A Behavioral Change-Based Mobile Intervention for Promoting Regular Physical Activity in Medical Rehabilitation Maintenance of Patients With Coronary Artery Disease: Controlled Trial.

BACKGROUND: Cardiac rehabilitation is known to reduce coronary artery disease (CAD) severity and symptoms, but adoption of a healthy postrehabilitation lifestyle remains challenging. Innovative eHealth solutions could help, but behavioral change-based eHealth maintenance programs for patients with CAD are scarce. RehaPlus+ aims to improve postrehabilitation outcomes with a personalized eHealth intervention built on behavioral change concepts emphasizing healthy lifestyle changes, especially regular physical activity (PA). OBJECTIVE: This study aims to evaluate the effectiveness of the personalized eHealth program RehaPlus+ for promoting regular PA against usual care. METHODS: A total of 169 patients with CAD who had undergone stent implantation or bypass surgery were recruited after completing center-based phase II rehabilitation. They were then divided, without blinding, into 2 groups using a quasi-experimental approach: a case manager-assisted 24-week eHealth program (RehaPlus+; n=84) and a conventional physician-assisted outpatient program (usual care; n=85). The study was designed as a noninferiority trial. RehaPlus+ participants received motivational messages twice weekly for 6 months, and the usual care group engaged in a 6-month outpatient program (twenty-four 90-minute strength and endurance training sessions). The primary outcomes, evaluated using the self-assessed Bewegungs- und Sportaktivität questionnaire, were regular PA (≥150 min/wk) and weekly activities of daily living (ADLs) 6 months after rehabilitation. Secondary outcomes involved PA during work and floors climbed weekly (measured by Bewegungs- und Sportaktivität questionnaire), psychological well-being (assessed by the 5-item World Health Organization Well-Being Index), cardiac self-efficacy, health-related quality of life (measured by the 36-Item Short Form Survey), and work ability (using the Work Ability Index). RESULTS: Data of 105 patients (RehaPlus+: n=44, 41.9%; usual care: n=61, 58.1%; male patients: n=80, 76.2%; female patients: n=25, 23.8%; mean age 56.0, SD 7.3 years) were available at the 6-month follow-up. At 6 months after discharge from phase II cardiac rehabilitation, the RehaPlus+ group exhibited 182 (SD 208) minutes per week of PA and the usual care group exhibited 119 (SD 175) minutes per week of PA (P=.15), with no interaction effect (P=.12). The RehaPlus+ group showed an ADL level of 443 (SD 538) minutes per week compared to the usual care group with 308 (SD 412) minutes per week at the 6-month follow-up, with no interaction effect (P=.84). The differences observed in PA and ADL levels between the RehaPlus+ and usual care groups were within the predefined 1-sided noninferiority margin, indicating that the RehaPlus+ intervention is not inferior to usual care based on these outcomes. There were no differences between the groups for all secondary outcomes (P>.05). CONCLUSIONS: RehaPlus+ is not inferior to the usual care program, as both groups improved PA and ADLs to a similar extent. These findings emphasize the potential of eHealth interventions to assist in maintaining healthy lifestyles after rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov NCT06162793; https://clinicaltrials.gov/study/NCT06162793.

Analysis of fat oxidation capacity during cardiopulmonary exercise testing indicates long-lasting metabolic disturbance in patients with post-covid-19 syndrome.

BACKGROUND & AIMS: Post-COVID-19 Syndrome (PCS) is characterized by symptoms including fatigue, reduced physical performance, dyspnea, cognitive impairment, and psychological distress. The mechanisms underlying the onset and severity of PCS point to mitochondrial dysfunction as significant contributor. This study examined fat oxidation as a function of mitochondrial capacity during exercise. METHODS: Single-center prospective cohort study during inpatient rehabilitation. Cardiopulmonary exercise testing and assessment of fatigue using questionnaires were performed at admission and discharge. Detailed spirometric breath-by-breath data were used to calculate substrate oxidation rates. RESULTS: Patients (N = 187; 38 % women; 49.7 ± 11.4 years) were referred to rehabilitation 253.4 ± 130.6 days after infection. Lead symptoms included fatigue/exercise intolerance (79.9 %), shortness of breath (77.0 %), and cognitive dysfunction (55.1 %). Fat oxidation capacity was disturbed in PCS patients overall (AUC: 11.3 [10.7-11.9]) compared to healthy controls (p < 0.0001), with hospitalization during acute infection predicting the level of disturbance (p < 0.0001). Low exercise capacity and high fatigue scores resulted in reduced fat oxidation (both p < 0.0001). In particular, younger males were affected by significantly reduced fat oxidation capacity (sex: p = 0.002; age: p < 0.001). Metabolic disturbance was significantly improved during exercise-based rehabilitation (AUC: 14.9 [14.4-15.4]; p < 0.0001), even for the group of younger impaired males (+44.2 %; p < 0.0001). Carbohydrate oxidation was not impaired. CONCLUSIONS: PCS-specific restrictions in fat oxidation may indicate persistent mitochondrial dysfunction. Clinical assessment of PCS patients should include detailed breath-by-breath analysis during exercise to identify metabolic alterations especially in the group of younger males identified in this report. Exercise-based rehabilitation results in improved exercise capacity and fat oxidation and thus likely mitochondrial function. CLINICAL TRIALS: NCT06468722.

