IntroductionTo investigate the effect of exercise on the walking economy (WE) of patients with chronic neurological conditions (CNCs) and to determine the type of physical activity that best improves the WE of patients with CNCs.MethodsFour electronic databases were searched until December 2022 (Web of Science, PubMed, Cochrane, and CINAHL). Studies were screened using the following inclusion criteria: 1. randomized controlled or non-randomized controlled trials; 2. exercise interventions >4 weeks in duration; 3. patients aged ≥18 years with a diagnosis of CNCs. 4. walking economy of patients measured before and after the intervention. The PEDro scale was used to assess the methodological quality of the included studies.Results and discussionTwenty-two studies met the inclusion criteria. Meta-analysis results showed that exercise significantly improved WE (g = −0.352, 95% CI, −0.625 to −0.078, P = 0.012). Subgroup analysis revealed that patients who received exercise showed better WE compared with those who underwent no control intervention (g = −0.474, 95% CI, −0.636 to −0.311, P < 0.001). However, exercise therapy did not show a significant improvement of WE compared with control groups (g = −0.192, 95% CI, −0.451 to 0.067, P = 0.146). In addition, we found that endurance combined with resistance, high-intensity intermittent, and other training modalities resulted in better WE compared with the pre-intervention. Of these, interval training has the greatest effect on improving WE. In conclusion, exercise can improve WE in patients with CNCs. More randomized controlled trials are necessary for the future.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361455, identifier: CRD42022361455.

Streptomyces lividans normally accumulated high levels of ppGpp during nutritional shift-down. Its accumulation was, however, severely inhibited when a small amount of thiopeptin (an analogue of thiostrepton) was included in the transfer medium. In contrast, a S. lividans strain, which harbours the plasmid pIJ702 carrying the tsr gene resistant to thiopeptin through methylation of the 23S rRNA, was still capable of accumulating ppGpp in the presence of large amounts of thiopeptin. These results indicate that the rRNA methylation resulting from the action of tsr gene prevents thiopeptin not only from inhibiting cell-growth but also from inhibiting ppGpp synthesis. The results also indicate that the observed accumulation of ppGpp during nutritional shift-down was associated with ribosomal function, as has been shown in E. coli and B. subtilis.

1 病例介绍 患者女性,33岁,因"左侧肢体无力进行性加重5天"于2020年7月29日入院.患者5?d前无明显诱因出现左侧肢体无力,初起可自行行走,持物不稳,无言语不利、饮水呛咳,无头痛头晕、肢体麻木或抽搐,无二便失禁,无意识、视听障碍.外院以"缺血性卒中"收住院治疗,住院期间发现血压和血糖增高,最高血压155/90?mmHg(1?mmHg=0.133?kPa)(具体用药不详),左侧肢体无力进行性加重,出现左侧上肢不能活动、下肢无法站立行走.为求进一步治疗,遂至焦作市人民医院就诊.

