scholarly journals Continuation of Growth Hormone (GH) Replacement in GH-Deficient Patients during Transition from Childhood to Adulthood: A Two-Year Placebo-Controlled Study

2000 ◽  
Vol 85 (5) ◽  
pp. 1874-1881 ◽  
Author(s):  
Nina Vahl ◽  
Anders Juul ◽  
Jens O. L. Jørgensen ◽  
Hans Ørskov ◽  
Niels E. Skakkebæk ◽  
...  
Keyword(s):  
Body Composition ◽  
Controlled Trial ◽  
Muscle Volume ◽  
Thigh Muscle ◽  
Controlled Study ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Double Blind ◽  
Gh Replacement ◽  
Igf I

Abstract Previous studies have demonstrated beneficial effects of GH replacement, in adults with GH deficiency (GHD), on body composition, physical fitness, and quality of life. These studies, however, concern patients with adult-onset GHD or childhood-onset (CO) patients enrolled several years after withdrawal of initial therapy. So far, the effects of continuation of GH-administration in patients with CO-GHD have not been examined. We studied a group of nineteen young adults (13 males+ 6 females; 16–26 yr old; mean age, 20.2 ± 0.65 yr) with CO-GHD, in a randomized, parallel, double-blind, placebo-controlled trial for 1 yr, followed by an open phase with GH for 1 yr. All patients received GH therapy at the start of study, and trial medication (GH/placebo) was given in a similar dose. Patients randomized to continued GH treatment exhibited no significant changes in any parameters tested, but intra- and interindividual variations in insulin-like growth factor (IGF)-I levels could suggest compliance problems. Discontinuation of GH for 1 yr resulted in a decrease in serum IGF-I, from 422.0 ± 56.8 to 147.8 ± 33.4 μg/L, in the placebo group (P = 0.003). After discontinuation of GH for 1 yr, an increase in total body fat (TBF, kg), measured by dual-energy x-ray absorptiometry scan, was seen[ placebo: 22.7 ± 2.7 to 26.5 ± 2.5 (P = 0.01); GH:16.2 ± 2.1 to 17.2 ± 2.1 (not significant)]. Resumption of GH after placebo was followed by increments in serum IGF-I (μg/L) [from 147.8 ± 33.4 to 452 ± 76 (P = 0.001)] and IGF-binding protein 3, as well as in fasting glucose (mmol/L) [4.9 ± 0.2 vs. 5.3 ± 0.2 (P = 0.03)]. After resumption of GH lean body mass (kg) increased [52.4 ± 4.9 vs. 60.7 ± 5.6 (P = 0.006)]. Likewise, resumption of GH therapy increased thigh muscle volume and thigh muscle/fat ratio, as assessed by computed tomography [muscle volume (cm2/10 mm): 118.2 ± 11.7 vs. 130.0 ± 10.9 (P = 0.002); muscle/fat ratio: 1.33 ± 0.24 vs. 1.69 ± 0.36 (P = 0.02)]. In conclusion, discontinuation of GH treatment in GHD patients, during the transition from childhood to adulthood, induces significant and potentially unfavorable changes in IGF-I and body composition, both of which are reversed after resumption of GH treatment. By contrast, continuation of GH therapy results in unaltered IGF-I and body composition. We recommend continuation of GH therapy in these patients, to be undertaken in collaboration between pediatricians and adult endocrinologists.

scholarly journals Growth Hormone Replacement Therapy Improves Body Composition and Increases Bone Metabolism in Elderly Patients with Pituitary Disease1

2000 ◽  
Vol 85 (11) ◽  
pp. 4104-4112 ◽  
Author(s):  
Rita Fernholm ◽  
Margareta Bramnert ◽  
Erik Hägg ◽  
Agneta Hilding ◽  
David J. Baylink ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Body Composition ◽  
Side Effects ◽  
Replacement Therapy ◽  
Bone Metabolism ◽  
Mineral Density ◽  
Normal Range ◽  
Gh Treatment ◽  
Gh Replacement ◽  
Igf I