Sex-specific differences of cardiopulmonary fitness and pulmonary function in exercise-based rehabilitation of patients with long-term post-COVID-19 syndrome.

BACKGROUND: Post-COVID-19 Syndrome (PCS) entails a spectrum of symptoms, including fatigue, reduced physical performance, dyspnea, cognitive impairment, and psychological distress. Given the effectiveness of exercise-based rehabilitation for PCS, this study examined the efficacy of rehabilitation for PCS patients, focusing on sex-specific differences. METHODS: Prospective cohort study during inpatient rehabilitation. Cardiopulmonary exercise testing and spirometry were performed at admission and discharge. Questionnaires were used to assess fatigue, health-related quality of life, wellbeing, and workability for up to 6 months. RESULTS: 145 patients (36% female, 47.1 ± 12.7 years; 64% male, 52.0 ± 9.1 years; p = 0.018) were referred to rehabilitation 262.0 ± 128.8 days after infection (female, 285.5 ± 140.6 days; male, 248.8 ± 112.0 days; p = 0.110). Lead symptoms included fatigue/exercise intolerance (81.4%), shortness of breath (74.5%), and cognitive dysfunction (52.4%). Women presented with higher relative baseline exercise capacity (82.0 ± 14.3%) than males (68.8 ± 13.3%, p < 0.001), but showed greater improvement in submaximal workload (p = 0.026). Men exhibited higher values for FEV1, FEV1/VC, PEF, and MEF and lower VC at baseline (p ≤ 0.038), while FEV1/VC improvement more in women (p = 0.027). Higher baseline fatigue and lower wellbeing was detected in women and correlated with impaired pulmonary function (p < 0.05). Disease perception including fatigue, health-related quality of life, wellbeing and workability improved with rehabilitation for up to six-month. CONCLUSIONS: Rehabilitation improves cardiopulmonary fitness, pulmonary function and disease burden in women and men with long-term PCS. Women with PCS may benefit from intensified respiratory muscle training. Clinical assessment should include cardiopulmonary exercise testing and pulmonary function tests and fatigue assessments for all PCS patients to document limitations and tailor therapeutical strategies.

Patient-reported preferences in eHealth-based cardiac rehabilitation: A qualitative investigation of behavior change techniques, barriers and facilitators.

Background: Cardiac rehabilitation (CR) reduces recurrent cardiac events and mortality in patients with cardiovascular diseases (CVD). Innovative eHealth methods can facilitate CR uptake and effectiveness by addressing barriers associated with clinic-based rehabilitation. Tailoring eHealth-based CR to patient preferences is needed to further enhance CR. Purpose: To identify preferred behavior change techniques (BCTs) as well as barriers and facilitators for the different health behaviors targeted in eHealth-based CR among patients who have been referred to CR. Methods: Thirty-nine patients were interviewed in nine focus groups in The Netherlands, Germany, and Spain. A thematic analysis, using a combined deductive and inductive approach to coding, was conducted to identify BCTs and barriers and facilitators to behavior change. Behaviors under investigation included physical activity, medication adherence, eating a cardiac healthy-diet, stress reduction and smoking cessation. Results: The perceived helpfulness of BCTs depended on the specific behavior targeted. Common barriers were negative emotional state and physical limitations. A desire to feel physically or mentally well and having experienced a cardiac life event were the most common facilitators across health behaviors. Specific BCTs, barriers and facilitators were found for each of the health behavior. Conclusions: Behavior change techniques that patients preferred for each health behavior targeted in eHealth-based CR were identified. A negative emotional state, experiencing a life event, and improving physical functioning are important barriers and facilitators in multiple behaviors targeted in eHealth-based CR programs. Additional tailoring of interventions to patient preferences for BCTs and patient-specific barriers and facilitators per health behavior could lead to further improvement of eHealth-based CR.

Living Lab Data of Patient Needs and Expectations for eHealth-Based Cardiac Rehabilitation in Germany and Spain From the TIMELY Study: Cross-Sectional Analysis.

