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Effects Of Lactic Acidosis

Metformin And Fatal Lactic Acidosis

Metformin And Fatal Lactic Acidosis

Publications Published: July 1998 Information on this subject has been updated. Read the most recent information. Dr P Pillans,former Medical Assessor, Centre for Adverse Reactions Monitoring (CARM), Dunedin Metformin is a useful anti-hyperglycaemic agent but significant mortality is associated with drug-induced lactic acidosis. Significant renal and hepatic disease, alcoholism and conditions associated with hypoxia (eg. cardiac and pulmonary disease, surgery) are contraindications to the use of metformin. Other risk factors for metformin-induced lactic acidosis are sepsis, dehydration, high dosages and increasing age. Metformin remains a major reported cause of drug-associated mortality in New Zealand. Of the 12 cases of lactic acidosis associated with metformin reported to CARM since 1977, 2 occurred in the last year and 8 cases had a fatal outcome. Metformin useful but small risk of potentially fatal lactic acidosis Metformin is a useful therapeutic agent for obese non-insulin dependent diabetics and those whose glycaemia cannot be controlled by sulphonylurea monotherapy. Lactic acidosis is an uncommon but potentially fatal adverse effect. The reported frequency of lactic acidosis is 0.06 per 1000 patient-years, mostly in patients with predisposing factors.1 Examples of metformin-induced lactic acidosis cases reported to CARM include: A 69-year-old man, with renal and cardiac disease, was prescribed metformin due to failing glycaemic control on glibenclamide monotherapy. He was well for six weeks, then developed lactic acidosis and died within 3 days. Post-surgical lactic acidosis caused the death of a 70-year-old man whose metformin was not withdrawn at the time of surgery. A 56-year-old woman, with no predisposing disease, died from lactic acidosis following major Continue reading >>

Lactic Acidosis: Background, Etiology, Epidemiology

Lactic Acidosis: Background, Etiology, Epidemiology

Author: Kyle J Gunnerson, MD; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM more... In basic terms, lactic acid is the normal endpoint of the anaerobic breakdown of glucose in the tissues. The lactate exits the cells and is transported to the liver, where it is oxidized back to pyruvate and ultimately converted to glucose via the Cori cycle. In the setting of decreased tissue oxygenation, lactic acid is produced as the anaerobic cycle is utilized for energy production. With a persistent oxygen debt and overwhelming of the body's buffering abilities (whether from chronic dysfunction or excessive production), lactic acidosis ensues. [ 1 , 2 ] (See Etiology.) Lactic acid exists in 2 optical isomeric forms, L-lactate and D-lactate. L-lactate is the most commonly measured level, as it is the only form produced in human metabolism. Its excess represents increased anaerobic metabolism due to tissue hypoperfusion. (See Workup.) D-lactate is a byproduct of bacterial metabolism and may accumulate in patients with short-gut syndrome or in those with a history of gastric bypass or small-bowel resection. [ 3 ] By the turn of the 20th century, many physicians recognized that patients who are critically ill could exhibit metabolic acidosis unaccompanied by elevation of ketones or other measurable anions. In 1925, Clausen identified the accumulation of lactic acid in blood as a cause of acid-base disorder. Several decades later, Huckabee's seminal work firmly established that lactic acidosis frequently accompanies severe illnesses and that tissue hypoperfusion underlies the pathogenesis. In their classic 1976 monograph, Cohen and Woods classified the causes of lactic acidosis according to the presence or absence of adequate tissue oxygenation. (See Presentationand Differe Continue reading >>

