In recent years, regular aerobic exercise has been popularized widely and advocated by the medical community and others because of its associated health and fitness benefits. Although considerable epidemiologic evidence suggests that chronic exercise and/or increased cardiorespiratory fitness (9) may help to protect against and treat aging-related chronic diseases, exertion-related cardiovascular and musculoskeletal complications have been reported in the medical literature and the lay press (2,13,17,39,65), suggesting that vigorous physical activity actually may precipitate untoward events in selected individuals (60). This article was written to enable physicians and allied health care workers to respond more accurately to common questions emanating from occasional disconcerting coverage in the popular press and media regarding exercise-related injuries and deaths: “Exercise can kill you; details at eleven.” These considerations should also help health fitness professionals to put these complications in proper perspective, by highlighting the associated benefits of regular aerobic exercise.
Exercise-Related Cardiovascular Events: Pathophysiological Considerations
Although numerous epidemiologic studies suggest that regular physical activity, moderate-to-high levels of cardiorespiratory fitness, expressed as metabolic equivalents (METs; 1 MET = 3.5 mL O2·kg−1·min−1), or both may help protect against the development of cardiovascular disease (CVD) and its adverse clinical sequelae, considerable evidence now indicates that acute cardiovascular events, including acute myocardial infarction (AMI), sudden cardiac death (SCD), and stroke, can be triggered by vigorous to near-maximal physical exertion (≥6 METs) (24).
Several hypotheses have been suggested as potential triggering mechanisms for plaque rupture and acute coronary thrombosis, including abrupt increases in exercise heart rate and systolic blood pressure, induced spasm in diseased artery segments, or transient alterations in coronary artery shear forces (58). An increase in platelet aggregation, which could contribute to (or even initiate) coronary thrombosis, has been reported in inactive individuals who engaged in sporadic high-intensity exercise but not in physically trained individuals (11,38).
By increasing the rate-pressure product, a key determinant of myocardial oxygen consumption, and simultaneously shortening diastole and coronary perfusion time, exercise may evoke a temporary oxygen deficiency at the subendocardial level, which is exacerbated by abrupt cessation of exercise and decreased venous return. The associated cascade of physiologic responses (Fig. 1) may trigger threatening ventricular arrhythmias that, in extreme cases, may be harbingers of ventricular tachycardia or fibrillation. In addition, signs or symptoms of myocardial ischemia (33), sodium-potassium imbalance, increased catecholamine excretion, and circulating free fatty acids also may heighten electrical instability.
To a large extent, the cause of exertion-related cardiovascular complications depends on the exerciser’s age. Atherosclerotic CVD is the most frequent autopsy finding in individuals older than 40 years who experience cardiac arrest and SCD during strenuous exercise (62). However, inherited structural cardiovascular abnormalities, including hypertrophic cardiomyopathy and malformations of the coronary arteries, are the major causes of SCD in younger athletes (45). Thus, it is the combination of vigorous physical exertion and known or occult CVD, rather than the activity per se, that seems to be the major cause of exercise-related fatalities.
Relative versus Absolute Risk: Role of Habitual Physical Activity
The relative risk for AMI and SCD during very light- to moderate-intensity activities is extremely low and similar to that at rest. In persons with known or occult CVD, vigorous physical activity, such as jogging or racquet sports, seems to be associated with a greater incidence of acute cardiovascular events compared with the risk at other times. Nearly two decades ago, the commonly held notion that vigorous physical activity can trigger AMI was substantiated strongly by two consecutive reports — one by Mittleman et al. (47) in the United States, the other by Willich et al. (67) in Germany. In each study, the researchers interviewed >1,000 patients (mostly men) within 2 wk of their hospitalization for AMI. Interviews were designed to assess the usual frequency of vigorous physical exertion, as well as the type and intensity of physical activity that preceded the onset of symptoms and AMI. Overall, the studies showed the “relative risk” of AMI during or soon after vigorous physical exertion was two to six times greater than the risk during periods of lighter activity or no exertion. However, the relative risk varied greatly depending on the patient’s usual frequency of physical activity. An interesting observation by both studies was the protective effect of regular exercise in decreasing the risk of exertion-related AMI. In the German study (67), patients who exercised less than four times and four or more times per week had relative risks of 6.9 and 1.3, respectively. The U.S. study (47) revealed that, among persons who exercised usually less than once a week, once to twice a week, three to four times a week, or five or more times per week, the relative risks were 107, 19.4, 8.6, and 2.4, respectively (Fig. 2). In other words, the likelihood of a habitually sedentary person experiencing an exertion-related AMI was nearly 50 times that encountered by persons who exercise five or more times per week. Exercising for just once or twice per week reduced the risk for exertion-related AMI by >80%.