Although a specific GH deficiency (GHD) syndrome in the adult and the response to GH replacement therapy are well recognized, there are few data available on the effect of GH replacement therapy in elderly GH-deficient patients. We studied the effect of GH therapy on body composition and bone mineral density measured by dual energy x-ray absorptiometry, markers for bone metabolism, insulin-like growth factors (IGFs), and IGF-binding proteins (IGFBPs) in 31 patients (6 women and 25 men; aged 60–79 yr; mean, 68 yr) with multiple pituitary hormone deficiencies. The GH response to arginine or insulin was below 3 μg/L (9 mU/L) in all subjects. They were randomized to GH (Humatrope, Eli Lilly & Co.) or placebo for 6 months, followed by 12 months of open treatment. The dose was 0.05 IU/kg·week for 1 month, and after that it was 0.1 IU/kg·week divided into daily sc injections (0.75–1.25 IU/day). There were no changes in any of the measured variables during placebo treatment. GH treatment normalized serum IGF-I in a majority of the patients and increased IGFBP-3 and -5 as well as IGFBP-4 and IGF-II to values within normal range. Lean body mass was increased, and the increase at 6 and 12 months correlated with the increase in IGF-I (r = 0.46; P = 0.010 and r = 0.54, respectively; P = 0.003). GH treatment caused a modest, but highly significant, reduction of total body fat. Mean bone mineral density was not different from that in healthy subjects of the same age and did not change during the observation period. Markers for bone formation (bone-specific alkaline phosphatase activity, osteocalcin, and procollagen I carboxyl-terminal peptide in serum) increased within the normal range, and levels were sustained throughout the study. The bone resorption marker (pyridinoline in urine) was significantly elevated for 12 months. Side-effects were mild, mostly attributed to fluid retention. In two patients with normal glucose tolerance at the start of the study, pathological glucose tolerance occurred in one patient and was impaired in one. In conclusion, elderly patients with GHD respond to replacement therapy in a similar manner as younger subjects, with an improvement in body composition and an increase in markers for bone metabolism. Side-effects are few, and elderly GHD patients can be offered treatment. As long-term risks are unknown, GH doses should be titrated to keep IGF-I within the age-related physiological range.

scholarly journals Circulating levels of incretin hormones and amylin in the fasting state and after oral glucose in GH-deficient patients before and after GH replacement: a placebo-controlled study

2000 ◽  
pp. 593-599 ◽  
Author(s):  
JO Jorgensen ◽  
AM Rosenfalck ◽  
S Fisker ◽  
B Nyholm ◽  
MS Fineman ◽  
...  
Keyword(s):  
Placebo Group ◽  
Pancreatic Beta Cells ◽  
Plasma Concentrations ◽  
Controlled Study ◽  
Oral Glucose ◽  
Fasting State ◽  
Gh Treatment ◽  
Double Blind ◽  
Gh Replacement ◽  
Before And After

OBJECTIVE: Hyperinsulinemia in association with GH excess is considered a compensatory response to insulin resistance, but the possibility of alternative insulinotropic mechanisms has not been investigated in vivo. It is also unknown how GH influences the secretion from pancreatic beta-cells of amylin, a peptide which regulates prandial glucose homeostasis and may be linked to development of beta-cell dysfunction. We therefore measured plasma concentrations of two gut insulinotropic hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin-releasing peptide (GIP), and total as well as non-glycosylated amylin, in 24 GH-deficient adults before and after 4 months of GH replacement (daily evening injections of 2 IU GH/m). DESIGN: Double-blind, placebo-controlled, parallel study. METHODS: All participants underwent an oral glucose tolerance test (OGTT) at 0 and 4 months. RESULTS: A 33% suppression of fasting GLP-1 concentrations was measured in the GH group at 4 months (P=0.02), whereas a non-significant increase occurred in the placebo group (P=0.08). Fasting levels of GIP and amylin did not change significantly after 4 months in either group. The incremental response in GLP-1 during the OGTT was significantly lower after GH treatment as compared with both baseline (P=0.02) and the response in the placebo group (P=0. 03). The stimulation of GIP secretion following OGTT was similar on all occasions. The OGTT-induced incremental response in non-glycosylated amylin was moderately elevated after GH treatment as compared with placebo (P=0.05). Plasma concentrations of glucose and insulin, both in the fasting state and after the OGTT, were higher after GH treatment, but the ratio between amylin and insulin remained unchanged. CONCLUSIONS: GH-induced hyperinsulinemia is accompanied by proportionate elevations in amylin concentrations and a blunting of gut GLP-1 secretion. The mechanisms underlying the suppression of GLP-1 remain to be elucidated.

Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes

1993 ◽  
Vol 128 (4) ◽  
pp. 313-318 ◽  
Author(s):  
Roman Deyssig ◽  
Herwig Frisch ◽  
Werner F Blum ◽  
Thomas Waldhör
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Body Fat ◽  
Fat Mass ◽  
Binding Protein ◽  
Controlled Study ◽  
Gh Treatment ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

The effect of recombinant GH on strength, body composition and endocrine parameters in power athletes was investigated in a controlled study. Twenty-two healthy, non-obese males (age 23.4±0.5 years; ideal body weight 122±3.1%, body fat 10.1±1.0%; mean±sem) were included. Probands were assigned in a double-blind manner to either GH treatment (0.09U (kg BW)−1 day−1 sc) or placebo for a period of six weeks. To exclude concurrent treatment with androgenic-anabolic steroids urine specimens were tested at regular intervals for these substances. Serum was assayed for GH, IGF-I, IGF-binding protein, insulin and thyroxine before the onset of the study and at two-weekly intervals thereafter. Maximal voluntary strength of the biceps and quadriceps muscles was measured on a strength training apparatus. Fat mass and lean body mass were derived from measurements of skinfolds at ten sites with a caliper. For final evaluation only data of those 8 and 10 subjects in the two groups who completed the study were analyzed. GH, IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group. Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated probands. There was no effect of GH treatment on maximal strength during concentric contraction of the biceps and quadriceps muscles. Body weight and body fat were not changed significantly during treatment. We conclude that the anabolic, lipolytic effect of GH therapy in adults depends on the degree of fat mass and GH deficiency. In highly trained power athletes with low fat mass there were no effects of GH treatment on strength and body composition.

scholarly journals Insulin Growth Factor-Based Dosing of Growth Hormone Therapy in Children: A Randomized, Controlled Study

2007 ◽  
Vol 92 (7) ◽  
pp. 2480-2486 ◽  
Author(s):  
Pinchas Cohen ◽  
Alan D. Rogol ◽  
Campbell P. Howard ◽  
George M. Bright ◽  
Anne-Marie Kappelgaard ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Primary Outcome Measure ◽  
Target Range ◽  
Dose Titration ◽  
Controlled Study ◽  
Growth Responses ◽  
Open Label ◽  
Gh Treatment ◽  
Short Children ◽  
Igf I

Abstract Context: Weight-based dosing of GH is the standard of care for short children, although IGF-I is thought to be the main mediator of GH actions on growth. Objective: The objective of the study was to test whether IGF-I levels achieved during GH therapy are determinants of the growth responses to GH treatment. Design: This was a 2-yr, open-label, randomized, IGF-I concentration-controlled trial. Prepubertal short children [n = 172, mean age 7.53 yr, mean height sd score (HT-SDS) −2.64] with low IGF-I levels (mean IGF-I SDS −3.56) were randomized to receive one of two GH dose-titration arms in which GH dosage was titrated to achieve an IGF-I SDS at the mean [IGF(low) group, n = 70] or the upper limit of the normal range [+2 SDS, IGF(high) group, n = 68] or to a comparison group of conventional GH dose of 40 μg/kg/d (n = 34). Setting: The study was conducted in a multicenter, outpatient setting. Primary Outcome Measure: Change in HT-SDS over 2 yr was measured. Results: One hundred forty-seven patients completed the trial. Target IGF-I levels were achieved in the dose-titration arms within 6–9 months. The changes in HT-SDS were +1.0, +1.1, and +1.6 for conventional, IGF(low), and IGF(high), respectively, with IGF(high) showing significantly greater linear growth response (P < 0.001, compared with the other two groups). The IGF(high) arm required higher doses (>2.5 times) than the IGF(low) arm, and these GH doses were highly variable (20–346 μg/kg/d). Multivariate analyses suggested that the rise in the IGF-I SDS significantly impacted height outcome along with the GH dose and the pretreatment peak-stimulated GH level. Conclusion: IGF-I-based GH dosing is clinically feasible and allows maintaining serum IGF-I concentrations within the desired target range. Titrating the GH dose to achieve higher IGF-I targets results in improved growth responses, although at higher average GH doses.

scholarly journals Effects of Growth Hormone (GH) on Ghrelin, Leptin, and Adiponectin in GH-Deficient Patients

2003 ◽  
Vol 88 (11) ◽  
pp. 5193-5198 ◽  
Author(s):  
Britt Edén Engström ◽  
Pia Burman ◽  
Camilla Holdstock ◽  
F. Anders Karlsson
Keyword(s):  
Body Composition ◽  
Body Fat ◽  
Fat Mass ◽  
Glucose Production ◽  
Serum Levels ◽  
Fat Free Mass ◽  
Metabolic Effects ◽  
Controlled Study ◽  
Gh Treatment ◽  
Igf I