HomeStrokeVol. 51, No. 1Translating Research Into Clinical Practice Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessReview ArticlePDF/EPUBTranslating Research Into Clinical PracticeImportance of Improving Cardiorespiratory Fitness in Stroke Population Qiwei Fan, MS and Jie Jia, PhD Qiwei FanQiwei Fan From the Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China (Q.F., J.J.) and Jie JiaJie Jia Correspondence to Jie Jia, PhD, Department of Rehabilitation Medicine, Huashan Hospital Fudan University, 12 Middle Wulumuqi Rd, Jing'an District, 200040, Shanghai, China. Email E-mail Address: [email protected] From the Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China (Q.F., J.J.) School of Life and Environmental Sciences, University of Sydney, Australia (J.J.). Originally published9 Dec 2019https://doi.org/10.1161/STROKEAHA.119.027345Stroke. 2020;51:361–367Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 9, 2019: Ahead of Print Cardiovascular fitness (CRF), measured by maximal cardiopulmonary exercise test and expressed as peak oxygen uptake (VO2peak), can well reflect the integrated function of whole-body physiological responses of involved cardiovascular, metabolic, musculoskeletal, and neuropsychiatric systems under exercise stress. Studies have firmly established the inverse association between CRF and cardiovascular disease (CVD) and all-cause mortality.1–4 Recent studies demonstrate that CRF is a stronger independent predictor for health outcomes than traditional risk factors.5–8 Improvement of CRF, irrespective of traditional risk factors and initial CRF level, produces substantial health benefits.Emerging studies have also supported CRF as a strong predictor for stroke incidence.9–19 These studies have observed a graded and inverse association between CRF and all types of stroke risk in the young11,12 and old,10,14,15,18,19 men9,11 and women,10 healthy15,19 and unhealthy16 population. Review, observational, and trail studies suggest that high CRF contributes to walking capacity and functional recovery in subacute and chronic phases of stroke.20–23 Despite these health benefits, low CRF is prevalent in stroke population. Reviews have reported an average VO2peak of 14.6 mL/kg per minute,24 and VO2peak level in stroke survivor is about 53% of the age- and sex-matched health controls.25 Muscle atrophy,26–28 increased muscle fat mass,29 impaired cardiac function,30 and respiratory function,31 reduced peripheral blood flow,32,33 as well as diminished muscle strength,34 and impaired gait performance35,36 all contribute to the decline of CRF after stroke.Exercise training (ET) particularly aerobic training (AT) has been well established for improving CRF in stroke population.37–39 Cochrane review has shown that AT can elicit an increase of VO2peak of 2.86 mL/kg per minute (95% CI, 1.76–3.96; P=0.00001).39 Actually, regular physical activity (PA) can substantially reduce stroke risk in a dose-response fashion.40 A 7.5-year follow-up in 487 334 participants displayed that every 4 metabolic equivalents (METs)-h/d (1 MET = a whole-body oxygen consumption of 3.5 mL O2/kg/min) increase in PA was associated with 5% and 6% decrease in ischemic stroke and intracerebral hemorrhage respectively.41 Study in 336 326 Koreans with an even age distribution showed that 1 to 2 times per week moderate- to vigorous-intensity PA was associated with 16% lower stroke incident.42 Strategies to promote PA and ET in stroke population are critical.We provide a narrative review to address the association of CRF with stroke, examine the level and evolution of CRF poststroke, aiming to propose that improving CRF is essential in stroke rehabilitation, particularly in acute and early subacute phase, and assessing CRF level and prescribing ET in clinical practice should be considered as a strategy to promote PA and ET in stroke population. We assume that there is a substantial decline of CRF after stroke, particularly in subacute phase.BackgroundCRF and Health BenefitsCRF is an independent risk factor of CVD and all-cause mortality.1–4 Recent studies have strongly supported that CRF is a more powerful predictor for health outcomes than traditional risk factors.6,7,40 American Heart Association states that CRF should be screened in clinical practice as a vital sign.1 Additionally, high CRF is protective across lifespan in healthy and unhealthy population, also strongly associated with reduced incidence of CVD risk factors.8,43,44 More importantly, improvement of CRF, irrespective of traditional risk factors and initial CRF