The Impact of Physical Exercise on microRNAs in Hemodialysis Patients: A Review and a Protocol for an Ancillary Study.

Physical inactivity is considered a significant risk factor for mortality and morbidity among chronic hemodialysis (HD) patients. Therefore, physical exercise is recommended in the treatment of HD patients. Although the beneficial effects of physical exercise in HD patients are well-described in the literature, the underlying physiological mechanisms still need to be fully understood. Recently, microRNAs (miRNAs) have emerged as potential mediators of the therapeutic effects of physical exercise in healthy individuals. miRNAs are short, single-stranded, noncoding RNAs involved in gene expression regulation. Specifically, upon forming the RNA-induced silencing complex, miRNAs selectively bind to specific miRNAs within cells, reducing gene expression. miRNAs can be secreted by cells in an accessible form or enclosed within exosomes or extracellular vesicles. They can be detected in various body fluids, including serum (circulating miRNAs), facilitating the study of their diverse expression. Currently, there is no available data regarding the impact of physical exercise on the expression of miRNAs involved in osteogenic differentiation, a fundamental mechanism in the development of vascular calcification, for HD patients. Therefore, we have designed an observational and longitudinal case-control study to evaluate the expression of miR-9 and miR-30b in HD patients participating in a 3-month interdialytic physical exercise program. This paper aims to present the study protocol and review the expression of circulating miRNAs in HD patients and their modulation through physical exercise.

The Issue of Gender Bias Represented in Authorship in the Fields of Exercise and Rehabilitation: A 5-Year Research in Indexed Journals.

Despite progress made in recent decades, gender bias is still present in scientific publication authorship. The underrepresentation of women and overrepresentation of men has already been reported in the medical fields but little is known in the fields of exercise sciences and rehabilitation. This study examines trends in authorship by gender in this field in the last 5 years. All randomized controlled trials published in indexed journals from April 2017 to March 2022 through the widely inclusive Medline dataset using the MeSH term "exercise therapy" were collected, and the gender of the first and last authors was identified through names, pronouns and photographs. Year of publication, country of affiliation of the first author, and ranking of the journal were also collected. A chi-squared test for trends and logistic regression models were performed to analyze the odds of a woman being a first or last author. The analysis was performed on a total of 5259 articles. Overall, 47% had a woman as the first author and 33% had a woman as the last author, with a similar trend over five years. The trend in women's authorship varied by geographical area, with the higher representation of women authors in Oceania (first: 53.1%; last: 38.8%), North-Central America (first: 45.3%; last: 37.2%), and Europe (first: 47.2%; last: 33.3%). The logistic regression models (p < 0.001) indicated that women have lower odds of being authors in prominent authorship positions in higher-ranked journals. In conclusion, over the last five years, in the field of exercise and rehabilitation research, women and men are almost equally represented as first authors, in contrast with other medical areas. However, gender bias, unfavoring women, still exists, especially in the last authorship position, regardless of geographical area and journal ranking.

Foot Temperature by Infrared Thermography in Patients with Peripheral Artery Disease before and after Structured Home-Based Exercise: A Gender-Based Observational Study.

Decreased arterial perfusion is a typical condition of patients with peripheral artery disease (PAD), with the microvascular picture particularly present among women. This observational study aimed to detect foot perfusion changes by infrared thermography (IRT) after a home-based exercise program in both sexes. A total of 76 PAD patients with claudication (72 ± 4 years; 52 males) were enrolled in a structured in-home exercise program composed of two daily 8 min interval walking sessions (1:1 walk:rest ratio) with progressively increasing speed. Outcome measures collected at baseline (T0) and at each hospital visit after 5 weeks, 12 weeks and 20 weeks included foot temperature measured by IRT (anterior tibial, posterior tibial, dorsalis pedis and arcuate artery regions), ankle brachial index and the 6 min walking test. After 20 weeks, foot temperature in both limbs showed a significant increasing trend, with a mean variation of 1.3 °C for the more impaired limb and 0.9 °C for the contralateral limb (t = 8.88, p < 0.001 and t = 5.36; p < 0.001, respectively), with significant changes occurring after 5 weeks of training. The sex-oriented analysis did not highlight any significant difference, with an improvement of mean foot temperature of 1.5 ± 0.6 °C in females versus 1.2 ± 0.5 °C in males (p = 0.42). Ankle brachial index and performance also significantly improved over time (p < 0.001) without gender differences. In patients with PAD, a structured low-intensity exercise program significantly improved foot temperature and exercise capacity without any sex-related difference.