Abstract Ghrelin is a recently discovered gastric peptide that increases appetite, glucose oxidation, and lipogenesis and stimulates the secretion of GH. In contrast to ghrelin, GH promotes lipolysis, glucose production, and insulin secretion. Both ghrelin and GH are suppressed by intake of nutrients, especially glucose. The role of GH in the regulation of ghrelin has not yet been established. We investigated the effect of GH on circulating levels of ghrelin in relation to its effects on glucose, insulin, body composition, and the adipocyte-derived peptides leptin and adiponectin. Thirty-six patients with adult-onset GH deficiency received recombinant human GH for 9 months in a placebo-controlled study. Body composition and fasting serum analytes were assessed at baseline and at the end of the study. The GH treatment was accompanied by increased serum levels of IGF-I, reduced body weight (−2%) and body fat (−27%), and increased serum concentrations of glucose (+10%) and insulin (+48%). Ghrelin levels decreased in 30 of 36 subjects by a mean of −29%, and leptin decreased by a mean of −24%. Adiponectin increased in the women only. The decreases in ghrelin and leptin correlated with changes in fat mass, fat-free mass, and IGF-I. The reductions in ghrelin were predicted independently of the changes in IGF-I and fat mass. It is likely that the reductions in ghrelin and leptin reflect the metabolic effects of GH on lipid mobilization and glucose production. Possibly, a suppression of ghrelin promotes loss of body fat in GH-deficient patients receiving treatment. The observed correlation between the changes in ghrelin and IGF-I may suggest that the GH/IGF-I axis has a negative feedback on ghrelin secretion.

scholarly journals Low-dose GH improves exercise capacity in adults with GH deficiency: effects of a 22-month placebo-controlled, crossover trial

2005 ◽  
Vol 153 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Jens Bollerslev ◽  
Jostein Hallén ◽  
Kristian J Fougner ◽  
Anders Palmstrøm Jørgensen ◽  
Cybele Kristo ◽  
...  
Keyword(s):  
Body Composition ◽  
Exercise Capacity ◽  
Gh Deficiency ◽  
Endurance Performance ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Positive Effects ◽  
Cholesterol Levels ◽  
Igf I

Fifty-five patients with adult-onset GH deficiency (mean age, 49 years) were enrolled in a placebo-controlled, crossover study to investigate the effects of GH therapy on exercise capacity, body composition, and quality of life (QOL). GH and placebo were administered for 9 months each, separated by a 4-month washout period. GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. The final mean daily dose of GH was 1.2 IU/day for men and 1.8 IU/day for women. Mean IGF-I concentration at baseline was higher in men than in women (95±33 vs 68±41 μg/l respectively; P < 0.04) and increased to a similar level on GH therapy. Body fat mass was reduced by 1.9±2.9 kg and lean body mass was increased by 1.8±2.8 kg (P = 0.0001 for each) with GH treatment. Total and low-density cholesterol levels decreased. Absolute maximal oxygen uptake increased by 6% (P = 0.01), relative to body weight by 9% (P = 0.004), and there was a trend toward increased endurance performance by 7% (P = 0.07). There were no significant effects on QOL. In conclusion, treatment with a low, physiologic dose of GH produced positive effects on body composition and lipids and improved exercise capacity, likely to be of clinical relevance. No changes in QOL were seen, possibly because of a good QOL at baseline.

Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study

1995 ◽  
Vol 133 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Jens OL Jørgensen ◽  
Sten B Pedersen ◽  
Jens Børglum ◽  
Jan Frystyk ◽  
Ken KY Ho ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factors ◽  
Binding Proteins ◽  
Controlled Study ◽  
Obese Women ◽  
Gh Treatment ◽  
Double Blind ◽  
Igf I ◽  
Igfbp 3 ◽  
Insulin Like Growth Factors

Jørgensen JOL, Pedersen SB, Borglum J, Frystyk J, Ho KKY, Christiansen JS, Ørskov H, Blum WF, Richelsen B. Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study. Eur J Endocrinol 1995;133:65–70. ISSN 0804–4643 Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg·kg−1 body wt·day−1) in nine obese women (mean± sem; age 30.4 ± 2.4 years; body mass index 37.0 ± 2.8kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (μg/l) levels were subnormal and increased significantly following GH (117 ± 16 (placebo) vs 434 ± 33 (GH) vs 198 ± 15 (control (p < 0.01)). By contrast, serum IGF-II (μg/l) levels were in the normal range and remained unchanged (608 ± 20 (placebo) vs 647 ± 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 ± 0.36 (placebo) vs 2.21 ± 0.25 (GH) vs 0.80 ± 0.19 (control)). In conclusion. obese subjects have low total IGF-I levels but may exhibit relatively increased free IGF-I levels due to the suppression of IGFBP-1. This presumed elevation in free IGF-1 in obesity may explain the normal levels of IGFBP-3 and IGF-II, which contrasts with classic GH deficiency. Furthermore, obese subjects are responsive to exogenous GH in terms of total IGF-I generation and normalization of the ratio between IGF-I and IGFBP-3. Finally, obesity is associated with marked elevations in GHBP levels that were unaffected by 5 weeks of GH administration. Jens OL Jørgensen, Medical Department M, Aarhus Kommunehospital, DK-8000 C, Aarhus, Denmark

scholarly journals Once/Day Provision of Essential Amino Acid Enriched Meal Replacement Improves Body Composition and Physical Function in Obese Elderly