level, produces substantial benefits.4,45Studies have quantified the dose-response threshold between CRF and health outcomes. Meta-analysis based on 33 epidemiological studies demonstrated that each 1-MET higher level of CRF was associated with a 13% and 15% risk reduction of all-cause mortality and CVD, respectively.46 American Heart Association has documented that the CRF level of <5 METs is associated with a high risk for mortality, and CRF level of >8 to 10 METs is necessary for the normal health status. Recent study has demonstrated that the order of highest to lowest risk CRF levels are <5 METs, <6 METs, <8.8 METs, and <11.2 METs.4Overall, these evidence underscores routine measurement of CRF to assess risk and improving CRF in the public.CRF as a Predictor of Stroke RiskStudies have consistently observed a graded, independent, and inverse association between CRF and stroke risk in young11,12 and old,10,14,15,18,19 men9,11 and women,10 healthy15,19 and unhealthy16 population, irrespective of age, sex, body mass index, smoking, alcohol intake, hypertension, dyslipidemia, diabetes mellitus, and atrial fibrillation.10,14,16,17,19 However, the CRF level may be different due to race. Study with 24 162 individuals found only whites rather than blacks was protected by CRF.17 A 1-METs increase in CRF was associated with 12% lower stroke risk in whites.The protective effect of higher CRF level starts since adulthood (≥18 years). During 42-year follow-up, low CRF at the age of 18 years was independently associated with high incidents of ischemic, intracerebral hemorrhage, subarachnoid hemorrhage strokes, as well as fatal and nonfatal strokes in a dose-response fashion.11 This fashion has also been found in middle-age population.10,14,15,18,19 An 18-year follow-up in 46 405 men aged 43.7 years and 15 282 women aged 42.9 years without stroke or myocardial infarction, showed that CRF level was independently inverse to stroke incident regardless of traditional risk factors.10 Out of the same cohort, in 19 815 middle-aged individuals, Pandey et al15 reported that 1-MET increase of CRF was associated with 7% reduction for stroke hospitalization. This finding is important. It means that patients with higher CRF probably have less-severe impairment, and better and faster recovery; it also implies that improving CRF during hospitalization may let the patients recover faster, more immune to comorbidities and recurrent stroke. Collectively, these studies demonstrate the importance of maintaining high CRF across lifespan to reduce stroke incidence. Improving CRF in middle age is a cost-effective option to prevent and delay stroke development.The mechanism behind the protective effect of CRF can be partly explained by the independent contribution of CRF to carotid vasculature.18 Lee et al investigated CRF levels among 1094 participants aged 40 to 59 years without CVD and found that individuals with high CRF had 40% lower odds of having atherosclerotic carotid artery disease compared with those with low CRF; each 1-MET increase in CRF was associated with 10% lower odds of having carotid artery disease (odds ratio=0.89 [95% CI, 0.80–0.99]).Improvement in CRF also brings substantial benefits.19 A 23.6-year follow-up among 1403 healthy participants aged 40 to 59 years demonstrate that the group with lower baseline CRF had the higher risk of stroke; those who were fit but became unfit had significantly increased risk. In contrast, those with lower fitness but became fit had significantly reduced risk. Overall, those with greater improvement in CRF had significantly lower risk irrespective of traditional risk factors. These findings underscore the value of improving CRF that those at high stroke risk, or with lower level of CRF may benefit greatly from improving CRF.Taken together, the literature supported the dose-response inverse association between CRF and stroke risk from early adulthood to later ages. Whereas the threshold benefits of CRF level are yet to be established, assessing CRF to identify those at high risk and thus improving CRF is paramount to prevent and delay stroke development in both healthy and unhealthy, early and mid-life.Exercise and CRFET particularly AT is strongly associated with CRF improvement in stroke population. This has been consistently confirmed in meta-analysis reviews.37–39,47,48 Recent meta-analysis with meta-regression showed an increase of 2.2 mL/kg per minute in VO2peak.24 This is similar to the result from the Cochrane review which demonstrated a mean increase of 2.86 mL/kg per min VO2peak.39 Additionally, 