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Paired associative stimulation (PAS) is a non-invasive brain stimulation technique combining transcranial magnetic stimulation and peripheral nerve stimulation. PAS allows connections between cortical areas and peripheral nerves (C/P PAS) or between cortical regions (C/C PAS) to be strengthened or weakened by spike-timing-dependent neural plasticity mechanisms. Since PAS modulates both neurophysiological features and motor performance, there is growing interest in its application in neurorehabilitation. We aimed to synthesize evidence on the motor rehabilitation role of PAS in stroke patients. We performed a literature search following the PRISMA Extension for Scoping Reviews Framework. Eight studies were included: one investigated C/C PAS between the cerebellum and the affected primary motor area (M1), seven applied C/P PAS over the lesional, contralesional, or both M1. Seven studies evaluated the outcome on upper limb and one on lower limb motor recovery. Although several studies omit crucial methodological details, PAS highlighted effects mainly on corticospinal excitability, and, more rarely, an improvement in motor performance. However, most studies failed to prove a correlation between neurophysiological changes and motor improvement. Although current studies seem to suggest a role of PAS in post-stroke rehabilitation, their heterogeneity and limited number do not yet allow definitive conclusions to be drawn.

Background: After ischemic stroke, there is no general consensus on the optimal position for the head of patients in the acute phase. This observational study aimed to measure the variations in cortical oxygenation using noninvasive functional near-infrared spectroscopy (fNIRS) at different degrees of head positioning on a bed. Methods: Consecutive ischemic stroke patients aged 18 years or older with anterior circulation ischemic stroke within 48 h of symptom onset who could safely assume different positions on a bed were included. A 48-channel fNIRS system was placed in the bilateral sensorimotor cortex. Then, the bed of each patient was moved into four consecutive positions: (1) seated (90° angle between the head and bed surface); (2) lying at 30°; (3) seated again (90°); and (4) lying flat (0°). Each position was maintained for 90 s; the test was conducted 48 h after stroke onset and after 5 ± 1 days. The variations in oxygenated hemoglobin in the global brain surface and for each hemisphere were recorded and compared. Results: Twenty-one patients were included (males, n = 11; age, 79 ± 9 years; ASPECTS, 8 ± 2). When evaluating the affected side, the median oxygenation was significantly greater in the lying-flat (0°) and 30° positions than in the 90° position (p < 0.001 for both comparisons). No significant differences between the supine position and the 30° position were found, although oxygenation was slightly lower in the 30° position than in the supine position (p = 0.063). No differences were observed when comparing recanalized and nonrecanalized patients separately or according to stroke severity. The evaluation conducted 5 days after the stroke confirmed the previous data, with a significant difference in oxygenation at 0° and 30° compared to 90°. Conclusions: This preliminary study suggested that there are no substantial differences in brain oxygenation between the lying-flat head position and the 30° laying position.

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.

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.

Disorders of consciousness (DoC) due to severe traumatic brain injury (TBI) are associated with severe disability and an alteration of cortical activation, angiogenesis, and inflammation, which are crucial elements for behavioural recovery. This exploratory study aimed to evaluate anti-inflammatory and cortical responses after transcranial direct current stimulation (tDCS) in traumatic prolonged disorders of consciousness. Ten minimally conscious state (MCS) patients underwent ten sessions of anodal tDCS (five sessions/week, two weeks, 40 min/session) on the primary motor cortex bilaterally. Clinical evaluations were performed using the Coma Recovery Scale–Revised (CRS-R) pre- and post-treatment. In contrast, after single and multiple tDCS sessions, the haemodynamic cortical response was obtained with functional near-infrared spectroscopy (fNIRS). Moreover, angiogenesis (angiopoietin-2, BMP9, endoglin, HbEFG, HGF, IL8, Leptin, PLGF, VEGF-A, and VEGF-C) and inflammation (GM-CSF, IFNg, IP10, MCP1, and TNFα) circulating biomarkers were collected. A significant haemodynamic response was observed after a single tDCS session, with an increased activation from 4.4 (3.1–6.1) to 7.6 (2.9–15.7) a.u. (p = 0.035). After ten tDCS sessions, a significant reduction of angiopoietin-2, VEGF-C, and IP-10 was detected. Moreover, a correlation between behavioural (CRS-R), TNFα (r = 0.89; p = 0.007), and IP10 (r = 0.81; p = 0.014) variation was found. In conclusion, a single tDCS session can increase the cortical activation in MCS patients. Moreover, multiple tDCS sessions showed an anti-inflammatory effect related to behavioural improvement.

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.

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.

