.25- and 30-mg dose groups in 78.4 and 95.2%, respectively, of children from months 2 through 6. There were nine treatment failures (peak-stimulated LH >4 IU/liter) in the 11.25-mg group and two in the 30-mg group. Basal sex steroid suppression, growth rates, pubertal progression, bone age advancement, and adverse events were similar with either dose. CONCLUSIONS: Treatment with leuprolide acetate 3-month depot formulations (11.25 and 30 mg) effectively suppressed the GnRH axis, was well tolerated, and may positively impact patient convenience and compliance.


Assuntos
Leuprolida/uso terapêutico , Puberdade Precoce/tratamento farmacológico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Lactente , Leuprolida/administração & dosagem , Leuprolida/efeitos adversos , Hormônio Luteinizante/sangue , Masculino , Puberdade Precoce/sangue , Testosterona/sangue , Resultado do Tratamento
8.
Int J Pediatr Endocrinol ; 2011(1): 7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21860633

RESUMO

INTRODUCTION: Gonadotropin-releasing hormone analogs (GnRHa) are the treatment of choice for CPP. We investigated growth in GnRHa-naïve subjects, treated with leuprolide acetate 1-month depot for CPP. METHODS: This prospective, open-label study had a long-term, observational, follow-up period. Forty-nine females and 6 males were enrolled. Leuprolide acetate depot was administered intramuscularly every 28 days. Height and growth rate during and after treatment until adulthood were measured. RESULTS: Among 30 of 49 females having an adult height (AH) measurement, 29 had target heights available (mean = 163.8 cm) and 27 had pretreatment predicted adult heights (PAHs; mean = 157.4 cm). After treatment, the mean AH at mean age 21.8 years [range 13.7-26.7 years] was 162.5 cm, a mean height gain over baseline PAH of 4.0 cm. The mean height standard deviation score was -0.1 at AH. CONCLUSIONS: Treatment of CPP with leuprolide acetate 1-month depot had beneficial effects on growth rate and preservation of AH. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00660010.

9.
Int J Pediatr Endocrinol ; 2010: 398639, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21437000

RESUMO

Methods. This prospective US multicenter trial of leuprolide acetate 1-month depot (7.5-15 mg) for central precocious puberty utilized an open-label treatment period, long-term follow-up, and adult callback. Forty-nine females <9 years old with Tanner breast stage ≥2 before 8 years and 6 males <10 years old with Tanner genital stage ≥2 before 9 years with stimulated LH ≥10 IU/L and bone age advance ≥1 year were enrolled. Results. Subjects were treated for 3.9 ± 2.0 years. Mean peak GnRH-stimulated LH and FSH were prepubertal after the first dose and remained suppressed throughout treatment. During treatment, mean estradiol decreased to the limit of detection and mean testosterone decreased but remained above prepubertal norms. During posttreatment follow-up (3.5 ± 2.2 years), all patients achieved a pubertal hormonal response within 1 year and menses were reported in all females ≥12 years old. No impairment of reproductive function was observed at adulthood (mean age: 24.8 years).

10.
Am J Obstet Gynecol ; 199(4): 435.e1-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18928998

RESUMO

OBJECTIVE: The objective of the study was to evaluate the efficacy, safety, and tolerability of intravenous ferric carboxymaltose, compared with oral ferrous sulfate in women with postpartum anemia. STUDY DESIGN: In a multicenter, randomized, controlled study, 291 women less than 10 days after delivery with hemoglobin 10 g/dL or less were randomized to receive ferric carboxymaltose (n = 143) 1000 mg or less intravenously over 15 minutes or less, repeated weekly to a calculated replacement dose (maximum 2500 mg) or ferrous sulfate (n = 148) 325 mg orally thrice daily for 6 weeks. RESULTS: Ferric carboxymaltose-treated subjects were significantly more likely to: (1) achieve a hemoglobin greater than 12 g/dL in a shorter time period with a sustained hemoglobin greater than 12 g/dL at day 42, (2) achieve hemoglobin rise 3 g/dL or greater more quickly, and (3) attain higher serum transferrin saturation and ferritin levels. Drug-related adverse events occurred less frequently with ferric carboxymaltose. CONCLUSION: Intravenous ferric carboxymaltose was safe and well tolerated with an efficacy superior to oral ferrous sulfate in the treatment of postpartum iron deficiency anemia.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/administração & dosagem , Hematínicos/administração & dosagem , Maltose/análogos & derivados , Transtornos Puerperais/tratamento farmacológico , Administração Oral , Adulto , Feminino , Compostos Ferrosos/administração & dosagem , Humanos , Injeções , Maltose/administração & dosagem , Resultado do Tratamento
11.
Fertil Steril ; 87(6): 1399-412, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17307170