BACKGROUND: The use of eHealth technology in cardiac rehabilitation (CR) is a promising approach to enhance patient outcomes since adherence to healthy lifestyles and risk factor management during phase III CR maintenance is often poorly supported. However, patients' needs and expectations have not been extensively analyzed to inform the design of such eHealth solutions. OBJECTIVE: The goal of this study was to provide a detailed patient perspective on the most important functionalities to include in an eHealth solution to assist them in phase III CR maintenance. METHODS: A guided survey as part of a Living Lab approach was conducted in Germany (n=49) and Spain (n=30) involving women (16/79, 20%) and men (63/79, 80%) with coronary artery disease (mean age 57 years, SD 9 years) participating in a structured center-based CR program. The survey covered patients' perceived importance of different CR components in general, current usage of technology/technical devices, and helpfulness of the potential features of eHealth in CR. Questionnaires were used to identify personality traits (psychological flexibility, optimism/pessimism, positive/negative affect), potentially predisposing patients to acceptance of an app/monitoring devices. RESULTS: All the patients in this study owned a smartphone, while 30%-40% used smartwatches and fitness trackers. Patients expressed the need for an eHealth platform that is user-friendly, personalized, and easily accessible, and 71% (56/79) of the patients believed that technology could help them to maintain health goals after CR. Among the offered components, support for regular physical exercise, including updated schedules and progress documentation, was rated the highest. In addition, patients rated the availability of information on diagnosis, current medication, test results, and risk scores as (very) useful. Of note, for each item, except smoking cessation, 35%-50% of the patients indicated a high need for support to achieve their long-term health goals, suggesting the need for individualized care. No major differences were detected between Spanish and German patients (all P>.05) and only younger age (P=.03) but not sex, education level, or personality traits (all P>.05) were associated with the acceptance of eHealth components. CONCLUSIONS: The patient perspectives collected in this study indicate high acceptance of personalized user-friendly eHealth platforms with remote monitoring to improve adherence to healthy lifestyles among patients with coronary artery disease during phase III CR maintenance. The identified patient needs comprise support in physical exercise, including regular updates on personalized training recommendations. Availability of diagnoses, laboratory results, and medications, as part of a mobile electronic health record were also rated as very useful. TRIAL REGISTRATION: ClinicalTrials.gov NCT05461729; https://clinicaltrials.gov/study/NCT05461729.

Non-coding RNAs in exercise immunology: A systematic review.

Regular physical exercise has been recognized as a potent modulator of immune function, with its effects including enhanced immune surveillance, reduced inflammation, and improved overall health. While strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs (ncRNAs) also involved in immune system regulation, heterogeneity in individual study designs and analyzed exercise protocols exists, and a condensed list of functional, exercise-dependent ncRNAs with known targets in the immune system is missing from the literature. A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical exercise. Two combined approaches were used: (a) a systematic literature search for "ncRNA and exercise immunology", (b) and a database search for microRNAs (miRNAs) (miRTarBase and DIANA-Tarbase v8) aligned with known target genes in the immune system based on the Reactome database, combined with a systematic literature search for "ncRNA and exercise". Literature searches were based on PubMed, Web of Science, and SPORTdiscus; and miRNA databases were filtered for targets validated by in vitro experimental data. Studies were eligible if they reported on exercise-based interventions in healthy humans. After duplicate removal, 95 studies were included reporting on 164 miRNAs, which were used for the qualitative synthesis. Six studies reporting on long-noncoding RNAs (lncRNAs) or circular RNAs were also identified. Results were analyzed using ordering tables that included exercise modality (endurance/ resistance exercise), acute or chronic interventions, as well as the consistency in reported change between studies. Evaluation criteria were defined as "validated" with 100% of ≥3 independent studies showing identical direction of regulation, "plausible" (≥80%), or "suggestive" (≥70%). For resistance exercise, upregulation of miR-206 was validated while downregulation of miR-133a appeared plausible. For endurance exercise, 15 miRNAs were categorized as validated, with 12 miRNAs being consistently elevated and 3 miRNAs being downregulated, most of them after acute exercise training. In conclusion, our approach provides evidence that miRNAs play a major role in exercise-induced effects on the innate and adaptive immune system by targeting different pathways affecting immune cell distribution, function, and trafficking as well as production of (anti-)inflammatory cytokines. miRNAs miR-15, miR-29c, miR-30a, miR-142/3, miR-181a, and miR-338 emerged as key players in mediating the immunomodulatory effects of exercise predominantly after acute bouts of endurance exercise.

Medical Rehabilitation of Patients with Post-COVID-19 Syndrome-A Comparison of Aerobic Interval and Continuous Training.