Effects of Exercise, Rehabilitation, and Nutritional Approaches on Body Composition and Bone Density in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

People with multiple sclerosis (pwMS) are affected by a wide range of disabilities, including a decrease in bone mineral density (BMD) and a worsening of body composition (BC), which negatively impact their quality of life quality. This study aims to analyze the effects of nonpharmacological interventions-in particular, physical activity, nutritional approaches, and rehabilitation-on BC and BMD in pwMS. This systematic review and meta-analysis was performed following the updated version of the PRISMA guidelines. In July 2022, five databases (MEDLINE, Embase, The Cochrane Library, Google Scholar, Web of Science) and gray literature were screened. Relevant articles published between 1 January 1990 and 1 September 2022 in any language were included. Outcomes of interest were anthropometric, BC measures, and BMD. The RoB 2.0 tool was used to assess the risk of bias. After duplicates elimination, 1120 records were screened, and 36 studies were included. A total of 25 articles were focused on physical activity and rehabilitation, 10 on nutrition, and 1 on multimodal intervention. One-third of the studies were judged to be at high risk of bias. The meta-analysis showed a high degree of heterogeneity due to the high variability in disease severity and intervention duration, intensity, frequency, and type. In general, no intervention showed consistent positive effects on BC. However, the most promising interventions seemed to be high-intensity training and ketogenic diets. Only a few studies considered BMD, and the results are inconsistent. Nevertheless, more studies are needed in order to confirm these results.

Inspiratory-Expiratory Muscle Training Improved Respiratory Muscle Strength in Dialysis Patients: A Pilot Randomised Trial.

End-stage kidney disease (ESKD) exposes patients to progressive physical deconditioning involving the respiratory muscles. The aim of this pilot randomized controlled trial was to determine the feasibility and effectiveness of low-intensity respiratory muscle training (RMT) learned at the hospital and performed at home. A group of ESKD patients (n = 22) were randomized into RMT or usual care (control group, CON) in a 1:1 ratio. The respiratory training was performed at home with an inspiratory-expiratory system for a total of 5 min of breathing exercises in a precise rhythm (8 breaths per minute) interspersed with 1 min of rest, two times per day on nondialysis days for a total of 4 weeks, with the air resistance progressively increasing. Outcome measures were carried out every 4 weeks for 3 consecutive months, with the training executed from the 5th to the 8th week. Primary outcomes were maximal inspiratory and expiratory pressure (MIP, MEP), while secondary outcomes were lung capacity (FEV1, FVC, MVV). Nineteen patients without baseline between-group differences completed the trial (T: n = 10; Age: 63 ± 10; Males: n = 12). Both MIP and MEP significantly improved at the end of training in the T group only, with a significant difference of MEP of 23 cmH2O in favor of the RMT group (p = 0.008). No significant variations were obtained for FVC, FEV1 or MVV in either group, but there was a greater decreasing trend over time for the CON group, particularly for FVC (t = -2.00; p = 0.046). Low-fatiguing home-based RMT, with a simple device involving both inspiratory and expiratory muscles, may significantly increase respiratory muscle strength.

A Fitness-Fatigue Model of Performance in Peripheral Artery Disease: Predicted and Measured Effects of a Pain-Free Exercise Program.