More recently, numerous independent studies have reported that cardiovascular events can be triggered by vigorous physical activity and that the risk decreases with increasing frequencies of regular exercise and vice versa. Accordingly, the estimated relative risk (95% confidence interval (CI)) of exercise-related primary cardiac arrest, SCD, or nonfatal AMI ranges from 2.1 (95% CI = 1.1 to 3.6) to 56 (95% CI = 23 to 131) (48). Although it appears that strenuous exercise transiently increases the risk of AMI or SCD, especially in habitually sedentary persons with underlying CVD who were performing unaccustomed vigorous physical activity (60), it is important to clarify the difference between absolute risk and relative risk. The absolute risk that a nonfatal or fatal cardiovascular event will occur during or soon after vigorous physical activity has been estimated to be between 1 in 500,000 h and 1 in 2,600,000 h of exercise (24,48). Thus, isolated bouts of vigorous physical activity transiently may increase the risk of acute cardiac events; however, the absolute risk associated with each episode of exercise is extremely low.
Highly strenuous activities (i.e., vigorous-to-near-maximal physical exertion (≥60% of the oxygen uptake reserve)), especially when sudden, unaccustomed, or involving high levels of anaerobic metabolism, are more likely to be associated with acute cardiac events. In some individuals, these activities may place disproportionate cardiac demands on a diseased or susceptible heart, increasing the risk of cardiovascular complications (29). For example, racquet sports, water, downhill or cross-country skiing, marathon running, and certain highly competitive sports (e.g., basketball) seem to be associated with a greater incidence of AMI and SCD than other activities (26). The excitement of competition may increase sympathetic activity and catecholamine levels and lower the threshold for ventricular fibrillation (43). Other recreational and domestic activities that are associated with increased cardiac demands and a greater incidence of cardiovascular events include deer hunting and snow removal, both of which may involve isometric and/or heavy upper extremity exertion and substantial increases in left ventricular afterload in a cold environment (2,17,28). These responses, coupled with the body’s normal thermoregulatory responses to cold, including increased platelet aggregability and plasma viscosity, coronary spasm or vasoconstriction, and superimposed emotional/hyperadrenergic responses, may present a hazardous milieu for cardiovascular events.
Regular Exercise: Does the Cardiovascular Benefit Outweigh the Risk?
Clearly, the risk of cardiovascular complications transiently is increased during vigorous exercise compared with that at other times. This appears to be particularly true among persons with latent or known CVD who were performing unaccustomed vigorous physical activity. The “critical question,” however, is whether the cardiovascular benefits of regular exercise outweigh the risk.
To address the question, “Is vigorous exercise worth the risk?,” Siscovick et al. (57) studied the incidence of SCD during vigorous physical exertion. The relative risk of cardiac arrest during exercise compared with that at other times was 56 times greater among men with low levels of habitual activity and only 5 times greater among men with high levels of habitual activity. However, the total risk of cardiac arrest among habitually active men was only 40% of that for sedentary men. These findings support the hypothesis that vigorous physical activity both protects against and provokes cardiac events (59).
Two meta-analyses (7,54) have now shown that regular exercise participation can decrease the overall risk of cardiovascular events by up to 50%, presumably from multiple mechanisms, including anti-atherosclerotic, anti-ischemic, anti-arrhythmic, anti-thrombotic, and psychological effects (Table). Because >40% of the risk reduction associated with exercise cannot be explained by changes in conventional risk factors, Green et al. (31) proposed a cardioprotective “vascular conditioning” effect, including enhanced nitric oxide vasodilator function, improved vascular reactivity, altered vascular structure, or combinations thereof. Decreased vulnerability to arrhythmias and increased resistance to ventricular fibrillation also have been postulated to reflect exercise-related adaptations in autonomic control, including augmented vagal tone and reduced sympathetic drive. Ischemic preconditioning before coronary occlusion, at least in animal models, has been shown to reduce subsequent infarct size and/or the potential for malignant ventricular arrhythmias (8). Moreover, numerous epidemiologic and clinical studies have now shown that each 1-MET increase in cardiorespiratory fitness appears to confer an 8% to 55% reduction in mortality (25,51).
