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Can Metformin Affect Kidney Function?

Renal Side Effects Of Metformin

Renal Side Effects Of Metformin

Metformin, or Glucophage, is a drug commonly used to treat type 2 diabetes mellitus. It is available in both short and long-acting forms. RxList reports the most common side effects associated with metformin, occurring in more than 5 percent of patients using the drug, are diarrhea, nausea, vomiting, flatulence, diffuse lack of strength, headache, indigestion and abdominal discomfort. Metformin-induced renal side effects are rare but can be lethal. Video of the Day Metformin is excreted out of the body by the kidneys. When the kidneys are not functioning properly, metformin can accumulate in high concentrations which may result in lactic acidosis. Lactic acidosis is a rare, serious metabolic abnormality that occurs with uncontrolled diabetes, severe hypotension as well as high metformin levels. According to Drugs.com, metformin-induced lactic acidosis is fatal in more than 50 percent of cases and usually occurs in diabetic patients with significant kidney dysfunction. Metformin should be used with great caution in patients with chronic renal disease and should be temporarily discontinued for surgery or procedures requiring radiocontrast agents. Symptoms of lactic acidosis are usually nonspecific but may include hypothermia, hypotension and a slow heart rhythm. Lactic acidosis always mandates immediate hospitalization with intensive supportive care and usually hemodialysis. Acute Renal Failure Acute renal failure is characterized by the kidneys' inability to filter toxins out of the blood as a result of injury to the kidney. There are numerous causes of acute renal failure but one of the more common is dehydration. Gastrointestinal side effects are common with metformin therapy and significant diarrhea or vomiting, particularly when there is underlying chronic renal dise Continue reading >>

Metformin (glucophage) Side Effects & Complications

Metformin (glucophage) Side Effects & Complications

The fascinating compound called metformin was discovered nearly a century ago. Scientists realized that it could lower blood sugar in an animal model (rabbits) as early as 1929, but it wasn’t until the late 1950s that a French researcher came up with the name Glucophage (roughly translated as glucose eater). The FDA gave metformin (Glucophage) the green light for the treatment of type 2 diabetes in 1994, 36 years after it had been approved for this use in Britain. Uses of Generic Metformin: Glucophage lost its patent protection in the U.S. in 2002 and now most prescriptions are filled with generic metformin. This drug is recognized as a first line treatment to control blood sugar by improving the cells’ response to insulin and reducing the amount of sugar that the liver makes. Unlike some other oral diabetes drugs, it doesn’t lead to weight gain and may even help people get their weight under control. Starting early in 2000, sales of metformin (Glucophage) were challenged by a new class of diabetes drugs. First Avandia and then Actos challenged metformin for leadership in diabetes treatment. Avandia later lost its luster because it was linked to heart attacks and strokes. Sales of this drug are now miniscule because of tight FDA regulations. Actos is coming under increasing scrutiny as well. The drug has been banned in France and Germany because of a link to bladder cancer. The FDA has also required Actos to carry its strictest black box warning about an increased risk of congestive heart failure brought on by the drug. Newer diabetes drugs like liraglutide (Victoza), saxagliptin (Onglyza) and sitagliptin (Januvia) have become very successful. But metformin remains a mainstay of diabetes treatment. It is prescribed on its own or sometimes combined with the newer d Continue reading >>

Oncotarget | Effect Of Metformin On Kidney Function In Patients With Type 2 Diabetes Mellitus And Moderate Chronic Kidney Disease

Oncotarget | Effect Of Metformin On Kidney Function In Patients With Type 2 Diabetes Mellitus And Moderate Chronic Kidney Disease

