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1.
J Nephrol ; 36(7): 2047-2056, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37768547

RESUMO

BACKGROUND: Diuretics can reduce fluid overload but their effects on conditions of dialysis start remain elusive. We aimed to determine whether loop diuretics exposure in the year before inception can delay the need for dialysis, affect the conditions of dialysis start, and cause early mortality three months after initiation in pre-dialysis patients. METHODS: All adult patients starting dialysis from 2009 to 2015 in the REIN registry were included. Three subgroups were defined according to diuretics exposure: "continuous", "stopped", or "no diuretics" over the year before inception and compared for pre-dialysis hospitalization rates, and 3-month mortality after dialysis. RESULTS: Among 59,302 patients, we found fewer emergency initiations of dialysis in the continuous diuretics group than in the stopped diuretics and no diuretics groups: 9492 (27.5%) vs 1905 (32.3%) and 5226 (35.0%), respectively; p < 0.0001. In the continuous diuretics group, there were fewer starts on central venous catheters than in the stopped diuretics and no diuretics groups: 16,677 (49.4%) vs. 3246 (56.0%) vs. 8,639 (58.4%); p < 0.0001. Patients with continuous diuretic exposure had a lower hospitalization rate than the stopped diuretics group in the year prior to dialysis, except for heart failure. The unadjusted 3-month hazard ratio of mortality after dialysis inception was significantly higher in the "no diuretics" or "stopped diuretics" groups compared with "continuous diuretics", but the excess of risk was blunted after adjustment for emergency start and pre-dialysis visits to a nephrologist. CONCLUSION: Continuous loop diuretics exposure in the year before dialysis was associated with better conditions of dialysis inception, and possibly lower mortality rates in the three months after inception.


Assuntos
Insuficiência Cardíaca , Insuficiência Renal Crônica , Adulto , Humanos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Diálise , Diuréticos/efeitos adversos , Estudos de Coortes , Insuficiência Cardíaca/terapia
2.
Kidney Int Rep ; 7(5): 1049-1061, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35571001

RESUMO

Introduction: Incremental hemodialysis (iHD) may attenuate "dialysis shock" and reduce costs, preserving quality of life. It is considered difficult to reconcile with HD wards' routine; fear of underdialysis and increasing mortality are additional concerns. The aim of this study was to evaluate mortality, morbidity, and costs in a large HD ward where iHD is the standard of HD start. Methods: This observational study included all incident HD patients in 2017 to 2021, stratified according to HD start: iHD (1-2 sessions/wk), decremental HD (dHD, 3 sessions/wk at start, later reduced), or standard (3 sessions/wk). Results were compared with data recorded in the same unit before the incremental program (2015-2017) and with a propensity score-matched cohort from the French Renal Epidemiology and Information Network (REIN) registry. Results: A total of 158 patients started HD in 2017 to 2021, 57.6% on iHD, 8.9% dHD, and 33.5% standard HD schedule. Patients on the standard schedule had lower initial estimated glomerular filtration rate (eGFR) (5 vs. 7 ml/min per 1.72 m2, P = 0.003). We found no survival differences according to period of start (same center) and propensity score matching (REIN). Patients intensively followed in the pre-HD period were more likely to start on iHD-dHD. Persistence on iHD-dHD was about 50% at 1 year and 35% at 2 years. Hospitalization rates and time to first hospitalization or death did not differ between the schedules. The iHD-dHD policy allowed a 16% cost saving, even accounting for supplemental biochemical tests. Conclusion: Our study reveals that iHD can be a new standard of care, as it is safe and feasible in up to two-thirds of patients on incident HD.

3.
Clin J Am Soc Nephrol ; 16(11): 1665-1675, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34750159

RESUMO

BACKGROUND AND OBJECTIVES: Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation. RESULTS: In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation (P=0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse. CONCLUSIONS: The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3.


Assuntos
Doenças Cardiovasculares/epidemiologia , Granulomatose com Poliangiite/tratamento farmacológico , Infecções/epidemiologia , Poliangiite Microscópica/tratamento farmacológico , Neoplasias/epidemiologia , Insuficiência Renal Crônica/terapia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/metabolismo , Causas de Morte , Feminino , Seguimentos , França/epidemiologia , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/mortalidade , Humanos , Imunossupressores/uso terapêutico , Incidência , Infecções/mortalidade , Transplante de Rim , Masculino , Poliangiite Microscópica/complicações , Poliangiite Microscópica/mortalidade , Pessoa de Meia-Idade , Neoplasias/mortalidade , Intervalo Livre de Progressão , Recidiva , Sistema de Registros , Indução de Remissão , Diálise Renal , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Taxa de Sobrevida
4.
Trials ; 22(1): 364, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034786

RESUMO

BACKGROUND: Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength. METHODS/DESIGN: VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient's autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective. DISCUSSION: In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient's muscle strength. TRIAL REGISTRATION: ClinicalTrials.gov NCT04262934 . Registered on 10 February 2020 - Retrospectively registered.