To put these data in perspective, it is important to consider that the absolute risk associated with each bout of exercise is extremely low, that the relative risk is inversely related to the habitual level of physical activity, and that the cardioprotective effects of increased physical activity and/or exercise capacity are substantial. Using data from the Onset study (47), the risk of AMI during a bout of vigorous physical exertion approximately is doubled for an individual who participates in vigorous 1-h exercise sessions ≥5 d·wk−1. Thus, during the acute exercise bout, his or her risk would approximate the level that it would have been at all times if he or she were habitually sedentary. However, over the remaining 23 h of the day, his or her risk would be up to 50% lower, highlighting the clear net benefit of regular exercise.
Recommendations to Reduce the Risk of Exercise-Related Cardiovascular Events
Recommendations to reduce potentially the risk of exertion-related cardiovascular events include (24): encourage sedentary individuals to engage in regular, brisk walking so as to move them out of the least fit, least active, “high-risk” cohort; counsel inactive individuals to avoid unaccustomed, vigorous-to-near maximal physical activity (e.g., racquet sports, water skiing, snow shoveling); advocate appropriate warm-up (3,32) and cool-down (20) procedures; promote education of warning signs/symptoms (e.g., chest pain or pressure, lightheadedness, heart palpitations/arrhythmias; unusual shortness of breath); emphasize strict adherence to prescribed training pulse rates, using perceived exertion as an adjunctive intensity modulator; use continuous or instantaneous electrocardiographic monitoring in selected coronary exercisers (27), including suspected intensity violators; minimize competition and modify recreational games to decrease the aerobic requirements and heart rate response to play (e.g., allow one bounce of the ball per side during volleyball play); and adapt the exercise to the environment.
Coronary patients can exercise safely in cold weather if proper precautions are taken. Nevertheless, inhalation of or exposure to cold air may evoke ischemic ST-segment depression, angina pectoris, or both. A cold-weather “jogging mask” or scarf over the nose and mouth may serve to attenuate signs or symptoms of myocardial ischemia in selected angina patients (37). Hyperthermic conditions may pose an even greater hazard than cold weather for cardiac patients who exercise. For example, persons who are not acclimated to heat and who are exposed to temperatures >24°C experience added heart rate increases of 1 beat·min−1·°C−1 while exercising and 2 to 4 beats·min−1·°C−1 with concomitant increased humidity (52). Accordingly, patients may need to reduce their exercise intensity in hot and/or humid conditions. Because symptomatic or silent myocardial ischemia may be highly arrhythmogenic, the target heart rate for endurance exercise should be set safely below (≥10 beats·min−1) the ischemic electrocardiographic or anginal threshold (1).
High-Volume and High-Intensity Endurance Training — Too Much of a Good Thing?
There is a wealth of epidemiologic and observational data demonstrating that regular aerobic exercise is a powerful intervention in both the prevention and treatment of many of the most common chronic diseases — obesity, diabetes, metabolic syndrome, atherosclerotic CVD, and some cancers (10,30). Blair et al. (9) reported an inverse relationship between peak METs and cardiovascular and all-cause mortality in a large cohort (n = 13,344) of healthy middle-aged subjects, but suggested simultaneously an “asymptote of gain” beyond which further improvements in cardiorespiratory fitness conveyed no additional survival benefit. This asymptote was estimated to be about 9 METs for women and 10 METs for men (Fig. 3), approximate cut points that have been substantiated recently by others (40). Blair et al. (9) concluded that the aerobic capacity values associated with the lowest death rates are attainable by most men and women who engage regularly in moderate exercise. It was further suggested that a brisk walk of 30 to 60 min each day will be sufficient to produce the fitness standard (9), that is, 9 and 10 METs for women and men, respectively. On the other hand, few data are available regarding the health outcomes in those engaged in regular training and competition at high volume and/or intensities beyond this relatively modest exercise prescription (41). Moreover, case reports and circumstantial evidence raise the possibility that more extreme exercise may have some adverse effects, potentially increasing the risk-benefit ratio.