1-year follow-up trial has suggested that the improved CRF levels in chronic patients can be maintained.49Although most of the studies in the reviews are patients in chronic phase, studies have established that AT can enhance CRF in subacute phase as well.37,50 Billinger et al51 demonstrated that AT can improve VO2peak by 13% in subacute phase. Meta-analysis confirmed that AT can be started as early as 6 days poststroke to improve VO2peak.47Collectively, the literature has demonstrated that AT or mixed training incorporating AT from 3 weeks to 6 months, 20 to 60 minutes per session, 3 to 5 days per week, and at 40% to 80% heart rate reserve is efficient to improve VO2peak.MethodsSelection of StudiesWe intended to identify studies measuring CRF in stroke survivors by standard cardiopulmonary exercise test. Based on the suggestions from statement of American Stroke Association,37 and previous review on testing protocol in stroke population,52 we chose studies based on the following criteria:Participants were diagnosed with stroke or transient ischemic attack.Studies which directly measured highest or maximum oxygen uptake by symptom-limited graded exercise test (GXT) using gas exchange by open-circuit spirometry rather than submaximal exercise test, field test or indirect estimations, while both legs rather than one leg were used. The test may be terminated due to disease symptoms and clinical safety criteria. For this reason, VO2peak rather than maximum oxygen uptake is applied in the studies identified.Studies published in English with full text, with at least 8 participants.Data Source and Search StrategyWe searched articles published in the PubMed of NCBI databases from 1995 to November 1, 2019. The following key words were used:Stroke-related words: cerebrovascular, cerebral, brain, subarachnoid, intracerebral, hemorrhage, stroke, infarct, ischemia, and transient ischemic attack.CRF-related words: exercise test, stress test, cardiopulmonary test, fitness test, walking test, cardiorespiratory fitness, cardiopulmonary fitness, maximal/peak oxygen consumption/uptake, VO2peak, maximum oxygen uptake, aerobic/cardio capacity/utilization/consumption/uptake, fitness, capacity, and power.Data ExtractionData were extracted including participant demographics (number, sex, age, time since stroke, and stroke severity), exercise test protocol and termination criteria, VO2peak levels. Stroke severity was reported by the National Institutes of Health Stroke Scale. If the National Institutes of Health Stroke Scale was not available, severity was extracted by the authors' reports. Stroke phase was defined by recent established standards: acute (1–7 days), subacute (7 days to 6 months), and chronic phases (>6 months).53 VO2peak was extracted in baseline exercise tests.ResultsEighty-one studies with overall 3082 participants were identified. The searching flow diagram, participants demographics, and exercise test characteristics can be found in Figure I and Tables I and II in the online-only Data Supplement, respectively. Briefly, participants were with an average age from the 50s to 70s, with mild or moderate stroke and capable of walking with or without aid. VO2peak values in all studies were majorly in the range of 10 to 20 mL/kg per minute, with an average value of 15.78 mL/kg per minute in all participants, 14.34 mL/kg per minute in subacute phase, 16.54 mL/kg per minute in chronic phase. For the purpose of this study, we divided the studies into subacute and chronic phases and particularly discussed the evolution of CRF after stroke.CRF in Subacute PhaseMacKay-Lyons' team particularly investigated CRF level of stroke patients in early subacute phase of stroke (in 1-month poststroke).49,54,55 While VO2peak was all measured by treadmill GXT following American College of Sports Medicine guidelines, their studies in 29 patients (aged 64.9 years, 22men),54 25 patients (aged 64.1 years, 20 men),55 and 50 patients (aged 60 years, 29men)49 demonstrated VO2peak of 14.4±5.1, 14.8±5.3, and 14.4 mL/kg per minute, respectively. In the similar time period poststroke (21.56±7.98 days), Han et al56 reported an average VO2peak of 14.51 mL/kg per minute in 56 participants (32 men) aged 60s. In 1-month poststroke, other studies found an average VO2peak level of 14.9 mL,57 12.3,58 and 11.4 mL/kg per minute.59 However, in the exact same method of measuring VO2peak as MacKay-Lyons' team, Kim et al20 found an average of 19.7±6.7 mL/kg per minute in 55 participants (37 men) aged 62.2 years. The possible reason of the higher VO2peak in Kim's