2021 ◽  
Author(s):  
Melynda Coker ◽  
Kaylee Ladd ◽  
Zeinab Barati ◽  
Carl Murphy ◽  
Terry Bateman ◽  
...  
Keyword(s):  
Amino Acids ◽  
Body Composition ◽  
Physical Function ◽  
Body Mass ◽  
Fat Mass ◽  
Controlled Trial ◽  
Essential Amino Acids ◽  
Thigh Muscle ◽  
Meal Replacement ◽  
Double Blind

We have previously demonstrated that the acute ingestion of essential amino acids may augment net protein balance in the elderly. Using a double blind, randomized controlled trial, our objective was to compare an experimental meal replacement enriched with essential amino acids (EMR) compared to a commercial meal replacement (Optifast&reg;) provided once/day (q.d.) for four weeks on body composition and physical function in older, obese participants. Twenty-seven individuals (69&plusmn;5 yrs; body mass index of 32&plusmn;4 kg/m2) were randomly assigned to EMR (n=13) or Optifast&reg; (n=15) supplementation. Measurements of body composition, skeletal muscle cross-sectional area (CSA), intrahepatic lipid and physical function were completed pre- and post-supplementation. Body mass, fat mass, and visceral fat mass were reduced with EMR but not altered with Optifast&reg;. Thigh muscle CSA increased ( 4.1 &plusmn; 1.9 cm2, P = 0.03) with EMR but not Optifast&reg;. There was a significant increase in the distance covered during the six-minute walk test with EMR ( 21&plusmn;26 m) but no change in Optifast&reg; ( 22&plusmn;54 m). Improvements in body composition and physical function support the efficacious use of EMR-based meal replacements in the obese elderly.

scholarly journals Once-weekly Somapacitan is Effective and Well Tolerated in Adults with GH Deficiency: A Randomized Phase 3 Trial

2020 ◽  
Vol 105 (4) ◽  
pp. e1358-e1376 ◽  
Author(s):  
Gudmundur Johannsson ◽  
Murray B Gordon ◽  
Michael Højby Rasmussen ◽  
Ida Holme Håkonsson ◽  
Wolfram Karges ◽  
...  
Keyword(s):  
Body Composition ◽  
Gh Deficiency ◽  
Standard Deviation Score ◽  
Fat Percentage ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Gh Replacement ◽  
Igf I ◽  
Extension Period

Abstract Context Growth hormone (GH) replacement requires daily GH injections, which is burdensome for some adult patients with GH deficiency (AGHD). Objective To demonstrate efficacy and safety of somapacitan, a once-weekly reversible albumin-binding GH derivative, versus placebo in AGHD. Design Randomized, parallel-group, placebo-controlled (double-blind) and active-controlled (open-label) phase 3 trial, REAL 1 (NCT02229851). Setting Clinics in 17 countries. Patients Treatment-naïve patients with AGHD (n = 301 main study period, 272 extension period); 257 patients completed the trial. Interventions Patients were randomized 2:2:1 to once-weekly somapacitan, daily GH, or once-weekly placebo for 34 weeks (main period). During the 52-week extension period, patients continued treatment with somapacitan or daily GH. Main outcome measures Body composition measured using dual-energy x-ray absorptiometry (DXA). The primary endpoint was change in truncal fat percentage to week 34. Insulin-like growth factor 1 (IGF-I) standard deviation score (SDS) values were used to dose titrate. Results At 34 weeks, somapacitan significantly reduced truncal fat percentage (estimated difference: −1.53% [−2.68; −0.38]; P = 0.0090), demonstrating superiority compared with placebo, and it improved other body composition parameters (including visceral fat and lean body mass) and IGF-I SDS. At 86 weeks, improvements were maintained with both somapacitan and daily GH. Somapacitan was well tolerated, with similar adverse events (including injection-site reactions) compared with daily GH. Conclusions In AGHD patients, somapacitan administered once weekly demonstrated superiority over placebo, and the overall treatment effects and safety of somapacitan were in accordance with known effects and safety of GH replacement for up to 86 weeks of treatment. Somapacitan may provide an effective alternative to daily GH in AGHD. A short visual summary of our work is available (1).

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