Participation in marathon and half-marathon races has increased annually in the United States. In 2010, there were approximately 2 million participants (42), as compared with 25,000 in 1976. There has been a similar exponential growth in other endurance events with, for example, 1.2 million triathlon competitors in the United States last year — a 50% increase in the last 3 years. Thus, we have a paradox in which there is an expansion in the number of overweight/obese and sedentary individuals paralleling a concomitant increase in those taking part in unprecedented hours of vigorous to near-maximal exercise. While there is a concerted, research-based effort to reduce inactivity and prolonged periods of sitting, only limited data are available regarding the other end of the exercise continuum – can you have too much (41)?
Reports documenting the favorable risk factor profiles and superb cardiac performance of long-distance runners have led to speculation that marathon running may promote “immunity to coronary heart disease (4).” Among >107,000 male and female runners who regularly achieve larger doses of exercise than currently are recommended, antidiabetic, antihypertension, and low-density lipoprotein cholesterol-lowering medications are related inversely to vigorous physical activity and cardiorespiratory fitness (66). These data, coupled with the recent finding that regular exercise prevents cellular senescence in animals and humans, as suggested by differences in telomere length (15,64), have led an increasing number of middle-aged and older adults to the conclusion that “more exercise is better.”
Despite the potential cardioprotective and antiaging effects of distance running, numerous reports of race-related AMI and cardiac arrest occur in marathon runners each year. In 2009, three runners died within 15 min of each other while competing in The Detroit Free Press Flagstar Marathon (65). These unexpected tragedies attract considerable media attention and have led to escalating concerns regarding the health risks of this activity. To clarify the risk of cardiac arrest associated with marathon and half-marathon races in the United States from January 1, 2000, to May 31, 2010, investigators recently reported on the incidences and outcomes of events among 10.9 million registered marathon runners (39). Of the 59 cases of cardiac arrest (mean ± SD age: 42 ± 13 years; 51 men), 42 (71%) were fatal. Sufficient information was available to determine the cause of cardiac arrest in only 31 of the 59 cases. The most frequent clinical and autopsy findings were hypertrophic cardiomyopathy and atherosclerotic CVD, respectively. It was concluded that the cardiac event rates among marathon and half-marathon runners are relatively low, as compared with other vigorous physical activities.
In recent years, considerable attention has focused on the postexercise rise in cardiac biomarkers and evidence of transient myocardial dysfunction using echocardiographic studies or cardiovascular magnetic resonance imaging in both elite and recreational athletes. Douglas et al. (21) first reported abnormalities in left ventricular systolic and diastolic function after an ultraendurance race that included a 2.4-, 112-, and 26.2-mile swim, bike ride, and run, respectively. Numerous subsequent investigations have shown that prolonged endurance exercise (e.g., marathon running) causes acute dilation of the right atrium and right ventricle, reduction of the right ventricular ejection fraction, and elevations in cardiac troponin I and B-type natriuretic peptide (61). Whether these findings represent possible harbingers of long-term sequelae, including fibrosis, or are simply part of the normal physiological process of stress, repair, and recovery, remains unclear. Recently, investigators reported myocardial inflammation, fibrosis, and a reduced arrhythmia threshold in rats subjected to regular intensive exercise training (5). Moreover, newer tissue characterization techniques, including cardiovascular magnetic resonance imaging, have now been used to describe diverse patterns of myocardial fibrosis in highly trained veteran endurance athletes (68). Collectively, these studies suggest that long-term endurance exercise may, at least in some athletes, create a substrate for threatening ventricular arrhythmias.
If the current mantra “exercise is medicine” is embraced, there are indications and contraindications, especially for prescribed physical activity, and underdosing and overdosing are possible. The potential cardiovascular risks of vigorous to near-maximal exercise, especially over short bursts or extended durations, should be weighed against the benefits. Unfortunately, at these high volumes and/or intensities, only limited data are available regarding the risk-benefit ratio (41). Accordingly, in individuals with a diseased or susceptible heart, there is the potential for a plateau or even a decline in benefit at more extreme levels of exercise, with a heightened risk for acute coronary syndrome and/or SCD (41). As an increasing proportion of the population are investing an unprecedented number of hours in intense endurance training and competition, the need to clarify the associated health outcomes of this practice is apparent.
