Occlusive Peripheral Arterial Disease
Occlusive peripheral arterial disease is common among older people because it often results from atherosclerosis, which becomes more common with age. Occlusive peripheral arterial disease may affect 15 to 20% of people older than 70. The disease is particularly common among people who have ever smoked regularly and among those who have diabetes, whether type 1 or type 2 (see Section 13, Chapter 165).
Occlusive peripheral arterial disease is also common among people who have a family history of atherosclerosis, high blood pressure, high cholesterol levels, or high homocysteine levels; people who are obese; and people who are physically inactive. Each of these conditions contributes not only to the development of occlusive peripheral arterial disease but also to the worsening of the disease.
Occlusive peripheral arterial disease may result from gradual narrowing or sudden blockage of an artery. When an artery narrows, the parts of the body it supplies may not receive enough blood. An inadequate blood supply is called ischemia. Ischemia may develop suddenly or gradually. When an artery is suddenly and completely blocked, the tissue it supplies may die.
Gradual narrowing of arteries is usually due to atherosclerosis, in which deposits of cholesterol and other fatty materials (atheromas or atherosclerotic plaques) develop in the walls of arteries. Atheromas may gradually narrow the interior (lumen) of the artery and reduce blood flow (see Section 3, Chapter 32). Also, calcium may accumulate in the atheromas, making the arteries stiff.
Less commonly, arteries are gradually narrowed by an abnormal growth of muscle in the artery's wall (fibromuscular dysplasia) or pressure from an expanding mass, such as a tumor or fluid-filled sac (cyst), outside the artery.
Sudden, complete blockage may result when a blood clot (thrombus) forms in an artery that is already narrowed. A sudden blockage may also result when a clot breaks off (becoming an embolus) from a site such as the heart or aorta, travels through the bloodstream, and lodges in an artery downstream. Some disorders increase the risk of blood clot formation. They include atrial fibrillation, other heart disorders, clotting disorders, and inflammation of blood vessels (vasculitis), which may be due to an autoimmune disorder.
Sometimes a piece of fatty material breaks off from an atheroma and suddenly blocks an artery. Sudden blockage may also result from an aortic dissection (see Section 3, Chapter 35), in which the inner layer of the aorta tears, allowing blood to surge through the tear into the middle layer. As the dissection enlarges, it can block one or more arteries connected to the aorta.
Obstructive peripheral arterial disease may also be caused by the thoracic outlet syndrome (see Section 6, Chapter 95). In this syndrome, blood vessels (as well as nerves) in the passageway between the neck and the chest become compressed.
Obstructive peripheral arterial disease can affect arteries in different parts of the body. It commonly develops in the arteries of the legs, including the main arteries of the thighs (femoral arteries), of the knees (popliteal arteries), and of the calves (tibial and peroneal arteries). Much less commonly, the disease develops in the arteries of the shoulders or arms. It may develop in the part of the aorta that passes through the abdomen (abdominal aorta) or in its branches, including the lower aorta where it divides into two branches that supply blood to the legs (common iliac arteries). The branches that supply the kidneys (renal arteries) are a relatively common site of gradual narrowing due to atherosclerosis. But sudden, complete blockage of one of the renal arteries is relatively rare. The branch that supplies the intestines (superior mesenteric artery) is also blocked less commonly. Blockage of the branches that supply the liver (hepatic artery) and spleen (splenic artery) is very rare.
Symptoms
Symptoms vary depending on which artery is affected, how completely the artery is blocked, and whether the artery is gradually narrowed or suddenly blocked. Usually, about 70% of the artery's interior has to be blocked before symptoms occur. Gradual narrowing of an artery may result in less severe symptoms than sudden blockage--even if the artery eventually becomes completely blocked. Symptoms may be less severe because gradual narrowing allows time for nearby blood vessels to expand or new blood vessels (called collateral vessels) to grow. Thus, the affected tissue can still be supplied with blood. If an artery is suddenly blocked, there is no time for collateral vessels to develop, so symptoms are usually severe.
Arteries of the Legs and Arms: Sudden, complete blockage of an artery in a leg or an arm may cause severe pain, coldness, and numbness in the affected limb. The person's leg or arm is either pale or bluish (cyanotic). No pulse can be felt below the blockage. The sudden, drastic decrease in blood flow to the limb is a medical emergency. The absence of blood flow can quickly result in loss of sensation in or paralysis of a limb.