RESUMO

OBJECTIVE: To determine efficacy and safety of asoprisnil in patients with leiomyomata. DESIGN: Phase 2, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Twenty-eight sites in the United States and 1 in Canada. PATIENT(S): One hundred twenty-nine women with leiomyomata. INTERVENTION(S): Asoprisnil (5, 10, or 25 mg) or placebo orally daily for 12 weeks. MAIN OUTCOME MEASURE(S): Uterine bleeding changes by using daily bleeding diaries, hemoglobin concentrations, dominant leiomyoma and uterus volume measured sonographically, patient-reported symptoms related to bloating and pelvic pressure, endometrial thickness and morphology, hormonal parameters, and standard safety measures. RESULT(S): Asoprisnil suppressed uterine bleeding in 28%, 64%, and 83% of subjects at 5, 10, and 25 mg, respectively, and reduced leiomyoma and uterine volumes. Median percentage decrease from baseline in leiomyoma volume was statistically significant at 25 mg compared with placebo after 4 and 8 weeks of treatment; by week 12, leiomyoma volume was reduced by 36%. There was a significant reduction in bloating with the two highest doses and in pelvic pressure with 25 mg by week 12. Asoprisnil was associated with follicular-phase estrogen concentration and minimal hypoestrogenic symptoms. CONCLUSION(S): After 12-week treatment, asoprisnil controlled uterine bleeding while reducing leiomyoma volume and the associated pressure symptoms. Asoprisnil was well tolerated.


Assuntos
Estrenos/uso terapêutico , Leiomioma/tratamento farmacológico , Oximas/uso terapêutico , Ocitócicos/uso terapêutico , Receptores de Progesterona/fisiologia , Neoplasias Uterinas/tratamento farmacológico , Adolescente , Adulto , Método Duplo-Cego , Estrenos/toxicidade , Feminino , Humanos , Pessoa de Meia-Idade , Oximas/toxicidade , Seleção de Pacientes , Placebos , Receptores de Progesterona/efeitos dos fármacos , Hemorragia Uterina/epidemiologia
12.
Hum Reprod ; 20(4): 1090-9, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15665012

RESUMO

BACKGROUND: Asoprisnil (J867) is a novel selective progesterone receptor modulator (SPRM) that exhibits partial agonist and antagonist activities and tissue selective effects. This double-blind, dose-escalation study was conducted to evaluate the effects of asoprisnil in 60 regularly cycling premenopausal women. METHODS: Asoprisnil or placebo was administered orally for 28 days starting at the beginning of the menstrual cycle in doses of 5 mg once daily (QD), 5 mg twice daily (BID), 10 mg QD, 25 mg QD, 25 mg BID and 50 mg BID. Within each dose group, two women were randomized to placebo and eight to asoprisnil. Progesterone concentrations indicative of luteinization were defined as at least one progesterone measurement during the luteal phase exceeding 3.5 ng/ml. RESULTS: Asoprisnil consistently prolonged the menstrual cycle at doses > or = 10 mg QD. However, the effects on luteal phase progesterone indicative of luteinization were inconsistent and lacked dose dependency. Asoprisnil suppressed periovulatory estradiol but not below follicular phase levels. No significant changes were observed in cortisol and prolactin. Asoprisnil was well tolerated. CONCLUSIONS: Asoprisnil reversibly suppressed menstruation at doses > or = 10 mg QD irrespective of the effect on luteal phase progesterone concentrations indicative of luteinization. It induces amenorrhea primarily by targeting the endometrium in the absence of estrogen deprivation.


