Ablation of specific insulin-like growth factor I forms reveals the importance of cleavage for regenerative capacity and glycosylation for skeletal muscle storage.

Insulin-like growth factor-I (IGF-I) facilitates mitotic and anabolic actions in all tissues. In skeletal muscle, IGF-I can promote growth and resolution of damage by promoting satellite cell proliferation and differentiation, suppressing inflammation, and enhancing fiber formation. While the most well-characterized form of IGF-I is the mature protein, alternative splicing and post-translational modification complexity lead to several additional forms of IGF-I. Previous studies showed muscle efficiently stores glycosylated pro-IGF-I. However, non-glycosylated forms display more efficient IGF-I receptor activation in vitro, suggesting that the removal of the glycosylated C terminus is a necessary step to enable increased activity. We employed CRISPR-Cas9 gene editing to ablate IGF-I glycosylation sites (2ND) or its cleavage site (3RA) in mice to determine the necessity of glycosylation or cleavage for IGF-I function in postnatal growth and during muscle regeneration. 3RA mice had the highest circulating and muscle IGF-I content, whereas 2ND mice had the lowest levels compared to wild-type mice. After weaning, 4-week-old 2ND mice exhibited higher body and skeletal muscle mass than other strains. However, by 16 weeks of age, muscle and body size differences disappeared. Even though 3RA mice had more IGF-I stored in muscle in homeostatic conditions, regeneration was delayed after cardiotoxin-induced injury, with prolonged necrosis most evident at 5 days post injury (dpi). In contrast, 2ND displayed improved regeneration with reduced necrosis, and greater fiber size and muscle mass at 11 and 21 dpi. Overall, these results demonstrate that while IGF-I glycosylation may be important for storage, cleavage is needed to enable IGF-I to be used for efficient activity in postnatal growth and following acute injury.

Major adverse cardiac events and functional capacity in patients at intermediate risk undergoing transcatheter versus surgical aortic valve replacement for aortic stenosis with bicuspid valves.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is not always the optimal option for aortic valve stenosis (AS) patients with bicuspid aortic valves (BcAVs) and many studies exclude this group of patients. The aim of our study was to compare the rate of a major adverse cardiovascular event (MACE) and functional capacity in AS patients with BcAV after surgical aortic valve replacement (SAVR) and TAVR. METHODS: This study included 130 patients who underwent SAVR or TAVR from July 2013 to August 2018 at the Cheng Hsin General Hospital. The main outcome was MACE. Events recorded included noncardiovascular (CV) mortality, CV mortality, recurrent nonfatal stroke, recurrent nonfatal myocardial infarction (MI), and important events. The secondary outcome was functional recovery, which was defined according to the metabolic equivalent (MET) 6 months after the aortic procedure. RESULTS: The mean age of patients was 56.8 ± 26.9 years and the mean Society of Thoracic Surgeons score was 3.29 ± 4.69. Logistic regression analyses indicated that SAVR was a significant predictor of functional recovery. Patients who underwent SAVR had a higher rate of functional recovery (>3 METs; 87.8%, p = .000) and had a significantly higher odds ratio (3.56; 95% confidence interval, 1.19-10.63, p = .023). The Kaplan-Meier survival analysis showed that the MACE rate was not associated with the aortic procedure. CONCLUSIONS: Our analysis showed that SAVR is a significant predictor of better functional recovery and TAVR is associated with a lower level of functional capacity. In summary, TAVR is an acceptable option for AS patients with BcAV, and for a better prognosis, an early intervention aimed at improving functional capacity is highly recommended for this group of patients.

Predicting exercise capacity recovery immediately after mitral valve surgery.