Intermittent claudication, the most common symptom of peripheral arterial disease, results from gradual narrowing of a leg artery. It is a painful, aching, cramping, or tired feeling in the muscles of the leg--not in the joints. Intermittent claudication occurs regularly and predictably during physical activity but is always relieved promptly by rest. The muscles ache when a person walks, and the pain begins more quickly and is more severe when the person walks quickly or uphill. Usually, after 1 to 5 minutes of rest (sitting is not necessary), the person can walk the same distance already covered, although continued walking will again provoke the pain at a comparable distance. Most commonly, the pain occurs in the calf, but it can also occur in the thigh, hip, or buttock, depending on the location of the blockage. Very rarely, pain occurs in the foot.
As a leg artery is narrowed further, the distance a person can walk without pain decreases. Eventually, as the disease becomes very severe, leg muscles may ache even at rest, especially when the person is lying down. Such pain usually begins in the lower leg or front of the foot, is severe and unrelenting, and worsens when the leg is elevated. The pain often interferes with sleep. For relief, the person may hang the feet over the side of the bed or rest sitting up with the legs hanging down.
Large blockages of the arm arteries, which are rare, may cause fatigue, cramping, or pain felt in the arm muscles when the arm is used repeatedly.
When the blood supply is only mildly or moderately reduced, the leg or arm may look almost normal. When the blood supply to a foot is severely reduced, the foot may be cold. The skin of the foot or leg may be dry, scaly, shiny, or cracked. Nails may not grow normally, and the hair on the limb may not grow. As the artery is narrowed further, a person may develop sores that do not easily heal, typically on the toes or heel and occasionally on the lower leg, especially after an injury. Infections occur easily and become serious quickly. In people with severe occlusive peripheral arterial disease, wounds in the skin may take weeks or months to heal or may not heal. Foot ulcers may develop. Leg muscles usually shrink (atrophy). A large blockage may cause gangrene.
In some people who have had predictable, stable claudication, claudication can suddenly worsen. For example, calf pain that occurs after walking 10 blocks may suddenly occur after walking one block. This change may indicate that a new clot has formed in a leg artery. Such people should be evaluated by a specialist as soon as possible.
Lower Aorta and Common Iliac Arteries: Sudden blockage of the lower aorta where it divides into the common iliac arteries causes both legs to suddenly become painful, pale, and cold. No pulse can be felt in the legs, which may become numb.
Gradual narrowing of the lower aorta or of both common iliac arteries can cause intermittent claudication that affects the buttocks and thighs of both legs. The legs may also feel cold or appear pale, although they usually appear normal. This combination of symptoms is sometimes called Leriche's syndrome. Leriche's syndrome usually occurs in men and commonly also causes impotence (erectile dysfunction).
Renal Arteries: Sudden, complete blockage of one of the renal arteries, which supply the kidneys, may cause a sudden pain in the side, and the urine may become bloody. These symptoms indicate a medical emergency.
Gradual, moderate narrowing of one or both renal arteries may not cause symptoms or affect kidney function. More rarely, more complete narrowing of one or both renal arteries contributes to the development of kidney failure or high blood pressure (a disorder called renovascular hypertension). Less than 5% of people with high blood pressure have renovascular hypertension.
Superior Mesenteric Artery: Sudden, complete blockage of the superior mesenteric artery is a medical emergency. Initially, most people with such a blockage vomit and feel an urgent need to have a bowel movement. They may become seriously ill and have severe abdominal pain because the superior mesenteric artery supplies a large part of the intestine. The abdomen may feel tender when a doctor presses on it, but the severe abdominal pain is usually more prominent than the tenderness, which is widespread and vague. The abdomen may be slightly swollen (distended). Through a stethoscope, a doctor initially hears fewer bowel sounds in the abdomen than normal. Later, no bowel sounds can be heard. The stool initially contains small amounts of blood but soon looks bloody. Blood pressure falls, and shock may result as gangrene develops in the intestine.
 See the figure When the Blood Supply to the Intestine Is Blocked.