INTRODUCTION: Post-COVID-19 syndrome (PCS) is a multisystemic disorder marked by impaired physical performance as one lead symptom. Since it has been suggested that endurance training as part of medical rehabilitation may be effective in improving physical performance capacity in PCS, this study aimed to compare different modes of aerobic endurance training. METHODS: A total of 110 PCS patients (49.3 ± 11.8 years; 38% women; time after infection = 260.2 ± 127.5 days) underwent detailed clinical screening including symptom-limited cardiopulmonary exercise testing at admission and after 4-6 weeks of inpatient medical rehabilitation. Questionnaires were used to assess disease perception. Patients performed controlled isocaloric cycle ergometer training (3-5 sessions/week; 18 min) as either continuous training (CT) at 50% of maximal workload or as interval training (IT; load = 60%, relief = 30%). Outcomes of PCS patients were compared to coronary artery disease patients (CAD; n = 96) to evaluate overall training effectiveness. RESULTS: Training participation was comparable between the groups, with no indication of training-specific exercise-induced fatigue. Overall, PCS patients improved significantly by a mean of 6.8 ± 12.1% for W at VT1; 3.1 ± 10.0% for VO2 at VT1; 5.5 ± 14.7% for O2 pulse at VT1; 7.5 ± 15.0% for W at VO2peak; 2.7 ± 11.0% for VO2peak and 4.6 ± 12.4% for O2 pulse at VO2peak (all p < 0.05) with no significant differences between groups (p > 0.05). Both groups showed reduced levels of fatigue, anxiety, and depression as well as improved quality of life and wellbeing (all p < 0.05). Compared to guideline-based cardiac rehabilitation, PCS patients showed a similar improvement in workload and oxygen uptake compared to CAD patients. CONCLUSION: PCS patients benefit from aerobic endurance training performed as moderate continuous or interval training as part of a medical rehabilitation program in terms of improved physical exercise capacity and disease perception. The results for PCS patients are comparable to the guideline-based rehabilitation of CAD patients.

Autonomic dysregulation in long-term patients suffering from Post-COVID-19 Syndrome assessed by heart rate variability.

Post-COVID-19 Syndrome (PCS) is a condition with multiple symptoms partly related to dysregulation of the autonomic nerve system. Assessment of heart rate variability (HRV) using 24 h Holter-ECG may serve as a surrogate to characterize cardiac autonomic activity. A prospective study including 103 PCS patients (time after infection = 252 days, age = 49.0 ± 11.3 years, 45.7% women) was performed and patients underwent detailed clinical screening, cardiopulmonary exercise testing, and 24 h Holter monitoring. Data of PCS patients was compared to 103 CAD patients and a healthy control group (n = 90). After correction for age and sex, frequency-related variables differed in PCS patients compared to controls including LF/HFpower, LF/HFnu, and LF/HF ratio (24 h; p ≤ 0.001). By contrast, these variables were largely comparable between PCS and CAD patients, while sympathetic activation was highest in PCS patients during the 24 h period. Overall, PCS patients showed disturbed diurnal adjustment of HRV, with impaired parasympathetic activity at night. Patients hospitalized during acute infection showed an even more pronounced overactivation of sympathetic activity compared to patients who underwent ambulant care. Our data demonstrate persistent HRV alterations in PCS patients with long-term symptom duration, suggesting a sustained impairment of sympathovagal balance. Moreover, sympathetic overstimulation and diminished parasympathetic response in long-term PCS patients are comparable to findings in CAD patients. Whether HRV variables have a prognostic value in PCS and/or might serve as biomarkers indicating a successful interventional approach warrants further longitudinal studies.

Improving accessibility of scientific research by artificial intelligence-An example for lay abstract generation.

The role of scientific research in modern society is essential for driving innovation, informing policy decisions, and shaping public opinion. However, communicating scientific findings to the general public can be challenging due to the technical and complex nature of scientific research. Lay abstracts are written summaries of scientific research that are designed to be easily understandable and provide a concise and clear overview of key findings and implications. Artificial intelligence language models have the potential to generate lay abstracts that are consistent and accurate while reducing the potential for misinterpretation or bias. This study presents examples of artificial intelligence-generated lay abstracts of recently published articles, which were produced using different currently available artificial intelligence tools. The generated abstracts were of high linguistic quality and accurately represented the findings of the original articles. Adopting lay summaries can increase the visibility, impact, and transparency of scientific research, and enhance scientists' reputation among peers, while currently, available artificial intelligence models offer solutions to produce lay abstracts. However, the coherence and accuracy of artificial intelligence language models must be validated before they can be used for this purpose without restrictions.

eHealth for maintenance cardiovascular rehabilitation: a systematic review and meta-analysis.