Assuntos
Colecalciferol , Deficiência de Vitamina D , Idoso , Colecalciferol/efeitos adversos , Suplementos Nutricionais , Força da Mão , Humanos , Metanálise como Assunto , Estudos Multicêntricos como Assunto , Força Muscular , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal , Vitamina D , Deficiência de Vitamina D/diagnóstico
6.
JACC Clin Electrophysiol ; 4(3): 397-408, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-30089568

RESUMO

OBJECTIVES: The aim of this study was to identify using implantable loop recorder (ILR) monitoring the mechanisms leading to sudden death (SD) in patients undergoing hemodialysis (HD). BACKGROUND: SD accounts for 11% to 25% of death in HD patients. METHODS: Continuous rhythm monitoring was performed using the remote monitoring capability of the ILR device in patients undergoing HD at 8 centers. Clinical, biological, and technical HD parameters were recorded and analyzed. RESULTS: Seventy-one patients (mean age 65 ± 9 years, 73% men) were included. Left ventricular ejection fraction was <50% in 16%. Twelve patients (17%) had histories of atrial fibrillation or flutter at inclusion. During a mean follow-up period of 21.3 ± 6.9 months, 16 patients died (14% patient-years), 7 (44%) of cardiovascular causes. Four SDs occurred, with progressive bradycardia followed by asystole. The incidence of patients presenting with significant conduction disorder and with ventricular arrhythmia was 14% and 9% patient-years, respectively. In multivariate survival frailty analyses, a higher risk for conduction disorder was associated with plasma potassium >5.0 mmol/l, bicarbonate <22 mmol/l, hemoglobin >11.5 g/dl, pre-HD systolic blood pressure >140 mm Hg, the longer interdialytic period, history of coronary artery disease, previous other arrhythmias, and diabetes mellitus. A higher risk for ventricular arrhythmia was associated with potassium <4.0 mmol/l, no antiarrhythmic drugs, and previous other arrhythmias. With ILR monitoring, de novo atrial fibrillation or flutter was diagnosed in 14 patients (20%). CONCLUSIONS: ILR may be considered in HD patients prone to significant conduction disorders, ventricular arrhythmia, or atrial fibrillation or flutter to allow early identification and initiation of adequate treatment. Therapeutic strategies reducing serum potassium variability could decrease the rate of SD in these patients. (Implantable Loop Recorder in Hemodialysis Patients [RYTHMODIAL]; NCT01252823).


Assuntos
Arritmias Cardíacas/diagnóstico , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia Ambulatorial/instrumentação , Diálise Renal/efeitos adversos , Idoso , Eletrodos Implantados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Eur J Emerg Med ; 25(2): 110-113, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28338532

RESUMO

OBJECTIVE: Severe hypercalcemia is often considered an emergency because of a potential risk of cardiac arrest or coma. However, there is little evidence to support this. The aim of our study was to assess whether severe hypercalcemia (Ca>4 mmol/l or 16 mg/dl) was associated with immediately life-threatening cardiac arrhythmias or neurological complications in patients admitted to the Emergency Department (ED). METHODS: A retrospective observational study was carried out over a 5-year period (2008-2012). Eligible patients were admitted to the Adult Emergency Department of Nantes University Hospital and had a calcium concentration in excess of 4 mmol/l. There were no exclusion criteria. The primary outcome was the number of life-threatening cardiac arrhythmias and/or neurological complications during the stay in the ED. The secondary outcomes were correlation between calcium concentrations/ECG QTc intervals and mortality. RESULTS: A total of 126 204 adult patients had calcium concentrations measured. Thirty one (0.025%) patients had severe hypercalcemia as defined in our study. The median calcium concentration was 4.3 mmol/l (Q1, 4.2; Q3, 4.7) and the median albumin-adjusted calcium concentration was 4.3 mmol/l (Q1, 4.1; Q3, 4.7). No patient presented with a life-threatening cardiac event during stay in the ED. The median ED stay was 7 h 32 min. One patient presented with a coma of multifactorial origin. There was no correlation between calcemia and QTc intervals (P=0.60). Mortality at 1 year was 55% (17 patients). CONCLUSION: We found no cases of immediately life-threatening cardiac arrhythmias or neurological complications associated with hypercalcemia above 4 mmol/l over a 5-year period in a large tertiary ED.