BACKGROUND: This study presents the exercise capacity of postmitral valve surgery patients and determines predictors capable of affecting recovery. METHODS: A total of 302 patients with mitral regurgitation who had undergone mitral surgery at the Heart Center in Taiwan from 1 August 2013 to 31 December 2015 were included in the present study. Data related to specific predictors of operative outcome were collected, including demographic data, intraoperative factors, exercise tolerance, echocardiogram data, concurrent cardiovascular disease history, comorbidities, lifestyle risk factors, and surgery types. Postoperative exercise capacity was presented as peak oxygen consumption (VO2 ; mL of O 2 /kg/min) determined by exercise tests 3 weeks after surgery. Subjects were separated into two groups: a preserved recovery (peak VO 2 ≥ 65% of predicted VO 2max ) group and a poor recovery group (peak VO 2 < 65% of predicted VO 2max ). Preliminary univariate analysis was performed to test for possible relationships between predictive variables and exercise capacity. An analysis of all items shown to be significantly different between the two groups was then subjected to multivariate logistic regression analysis. Detected differences with P < .05 were considered significant. RESULTS: Among the 302 patients sampled, female sex (odds ratio [OR], 2.65; 95% confidence interval [95% CI], 1.58-4.47), obesity (OR, 0.26; 95% CI, 0.10-0.64), sedentary lifestyle (OR, 0.47; 95% CI, 0.28-0.79), and high preoperative New York Heart Association Functional Classification level (OR, 0.52; 95% CI, 0.31-0.87) were significant predictors of poor exercise capacity. CONCLUSIONS: Without complicated clinical procedures, physicians and medical teams could easily use these items of information to screen the exercise capacity of mitral valve surgery patients and prepare a suitable after surgery plan if needed or request a consultation as early as possible.

Application of the Transtheoretical Model to Exercise Behavior and Physical Activity in Patients after Open Heart Surgery.

PURPOSE: To assess exercise behavior and physical activity levels after open heart surgery. METHODS: This prospective cohort study included 130 patients (70.8% male, aged 61.0 ± 12.2 years, 53.8% coronary bypass grafting) who underwent open heart surgery. The exercise behavior and physical activity of these patients were assessed at the 3- and 6-month follow-up appointments. Additional interviews were also conducted to further assess exercise behavior. Physical activity duration and metabolic equivalents were calculated from self-reported questionnaire responses. Moreover, possible related demographic factors, clinical features, participation in cardiac rehabilitation programs, and physical activity levels were additionally evaluated. RESULTS: Six months after hospital discharge, most patients were in the action (39.2%) and maintenance (37.7%) stages. Other subjects were in the precontemplation (11.5%), contemplation (5.4%), and preparation (6.2%) stages. The average physical activity level was 332.6 ± 377.1 min/week and 1198.1 ± 1396.9 KJ/week. Subjects in the action and maintenance stages exercised an average of 399.4 ± 397.6 min/week, significantly longer than those in other stages (116.2 ± 176.2 min/week, p = 0.02). Subjects that participated in outpatient cardiac rehabilitation programs after discharge may have the better exercise habit. Gender had no significant effect on exercise behavior 6 months after hospital discharge. CONCLUSIONS: Most subjects following open heart surgery may maintain regular exercise behavior at 6 months after hospital discharge. Physical activity levels sufficient for cardiac health were achieved by subjects in the active and maintenance stages. Outpatient cardiac rehabilitation programs are valuable for encouraging exercise behavior after heart surgery. KEY WORDS: Exercise behavior; Open heart surgery; Physical activity; Transtheoretical model.

The association between ankle-brachial index and quality of life in chronic hemodialysis patients.

Ankle-brachial index (ABI) is an important indicator of peripheral arterial disease (PAD) and PAD has a negative impact on quality of life (QOL). However, the correlation between ABI and QOL is unknown among chronic hemodialysis patients. Ankle-brachial index was measured, and WHOQOL-BRIEF (TW) questionnaire was completed. The association between ABI and QOL was analyzed using linear regression. A total of 54 chronic hemodialysis patients (mean age of 56.2 +/- 14.6 years) were included. Ankle-brachial index was positively associated with QOL (r = .448, P = .001). The QOL scores were 3.1 +/- 2.9 and 2.6 +/- 0.4 for 37 patients with an ABI more than 0.9 and 17 patients with an ABI less than 0.9 or more than 1.3 (p < .001). In linear regression, only ABI was significantly associated with QOL scores with a beta of .448 (95% CI: 0.443 to 1.55, P = .001). Ankle-brachial index is positively correlated to QOL among chronic hemodialysis patients.