Gradual narrowing of the superior mesenteric artery typically causes pain about 30 to 60 minutes after each meal, because the intestine requires more blood during digestion. The pain is steady, severe, and usually centered at the navel. This pain makes people afraid to eat, so they may lose considerable weight. Because the blood supply to the intestine is reduced, nutrients may be poorly absorbed into the bloodstream, contributing to the weight loss.
Hepatic and Splenic Arteries: Blockage of the hepatic artery, which supplies the liver, or the splenic artery, which supplies the spleen, is usually not as dangerous as blockage of the major arteries that supply the intestine. However, parts of the liver or spleen may be damaged.
Diagnosis
The diagnosis of occlusive peripheral arterial disease is based on the symptoms and the results of a physical examination. Procedures that directly measure blood pressure or blood flow are also performed.
A doctor or nurse assesses each pulse, including those at the armpits, elbows, wrists, groin, and ankles and those behind the knees. The pulse in arteries beyond the blockage may be weak or absent. For example, if doctors suspect a blockage in a leg artery, they check the pulse below a certain point in the leg. (For arteries in which the pulse is inaccessible, such as the renal arteries, procedures that provide images of blood flow are performed.) A stethoscope is used to listen for abnormal sounds caused by turbulent blood flow through a narrowed artery (bruits). Doctors examine the skin of the limbs, noting the color and temperature and pressing gently to see how quickly color returns after pressure is removed. These observations can help doctors determine whether circulation is adequate.
Most of the procedures used in the diagnosis of peripheral arterial disease are noninvasive and can be performed in a doctor's office or in a hospital on an outpatient basis. Most commonly, a standard blood pressure cuff and a special electronic stethoscope are used to measure the systolic blood pressure in both arms and both legs. If blood pressure in the ankle is lower than that in the arms by a certain amount, blood flow to the legs is inadequate, and occlusive peripheral arterial disease is diagnosed. If doctors suspect a blockage in an arm artery, they measure systolic blood pressure in both arms. Pressure that is consistently higher in one arm suggests a blockage in the arm with lower blood pressure, and occlusive peripheral arterial disease is diagnosed. However, the blood pressure measurement is not always accurate in people who have arteries stiffened by calcium deposits or in those who have had diabetes for a long time.
Doppler ultrasonography (see Section 3, Chapter 21) can be used to directly measure blood flow and can confirm the diagnosis of occlusive peripheral arterial disease. This procedure can accurately detect narrowing or blockage of blood vessels. Color Doppler is useful because it shows different rates of blood flow in different colors. Doppler ultrasonography to measure blood flow may be performed during exercise stress testing (see Section 3, Chapter 21), because some problems appear only during exercise. X-rays and other noninvasive procedures (for example, procedures to evaluate blood flow or to measure the amount of oxygen in the blood) may be performed.
Usually, angiography (see Section 3, Chapter 21), an invasive procedure, is performed only after the need for surgery or angioplasty has been established. In such cases, its purpose is to provide doctors with clear images of the affected arteries before surgery or angioplasty is performed. Rarely, angiography is needed to determine whether surgery or angioplasty is possible. In angiography, a radiopaque dye, which can be seen on x-rays, is injected into an artery. The dye outlines the artery. Thus angiography can show the precise diameter of the artery and is more accurate than Doppler ultrasonography in detecting some blockages. Alternatively, digital subtraction angiography may be used. It uses a computer to enhance images, so that less dye is needed. Thus, the procedure may be safer and cause less discomfort than standard angiography. At some medical centers, a less invasive type of angiography can be performed with spiral computed tomography (called CT angiography) or with a type of magnetic resonance imaging (called magnetic resonance angiography, or MRA (see Section 3, Chapter 21)).
For people with atherosclerosis, doctors try to identify risk factors, such as high levels of cholesterol, sugar, and homocysteine and high blood pressure. Blood tests are performed to measure levels of cholesterol, sugar, and, occasionally, homocysteine. Blood pressure is measured on more than one occasion to determine if it is consistently high.
Blood tests may be performed to identify other causes of narrowed or blocked arteries, such as inflammation of blood vessels due to an autoimmune disorder. Such procedures include the erythrocyte sedimentation rate (ESR) and tests for C-reactive protein, which is produced only when inflammation is present. For blockage of an arm artery, doctors try to determine if the cause is atherosclerosis, thoracic outlet syndrome, or arteritis.