Noncardiovascular Risks Associated with Exercise
Acute exercise-induced cardiovascular events, while representing potentially catastrophic complications, are far less common than musculoskeletal injuries such as strains, sprains, and fractures. Using data (2004 to 2009) from the National Health Interview Survey, a continuous multipurpose and multistage probability area survey of the U.S. adult noninstitutionalized population, sports and recreational injuries account for approximately 2,131,000 (±312,000) hospital visits each year (Fig. 4), with men experiencing a two- to threefold greater number of injuries than women. Estimated episodes of overexertion that required medical attention during this period ranged from 3,773,000 to 4,763,000, with men generally accounting for slightly more hospital visits than women do. Among specific activities resulting in injury, cycling-related accidents accounted for 198 deaths and 553,000 injuries in the United States in 2004 (6). Hospital data on ankle sprain from 2002 to 2006 identified via the National Electronic Injury Surveillance System database indicate an annual incidence of 2.15 injuries per 1000 person-years, with nearly half (49.3%) occurring during physical activity (63). These data highlight the frequency of sport- and exercise-related injuries in the general population.
The type of physical activity engaged in clearly influences the nature and magnitude of injury risk; however, specific conditions and populations present their own vulnerability issues. Identification of these conditions and groups, understanding their risk potential, and specific injury prevention approaches are key in reducing the incidence of musculoskeletal injury. In addition, certain genetic anomalies may contribute to the risks of exercise, especially those related to ligaments and bone formation. A brief discussion of general conditions, at-risk groups, and genetic factors follows.
Common Conditions Affecting Exercise Injury and Complications
Ambient conditions can be significant contributors to elevated exercise risk. Heat stress and dehydration are commonly associated with such injuries. Under these conditions, organ system competition for blood flow can result in lower body negative pressure, decreased venous return, and the inability to maintain adequate blood pressure, potentially leading to compensatory baroreceptor modulations and orthostatic intolerance, elevated cardiovascular strain, physical exhaustion, and collapse (16). Conversely, exercise in cold weather presents a different risk profile with some susceptible populations, most notably those with cardiovascular, cerebrovascular, and respiratory diseases, who may be at increased risk of morbidity and mortality (22). Hypothermia becomes a risk in cold environments and is exacerbated by water or rain; older individuals, because of their slower vasomotor adjustments in response to cold, tend to be at higher risk, as are children because of their body habitus. Winter athletes have a higher incidence of exercise-induced bronchoconstriction, and persons with asthma who exercise in cold environments are reported to have an 80% likelihood of experiencing an asthmatic episode (14). Further, hypoglycemia impairs shivering, thereby increasing the risk of hypothermia. The American College of Sports Medicine position stand on the prevention of exercise injuries in cold environments provides further details regarding exercise risks and appropriate preventative measures (14).
The potential for injury is clearly greater for some forms of leisure time and competitive physical activities; participation in team sports, water-based sports, and higher-risk endeavors (e.g., skydiving, skiing, motor sports, rock climbing) exposes participants to superimposed physical, emotional, and environmental stresses and varied potential trauma. Nevertheless, even exercises considered generally low impact or noncontact in nature may expose individuals to heightened risk. Data regarding accidents associated with exercise equipment, compiled over the past 25 years by the Consumer Product Safety Commission (49), indicate a rising trend. Injuries to individuals ≥17 years using aerobic exercise equipment have risen from an estimated 19,268 hospital visits nationally in 2001 to >40,000 incidents in 2010; injuries related to weight training equipment increased from 47,038 in 2005 to nearly 73,400 in 2010. In 2010, estimated occurrence rates for all exercise equipment-related injuries approximated 414.0 per 100,000 individuals aged ≥15 years, up from 290.9 per 100,000 reported in 2007. These injuries may occur as a result of overexertion, defective equipment, misuse, or combinations thereof. In addition, age, habitual physical inactivity, and obesity are also associated with increased exercise injuries.
While clinical trials tend to underreport adverse events in exercise program participants, body mass index has been shown to correlate with the incidence and onset of exercise-induced musculoskeletal injury both as a linear and categorical variable (35). Notably, the incidence of injuries in this report did not differ between individuals randomized to either the exercise (walking) or sedentary control group; however, these injuries were classified as “activity related.” Finally, adults with some previous injuries, such as those requiring anterior cruciate ligament reconstruction, are generally more susceptible to exercise-related injuries in the future (50).