Published in Oncotarget V9N4 , Jan 12, 2018 Effect of metformin on kidney function in patients with type 2 diabetes mellitus and moderate chronic kidney disease Wei-Hao Hsu, Pi-Jung Hsiao, Pi-Chen Lin, Szu-Chia Chen, Mei-Yueh Lee, _ Shyi-Jang Shin Metrics: PDF 164 views | HTML 141 views | ? Wei-Hao Hsu1,2, Pi-Jung Hsiao1,3, Pi-Chen Lin1, Szu-Chia Chen2,3,4,5, Mei-Yueh Lee1,2,3,4 and Shyi-Jang Shin1,3,6 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 2Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 3Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 4Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 6Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan Keywords: metformin; diabetes mellitus; chronic kidney disease; renal function decline; estimated glomerular filtration rate Received: September 12, 2017Accepted: December 04, 2017Published: December 17, 2017 Background: Impaired renal function can lead to the accumulation of metformin, and elevated concentrations of metformin have been associated with lactic acidosis. The aim of this study was to evaluate the effect of continuous metformin treatment in patients with type 2 diabetes mellitus (DM) and moderate chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 300 ml/min/1.73 m2) on renal function. Methods: A total of the 616 patients w Continue reading >>

Clinical Research Extending Metformin Use In Diabetic Kidney Disease: A Pharmacokinetic Study In Stage 4 Diabetic Nephropathy

Clinical Research Extending Metformin Use In Diabetic Kidney Disease: A Pharmacokinetic Study In Stage 4 Diabetic Nephropathy

Metformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease. In this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses of metformin, respectively. All patients underwent a first-dose pharmacokinetic profile and weekly trough metformin concentrations for the duration of 4 weeks of daily therapy. Prespecified clinical and biochemical safety endpoints of serum bicarbonate, venous pH, and serum lactate were assessed weekly. Efficacy was assessed by pre- and post-HbA1c and 72-hour capillary glucose monitoring. There was no evidence of accumulation of metformin in any cohort. There were no episodes of hyperlactatemia or metabolic acidosis and no significant change in any biochemical safety measures. Median (interquartile range) observed trough concentrations of metformin in cohorts 1, 2, and 3 were 0.083 (0.121) mg/l, 0.239 (0.603) mg/l, and 1.930 (3.110) mg/l, respectively. Average capillary glucose concentrations and mean HbA1c decreased in all cohorts. In our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes and revealed stable pharmacokinetics. Our study supports the liberalization of metformin use in this population and supports the use of metformin assays for more individualized dosing. Figure 2. Safety profile (venous lactate, bicarbonate, and pH) in all 3 cohorts across the study period. Venous lactate for patient 11 appears as a dotted line. Patients 2 and 19 commenced metformin therapy a few days Continue reading >>

Metformin In Patients With Type 2 Diabetes And Kidney Disease

Metformin In Patients With Type 2 Diabetes And Kidney Disease

Go to: Abstract Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies d Continue reading >>

Use Of Metformin In The Setting Of Mild-to-moderate Renal Insufficiency

Use Of Metformin In The Setting Of Mild-to-moderate Renal Insufficiency

ADVANTAGES OF METFORMIN There is some evidence that early treatment with metformin is associated with reduced cardiovascular morbidity and total mortality in newly diagnosed type 2 diabetic patients (4). However, the data come from a small subgroup of a much larger trial. In contrast, despite multiple trials of intensive glucose control using a variety of glucose-lowering strategies, there is a paucity of data to support specific advantages with other agents on cardiovascular outcomes (5–7). In the original UK Prospective Diabetes Study (UKPDS), 342 overweight patients with newly diagnosed diabetes were randomly assigned to metformin therapy (8). After a median period of 10 years, this subgroup experienced a 39% (P = 0.010) risk reduction for myocardial infarction and a 36% reduction for total mortality (P = 0.011) compared with conventional diet treatment. Similar benefits were not observed in those randomly assigned to sulfonylurea or insulin. In an 8.5-year posttrial monitoring study, after participants no longer were randomly assigned to their treatments, individuals originally assigned to metformin (n = 279) continued to demonstrate a reduced risk for both myocardial infarction (relative risk 33%, P = 0.005) and total mortality (relative risk 27%, P = 0.002) (9). The latter results are even more impressive when one considers that HbA1c levels in all initially randomly assigned groups had converged within 1 year of follow-up. Unlike sulfonylureas, thiazolidinediones, and insulin, metformin is weight neutral (10), which makes it an attractive choice for obese patients. Furthermore, the management of type 2 diabetes can be complicated by hypoglycemia, which can seriously limit the pursuit of glycemic control. Here, too, metformin has advantages over insulin and some Continue reading >>