study is likely that the subjects were healthier and a relatively late stage and larger time range poststroke (32.6±24.7 versus 26.0±8.8 days).Indeed, there is likely a precipitous decline of CRF because stroke onset. A measurement in 9.9±2.0 days poststroke among 19 male patients aged 62.7 years with mild impairment displayed a mean VO2peak of 11.8 mL/kg per minute.60 Another study reported a mean VO2peak of 8.3 mL/kg per minute in 12 male subjects aged 59 years at 15±7 days poststroke with also mild impairment.61 These VO2peak values are definitely lower than the above results. Bedrest, physical inactivity, impairment severity, or a low prestroke CRF level may account for the decline.Impairment severity of stroke is likely associated with low CRF. Boss et al62 investigated 113 participants aged 64 years after transient ischemic stroke (49 days poststroke) with National Institutes of Health Stroke Scale =0. The VO2peak was measured by cycle GXT following the American College of Sports Medicine guidelines. The authors found an average VO2peak of 22 mL/kg per minute. However, by the same approach of measuring VO2peak, Duncan et al63 found an average VO2peak of 11.5 mL/kg per minute among 92 participants aged 69.4 years (76 days poststroke) with Orpington prognostic score =3.4.Longitudinal observations may further provide the answer. MacKay-Lyons et al observed VO2peak value 6-month poststroke was significantly higher than that in the first month in 25 subjects (17.3±7.0 versus 14.8±5.3 mL/kg per minute). Another study involved in 92 patients found VO2peak level in 3-month poststroke was significantly higher than at 75 days poststroke (11.4±2.8 versus 10.5±2.8 mL/kg per minute, P<0.05).64 However, interestingly, they found another group with higher baseline VO2peak (12.4±3.2 mL/kg per minute) had no change in the second test (12.4±3.7 mL/kg per minute). This finding is clinically important. It means that those with deleterious decline of CRF may have a spontaneous improvement of CRF with the overall heath recovery. However, this magnitude of improvement is limited because a higher baseline CRF need additional training to improve CRF. Baert et al50 found that VO2peak measured by cycle GXT at 3, 6, and 12 months poststroke were 18.1±6.6 mL/kg/min,19.8±8.0 mL/kg/min, 19.7±8.4 mL/kg/min respectively. Although there was not significant increase of VO2peak over time, the authors found that the majority of patients had greater improvement from 3 to 6 months. Collectively, these longitudinal observations suggest that CRF may spontaneously recover to some extent in 6-month poststroke. The magnitude of improvement is larger in the first 3 months. Interestingly, when arranging the data in chronicle days since stroke onset, the results displayed a trend of CRF increase in subacute phase (Figure 1), which was consistent with the findings of the above longitudinal studies.Download figureDownload PowerPointFigure 1. Peak oxygen uptake (VO2peak) evolution in chronicles (d) in subacute phase. An average VO2peak value of 14.34 mL/kg per min from 25 studies with 967 participants.CRF in Chronic PhaseHow CRF evolves after 6 months is important to know. However, limited studies report the longitudinal evolution in this period. As mentioned above, Baert et al50 found no change of VO2peak between 6 and 12 months. Several studies measured VO2peak in 6 to 12 months. Michael et al65 investigated 79 participants aged 65 years, their average VO2peak measured by treadmill test was 13.02 mL/kg per minute. Also by treadmill test, Yang et al66 found an average VO2peak of 11.24 mL/kg per minute in 15 participants aged 64.1 years. Fujitani et al67 found average VO2peak measured by cycle test was 17.7 mL/kg per minute among 30 men aged 53.6 years. Studies also investigated CRF level after years of stroke. Patterson et al68 reported a mean VO2peak of 13.1 mL/kg per minute with treadmill GXT in 74 volunteers after 4 years poststroke. Tomczak et al30 reported VO2peak of 16.0 mL/kg per minute with cycle GXT in 10 volunteers 7.5 years poststroke. Collectively, it's difficult to conclude the change trend of CRF from several months to several years poststroke.Since subjects in chronic stage are generally mild to moderate severe, studies with larger sample size may be representative. Hinson et al69 examined 118 subjects (56% black aged 62 years, 44% white aged 66 years) with an average 45.5-month poststroke, VO2peak measure by treadmill GXT was 13.7±4.2 mL/kg per minute for the black and 14.0±4.0 mL/kg per minute for the whites. Jin et al70 found an average