Lactic Acidosis Clinical Presentation: History, Physical Examination

Lactic Acidosis Clinical Presentation: History, Physical Examination

Author: Kyle J Gunnerson, MD; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM more... The onset of acidosis may be rapid (ie, within minutes to hours) or progressive (ie, over a period of several days). Lactic acidosis frequently occurs during strenuous exercise in healthy people, bearing no consequence. However, development of lactic acidosis in disease states is ominous, often indicating a critical illness of recent onset. Therefore, a careful history should be obtained to evaluate the underlying pathophysiologic cause of shock that contributed to lactic acidosis. Furthermore, a detailed history of ingestion of various prescription drugs or toxins from the patient or a collateral history from the patient's family should be obtained. The clinical signs and symptoms associated with lactic acidosis are highly dependent on the underlying etiology. No distinctive features are specific for hyperlactatemia. Lactate acidosis is present in patients who are critically ill from hypovolemic, septic, or cardiogenic shock. Lactate acidosis always should be suspected in the presence of elevated anion gap metabolic acidosis. Lactic acidosis is a serious complication of antiretroviral therapy. A history of antiretroviral treatment should be obtained. Children who have a relatively mild form of congenital lactic acidosis may develop firmament metabolic acidosis during an acute illness such as respiratory infection. These patients have a deficiency in the activity of pyruvate dehydrogenase, and the stress-induced increases in the glycolytic rate may result in severe metabolic acidosis. D-lactic acidosis, a unique form of lactic acidosis, can occur in patients with jejunoileal bypass or small bowel resection causing short bowel syndrome. In these settings, the glucose and car Continue reading >>

Lactic Acidosis

Lactic Acidosis

Patient professional reference Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use. You may find one of our health articles more useful. Description Lactic acidosis is a form of metabolic acidosis due to the inadequate clearance of lactic acid from the blood. Lactate is a byproduct of anaerobic respiration and is normally cleared from the blood by the liver, kidney and skeletal muscle. Lactic acidosis occurs when the body's buffering systems are overloaded and tends to cause a pH of ≤7.25 with plasma lactate ≥5 mmol/L. It is usually caused by a state of tissue hypoperfusion and/or hypoxia. This causes pyruvic acid to be preferentially converted to lactate during anaerobic respiration. Hyperlactataemia is defined as plasma lactate >2 mmol/L. Classification Cohen and Woods devised the following system in 1976 and it is still widely used:[1] Type A: lactic acidosis occurs with clinical evidence of tissue hypoperfusion or hypoxia. Type B: lactic acidosis occurs without clinical evidence of tissue hypoperfusion or hypoxia. It is further subdivided into: Type B1: due to underlying disease. Type B2: due to effects of drugs or toxins. Type B3: due to inborn or acquired errors of metabolism. Epidemiology The prevalence is very difficult to estimate, as it occurs in critically ill patients, who are not often suitable subjects for research. It is certainly a common occurrence in patients in high-dependency areas of hospitals.[2] The incidence of symptomatic hyperlactataemia appears to be rising as a consequence of the use of antiretroviral therapy to treat HIV infection. It appears to increase in those taking stavudine (d4T) regimens.[3] Causes of lactic acid Continue reading >>

Lactic Acidosis - An Overview | Sciencedirect Topics

Lactic Acidosis - An Overview | Sciencedirect Topics

Lactic acidosis is a rare complication of malignancy and is seen in patients who have cancer with a high proliferative rate such as lymphoma, leukemia, and small cell carcinoma. Generoso G. Gascon, ... Bruce Cohen, in Textbook of Clinical Neurology (Third Edition) , 2007 Primary lactic acidosis of the neonate usually ends in death within months. In an occasional infant, the lactic acidosis becomes less severe, and the infant will develop nearly normally until adolescence, when neurodegeneration may be observed. If definite nuclear gene mutations are identified in the future in patients with primary lactic acidosis, prenatal diagnosis using chorionic villus sampling or amniocentesis should be feasible. The prognosis of the other congenital lactic acidoses depends on the underlying biochemical defectsbest with biotinidase deficiency and the gluconeogenic defects, less with PDH, PC, and Krebs' cycle defects. Ian W. Seetho, John P.H. Wilding, in Clinical Biochemistry: Metabolic and Clinical Aspects (Third Edition) , 2014 Lactic acidosis is a rare but serious complication that can occur whilst taking metformin. Lactic acidosis was more frequently reported with phenformin, another biguanide that was subsequently withdrawn in most countries in 1977 after 306 documented cases. While phenformin excretion relies upon hepatic hydroxylation (pharmacogenetically deficient in approximately 10% of Caucasians), metformin is subject to renal tubular secretion, and its excretion depends only on renal function. Lactic acidosis presents with non-specific symptoms such as lethargy, nausea, vomiting, altered level of consciousness and abdominal pain. Biochemical features of lactic acidosis are those of an elevated anion gap metabolic acidosis with high blood lactate concentrations. There ap Continue reading >>