Side Effects Of Metformin: What You Should Know

Side Effects Of Metformin: What You Should Know

Metformin is a prescription drug used to treat type 2 diabetes. It belongs to a class of medications called biguanides. People with type 2 diabetes have blood sugar (glucose) levels that rise higher than normal. Metformin doesn’t cure diabetes. Instead, it helps lower your blood sugar levels to a safe range. Metformin needs to be taken long-term. This may make you wonder what side effects it can cause. Metformin can cause mild and serious side effects, which are the same in men and women. Here’s what you need to know about these side effects and when you should call your doctor. Find out: Can metformin be used to treat type 1 diabetes? » Metformin causes some common side effects. These can occur when you first start taking metformin, but usually go away over time. Tell your doctor if any of these symptoms are severe or cause a problem for you. The more common side effects of metformin include: heartburn stomach pain nausea or vomiting bloating gas diarrhea constipation weight loss headache unpleasant metallic taste in mouth Lactic acidosis The most serious side effect metformin can cause is lactic acidosis. In fact, metformin has a boxed warning about this risk. A boxed warning is the most severe warning from the Food and Drug Administration (FDA). Lactic acidosis is a rare but serious problem that can occur due to a buildup of metformin in your body. It’s a medical emergency that must be treated right away in the hospital. See Precautions for factors that raise your risk of lactic acidosis. Call your doctor right away if you have any of the following symptoms of lactic acidosis. If you have trouble breathing, call 911 right away or go to the nearest emergency room. extreme tiredness weakness decreased appetite nausea vomiting trouble breathing dizziness lighthea Continue reading >>

Can Metformin Cause Kidney Problems?

Can Metformin Cause Kidney Problems?

Actually, metformin is usually not the original cause of kidney problems. However, metformin is eliminated by the kidneys and when a patient has poor kidney function, the metformin can build up in the blood and cause a rare but serious condition called lactic acidosis. Lactic acidosis affects the chemistry balance of your blood and can lead to kidney failure and other organ failure. The risk of lactic acidosis is very low and most often occurs in patients with poor kidney function - so for most patients, the benefits of metformin outweigh the risks of treatment. Most doctors will regularly perform kidney function tests to make sure the kidney is working well in patients who are taking metformin. With that said, if you are taking metformin, contact your doctor immediately if you experience unexplained weakness, muscle pain, difficulty breathing, or increased drowsiness - these can be early signs of lactic acidosis. Also, if you are taking metformin and going to receive a radiocontrast dye study or have surgery, tell your doctors that you are taking metformin - in most cases, your doctor will instruct you to temporarily stop taking metformin during these procedures to help decrease the risk of lactic acidosis. Continue Learning about Metformin Videos Important: This content reflects information from various individuals and organizations and may offer alternative or opposing points of view. It should not be used for medical advice, diagnosis or treatment. As always, you should consult with your healthcare provider about your specific health needs. Continue reading >>

Could Metformin Be Used In Patients With Diabetes And Advanced Chronic Kidney Disease?

Could Metformin Be Used In Patients With Diabetes And Advanced Chronic Kidney Disease?

Abstract Diabetes is an important cause of end stage renal failure worldwide. As renal impairment progresses, managing hyperglycaemia can prove increasingly challenging, as many medications are contra-indicated in moderate to severe renal impairment. Whilst evidence for tight glycaemic control reducing progression to renal failure in patients with established renal disease is limited, poor glycaemic control is not desirable, and is likely to lead to progressive complications. Metformin is a first-line therapy in patients with Type 2 diabetes, as it appears to be effective in reducing diabetes related end points and mortality in overweight patients. Cessation of metformin in patients with progressive renal disease may not only lead to deterioration in glucose control, but also to loss of protection from cardiovascular disease in a cohort of patients at particularly high risk. We advocate the need for further study to determine the role of metformin in patients with severe renal disease (chronic kidney disease stage 4-5), as well as patients on dialysis, or pre-/peri-renal transplantation. We explore possible roles of metformin in these circumstances, and suggest potential key areas for further study. Continue reading >>

Clinical Research Extending Metformin Use In Diabetic Kidney Disease: A Pharmacokinetic Study In Stage 4 Diabetic Nephropathy

Clinical Research Extending Metformin Use In Diabetic Kidney Disease: A Pharmacokinetic Study In Stage 4 Diabetic Nephropathy

Metformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease. In this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses of metformin, respectively. All patients underwent a first-dose pharmacokinetic profile and weekly trough metformin concentrations for the duration of 4 weeks of daily therapy. Prespecified clinical and biochemical safety endpoints of serum bicarbonate, venous pH, and serum lactate were assessed weekly. Efficacy was assessed by pre- and post-HbA1c and 72-hour capillary glucose monitoring. There was no evidence of accumulation of metformin in any cohort. There were no episodes of hyperlactatemia or metabolic acidosis and no significant change in any biochemical safety measures. Median (interquartile range) observed trough concentrations of metformin in cohorts 1, 2, and 3 were 0.083 (0.121) mg/l, 0.239 (0.603) mg/l, and 1.930 (3.110) mg/l, respectively. Average capillary glucose concentrations and mean HbA1c decreased in all cohorts. In our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes and revealed stable pharmacokinetics. Our study supports the liberalization of metformin use in this population and supports the use of metformin assays for more individualized dosing. Continue reading >>

Risks Of Metformin In Type 2 Diabetes And Chronic Kidney Disease: Lessons Learned From Taiwanese Data

Risks Of Metformin In Type 2 Diabetes And Chronic Kidney Disease: Lessons Learned From Taiwanese Data

Abstract Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction. Case series have demonstrated a high fatality rate with metformin-associated lactic acidosis (MALA), and the real-life incidence of MALA may be underestimated by observational studies and clinical trials that have excluded patients with moderate-to-advanced kidney dysfunction. A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent. This timely study, as well as historical data documenting the toxicities of other biguanides, phenformin and buformin, suggest that the recent relaxation of FDA recommendations to expand metformin use in patients with kidney dysfunction (i.e., those with estimated glomerular filtration rates ≥30 instead of our recommended ≥45 ml/min/1.73 m2) may be too liberal. In this article, we will review the history of metformin use; its pharmacology, mechanism of action, and potential toxicities; and policy-level changes in its use over time. Continue reading >>

What Are The Possible Side Effects Of Glipizide And Metformin (metaglip)?

What Are The Possible Side Effects Of Glipizide And Metformin (metaglip)?

METAGLIP™ (glipizide and metformin HCl) Tablets 2.5 mg/250 mg 2.5 mg/500 mg 5 mg/500 mg DESCRIPTION METAGLIP™ (glipizide and metformin HCl) Tablets contain 2 oral antihyperglycemic drugs used in the management of type 2 diabetes, glipizide and metformin hydrochloride. Glipizide is an oral antihyperglycemic drug of the sulfonylurea class. The chemical name for glipizide is 1-cyclohexyl-3-[[p-[2-(5-methylpyrazinecarboxamido)ethyl]phenyl]sulfonyl]urea. Glipizide is a whitish, odorless powder with a molecular formula of C21H27N5O4S, a molecular weight of 445.55 and a pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 N NaOH; it is freely soluble in dimethylformamide. The structural formula is represented below. Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide monohydrochloride) is not chemically or pharmacologically related to sulfonylureas, thiazolidinediones, or α-glucosidase inhibitors. It is a white to off-white crystalline compound with a molecular formula of C4H12ClN5 (monohydrochloride) and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is as shown: METAGLIP (glipizide and metformin) is available for oral administration in tablets containing 2.5 mg glipizide with 250 mg metformin hydrochloride, 2.5 mg glipizide with 500 mg metformin hydrochloride, and 5 mg glipizide with 500 mg metformin hydrochloride. In addition, each tablet contains the following inactive ingredients: microcrystalline cellulose, povidone, crosc Continue reading >>

Could Metformin Actually Protect The Kidneys?

Could Metformin Actually Protect The Kidneys?