VO2peak of 13.2 mL/kg per minute measured by cycle GXT among 128 subjects aged 42 to 68 years with an average 18.3 months poststroke. Indeed, despite variations of VO2peak in these individual studies, these findings are consistent with our observation. When arranging VO2peak values based on the test day (Figure 2), we found that, over time, there was no trend of increase of VO2peak in chronic phases, and VO2peak values were still in the range of 10 to 20 mL/kg per minute.Download figureDownload PowerPointFigure 2. Peak oxygen uptake (VO2peak) evolution in chronicles (mo) in chronic phase. An average VO2peak value of 16.54 mL/kg per min from 56 studies with 2115 participants.DiscussionOverall, the present literature confirmed our assumption of low level of CRF after stroke. The average VO2peak of 15.78 mL/kg per minute is in line with previous reviews, where a meta-regression analysis reported a mean VO2peak value of 14.6 mL/kg per minute,24 and a scoping review found an average VO2peak value of 15.8 mL/kg per minute from 5008 participants.52 The comparison with healthy peers may give us a better peering. Severinsen et al71 measured an average VO2peak of 16.3±4.9 mL/kg per minute in 48 stroke survivors aged 68 years. They found that this value was 77% of the healthy population after adjusting for age and sex. Jakovljevic et al33 observed that VO2peak value in 28 male subjects aged 70 years with mild ischemic stroke was 31% lower than those age-matched healthy participants (18.4±4.6 versus 26.8±5.5 mL/kg per minute, P<0.01).33 According to recent national database in the United States, VO2peak levels of aged-matched individuals in 50 to 59 and 60 to 69 are 33.8±9.1 and 29.4±7.9 mL/kg per minute in men and 24.2±6.1 and 20.7±5.0 mL/kg per minute in women, respectively.72 A recent data from The Generation 100 Study with 1537 normal old population aged 70 to 77 years with or without CVD reported that VO2peak was 31.3±6.7 mL/kg per minute for men and 26.2±5.0 mL/kg per minute for women.73 In comparison, VO2peak values in stroke population are in the range of fifth to 25th age- and sex-specific percentile for CRF of the normal healthy population.72 This result is alarming: stroke population is living with poor fitness. Above that, CRF level <5 METs is associated with high risk of CVD and all-cause mortality. The physiological demands for routine daily activity are 3 to 5.9 METs.74 Undoubtedly, the low-CRF level severely impacts daily living and accelerates worse condition.The results also demonstrated a lower VO2peak level in subacute phase than in chronic phase (14.34 versus 16.54 mL/kg per minute) and a trend of increase of CRF in subacute phase but not in chronic phase (Figures 1 and 2). However, the findings should be explained with caution. First, the number of studies in chronic phase is double than in subacute phase. Additionally, whether the higher VO2peak value in chronic phase is a result that those survivors with higher prestroke CRF, rehabilitation treatment, or less-severe stroke survivors is a question needed to be answered. Furthermore, long-time bed rest and physical inactivity in early phase poststroke may also account for the decline.Previous reviews have documented the decline of CRF poststroke25 and its biological mechanisms.75 Furthermore, according to the suggestion of American Stroke Association37 and previous review on exercise testing in stroke population,52 this review particularly chose studies with symptom-limited GXT to better disclose the conditions of CRF. Besides, this review explored the evolution of CRF from the early subacute phase to years poststroke, stressing the change and level of CRF in subacute and chronic phases, respectively. These regards were addressed due to the possible clinical implications: First, the lower CRF in subacute phase than in chronic phase, and the trend of CRF increase in subacute phase, indicate the highly compromised health status on the stroke onset, thus the urgency of improving CRF in early rehabilitation especially for those with severe stroke. Second, the low level of CRF in early stage of stroke may be an indication of prestroke low CRF. Whether those stroke survivors had prestroke high-risk CRF level, whether their low CRF influences the recovery become critical to know. Third, longitudinal studies suggest a possible plateau of spontaneous recovery of CRF in the first 3 months poststroke, signifying the necessity of additional training to improve CRF in stroke population. Last, regardless of those recruited participants mostly with mild stroke and capable