Upper-limb paresis is common after stroke. An important tool to assess motor recovery is to use marker-based motion capture systems to measure the kinematic characteristics of patients’ movements in ecological scenarios. These systems are, however, very expensive and not readily available for many rehabilitation units. Here, we explored whether the markerless hand motion capabilities of the cost-effective Oculus Quest head-mounted display could be used to provide clinically meaningful measures. A total of 14 stroke patients executed ecologically relevant upper-limb tasks in an immersive virtual environment. During task execution, we recorded their hand movements simultaneously by means of the Oculus Quest’s and a marker-based motion capture system. Our results showed that the markerless estimates of the hand position and peak velocity provided by the Oculus Quest were in very close agreement with those provided by a marker-based commercial system with their regression line having a slope close to 1 (maximum distance: mean slope = 0.94 ± 0.1; peak velocity: mean slope = 1.06 ± 0.12). Furthermore, the Oculus Quest had virtually the same sensitivity as that of a commercial system in distinguishing healthy from pathological kinematic measures. The Oculus Quest was as accurate as a commercial marker-based system in measuring clinically meaningful upper-limb kinematic parameters in stroke patients.

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.

We evaluated the sex-specific difference in response upon participation in an exercise program with respect to the risk of adverse clinical outcomes among patients with peripheral artery disease (PAD) and claudication. The records of 400 PAD patients were assessed between 2012 and 2015. Two hundred of them were addressed to a walking program prescribed at the hospital and executed at home at symptom-free walking speed (Ex), while the remaining 200 acted as a control group (Co). The number and date of deaths, all-cause hospitalizations, and amputations for a 7-year period were collected from the regional registry. At baseline, no differences were observed (MEXn = 138; FEXn = 62; MCOn = 149; FCOn = 51). The 7-year survival rate was significantly higher in FEX (90%) than in MEX (82% hazard ratio, HR: 0.542 95% CI 0.331–0.885), FCO (45%, HR: 0.164 95% CI 0.088–0.305), and MCO (44%; HR: 0.157 95% CI 0.096–0.256). A significantly lower rate of hospitalization (p < 0.001) and amputations (p = 0.016) was observed for the Ex group compared to the Co group, without differences by sex. In conclusion, in PAD patients, active participation in a home-based pain-free exercise program was associated with a lower rate of death and better long-term clinical outcomes, particularly among women.

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.

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.

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.

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.

Background and Objectives: Robot-assisted gait training (RAGT) could be a rehabilitation option for patients after experiencing a stroke. This study aims to determine the sex-related response to robot-assisted gait training in a cohort of subacute stroke patients considering mixed results previously reported. Materials and Methods: In this study, 236 participants (145 males, 91 females) were admitted to a rehabilitation facility after experiencing a stroke and performed RAGT within a multidisciplinary rehabilitation program. Functional Independence Measure (FIM) and Functional Ambulatory Category (FAC) were assessed at admission and discharge to determine sex-related outcomes. Results: At the baseline, no significant difference among sexes was observed. At the end of rehabilitation, both males and females exhibited significant improvements in FIM (71% of males and 80% of females reaching the MCID cut-off value) and FAC (∆score: men 1.9 ± 1.0; women 2.1 ± 1.1). A more remarkable improvement was observed in women of the whole population during the study, but statistical significance was not reached. When analysing the FAC variations with respect to the total number of RAGT sessions, a more significant improvement was observed in women than men (p = 0.025). Conclusion: In conclusion, among subacute stroke patients, benefits were observed following RAGT during a multidisciplinary rehabilitation program in both sexes. A greater significant recovery for women with an ischemic stroke or concerning the number of sessions attended was also highlighted. The use of gait robotics for female patients may favour a selective functional recovery after stroke.

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.

Aim: The aim of this study was to evaluate the utility and reliability of temperature foot changes measured by infrared thermography (IRT) for the evaluation of patients with atherosclerotic peripheral arterial disease (PAD) before and after endovascular revascularisation. Methods: This is an observational prospective study carried out on symptomatic PAD patients. Evaluations consisted of a clinical examination, duplex scan with ankle–brachial index calculation (ABI) and IRT measurements with infrared camera FLIR-ONE connected to a smartphone with android technology. Locations on the foot sampled with IRT were the anterior tibial, pedal, posterior and arcuate arteries. Results obtained with IRT on the symptomatic foot were compared to the contralateral foot and with the ABI values obtained bilaterally before and 24 h after revascularisation. Results: Within one year, 40 patients were enrolled, among whom 87,5% suffered from critical limb ischaemia. In three patients, it was impossible to obtain ABI measurements because of ulcerations on the limb. Skin temperature changes obtained by IRT between the symptomatic limb and the contralateral limb had a mean difference of 1.7 °C (range: 1.1–2.2 °C), p < 0.001. There was a positive correlation between ABI and temperature values of the limb needed for treatment before revascularisation (p = 0.025; r = 0.36) and after revascularisation (p = 0.024, r = 0.31). The technical success rate was 100% in all cases, achieving a significant increase in temperature at all points of the foot analysed, with a median change of 2 °C (p < 0.001). Conclusion: IRT is a safe, reliable and simple application. It could be a valuable tool for the assessment of the clinical presentation and severity of foot blood perfusion in symptomatic PAD patients and the evaluation of the technical success of endovascular revascularisation. IRT might have a role in follow-up of revascularisation procedures.