Banister impulse-response (IR) model estimates the performance in response to the training impulses (TRIMPs). In 100 patients with peripheral artery disease (PAD), we tested by an IR model the predictability of the effects of a 6-month structured home-based exercise program. The daily TRIMPs obtained from prescribed walking speed, relative intensity and time of exercise determined the fitness-fatigue components of performance. The estimated performance values, calculated from the baseline 6-min and pain-free walking distance (6MWD and PFWD, respectively) were compared with values measured at visits through regression models. Interval pain-free walking at controlled speed prescribed during circa-monthly hospital visits (5 ± 1) was safely performed at home with good adherence (92% of scheduled sessions, 144 ± 25 km walked in 50 ± 8 training hours). The mean TRIMP rose throughout the program from 276 to 601 a.u. The measured 6MWD and PFWD values increased (+33 m and +121 m, respectively) showing a good fit with those estimated by the IR model (6MWD: R2 0.81; PFWD: R2 0.68) and very good correspondence (correlation coefficients: 0.91 to 0.95), without sex differences. The decay of performance without training was estimated at 18 ± 3 weeks. In PAD, an IR model predicted the walking performance following a pain-free exercise program. IR models may contribute to design and verify personalized training programs.

Cortical Oxygenation during a Motor Task to Evaluate Recovery in Subacute Stroke Patients: A Study with Near-Infrared Spectroscopy.

In subacute stroke patients we studied cortical oxygenation changes by near-infrared spectroscopy (NIRS) during a motor task performed with the hemiparetic arm (15 s of reaching and grasping, 45 s of rest, repeated 6 times). Twenty-three subjects were included at baseline, compared with six healthy subjects, and restudied after 6 weeks of rehabilitation. Motor/premotor cortical changes in oxyhemoglobin detected by NIRS were quantified as the area under the curve (AUC) for the total cortex (TOT-AUC) and for both affected (AFF-AUC) and unaffected hemispheres (UN-AUC). The ratio between AUC and the number of task repetitions performed identified the cortical metabolic cost (CMC) or the oxygenation increase for a single movement. Fugl−Meyer assessment of the upper extremity (FMA-UE) was also performed. At baseline, both total and hemispheric CMC were significantly higher in stroke patients than in healthy subjects and inversely correlated with FMA-UE. After rehabilitation, changes in total-CMC and unaffected-CMC, but not Affected-CMC, were inversely correlated with variations in the FMA-UE score. A value > 5000 a.u. for the ratio baseline TOT-CMC/days since stroke was associated with not reaching the clinically important difference for FMA-UE after rehabilitation. In subacute stroke the CMC, a biomarker assessed by NIRS during a motor task with the hemiparetic arm, may describe cortical time/treatment reorganization and favor patient selection for rehabilitation.

Effects of forest walking on physical and mental health in elderly populations: a systematic review.

There is a growing awareness that spending time in nature is associated with improvement of well-being; nevertheless, the prescription of forest bathing is still limited. The aim of this systematic review was to explore the physiological and psychological benefits of different forest therapies on healthy and pathological elderly populations (>60 years) to identify the most-effective type, duration, and frequency of these interventions. A search for literature was carried out in December 2021 using PubMed, EMBASE, ResearchGate, Google Scholar and Web of Science. Grey literature was searched as well. After removal of the duplicates, within the 214 articles identified, ten met the inclusion criteria. The methodological quality of the selected studies was rated. Forest walking, alone and in combination with other activities is the most effective intervention. The selected studies reported a positive impact on physical components, including reduction in blood pressure and heart rate and improvements in cardiopulmonary and neurochemical parameters. Favorable modifications have also been noted in the psychological field, with improvements in depression, stress levels and in quality of life perception. In conclusion, forest walking may play an important role in promoting physical and mental health in healthy and pathological elderly populations. However, the lack of high-quality studies limits the strength of the results, calling for more trials.

Home-Based Exercise in Elderly Patients with Claudication and Chronic Kidney Disease Is Associated with Lower Progressive Renal Function Worsening: A 5-Year Retrospective Study.