A Side Effect You Should Know About

A Side Effect You Should Know About

The glucose-lowering medication metformin (Glucophage) could cause lactic acidosis if your kidneys and liver are not working efficiently. Lactic acidosis is when high levels build up in the blood of a substance called lactic acid — a chemical that is normally produced by your body in small amounts and removed by your liver and kidneys. The risk of lactic acidosis goes up if you: have heart failure or a lung ailment have kidney or liver problems drink alcohol heavily In these cases, you might not be able to take metformin. If you don't have one of these problems, you are at a very low risk for developing lactic acidosis from metformin. You should, however, contact your doctor immediately if you suddenly develop any of these symptoms of lactic acidosis: diarrhea fast and shallow breathing muscle pain or cramping weakness tiredness or unusual sleepiness You should also let your doctor know if you get the flu or any illness that results in severe vomiting, diarrhea, and/or fever, or if your intake of fluids becomes significantly reduced. Severe dehydration can affect your kidney or liver function and increase your risk of lactic acidosis from metformin. Continue reading >>

Lactic Acidosis: What You Need To Know

Lactic Acidosis: What You Need To Know

Lactic acidosis is a form of metabolic acidosis that begins in the kidneys. People with lactic acidosis have kidneys that are unable to remove excess acid from their body. If lactic acid builds up in the body more quickly than it can be removed, acidity levels in bodily fluids — such as blood — spike. This buildup of acid causes an imbalance in the body’s pH level, which should always be slightly alkaline instead of acidic. There are a few different types of acidosis. Lactic acid buildup occurs when there’s not enough oxygen in the muscles to break down glucose and glycogen. This is called anaerobic metabolism. There are two types of lactic acid: L-lactate and D-lactate. Most forms of lactic acidosis are caused by too much L-lactate. Lactic acidosis has many causes and can often be treated. But if left untreated, it may be life-threatening. The symptoms of lactic acidosis are typical of many health issues. If you experience any of these symptoms, you should contact your doctor immediately. Your doctor can help determine the root cause. Several symptoms of lactic acidosis represent a medical emergency: fruity-smelling breath (a possible indication of a serious complication of diabetes, called ketoacidosis) confusion jaundice (yellowing of the skin or the whites of the eyes) trouble breathing or shallow, rapid breathing If you know or suspect that you have lactic acidosis and have any of these symptoms, call 911 or go to an emergency room right away. Other lactic acidosis symptoms include: exhaustion or extreme fatigue muscle cramps or pain body weakness overall feelings of physical discomfort abdominal pain or discomfort diarrhea decrease in appetite headache rapid heart rate Lactic acidosis has a wide range of underlying causes, including carbon monoxide poisoni Continue reading >>

Metformin-related Lactic Acidosis: Case Report - Sciencedirect

Metformin-related Lactic Acidosis: Case Report - Sciencedirect

Open Access funded by Sociedad Colombiana de Anestesiologa y Reanimacin Lactic acidosis is defined as the presence of pH <7.35, blood lactate >2.0mmol/L and PaCO2 <42mmHg. However, the definition of severe lactic acidosis is controversial. The primary cause of severe lactic acidosis is shock. Although rare, metformin-related lactic acidosis is associated with a mortality as high as 50%. The treatment for metabolic acidosis, including lactic acidosis, may be specific or general, using sodium bicarbonate, trihydroxyaminomethane, carbicarb or continuous haemodiafiltration. The successful treatment of lactic acidosis depends on the control of the aetiological source. Intermittent or continuous renal replacement therapy is perfectly justified, shock being the argument for deciding which modality to use. We report a case of a male patient presenting with metformin poisoning as a result of attempted suicide, who developed lactic acidosis and multiple organ failure. The critical success factor was treatment with continuous haemodiafiltration. Definimos acidosis lctica en presencia de pH <7.35, lactato en sangre >2.0mmol/L y PaCO2 <42mmHg. Por otro lado, la definicin de acidosis lctica grave es controvertida. La causa principal de acidosis lctica grave es el estado de choque. La acidosis lctica por metformina es rara pero alcanza mortalidad del 50%. La acidosis metablica incluyendo a la acidosis lctica puede recibir tratamiento especfico o tratamiento general con bicarbonato de sodio, trihidroxiaminometano, carbicarb o hemodiafiltracin continua. El xito del tratamiento de la acidosis lctica yace en el control de la fuente etiolgica; la terapia de reemplazo renal intermitente o continua est perfectamente justificada, donde el argumento para decidir cul utilizar ser el estado de Continue reading >>