Assuntos
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidade , Cálcio/sangue , Serviço Hospitalar de Emergência , Hipercalcemia/complicações , Índice de Gravidade de Doença , Arritmias Cardíacas/etiologia , Feminino , França , Humanos , Hipercalcemia/sangue , Hipercalcemia/diagnóstico , Masculino , Estudos Retrospectivos , Fatores de Risco
8.
Am J Hum Genet ; 98(6): 1193-1207, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-27259053

RESUMO

Autosomal-dominant polycystic kidney disease (ADPKD) is a common, progressive, adult-onset disease that is an important cause of end-stage renal disease (ESRD), which requires transplantation or dialysis. Mutations in PKD1 or PKD2 (∼85% and ∼15% of resolved cases, respectively) are the known causes of ADPKD. Extrarenal manifestations include an increased level of intracranial aneurysms and polycystic liver disease (PLD), which can be severe and associated with significant morbidity. Autosomal-dominant PLD (ADPLD) with no or very few renal cysts is a separate disorder caused by PRKCSH, SEC63, or LRP5 mutations. After screening, 7%-10% of ADPKD-affected and ∼50% of ADPLD-affected families were genetically unresolved (GUR), suggesting further genetic heterogeneity of both disorders. Whole-exome sequencing of six GUR ADPKD-affected families identified one with a missense mutation in GANAB, encoding glucosidase II subunit α (GIIα). Because PRKCSH encodes GIIß, GANAB is a strong ADPKD and ADPLD candidate gene. Sanger screening of 321 additional GUR families identified eight further likely mutations (six truncating), and a total of 20 affected individuals were identified in seven ADPKD- and two ADPLD-affected families. The phenotype was mild PKD and variable, including severe, PLD. Analysis of GANAB-null cells showed an absolute requirement of GIIα for maturation and surface and ciliary localization of the ADPKD proteins (PC1 and PC2), and reduced mature PC1 was seen in GANAB(+/-) cells. PC1 surface localization in GANAB(-/-) cells was rescued by wild-type, but not mutant, GIIα. Overall, we show that GANAB mutations cause ADPKD and ADPLD and that the cystogenesis is most likely driven by defects in PC1 maturation.


Assuntos
Cistos/genética , Hepatopatias/genética , Mutação/genética , Rim Policístico Autossômico Dominante/genética , alfa-Glucosidases/genética , Adulto , Idoso , Sequência de Aminoácidos , Sistemas CRISPR-Cas , Células Cultivadas , Criança , Feminino , Imunofluorescência , Humanos , Imunoprecipitação , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Linhagem , Rim Policístico Autossômico Dominante/patologia , Homologia de Sequência de Aminoácidos
9.
Nephrol Dial Transplant ; 29(6): 1225-31, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24516233

RESUMO

BACKGROUND: Soluble Flt1 (sFlt1) is a potent inhibitor of vascular endothelial growth factor, secreted mainly by the placenta, endothelial cells and monocytes. Increased sFlt1 serum levels correlate with endothelial dysfunction and cardiovascular complications in dialysis patients. However, the impact of dialysis by itself on sFlt1 serum levels remains unknown. METHODS: We assessed sFlt1 kinetics during dialysis and the impact of different dialysis techniques [high-flux haemodialysis (HD), haemodiafiltration (HDF)] and heparinization procedures on sFlt1 serum levels in 48 patients on regular dialysis. RESULTS: sFlt1 serum levels increased as early as 1 min after the start of dialysis and peaked at 15 min before returning to baseline at 4 h [mean peak level 2551 pg/mL, versus 102 before dialysis (P < 0.0001)]. sFlt1 kinetics were similar with two different dialysis membranes. In contrast, when unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) were omitted during dialysis (HD or pre-dilution HDF), no significant increase in sFlt1 levels occurred. Conversely, delayed administration of LMWH (after 30 min of a heparin-free HD) induced a sharp increase in sFlt1. Similarly, when UH and LMWH were omitted and citrate-based dialysate or a heparin-coated membrane was used, sFlt1 levels remained unchanged. When heparinization procedures were the same, no difference in sFlt1 levels was noted between HD and HDF. In vitro, UH and LMWH failed to induce sFlt1 release by monocytes from controls or HD patients. These findings suggest that priming of monocytes on the extracorporeal circuit is required for heparin-induced sFlt1 release or that endothelial cells contribute to this increase. CONCLUSIONS: Our results indicate that heparin-based HD induces a major sFlt1 release, which may exacerbate the anti-angiogenic state and thus endothelial dysfunction, commonly found in dialysis patients.