This observational study aimed to monitor the 5-year trends of kidney function in patients with peripheral artery disease (PAD) and concomitant chronic kidney disease (CKD) enrolled or not enrolled into a rehabilitative exercise program. Sixty-six patients (aged 72 ± 10, males n = 52) at KDOQI stages III-IV and PAD at Rutherford's stage I-III were included in the study, with a group (Exercise, EX; n = 32) receiving a 6-month structured pain-free home-based walking program and a group (Control, CO; n = 34) receiving walking advice and optimal nephrological care. Outcomes included kidney function measured through serum creatinine (sCr) and clinical outcomes, including the rate of advance of CKD stages and admission to dialysis, revascularizations, and hospitalizations. At baseline, the two groups were comparable for age, nephropathy, medications, comorbidities, and PAD severity. Patients in the EX group safely completed the exercise program. SCr values were slightly increased in EX (baseline: 2.35 ± 0.32; 5-year: 2.71 ± 0.39 mg/dL) and progressively worsened in CO (baseline: 2.30 ± 0.31; 5-year 4.22 ± 0.42 mg/dL), with a significant between-group difference (p = 0.002). The control group also showed a higher number of dialysis admissions (5 vs. 0, p = 0.025) and advancing CKD stage as well a higher risks for lower limb revascularization (hazard ratio: 2.59; 95%CI: 1.11-6.02; p = 0.027) and for all-cause hospitalization (hazard ratio: 1.77; 95%CI: 1.05-2.97; p = 0.031). PAD-CKD patients enrolled in a low-moderate intensity home-exercise program showed more favorable long-term trends in kidney function and clinical outcomes than patients with usual care. These preliminary observations need to be confirmed in randomized trials.

The Value of Infrared Thermography to Assess Foot and Limb Perfusion in Relation to Medical, Surgical, Exercise or Pharmacological Interventions in Peripheral Artery Disease: A Systematic Review.

Infrared thermography (IRT) is a promising imaging method in patients with peripheral artery disease (PAD). This systematic review aims to provide an up-to-date overview of the employment of IRT as both a diagnostic method and an outcome measure in PAD patients in relation to any kind of intervention. On September 2022, MEDLINE, EMBASE, CENTRAL, Google Scholar, Web of Science, and gray literature were screened. Eligible articles employing IRT in PAD were screened for possible inclusion. The RoB 2.0 tool was used to assess the risk of bias. Twenty-one eligible articles were finally included, recruiting a total of 1078 patients. The IRT was used for PAD diagnosis/monitoring in 11 studies or to assess the effect of interventions (revascularization, pharmacological therapy, or exercise rehabilitation) in 10 studies. The analysis of the included papers raised high concerns about the overall quality of the studies. In conclusion, IRT as a noninvasive technique showed promising results in detecting foot perfusion in PAD patients. However, limits related to devices, points of reference, and measurement conditions need to be overcome by properly designed trials before recommending its implementation in current vascular practice.

[Physical exercise in chronic kidney disease: an empty narrative or an effective intervention?]

Chronic kidney disease (CKD) is growing worldwide, with increasing numbers of patients facing end-stage renal disease, high cardiovascular risk, disability and mortality. Early recognition of CKD and improvements in lifestyle are crucial for maintaining or recovering both physical function and quality of life. It is well known that reducing sedentariness, increasing physical activity and initiating exercise programs counteract cardiovascular risk and frailty, limit deconditioning and sarcopenia, and improve mobility, without side-effects. However, these interventions, often requested by CKD patients themselves, are scarcely available. Indeed, it is necessary to identify and train specialists on exercise in CKD and to sensitize doctors and health personnel, so that they can direct patients towards an active lifestyle. On the other hand, effective and sustainable interventions, capable of overcoming patients' barriers to exercise, remain unexplored. Scientific societies, international research teams and administrators need to work together to avoid that exercise in nephrology remains an empty narrative, a niche interest without any translations into clinical practice, with no benefit to the physical and mental health of CKD patients.

Effectiveness of Home-Based Pain-Free Exercise versus Walking Advice in Patients with Peripheral Artery Disease: A Randomized Controlled Trial.