AIMS: To provide a quantitative analysis of eHealth-supported interventions on health outcomes in cardiovascular rehabilitation (CR) maintenance (phase III) in patients with coronary artery disease (CAD) and to identify effective behavioural change techniques (BCTs). METHODS AND RESULTS: A systematic review was conducted (PubMed, CINAHL, MEDLINE, and Web of Science) to summarize and synthesize the effects of eHealth in phase III maintenance on health outcomes including physical activity (PA) and exercise capacity, quality of life (QoL), mental health, self-efficacy, clinical variables, and events/rehospitalization. A meta-analysis following the Cochrane Collaboration guidelines using Review Manager (RevMan5.4) was performed. Analyses were conducted differentiating between short-term (≤6 months) and medium/long-term effects (>6 months). Effective behavioural change techniques were defined based on the described intervention and coded according to the BCT handbook. Fourteen eligible studies (1497 patients) were included. eHealth significantly promoted PA (SMD = 0.35; 95%CI 0.02-0.70; P = 0.04) and exercise capacity after 6 months (SMD = 0.29; 95%CI 0.05-0.52; P = 0.02) compared with usual care. Quality of life was higher with eHealth compared with care as usual (SMD = 0.17; 95%CI 0.02-0.32; P = 0.02). Systolic blood pressure decreased after 6 months with eHealth compared with care as usual (SMD = -0.20; 95%CI -0.40-0.00; P = 0.046). There was substantial heterogeneity in the adapted BCTs and type of intervention. Mapping of BCTs revealed that self-monitoring of behaviour and/or goal setting as well as feedback on behaviour were most frequently included. CONCLUSION: eHealth in phase III CR is effective in stimulating PA and improving exercise capacity in patients with CAD while increasing QoL and decreasing systolic blood pressure. Currently, data of eHealth effects on morbidity, mortality, and clinical outcomes are scarce and should be investigated in future studies. REGISTRATION: PROSPERO: CRD42020203578.

KEY FINDINGS: • eHealth interventions in cardiovascular rehabilitation maintenance may be used to increase physical activity and exercise capacity as well as quality of life while reducing systolic blood pressure.• Effective behavioural change techniques used in eHealth interventions may include self-monitoring of behaviour, goal setting, and feedback on behaviour; thus, future studies are needed to define effective eHealth components based on behavioural change theories and associated behavioural change techniques to assist patients with coronary artery disease.

• This paper reviews the impact of eHealth-supported interventions on health outcomes during cardiovascular rehabilitation maintenance phase III for patients with coronary artery disease, with a meta-analysis performed to differentiate between short-term (≤6 months) and medium/long-term effects (>6 months).

Altered tissue oxygenation in patients with post COVID-19 syndrome.

BACKGROUND: Post COVID-19 syndrome (PCS) is a complex condition with partly substantial impact on patients' social and professional life and overall life quality. Currently, the underlying cause(s) of PCS are unknown. Since PCS-specific symptoms could be associated with systemic alterations in tissue oxygen supply, we aimed to investigate changes in tissue oxygenation in patients with PCS. METHODS: A case-control study including 30 PCS patients (66.6 % males, 48.6 ± 11.2 years, mean time after (first) acute infection: 324 days), 16 cardiologic patients (CVD) (65.5 % males, 56.7 ± 6.3 years) and 11 young healthy controls (55 % males, 28.5 ± 7.4 years) was conducted. Near infrared spectroscopy (NIRS) was used to assess changes in tissue oxygenation during an arterial occlusion protocol on the non-dominant forearm (brachioradialis, 760/850 nm, 5 Hz). The protocol included 10-min rest, a 2-min baseline measurement followed by a 3-min ischemic period (upper-arm cuff, 50 mmHg above resting systolic blood pressure) and a 3-min reoxygenation period. PCS patients were grouped by presence of arterial hypertension and elevated BMI to assess the impact of risk factors. RESULTS: No differences in mean tissue oxygenation in the pre-occlusion phase existed between groups (p ≥ 0.566). During ischemia, comparisons of linear regressions slopes revealed slower oxygen desaturation for PCS patients (-0.064 %/s) compared to CVD patients (-0.08 %/s) and healthy subjects (-0.145 %/s) (p < 0.001). After cuff release, slowest speed for reoxygenation was detected in PCS patients at 0.84 %/s compared to CVD patients (1.04 %/s) and healthy controls (CG: 2.07 %/s) (p < 0.001). The differences between PCS patients and CVD patients during ischemia remained significant also after correction for risk factors. Analyses of complications during acute infection, persistence of PCS symptoms (time after acute infection), or PCS severity (number of lead symptoms) as confounding factors did not reveal a significant effect. CONCLUSIONS: This study provides evidence that the rate of tissue oxygen consumption is persistently altered in PCS and that PCS patients show an even slower decline in tissue oxygenation during occlusion than CVD patients. Our observations may at least partly explain PCS-specific symptoms such as physical impairment and fatigue.