of walking, their CRF level was far below the age-matched healthy population. This means that walking and functional performance do not necessarily lead to CRF improvement. Therefore, CRF after stroke is likely a reflection of health status, risk of stroke, and limitations of current stroke rehabilitation. Rather than associating CRF with walking and functional performance, the role of improving CRF may lie in facilitating medical treatment, contributing to fast and better recovery, prevention of secondary recurrence of stroke, improving long-term health status of stroke population.In summary, this review provides further evidence of substantially low level of CRF after stroke and a possibly lower CRF in subacute phase than in chronic phase. To improve this situation, assessment of CRF, and improving CRF may be considered early since stroke onset and persist in stroke rehabilitation. Patients will be stratified from low to high stroke risk, then being prescribed ET accordingly. Considering the efficacy of AT in improving CRF, ET primarily consisting of AT should be arranged but adjusted according to severity and stroke phases. For hemiparetic patients and patients with severe impairment, AT for the nonparetic limbs can be implemented in bed. For patients in acute phase, training program to improve muscle fitness and trunk balance may be incorporated with AT to facilitate the implementation of AT program. Essentially, training program to improve comprehensive physical fitness level should be adjusted from acute phase to chronic phase based on the conditions of patients to optimize the training effects.LimitationsThere are limitations in present review. We restricted the search in one database with English language publications. Besides, there are many factors impacting the reporting of CRF level after stroke. In many studies, there was a wide age distribution of participants, and more men were involved. In terms of exercise tests, different modalities (recumbent or upright cycle ergometer, stepper, or treadmill) were used; furthermore, recent review has pointed out the limitations of cardiopulmonary exercise test in stroke population.76 Another limitation of this review is that it intends to clarify the prevalence of low CRF in stroke survivors, and its clinical implications. However, whether and to what extent CRF affect the recovery and long-term health outcomes poststroke is not answered. Regrettably, among 81 studies involved, few studies20,23 examined the question, while these studies suggest that high CRF contributes to walking capacity and functional recovery in both subacute and chronic phases of stroke. Longitudinal clinical trails of examining the prognostic role of baseline CRF level and magnitude of change of CRF are needed to fulfill this gap.Future DirectionsSeveral aspects can be considered in future studies. Large longitudinal clinical trails and cohort studies further identify the conditions and evolution of CRF in acute, early subacute, subacute, and chronic phases, explore whether and how CRF level and the magnitude of change of CRF affect the recovery and long-term health outcomes and demonstrate whether improving CRF for patients with different severity would produce different effects. Meanwhile, methods and strategies to improve CRF in acute and early subacute phase and for those with severe stroke and unable to walk should be considered. Additionally, it's imperative to develop and standardize the efficient methods of measuring CRF in stroke population.ConclusionsResults from studies using symptom-limited GXT demonstrate the substantial low level of CRF from the early subacute phase to chronic phase. Less amount of studies demonstrate a lower level of CRF in subacute phase than in chronic phase. Given the strong association of CRF with stroke risk and overall health outcomes, and the efficacy of AT in improving CRF, stroke rehabilitation may consider incorporate AT as essential part in the continuum of stroke care.Sources of FundingThe article was supported by the National Key Research & Development Program of Ministry of Science and Technology of the People's Republic of China (Grant number 2018YFC2002300 and 2018YFC2002301).DisclosuresNone.FootnotesThe online-only Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.119.027345.Correspondence to Jie Jia, PhD, Department of Rehabilitation Medicine, Huashan Hospital Fudan University, 12 Middle Wulumuqi Rd, Jing'an District, 200040, Shanghai, China. Email [email protected]comReferences1. 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