Doctors must rule out spinal stenosis (narrowing of the spinal canal), which can also produce pain during physical activity. However, this pain, unlike intermittent claudication, is not relieved by rest.
Prevention
The best way to help prevent occlusive peripheral arterial disease is to modify or eliminate risk factors for atherosclerosis (see Section 3, Chapter 32 and Section 3, Chapter 33). Prevention includes quitting smoking; controlling diabetes; lowering high blood pressure, high cholesterol levels, and high homocysteine levels; losing weight; and engaging in regular physical activity. Good control of diabetes helps delay or prevent the development of occlusive peripheral arterial disease and reduce the risk of other complications (see Section 3, Chapter 33).
Treatment
The aims of treatment are to prevent the disease from progressing; to reduce the risk of heart attack, stroke, and death due to widespread atherosclerosis; to prevent amputation; and to improve the quality of life by relieving symptoms (such as intermittent claudication). Treatments include drugs such as those that relieve claudication and those that cause clots to dissolve (thrombolytic drugs (see Section 3, Chapter 33)), angioplasty, surgery, and other measures, such as exercise and foot care. Which treatments are used depends on the severity of the symptoms, the severity and location of the blockage, the risks related to the treatment (particularly for surgery), and the overall health of the person. Regardless of the specific treatments used, people still need to modify risk factors for atherosclerosis to improve their overall prognosis. Angioplasty and surgery are only mechanical measures for correcting the immediate problem. They do not cure the underlying disease.
Angioplasty is often performed immediately after angiography. Angioplasty may be performed to relieve symptoms and thus postpone or avoid surgery. Sometimes it is used in combination with surgery. Angioplasty consists of inserting a catheter with a balloon at its tip into the narrowed part of the artery and then inflating the balloon to clear the blockage (see Section 3, Chapter 33). To keep the artery open, doctors may insert a permanent wire mesh (a stent) into the artery. Angioplasty is usually performed as an outpatient procedure. Angioplasty is rarely painful but may be somewhat uncomfortable because the person has to lie still on a hard table. A mild sedative, but no general anesthetic, is given.
The success of angioplasty varies, depending on the location of the blockage and the severity of peripheral arterial disease. Afterward, the person is given an antiplatelet drug (such as aspirin or clopidogrel) to help prevent clots from forming in the arteries of the limb and to prevent a subsequent heart attack and stroke. Also, Doppler ultrasonography is performed regularly to monitor blood flow through the artery and thus detect whether the artery is narrowing again.
Angioplasty cannot be performed successfully if too many areas of an artery are narrowed, if the narrowed section is too long, or if the artery is severely and extensively hardened. After angioplasty, surgery may be needed if a blood clot (thrombus) forms in the narrowed area, if a piece of the clot (embolus) breaks off and blocks an artery downstream, if blood seeps into the lining of the artery causing a bulge inward that blocks blood flow (a disorder called dissection), or if severe bleeding occurs.
Other devices--including lasers, mechanical cutters, ultrasonic catheters, and rotational sanders--can be used instead of a balloon catheter during angioplasty, but none appear to be more effective.
Surgery to remove blood clots (thromboendarterectomy) can be performed when thrombolytic drugs are ineffective or too dangerous. Surgery to remove atheromas (endarterectomy) or other blockages may also be performed. Alternatively, bypass surgery may be performed. In bypass surgery, a graft consisting of a tube made of a synthetic material or a part of a vein from another part of the body is joined to the blocked artery above and below the blockage. Thus, blood is rerouted around the blocked artery. Another approach is to remove the narrowed or blocked section and insert a graft in its place. Usually before surgery, doctors assess heart function and blood flow through the heart to determine the relative safety of surgery, because many people with occlusive peripheral arterial disease also have coronary artery disease.
Arteries of the Legs and Arms: For sudden, complete blockage of these arteries, surgery is performed as soon as possible to prevent irreversible loss of limb function or amputation.
 See the figure Bypass Surgery in the Leg.
For most people with intermittent claudication, exercise or drugs can relieve the pain. Exercise is the most effective treatment and may be appropriate for motivated people who can follow a prescribed daily exercise program. Exactly how exercise relieves claudication is not well understood, but exercise probably improves muscle function. There is no evidence that exercise improves blood flow or causes new (collateral) blood vessels to grow. People with claudication should walk at least 30 minutes a day at least 3 times a week, if possible. For most people, following this routine increases the distance they can walk comfortably. Discomfort felt during walking is not dangerous. When discomfort is felt, a person should stop walking until the discomfort subsides and then walk again. The total walking time (excluding rest periods) must be at least 30 minutes to improve walking distance.