A single session of EMS training induces long-lasting changes in circulating muscle but not cardiovascular miRNA levels: a randomized crossover study.

Electromyostimulation (EMS) is used to maintain or build skeletal muscle and to increase cardiopulmonary fitness. Only limited data on the molecular mechanisms induced by EMS are available and effects on circulating microRNAs (c-miRNAs) have not been reported. This study aimed to evaluate whether EMS induces long-term changes in muscle- and cardiovascular-specific c-miRNA levels. Twelve healthy participants (33.0 ± 12.0 yr, 7 women) performed a 20-min whole body EMS training and a time- and intensity-matched whole body circuit training (CT) in random order. Blood samples were drawn pre-/posttraining and at 1.5, 3, 24, 48, and 72 h to determine creatine kinase (CK) and miRNA-21-5p, -126-3p, -133a-3p, -146a-5p, -206-3p, -222-3p, and -499a-5p levels. Muscular exertion was determined using an isometric strength test, and muscle soreness/pain was assessed by questionnaire. EMS participants reported higher muscle soreness 48 and 72 h postexercise and mean CK levels after EMS increased compared with CT at 48 and 72 h (time × group P ≤ 0.01). The EMS session induced a significant elevation of myomiR-206 and -133a levels starting at 1.5 and 3 h after exercise. Both miRNAs remained elevated for 72 h with significant differences between 24 and 72 h (time × group P ≤ 0.0254). EMS did not induce changes in cardiovascular miRNAs and no elevation in any miRNA was detected following CT. Time-course analysis of muscle damage marker CK and c-miR-133a and -206 levels did not suggest a common scheme (P ≥ 0.277). We conclude that a single EMS session induces specific long-lasting changes of miR-206 and miR-133 involved in muscle proliferation and differentiation. A single EMS session does not affect primary cardiovascular miRNA-21-5p, -126-3p, -146a-5p, and -222-3p levels.NEW & NOTEWORTHY Our study describes the long-term effects of electromyostimulation (EMS) on circulating miRNA levels. The observed increase of functional myomiR-206 and -133a levels over 72 h suggests long-lasting effects on muscle proliferation and differentiation, whereas cardiovascular miRNAs appear unaffected. Our findings suggest that circulating miRNAs provide useful insight into muscle regeneration processes after EMS and may thus be used to optimize EMS training effects.

Prognostic and therapeutic potential of microRNAs for fracture healing processes and non-union fractures: A systematic review.

BACKGROUND: Approximately 10% of all bone fractures result in delayed fracture healing or non-union; thus, the identification of biomarkers and prognostic factors is of great clinical interest. MicroRNAs (miRNAs) are known to be involved in the regulation of the bone healing process and may serve as functional markers for fracture healing. AIMS AND METHODS: This systematic review aimed to identify common miRNAs involved in fracture healing or non-union fractures using a qualitative approach. A systematic literature search was performed with the keywords 'miRNA and fracture healing' and 'miRNA and non-union fracture'. Any original article investigating miRNAs in fracture healing or non-union fractures was screened. Eventually, 82 studies were included in the qualitative analysis for 'miRNA and fracture healing', while 19 were selected for the 'miRNA and fracture non-union' category. RESULTS AND CONCLUSIONS: Out of 151 miRNAs, miR-21, miR-140 and miR-214 were the most investigated miRNAs in fracture healing in general. miR-31-5p, miR-221 and miR-451-5p were identified to be regulated specifically in non-union fractures. Large heterogeneity was detected between studies investigating the role of miRNAs in fracture healing or non-union in terms of patient population, sample types and models used. Nonetheless, our approach identified some miRNAs with the potential to serve as biomarkers for non-union fractures, including miR-31-5p, miR-221 and miR-451-5p. We provide a discussion of involved pathways and suggest on alignment of future research in the field.

Corrigendum: Health benefits of probiotics in sport and exercise-Non-existent or a matter of heterogeneity? A systematic review.

[This corrects the article DOI: 10.3389/fnut.2022.804046.].

Therapeutic Potential of Electromyostimulation (EMS) in Critically Ill Patients-A Systematic Review.