Exercise therapy in the intermediate stages of peripheral artery disease (PAD) represents an effective solution to improve mobility and quality of life (QoL). Home-based programs, although less effective than supervised programs, have been found to be successful when conducted at high intensity by walking near maximal pain. In this randomized trial, we aim to compare a low-intensity, pain-free structured home-based exercise (SHB) program to an active control group that will be advised to walk according to guidelines. Sixty PAD patients aged > 60 years with claudication will be randomized with a 1:1 ratio to SHB or Control. Patients in the training group will be prescribed an interval walking program at controlled speed to be performed at home; the speed will be increased weekly. At baseline and after 6 months, the following outcomes will be collected: pain-free walking distance and 6-min walking distance (primary outcome), ankle-brachial index, QoL by the VascuQoL-6 questionnaire, foot temperature by thermal camera, 5-time sit-to-stand test, and long-term clinical outcomes including revascularization rate and mortality. The home-based pain-free exercise program may represent a sustainable and cost effective option for patients and health services. The trial has been approved by the CE-AVEC Ethics Committee (898/20). Registration details: Clinicaltrials.gov NCT04751890 [Registered: 12 February 2021].

Beyond the Patient's Report: Self-Reported, Subjective, Objective and Estimated Walking Disability in Patients with Peripheral Artery Disease.

Among patients with peripheral artery disease, an altered estimation of walking ability reported to the physician may influence the choice of treatment. We compared claudication distance (CD) values reported by patients or assessed by validated protocols to elaborate a formula capable of estimating more reliable values. Three hundred fifty-nine patients with claudication were measured at the time of entry into a rehabilitation program. Walking performance was obtained by patients' reports (self-reported claudication distance, SR-CD) and was directly assessed to determine the claudication and maximal walking distance by the 6-min test (6-CD and 6-MWD) and an incremental treadmill test (T-CD and T-MWD). The degree of muscle deoxygenation was objectively determined at the calf by near-infrared spectroscopy (NIRS) during the treadmill test. Among the 289 subjects analyzed, SR-CD exceeded both 6-CD and T-CD (+155 and +182 m, respectively). SR-CD was moderately correlated with T-CD (r = 0.30), 6-CD (r = 0.32), and 6-MWD (r = 0.29) but not with muscle deoxygenation per meter walked, unlike T-CD and 6-CD. A formula adjusted for the presence of diabetes reduced patient overestimation by 92%. The patient's reported claudication distance was generally overestimated compared to objective measures, and it was made more reliable through a corrective factor for easy use in a clinical setting.

A Personalized Patient-Centered Intervention to Empower through Physical Activity the Patient in the Dialysis Center: Study Protocol for a Pragmatic Nonrandomized Clinical Trial.

Sedentariness of patients affected by end-stage kidney disease (ESKD) expose them to high risk of unfavorable clinical outcomes. Exercise training is effective in improving physical function, quality of life (QoL) and long-term outcomes. However, the existing barriers related to patients, programs and dialysis staff limit patient participation and call for new strategies. This pragmatic nonrandomized trial will test the impact on ESKD population of an intervention proposed by an exercise facilitator regularly present in a dialysis center. The patient will be free to choose among three-month walking and/or resistance low-intensity training programs: (a) guided physical activity increase; (b) home-based exercise; (c) in-hospital (pre/post dialysis) supervised exercise; (d) performance assessment only. The first phase will define feasibility and the characteristics and preference of responders. The second phase will evaluate safety and patients' adherence. Outcome measures will be collected at baseline, after three-month and at six-month follow-up. They will include: aerobic capacity, QoL, gait speed, strength, depression and long-term clinical outcomes (hospitalization and mortality). The trial was approved by the Area-Vasta Emilia-Romagna Centro Ethics Committee with approval number 48/2019. Written informed consent will be obtained from all participants. The results of the study will be presented in international congresses, published in peer-reviewed journals and communicated to the patient community. Registration details: Clinicaltrials.gov NCT04282616 [Registered:24/02/2020].