Assuntos
Anticoagulantes/farmacologia , Heparina/farmacologia , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Neovascularização Fisiológica/efeitos dos fármacos , Diálise Renal , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/fisiopatologia , Feminino , Hemodiafiltração , Heparina de Baixo Peso Molecular/farmacologia , Humanos , Masculino , Membranas Artificiais , Pessoa de Meia-Idade , Gravidez , Diálise Renal/métodos , Adulto Jovem
10.
Nephrol Ther ; 8(6): 451-5, 2012 Nov.
Artigo em Francês | MEDLINE | ID: mdl-22818349

RESUMO

Luer access valves are medical devices used to reduce infectious risks by securing repetitive handling in chronic hemodialysis using central catheter. Their impact on the effectiveness of a hemodialysis session still remains poorly studied. This in vivo study aims to evaluate its effectiveness. Tego(®) and Q-Syte(®) valves were used in alternation for each patient for four weeks (428 hemodialysis sessions). The two-luer access valves have led to a significant increase in the dysfunction of the hemodialysis sessions (51.8% compared to the usual care (39.3%) (P=0.012). The analysis by sub-category suggests a heterogeneous behavior of the two devices. The Q-Syte(®) valve showed significantly more dysfunction than the Tego(®) valve or the absence of valve. However, both valve systems tested can maintain the performance of the hemodialysis session as they don't change the dose of dialysis. This study highlights that an evaluation of each device must be performed prior to their use to assess the risk-benefit balance.


Assuntos
Cateterismo Venoso Central/instrumentação , Cateteres de Demora , Diálise Renal/instrumentação , Dispositivos de Acesso Vascular , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde , Medição de Risco
12.
Presse Med ; 40(11): 1053-8, 2011 Nov.
Artigo em Francês | MEDLINE | ID: mdl-21924862

RESUMO

The prevalence of peritoneal dialysis in France remains one of the lowest in Europe in spite of official recommendations in 2008. Progress in peritoneal catheter placement and a good knowledge of the management of catheter complications are essential. A more frequent use of biocompatible solutions should achieve a better preservation of the peritoneal membrane. Such physiological peritoneal fluids seem to decrease morbidity and mortality. Best peritoneal dialysis indications are mainly young patients waiting for a kidney transplantation, old patients without malnutrition and patients with cardiac insufficiency. Objective and complete information dedicated to both peritoneal dialysis and hemodialysis is necessary, even for patients seen in emergency or unplanned or late referral patients. A pre-end-stage renal disease education program has to be mandatory. Non-medical obstacles, mainly financial, are still common so that economic incitations are necessary for the development of peritoneal dialysis. A university formation of nephrologists is now available.


Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal/métodos , Adulto , Idoso , Líquido Ascítico/fisiologia , Cateteres de Demora , Comorbidade , Soluções para Diálise/administração & dosagem , Soluções para Diálise/efeitos adversos , França , Insuficiência Cardíaca/fisiopatologia , Humanos , Falência Renal Crônica/fisiopatologia , Testes de Função Renal , Transplante de Rim/fisiologia , Educação de Pacientes como Assunto , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/estatística & dados numéricos , Doenças Renais Policísticas/complicações , Doenças Renais Policísticas/fisiopatologia , Doenças Renais Policísticas/terapia , Prognóstico , Revisão da Utilização de Recursos de Saúde
13.
Eur J Immunol ; 37(11): 3054-62, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17948274

RESUMO

We have previously shown that human monocyte-derived dendritic cells (DC) express indoleamine 2,3-dioxygenase (IDO), as well as several other enzymes of the kynurenine pathway at the mRNA level upon maturation. The tolerogenic mechanisms of this pathway remain unclear. Here we show that LPS-treated DC metabolize tryptophan as far as quinolinate. We found that IDO contributes to LPS and TNF-alpha + poly(I:C)-induced DC maturation since IDO inhibition using two different inhibitors impairs DC maturation. IDO knock-down using short-hairpin RNA also led to diminished LPS-induced maturation. In line with these results, the tryptophan-derived catabolites 3-hydroxyanthranilic acid and 3-hydroxykynurenine increased maturation of LPS-treated DC. Concerning the molecular mechanisms of this effect, IDO acts as an intermediate pathway in LPS-induced production of reactive oxygen species and NF-kappaB activation, two processes that lead to DC maturation. Finally, we show that mature DC expand CD4(+)CD25(high) regulatory T cells in an IDO-dependent manner. In conclusion, we show that IDO constitutes an intermediate pathway in DC maturation leading to expansion of CD4(+)CD25(high) regulatory T cells.


Assuntos
Células Dendríticas/enzimologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Diferenciação Celular/imunologia , Células Cultivadas , Células Dendríticas/citologia , Células Dendríticas/imunologia , Humanos , Imuno-Histoquímica , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Lipopolissacarídeos/imunologia , Teste de Cultura Mista de Linfócitos , NF-kappa B , Espécies Reativas de Oxigênio/metabolismo , Triptofano/metabolismo
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