Ample evidence exists that intensive care unit (ICU) treatment and invasive ventilation induce a transient or permanent decline in muscle mass and function. The functional deficit is often called ICU-acquired weakness with critical illness polyneuropathy (CIP) and/or myopathy (CIM) being the major underlying causes. Histopathological studies in ICU patients indicate loss of myosin filaments, muscle fiber necrosis, atrophy of both muscle fiber types as well as axonal degeneration. Besides medical prevention of risk factors such as sepsis, hyperglycemia and pneumonia, treatment is limited to early passive and active mobilization and one third of CIP/CIM patients discharged from ICU never regain their pre-hospitalization constitution. Electromyostimulation [EMS, also termed neuromuscular electrical stimulation (NMES)] is known to improve strength and function of healthy and already atrophied muscle, and may increase muscle blood flow and induce angiogenesis as well as beneficial systemic vascular adaptations. This systematic review aimed to investigate evidence from randomized controlled trails (RCTs) on the efficacy of EMS to improve the condition of critically ill patients treated on ICU. A systematic search of the literature was conducted using PubMed (Medline), CENTRAL (including Embase and CINAHL), and Google Scholar. Out of 1,917 identified records, 26 articles (1,312 patients) fulfilled the eligibility criteria of investigating at least one functional measure including muscle function, functional independence, or weaning outcomes using a RCT design in critically ill ICU patients. A qualitative approach was used, and results were structured by 1) stimulated muscles/muscle area (quadriceps muscle only; two to four leg muscle groups; legs and arms; chest and abdomen) and 2) treatment duration (≤10 days, >10 days). Stimulation parameters (impulse frequency, pulse width, intensity, duty cycle) were also collected and the net EMS treatment time was calculated. A high grade of heterogeneity between studies was detected with major cofactors being the analyzed patient group and selected outcome variable. The overall efficacy of EMS was inconclusive and neither treatment duration, stimulation site or net EMS treatment time had clear effects on study outcomes. Based on our findings, we provide practical recommendations and suggestions for future studies investigating the therapeutic efficacy of EMS in critically ill patients. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021262287].

Health Benefits of Probiotics in Sport and Exercise - Non-existent or a Matter of Heterogeneity? A Systematic Review.

Background: The use of probiotics in sports has been growing in recent years, as up to 50% of athletes suffer from training- and performance-limiting gastrointestinal (GI) problems. Moreover, repeated exhaustive exercise and high training loads may lead to a transiently depressed immune function, associated with an increased risk of upper respiratory tract infection (URTI). Aim: To provide a qualitative analysis of probiotic effects on URTI, GI symptoms and the immune system in healthy individuals under consideration of performance level as main classifier. Methods: A systematic review of the literature was conducted (PubMed, SPORTDiscus with Full Text, Web of Science) to analyze the effects of probiotics in athletes and healthy active individuals on GI problems, URTI, and the immune system. A qualitative synthesis with performance level and treatment duration as main classifiers was performed. Results: Of 41 eligible studies, 24 evaluated the effects of probiotic supplements in athletes, 10 in recreationally active individuals and 7 in healthy untrained adults. Large heterogeneity was observed in terms of probiotic strains, mode of delivery, performance level, treatment duration and outcome assessment. Overall, studies provided inconsistent observations. Conclusion: The effects of probiotics on immune system, URTI, and GI symptoms in athletes, healthy adults and recreationally active individuals remain inconclusive. Based on the analyzed studies and identified parameters, this article provides suggestions to align future research on the effects of probiotics in exercise. Systematic Review Registration: PROSPERO, identifier: CRD42021245840.

Longitudinal choriocapillaris changes in the presence of reticular pseudodrusen.

To determine longitudinal changes in choriocapillaris (CC) measures in eyes with reticular pseudodrusen (RPD) using optical coherence tomography angiography (OCTA). In this observational prospective study, 20 patients with exclusively RPD and no other alteration due to age-related macular degeneration were included. Eight RPD patients were re-examined at 5-year follow-up. Multimodal imaging was performed at baseline and at 5-year follow-up. OCTA CC images were analyzed for number, size and total area of flow deficits (FD), mean signal intensity, signal intensity standard deviation and kurtosis of signal intensity distribution in the ring area between a circle of 4 mm diameter and a circle of 6 mm diameter and in the superior ring quadrant. Area affected by RPD increased from 19.36 ± 8.39 mm2 at baseline to 37.77 ± 9.03 mm2 at 5-year follow-up. At baseline, percent of CC FD area was greater in RPD eyes (quadrant: p < 0.001; ring: p < 0.001) compared to controls. Besides, RPD eyes revealed a lower mean intensity signal (quadrant: p < 0.001; ring: p < 0.001). Evaluation of CC parameters suggested significant group × time interaction effects for CC FD (p = 0.04) and mean intensity signal (p = 0.004), in that RPD eyes presented increased CC FD and decreased mean intensity signal at follow-up. OCTA CC decorrelation signal further decreases in RPD patients over 5 years in both RPD-affected and RPD-unaffected macular areas.