Assuntos
Fase Luteal/efeitos dos fármacos , Oximas/administração & dosagem , Ocitócicos/administração & dosagem , Pré-Menopausa , Receptores de Progesterona/metabolismo , Administração Oral , Adolescente , Adulto , Sulfato de Desidroepiandrosterona/sangue , Método Duplo-Cego , Endométrio/citologia , Endométrio/efeitos dos fármacos , Estradiol/sangue , Estrenos , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hidrocortisona/sangue , Luteinização/efeitos dos fármacos , Hormônio Luteinizante/sangue , Pessoa de Meia-Idade , Oligopeptídeos , Oximas/efeitos adversos , Ocitócicos/efeitos adversos , Progesterona/sangue , Globulina de Ligação a Hormônio Sexual/metabolismo
13.
Semin Reprod Med ; 22(2): 113-9, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15164306

RESUMO

Asoprisnil is a novel selective progesterone receptor modulator that exhibits partial agonist and antagonist activities in animals and humans. It demonstrates a high degree of progesterone receptor specificity and tissue selectivity. Although asoprisnil at high doses exhibited some antiglucocorticoid activity in animal models, no antiglucocorticoid effects were observed at therapeutic doses in humans. In male rats, asoprisnil showed mixed androgenic and antiandrogenic properties. Unlike antiprogestins, asoprisnil at high doses exhibited only marginal labor-inducing activity in guinea pigs during midpregnancy and was completely ineffective in inducing preterm parturition. In nonhuman primates, asoprisnil completely eliminated menstrual cyclicity and induced endometrial atrophy. Early clinical studies of asoprisnil in healthy volunteers demonstrated a dose-dependent suppression of menstruation, irrespective of the effects on ovulation, with no change in basal estrogen concentrations and no breakthrough bleeding. Phase 2 studies in subjects with uterine fibroids demonstrated that asoprisnil induced amenorrhea and reduced the volume of the dominant leiomyoma in a dose-dependent manner without altered basal estrogen and with virtually no clinical symptoms of estrogen deprivation. Asoprisnil seems to exhibit a direct inhibitory effect on both the endometrium and leiomyoma. In all studies to date, asoprisnil has maintained a favorable safety and tolerability profile. Thus, asoprisnil has the potential to target the major clinical symptoms of leiomyomata related to both menorrhagia and the size of the tumors and may, therefore, reduce or eliminate the need for surgery.


Assuntos
Leiomioma/tratamento farmacológico , Oximas/uso terapêutico , Ocitócicos/uso terapêutico , Receptores de Progesterona/efeitos dos fármacos , Neoplasias Uterinas/tratamento farmacológico , Animais , Endométrio/efeitos dos fármacos , Estrenos , Feminino , Humanos , Progesterona/fisiologia , Receptores de Progesterona/antagonistas & inibidores , Receptores de Progesterona/fisiologia , Hemorragia Uterina/tratamento farmacológico
14.
Rev. imagem ; 22(1): 49-51, jan.-mar. 2000. ilus
Artigo em Português | LILACS | ID: lil-259948

RESUMO

Os autores relatam um caso de pneumonia eosinofílica crônica em um paciente de 59 anos de idade, do sexo masculino, com febre e tosse seca há 15 dias. Na história pregressa havia tabagismo e asma de início há 12 anos. A radiografia do tórax mostrou opacidades homogêneas periféricas nos terços superiores. A tomografia computadorizada do tórax demonstrava consolidaçöes periféricas com broncogramas aéreos na periferia dos lobos superiores dos pulmöes. O paciente foi submetido a biópsia "a céu aberto", com diagnóstico histológico de processo intersticial difuso com predomínio de eosinófilos. O paciente foi tratado com corticosteróides, observando-se normalizaçäo dos exames radiológicos após 20 dias


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Doenças Pulmonares Intersticiais , Eosinofilia Pulmonar , Asma , Doença Crônica , Eosinófilos , Prednisona/uso terapêutico , Eosinofilia Pulmonar/tratamento farmacológico , Radiografia Torácica , Fumar , Tomografia Computadorizada por Raios X
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