Exercise is usually most effective when it is supervised by a trained therapist in a rehabilitation program. Doctors recommend that people with claudication undergo an exercise stress test (see Section 3, Chapter 21) before they begin a rehabilitation program to make sure that the blood supply to heart muscle is adequate.
People with very severe occlusive peripheral arterial disease (that is, who have pain during rest, gangrene, or wounds that do not heal) should avoid exposure to cold, which causes blood vessels to narrow (constrict), and the use of drugs that cause blood vessels to constrict. These drugs include ephedrine or pseudoephedrine, which are components of some headache and cold remedies.
Pentoxifylline or cilostazol may be used to treat claudication. These drugs may increase blood flow and thus the oxygen supply to muscles. Both drugs must be taken for 2 to 3 months to determine whether they are effective. However, the usefulness of pentoxifylline is now in doubt, and many experts no longer recommend its use. In contrast, cilostazol may result in a 50 to 100% increase in the distance that can be walked without pain. Cilostazol should not be used by people with heart failure. Drugs that cause the arteries to widen (dilate), such as calcium channel blockers, may be used, but they have not been shown to relieve claudication. The dietary supplements carnitine and ginkgo (see Section 2, Chapter 19) have been reported to relieve claudication. However, compared with prescribed drugs, these supplements have only a small effect.
Aspirin or clopidogrel is usually given because these drugs help prevent clot formation and reduce the risk of heart attack or stroke. They modify platelets so that they do not adhere to blood vessel walls. Normally, platelets, which circulate in the blood, gather and form a clot to stop bleeding when a blood vessel is injured.
Surgery to remove the blockage or bypass surgery may be performed if other treatments do not relieve claudication. Surgery is usually performed to avoid amputation of a leg when blood flow is greatly reduced--that is, when claudication is incapacitating or occurs during rest, when wounds do not heal, or when gangrene develops.
Good foot care is important. It helps prevent wounds or foot ulcers from becoming infected and painful or resulting in gangrene. Good foot care also helps prevent amputation. Foot ulcers require meticulous care. Such care is needed to treat infection, to protect the skin from further damage, and to enable the person to continue to walk.
A foot ulcer must be kept clean: It should be washed daily with a mild soap or antibacterial solution and covered daily with clean, dry dressings. The legs should be kept below the level of the heart to help improve blood flow. People with diabetes must control blood sugar levels as well as possible. As a rule, anyone with poor circulation to the feet or with diabetes should have a doctor check a foot ulcer that is not healing after about 7 days. Often, a doctor prescribes an antibiotic ointment.
If foot ulcers are not healing, a person may need complete bed rest. If bed rest is required, bandages with heel pads or foam-rubber booties should be worn to prevent bedsores (pressure sores) from developing on the feet. The head of the bed should be raised 6 to 8 inches and the legs kept at or below heart level, so that gravity helps blood flow through the arteries. If the ulcer is infected, doctors usually prescribe antibiotics to be taken by mouth, and the person may need to be hospitalized.
Rarely, amputation of the leg is required to remove infected tissue, relieve unrelenting pain, or stop worsening gangrene. Surgeons remove as little of the leg as possible. Preserving the knee is particularly important if the person plans to wear an artificial leg. Rehabilitation after leg amputation is important (see Section 1, Chapter 7).
 See the sidebar Performing Foot Care.
Lower Aorta and Common Iliac Arteries: For sudden, complete blockage of the lower aorta and common iliac arteries, surgery is performed immediately.
Renal Arteries: For sudden, complete blockage of a renal artery, angioplasty or surgery, if performed promptly, can restore blood flow and kidney function.
For gradual, moderate blockage of a renal artery, no specific treatment is required as long as blood pressure is controlled and blood tests indicate that the kidneys are functioning adequately. If renovascular hypertension develops, antihypertensives (see Section 3, Chapter 22) are used. Often, at least three antihypertensives are needed. Angiotensin-converting enzyme (ACE) inhibitors are particularly useful; however, kidney function must be monitored when these drugs are used. If renovascular hypertension persists and is severe or if kidney function is deteriorating, doctors may perform angioplasty or bypass surgery to restore blood flow to the kidney.