Four weeks of electromyostimulation improves muscle function and strength in sarcopenic patients: a three-arm parallel randomized trial.

BACKGROUND: Sarcopenia, defined as loss of muscle mass, quality, and function, is associated with reduced quality of life and adverse health outcomes including disability and mortality. Electromyostimulation (EMS) has been suggested to attenuate the loss of muscle mass and function in elderly, sedentary individuals. This study aimed to investigate the effects of EMS on muscle strength and function during 4 weeks of inpatient medical rehabilitation. METHODS: Patients receiving 4 weeks of inpatient medical rehabilitation diagnosed with sarcopenia using bioimpedance analysis were eligible to participate. One hundred and thirty-four patients (55.7 ± 7.9 years, 25.4% female) were randomly assigned to three groups: whole-body (WB) EMS (n = 48): stimulation of major muscle groups (pectoral muscles, latissimus, trapezius, abdominals, upper arm and leg, lower back muscles, gluteal muscles, and thighs); part-body (PB) EMS (n = 42): stimulation of leg muscles including gluteal muscles and thighs; and control group (CG, n = 44). All participants performed six 20 min training sessions including dynamic movements (squats, lunges, biceps curl, chest press, butterfly reverse, reverse lunges, standing diagonal crunches, etc.) with superimposed (WB-, PB-) EMS or without EMS (CG) in addition to the standard rehabilitation programme. Primary outcome variables included muscle function assessed by chair rise test and 6 min walking test as well as muscle strength (isometric grip strength, leg, arm, and back extension). RESULTS: Primary outcome variables chair rise test and leg extension improved significantly (P = 0.001, η2  = 0.06 and P = 0.008, η2  = 0.06; EMS vs. CG) in that chair rise test results increased in WB-EMS from 5 (4; 7) to 7 (5; 9), in PB-EMS from 5 (5; 7) to 7 (6; 8), and in CG from 6 (4; 7) to 7 (5; 8) repetitions. Knee extension increased in WB-EMS from 692.3 ± 248.6 to 831.7 ± 298.7 N, in PB-EMS from 682.8 ± 257.8 to 790.2 ± 270.2 N, and in CG from 638.5 ± 236.9 to 703.2 ± 218.6 N. No adverse events or side effects occurred. CONCLUSIONS: We conclude that EMS might be an additional training option to improve muscle function and strength in sarcopenic patients during a 4 week rehabilitation programme. EMS provides greater functional and strength improvements compared with standard treatment with additional potential health benefits for sarcopenic cardiac and orthopaedic patients.

Sex-specific differences and long-term outcome of patients with coronary artery disease and chronic kidney disease: the Coronary Artery Disease and Renal Failure (CAD-REF) Registry.

BACKGROUND: Cardiovascular morbidity and mortality are closely linked to chronic kidney disease (CKD). Sex-specific long-term outcome data of patients with coronary artery disease (CAD) and CKD are scarce. METHODS: In the prospective observational multicenter Coronary Artery Disease and REnal Failure (CAD-REF) Registry, 773 (23.1%) women and 2,579 (76.9%) men with angiographically documented CAD and different stages of CKD were consecutively enrolled and followed for up to 8 years. Long-term outcome was evaluated using survival analysis and multivariable Cox-regression models. RESULTS: At enrollment, women were significantly older than men, and suffered from more comorbidities like CKD, hypertension, diabetes mellitus, and multivessel coronary disease. Regarding long-term mortality, no sex-specific differences were observed (Kaplan-Meier survival estimates: 69% in women vs. 69% in men, plog-rank = 0.7). Survival rates decreased from 89% for patients without CKD at enrollment to 72% for patients with CKD stages 1-2 at enrollment and 49% for patients with CKD stages 3-5 at enrollment (plog-rank < 0.001). Cox-regression analysis revealed that sex or multivessel coronary disease were no independent predictors of long-term mortality, while age, CKD stages 3-5, albumin/creatinine ratio, diabetes, valvular heart disease, peripheral artery disease, and left-ventricular ejection fraction were predictors of long-term mortality. CONCLUSIONS: Sex differences in CAD patients mainly exist in the cardiovascular risk profile and the extent of CAD. Long-term mortality was not depended on sex or multivessel disease. More attention should be given to treatment of comorbidities such as CKD and peripheral artery disease being independent predictors of death. Clinical Trail Registration ClinicalTrials.gov Identifier: NCT00679419.