The drug metformin is not recommended for people with kidney disease. For this reason, some people think that metformin causes kidney disease. But new evidence suggests that metformin might actually protect the kidneys. For many people with type 2 diabetes, metformin is a very effective drug. In everyone, the liver is a sort of “mother” organ. When blood glucose (BG) levels go down, the liver releases some glucose into the blood to make sure all the other organs get enough glucose energy to work properly. When you eat and your BG levels start going up, the liver is supposed to stop pushing all this glucose out into the bloodstream. But for some reason, in people with type 2 diabetes, like an oversolitous mother, the liver doesn’t stop feeding the bloodstream after meals. “Eat eat” I can hear it say to a bloodstream already stuffed with glucose. And this continued release of glucose into the bloodstream after meals is one reason people with type 2 go high after meals. Metformin helps to stop this process, and this is its main action. But it also reduces insulin resistance. In addition, generic metformin is pretty cheap. So overall, it’s a good drug for type 2s or even for type 1s who have developed insulin resistance. Metformin can also cause side effects, especially gastrointestinal distress. Most people find that these side effects are reduced if they start with a low dose and work up to an effective dose. Taking the drug with meals also helps. Others have found that things like yogurt and milk thistle help with the GI symptoms. The extended-release form seems to cause fewer of these problems. But for those with kidney disease, metformin is not so great. This is because metformin is excreted through the kidneys. If the kidneys aren’t functioning well, the Continue reading >>

Changes In Metformin Use In Chronic Kidney Disease

Changes In Metformin Use In Chronic Kidney Disease

Background Glucose-lowering biguanides were discovered in the 1920s. One of these was metformin (dimethylbiguanide), but it was then forgotten [1]. The first human trial on biguanides that used the name Glucophage (glucose eater) was published in 1957 [2]. In the next couple of years reports were published on phenformin [3] and buformin [4]. However, due to their association with lactic acidosis (LA), both phenformin and buformin were withdrawn from many countries. Similar concerns were raised for metformin, but it remained on the market and has been available in the UK since 1958, although it only became available in the USA in 1994. Clinical benefits in diabetes mellitus type 2 Metformin acts primarily in the liver by reducing glucose output and also by enhancing peripheral uptake of glucose, mainly in muscles. It is not generally associated with a risk of hypoglycemia unless there is excessive exercise, severe calorie reduction or when mixed with other antidiabetic medicine. There is absence of weight gain along with modest reductions in triglycerides [5]. It causes a reduction in mortality by decreasing cardiovascular complications [6]. Metformin has shown some effectiveness in polycystic ovarian syndrome, some gynecological cancers, nonalcoholic fatty liver disease and for premature puberty. However, its main role remains in the management of diabetes mellitus type 2 (DM2). The International Diabetes Federation lists it as one of the first antidiabetic medicines to be used for DM2 [7]. The World Health Organization lists it as one of two essential medicines for diabetes [8]. Fear of LA Metformin is chemically similar to phenformin, but has a different mechanism of action. Although the fear of LA remains, no absolute definitive causal relationship has been proven be Continue reading >>

Diabetes Drug Metformin Safe For Patients With Kidney Disease: Review

Diabetes Drug Metformin Safe For Patients With Kidney Disease: Review

TUESDAY, Dec. 23, 2014 (HealthDay News) -- Although metformin, the popular type 2 diabetes medication, is usually not prescribed for people with kidney disease, a new analysis shows the drug may be safer for these patients than once thought. Metformin has been used in the United States for two decades to help lower blood sugar levels among people with type 2 diabetes. The U.S. Food and Drug Administration cautions that people with kidney disease should not take the drug because it could increase their risk for a potentially serious condition called lactic acidosis. This is when lactic acid builds up in the bloodstream after oxygen levels in the body are depleted. After reviewing published research to evaluate the risks associated with metformin among people with mild to moderate kidney disease, a team of researchers led by Dr. Silvio Inzucchi, a professor of medicine at Yale University, found these patients were at no greater risk for lactic acidosis than people who were not taking the drug. "What we found is that there is essentially zero evidence that this is risky," Inzucchi, who is also medical director of the Yale Diabetes Center, said in a university news release. "The drug could be used safely, so long as kidney function is stable and not severely impaired," he said. Despite warnings, many doctors are already prescribing metformin to patients with kidney disease, the study published in the Dec. 24/31 issue of the Journal of the American Medical Association revealed. "Many in the field know that metformin can be used cautiously in patients who have mild to moderate kidney problems," Inzucchi said. "Most specialists do this all the time." Still, the researchers said their findings are significant because many doctors stop prescribing metformin once their patients g Continue reading >>

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