Superior Mesenteric Artery: If the superior mesenteric artery is suddenly and completely blocked, only immediate surgery can restore the blood supply fast enough to save the person's life. Whether a person survives and whether the intestine can be saved depends on how fast the blood supply is restored. To save precious time, doctors may send a person for surgery without even taking x-rays.
If the superior mesenteric artery has gradually narrowed, nitroglycerin may relieve the abdominal pain, but angioplasty or surgery is needed to widen the artery. Doppler ultrasonography and angiography can determine how narrow the artery is and help doctors decide whether to operate.
Hepatic and Splenic Arteries: Surgery is needed to clear a blockage of the hepatic or splenic artery.
Buerger's Disease
Buerger's disease (thromboangiitis obliterans) is inflammation and subsequent blockage of small and medium-sized arteries of the legs or arms.
Buerger's disease is a rare disease that usually develops in smokers, most commonly in men aged 20 to 40. Buerger's disease was once considered a man's disease, but it is becoming increasingly common among women. Now, about one third of people with the disease are women, perhaps because more women are smoking.
How cigarette smoking relates to Buerger's disease is poorly understood, and what causes the disease is unknown. One theory is that smoking triggers inflammation and constriction of arteries. However, only a small number of smokers develop Buerger's disease; some people may be more susceptible than others for as yet unknown reasons. Nonetheless, Buerger's disease invariably worsens in people who continue to smoke, and amputation is commonly required. In contrast, if people with Buerger's disease quit smoking, amputation is rarely required.
Symptoms
Usually, symptoms of a reduced blood supply to the arms or legs--coldness, numbness, tingling, a burning sensation, or pain--develop gradually. These abnormal sensations start at the fingertips or toes and progress up the legs or arms. The legs are affected more often than the arms. People with Buerger's disease may feel abnormal sensations before their doctor sees any skin changes indicating an inadequate blood supply (ischemia) or gangrene. Raynaud's phenomenon (see Section 3, Chapter 34) and muscle discomfort during exertion (intermittent claudication (see Section 3, Chapter 34)) may develop. Cramps occur in the calf muscles or feet if the legs are affected and in the hands or forearms if the arms are affected.
As the disease progresses, cramps become more painful and last longer. Late in the disease, skin ulcers, gangrene, or both may appear, usually on one or more toes or fingers. The foot or hand feels cold and may turn bluish, probably because blood flow is greatly reduced.
A small percentage of people with this disease also have episodes of inflammation in the veins (migratory phlebitis), usually in the superficial veins.
Diagnosis
Usually, doctors suspect Buerger's disease on the basis of symptoms and results of the physical examination. In most people with Buerger's disease, the pulse is weak or absent in one or more arteries of the feet or wrists. Often, the affected hands, feet, fingers, or toes become pale when raised above the heart and red when lowered.
Ultrasonography detects a substantial decrease in blood pressure and blood flow in the affected feet, toes, hands, and fingers. Angiography (see Section 3, Chapter 21) can detect specific patterns of narrowing and thus can help confirm the diagnosis of Buerger's disease. Sometimes a biopsy (removal of a tissue sample for examination under a microscope) of the affected artery or referral to a specialist is needed to confirm the diagnosis.
Treatment
A person with Buerger's disease must stop smoking immediately, or symptoms will relentlessly worsen. Amputation is then likely to become necessary. Exposure to cold, which causes blood vessels to narrow (constrict), and use of certain drugs should be avoided. These drugs include those that cause blood vessels to constrict (such as ephedrine or pseudoephedrine, which are components of some headache and cold remedies) and those that increase the tendency of blood to clot (such as estrogen). Care should be taken to prevent any injury to the affected limb, including burns and injuries from cold or minor surgery (such as trimming calluses). Corns and calluses should be treated by a podiatrist. Wearing shoes that fit well and have wide toe spaces can help prevent injury to the feet.
For people who quit smoking but still have blocked arteries, surgeons may perform bypass surgery in an attempt to avoid amputation. Alternatively, they may cut certain nearby nerves (a procedure called sympathectomy) to prevent blood vessels from constricting. These procedures are seldom performed, because they usually improve blood flow only temporarily.
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