Lactic Acidosis

Lactic Acidosis

The buildup of lactic acid in the bloodstream. This medical emergency most commonly results from oxygen deprivation in the body’s tissues, impaired liver function, respiratory failure, or cardiovascular disease. It can also be caused by a class of oral diabetes drugs called biguanides, which includes metformin (brand name Glucophage). Another biguanide called phenformin was pulled from the market in the United States in 1977 because of an unacceptably high rate of lactic acidosis associated with its use. Concerns about lactic acidosis also delayed the introduction of metformin to the U.S. market until 1995, despite the fact that it had been widely used for years in other countries. There have been reports of lactic acidosis occurring in people taking metformin, and the U.S. Food and Drug Administration estimates that lactic acidosis occurs in 5 out of every 100,000 people who use metformin for any length of time. However, this risk is much lower than it was in people taking phenformin, and it is not clear whether the episodes of lactic acidosis associated with metformin have actually been due to metformin use. In fact, the lactic acidosis could have been explained by the person’s diabetes and related medical conditions. Nonetheless, diabetes experts recommend that metformin not be used in people with congestive heart failure, kidney disease, or liver disease. They also recommend that it be discontinued (at least temporarily) in people undergoing certain medical imaging tests called contrast studies. Symptoms of lactic acidosis include feeling very weak or tired or having unusual muscle pain or unusual stomach discomfort. Continue reading >>

Lactic Acidosis

Lactic Acidosis

Lactic acidosis is a medical condition characterized by the buildup of lactate (especially L-lactate) in the body, which results in an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's metabolism of lactic acid. Lactic acidosis is typically the result of an underlying acute or chronic medical condition, medication, or poisoning. The symptoms are generally attributable to these underlying causes, but may include nausea, vomiting, rapid deep breathing, and generalised weakness. The diagnosis is made on biochemical analysis of blood (often initially on arterial blood gas samples), and once confirmed, generally prompts an investigation to establish the underlying cause to treat the acidosis. In some situations, hemofiltration (purification of the blood) is temporarily required. In rare chronic forms of lactic acidosis caused by mitochondrial disease, a specific diet or dichloroacetate may be used. The prognosis of lactic acidosis depends largely on the underlying cause; in some situations (such as severe infections), it indicates an increased risk of death. Classification[edit] The Cohen-Woods classification categorizes causes of lactic acidosis as:[1] Type A: Decreased tissue oxygenation (e.g., from decreased blood flow) Type B B1: Underlying diseases (sometimes causing type A) B2: Medication or intoxication B3: Inborn error of metabolism Signs and symptoms[edit] Lactic acidosis is commonly found in people who are unwell, such as those with severe heart and/or lung disease, a severe infection with sepsis, the systemic inflammatory response syndrome due to another cause, severe physical trauma, or severe depletion of body fluids.[2] Symptoms in humans include all those of typical m Continue reading >>

Hemodynamic Consequences Of Severe Lactic Acidosis In Shock States: From Bench To Bedside

Hemodynamic Consequences Of Severe Lactic Acidosis In Shock States: From Bench To Bedside

Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside Antoine Kimmoun , Emmanuel Novy , Thomas Auchet , Nicolas Ducrocq , and Bruno Levy CHU Nancy, Service de Ranimation Mdicale Brabois, Pole Cardiovasculaire et Ranimation Mdicale, Hpital de Brabois, Vandoeuvre-les-Nancy, 54511 France Universit de Lorraine, Nancy, 54000 France INSERM U1116, Groupe Choc, Facult de Mdecine, Vandoeuvre-les-Nancy, 54511 France CHU Nancy, Service de Ranimation Mdicale Brabois, Pole Cardiovasculaire et Ranimation Mdicale, Hpital de Brabois, Vandoeuvre-les-Nancy, 54511 France Universit de Lorraine, Nancy, 54000 France CHU Nancy, Service de Ranimation Mdicale Brabois, Pole Cardiovasculaire et Ranimation Mdicale, Hpital de Brabois, Vandoeuvre-les-Nancy, 54511 France CHU Nancy, Service de Ranimation Mdicale Brabois, Pole Cardiovasculaire et Ranimation Mdicale, Hpital de Brabois, Vandoeuvre-les-Nancy, 54511 France CHU Nancy, Service de Ranimation Mdicale Brabois, Pole Cardiovasculaire et Ranimation Mdicale, Hpital de Brabois, Vandoeuvre-les-Nancy, 54511 France Universit de Lorraine, Nancy, 54000 France INSERM U1116, Groupe Choc, Facult de Mdecine, Vandoeuvre-les-Nancy, 54511 France CHU Nancy, Service de Ranimation Mdicale Brabois, Pole Cardiovasculaire et Ranimation Mdicale, Hpital de Brabois, Vandoeuvre-les-Nancy, 54511 France Universit de Lorraine, Nancy, 54000 France INSERM U1116, Groupe Choc, Facult de Mdecine, Vandoeuvre-les-Nancy, 54511 France Antoine Kimmoun, Email: [email protected] . Author information Copyright and License information Disclaimer Copyright Kimmoun et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution Continue reading >>

Lactic Acidosis: Symptoms, Causes, And Treatment

Lactic Acidosis: Symptoms, Causes, And Treatment

Lactic acidosis occurs when the body produces too much lactic acid and cannot metabolize it quickly enough. The condition can be a medical emergency. The onset of lactic acidosis might be rapid and occur within minutes or hours, or gradual, happening over a period of days. The best way to treat lactic acidosis is to find out what has caused it. Untreated lactic acidosis can result in severe and life-threatening complications. In some instances, these can escalate rapidly. It is not necessarily a medical emergency when caused by over-exercising. The prognosis for lactic acidosis will depend on its underlying cause. A blood test is used to diagnose the condition. Lactic acidosis symptoms that may indicate a medical emergency include a rapid heart rate and disorientaiton. Typically, symptoms of lactic acidosis do not stand out as distinct on their own but can be indicative of a variety of health issues. However, some symptoms known to occur in lactic acidosis indicate a medical emergency. Lactic acidosis can occur in people whose kidneys are unable to get rid of excess acid. Even when not related to just a kidney condition, some people's bodies make too much lactic acid and are unable to balance it out. Diabetes increases the risk of developing lactic acidosis. Lactic acidosis may develop in people with type 1 and 2 diabetes mellitus , especially if their diabetes is not well controlled. There have been reports of lactic acidosis in people who take metformin, which is a standard non-insulin medication for treating type 2 diabetes mellitus. However, the incidence is low, with equal to or less than 10 cases per 100,000 patient-years of using the drug, according to a 2014 report in the journal Metabolism. The incidence of lactic acidosis is higher in people with diabetes who Continue reading >>