Although genetic factors that heighten the risk of exercise-related cardiovascular events have been extensively reviewed (46), the genetic predisposition for noncardiovascular complications (e.g., musculoskeletal injuries) is often overlooked. At one extreme, individuals with certain monogenic disorders experience obvious physiologic limitations that can be exacerbated by physical activity. Examples include rare disorders such as osteogenesis imperfecta (wherein collagen deficiencies and impaired bone formation yield severe bone fragility) (55), alkaptonuria (a deficiency in tyrosine metabolism leading to accumulation of homogentisic acid in collagenous structures with subsequent arthritis exacerbated by physical activity) (23), and Marfan syndrome, wherein a mutation to the gene fibrillin-1 produces, in addition to severe ocular and vascular defects, back pain due to scoliosis and/or dural ectasia, joint weakness, and early-onset osteoarthritis (19). Ehlers-Danlos is a more common group of disorders encompassing eight or more collagen or tenascin (TNC) glycoprotein genes that has been classified into six categories; clinical manifestations include hyperflexibility, excessively stretchy skin, and blood vessels prone to tearing (12). While these genetic disorders are associated with obvious exercise risks, more subtle, multifactorial genetic mutations exist that have only recently been elucidated. These generally involve mutations to proteins involved in ligament and collagen-type tissues. Examples include identification of familial predisposition for full-thickness tears of the rotator cuff or tears of the anterior cruciate ligament (56). These observations may be due to mutations to COL1A1 (α1 chain of type I collagen), COL5A1 (α1 chain of type V collagen), or TNC variants, which have been found to be more prevalent in those experiencing exercise-related tendon and ligament injuries (56). Currently, the gene frequencies of such mutations and their contribution to exercise injuries remain unclear; thus, it is impractical to genotype individuals to potentially identify variants or use genetic profiles as a diagnostic tool for predicting future tendon/ligament injuries. However, a predisposition to such injuries based on family history should be considered when assessing risk. Future research may help to clarify the prognostic value of related genetic testing.
Although the relative risk of cardiovascular events appears to increase transiently during vigorous to near-maximal physical exertion compared with the risk at other times, the absolute risk is small. This seems to be particularly true among susceptible persons, that is, habitually sedentary individuals with known or occult CVD who were performing unaccustomed strenuous physical activity. On the other hand, the overall risk of a cardiovascular event appears to be up to 50% lower in persons who are regular exercisers (7,54). The essential feature of a prudent exercise regimen is a gradual progression during which an individual remains well below the duration and/or intensity that evokes abnormal signs or symptoms. At this time, considering the cardiovascular benefits and risks of exercise, the former outweighs the latter for the vast majority of adults, especially if one adopts a light- to moderate-intensity exercise.
Moderate-intensity physical activity is associated with a relatively low risk of musculoskeletal complications. On the other hand, the most common risk of vigorous physical activity is musculoskeletal injury, which can be as high as 55% among adults involved in jogging/running programs (34). An excessive frequency (≥5 d·wk−1) and/or duration (≥45 min per session) of training, particularly during the initial weeks of a walking-jogging program, often result in muscle soreness, orthopedic injury, and attrition (53). Similarly, near-maximal to maximal running intensities (≥90% of the heart rate reserve or oxygen uptake reserve) provide little additional improvement in aerobic capacity and are associated with an injury rate of ∼50% (44). Attention to warm-up, proper footwear, and terrain (avoiding hard and uneven surfaces) should aid in decreasing dropout due to injury.
Because regular physical activity is widely recognized as an integral component of a healthy lifestyle, the associated incidence of sports- and recreation-related injuries is substantial. Many of these individuals are treated in health care facilities other than hospital emergency departments, including clinics and doctors’ offices (18). These settings provide the opportunity to educate participants about injury prevention strategies. Policies and programs that identify high-risk activities, advocate appropriate safety gear to schools and sports facilities, establish defined outdoor recreation areas (e.g., bike paths or lanes, sidewalks, and cross walks), and promote safety in sports and leisure time physical activities (for example, laws requiring all bicycle riders to wear helmets) also should be helpful in reducing exercise-related injuries. The challenge is yours!
The authors declare no conflict of interest and do not have any financial disclosures.
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