Lactic Acidosis And Exercise: What You Need To Know

Lactic Acidosis And Exercise: What You Need To Know

Muscle ache, burning, rapid breathing, nausea, stomach pain: If you've experienced the unpleasant feeling of lactic acidosis, you likely remember it. It's temporary. It happens when too much acid builds up in your bloodstream. The most common reason it happens is intense exercise. Symptoms The symptoms may include a burning feeling in your muscles, cramps, nausea, weakness, and feeling exhausted. It's your body's way to tell you to stop what you're doing The symptoms happen in the moment. The soreness you sometimes feel in your muscles a day or two after an intense workout isn't from lactic acidosis. It's your muscles recovering from the workout you gave them. Intense Exercise. When you exercise, your body uses oxygen to break down glucose for energy. During intense exercise, there may not be enough oxygen available to complete the process, so a substance called lactate is made. Your body can convert this lactate to energy without using oxygen. But this lactate or lactic acid can build up in your bloodstream faster than you can burn it off. The point when lactic acid starts to build up is called the "lactate threshold." Some medical conditions can also bring on lactic acidosis, including: Vitamin B deficiency Shock Some drugs, including metformin, a drug used to treat diabetes, and all nucleoside reverse transcriptase inhibitor (NRTI) drugs used to treat HIV/AIDS can cause lactic acidosis. If you are on any of these medications and have any symptoms of lactic acidosis, get medical help immediately. Preventing Lactic Acidosis Begin any exercise routine gradually. Pace yourself. Don't go from being a couch potato to trying to run a marathon in a week. Start with an aerobic exercise like running or fast walking. You can build up your pace and distance slowly. Increase the Continue reading >>

Hiv And Lactic Acidosis

Hiv And Lactic Acidosis

What is lactic acidosis? Lactic acidosis is a condition caused by the buildup of lactic acid in the blood. The condition is a rare but serious side effect of some HIV medicines. HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class can cause the body to produce too much lactic acid. NRTIs can also damage the liver so that it can’t break down a molecule called lactate, leading to a buildup of lactic acid in the blood. If you are taking NRTIs, it’s important to know about lactic acidosis. Although lactic acidosis is a rare side effect of NRTIs, the condition can be life-threatening. Are there other risk factors for lactic acidosis? In addition to use of some HIV medicines, risk factors for lactic acidosis include the following: What are the symptoms of lactic acidosis? Lactic acidosis often develops gradually. Early signs of lactic acidosis can include fatigue, nausea and vomiting, stomach pain, and weight loss. These symptoms may not seem serious, but they can be the first signs of life-threatening lactic acidosis. If you are taking HIV medicines, always tell your health care provider about any symptoms that you are having—even symptoms that may not seem serious. Lactic acidosis can advance rapidly. Signs of dangerously high levels of lactate in the blood include: Above-normal heart rate Rapid breathing Jaundice (yellowing of the skin and the whites of the eyes) Muscle weakness If you are taking HIV medicines and have any of these symptoms, get medical help immediately. What tests are used to detect lactic acidosis? Tests used to diagnose lactic acidosis include: A test to measure the level of lactate in the blood Other blood tests to check the functioning of the liver What is the treatment for lactic acidosis? An HIV medicine that is ca Continue reading >>

Type B Lactic Acidosis: A Rare But Life Threatening Hematologic Emergency. A Case Illustration And Brief Review

Type B Lactic Acidosis: A Rare But Life Threatening Hematologic Emergency. A Case Illustration And Brief Review

Type B lactic acidosis: a rare but life threatening hematologic emergency. A case illustration and brief review Wederson M Claudino ,* Ajoy Dias ,* William Tse ,* and Vivek R Sharma * Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, Kentucky, USA Address correspondence to: Dr. Vivek R Sharma, Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, 529 South Jackson Street, Louisville, Kentucky 40202, USA. E-mail: [email protected] Major strides have been made in improving the treatment of medical emergencies associated with malignancies. Nonetheless, metabolic emergencies in cancer patients can often times be life-threatening. Type B lactic acidosis is a rare but potentially fatal paraneoplastic phenomenon that has been described in association with hematologic and solid malignancies and portends a poor prognosis if not rapidly recognized and treated. It is believed that this occurs as a result of cancer cells switching their glucose metabolism from an oxidative oxygen- dependent pathway towards a glycolytic phenotype, also known as the Warburg effect. Though rare, it is important to consider this entity in the differential diagnosis of type B lactic acidosis since prompt identification and treatment may help improve outcomes in this otherwise fatal process. We present a case of type B lactic acidosis in a patient with chronic lymphocytic leukemia along with a brief review of the literature. Keywords: Lactic acidosis, malignancy, hematologic emergency Otto Warburg was a German physiologist awarded a Nobel Prize in 1931 for his pioneering work with respiratory enzymes [ 1 ]. Later on, his continued investigations led to the discovery that canc Continue reading >>

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