This study aimed to determine cortical activation responses to two different rehabilitative programs, as measured through functional near-infrared spectroscopy (fNIRS). As a secondary analysis of the RAGTIME trial, we studied 24 patients with progressive multiple sclerosis (MS) and severe disability who were randomized to a regimen of robot-assisted gait training (RAGT) or overground walking (OW). Cortical activation during a treadmill walking task, assessed through fNIRS recordings from the motor and premotor cortexes (M1/PM), was calculated as the area under the curve (AUC) of oxyhemoglobin for each hemisphere and the total area (Tot-OxyAUC). Gait speed, endurance, and balance were also measured, along with five healthy control subjects. At baseline, Tot-OxyAUC during walking was significantly increased in MS patients compared to healthy people and was significantly higher for those with more severe disabilities; it was also inversely correlated with physical performance. After rehabilitation, significant opposite variations in Tot-OxyAUC were observed, with activity levels being increased after OW and decreased after RAGT (+242,080 ± 361,902 and −157,031 ± 172,496 arbitrary units, respectively; p = 0.002), particularly in patients who were trained at a lower speed. Greater reductions in the cortical activation of the more affected hemisphere were significantly related to improvements in gait speed (r = −0.42) and endurance (r = −0.44). Cortical activation, assessed through fNIRS, highlighted the brain activity in response to the type and intensity of rehabilitation.

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].

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].

Abnormal levels of pyruvate and lactate were reported in multiple sclerosis (MS). We studied the response of markers of mitochondrial function to rehabilitation in relation to type, intensity and endurance performance in severely disabled MS patients. Forty-six progressive MS patients were randomized to receive 12 walking sessions of robot-assisted gait training (RAGT, n = 23) or conventional overground therapy (CT, n = 23). Ten healthy subjects were also studied. Blood samples were collected to determine lactate, pyruvate, and glutathione levels and lactate/pyruvate ratio pre–post rehabilitation. In vivo muscle metabolism and endurance walking capacity were assessed by resting muscle oxygen consumption (rmVO2) using near-infrared spectroscopy and by six-minute walking distance (6MWD), respectively. The levels of mitochondrial biomarkers and rmVO2, altered at baseline with respect to healthy subjects, improved after rehabilitation in the whole population. In the two groups, an enhanced response was observed after RAGT compared to CT for lactate (p = 0.012), glutathione (p = 0.08) and rmVO2 (p = 0.07). Metabolic biomarkers and 6MWD improvements were exclusively correlated with a training speed markedly below individual gait speed. In severely disabled MS patients, rehabilitation rebalanced altered serum metabolic and muscle parameters, with RAGT being more effective than CT. A determinable slow training speed was associated with better metabolic and functional recovery. Trial Registration: ClinicalTrials.gov NCT02421731.

Background: The aim of this study was to relate the weekend (WE) effect and acute kidney injury (AKI) in elderly patients by using the Italian National Hospital Database (NHD). Methods: Hospitalizations with AKI of subjects aged ≥ 65 years from 2000–2015 who were identified by the ICD-9-CM were included. Admissions from Friday to Sunday were considered as WE, while all the other days were weekdays (WD). In-hospital mortality (IHM) was our outcome, and the comorbidity burden was calculated by the modified Elixhauser Index (mEI), based on ICD-9-CM codes. Results: 760,664 hospitalizations were analyzed. Mean age was 80.5 ± 7.8 years and 52.2% were males. Of the studied patients, 9% underwent dialysis treatment, 24.3% were admitted during WE, and IHM was 27.7%. Deceased patients were more frequently comorbid males, with higher age, treated with dialysis more frequently, and had higher admission during WE. WE hospitalizations were more frequent in males, and in older patients with higher mEI. IHM was independently associated with dialysis-dependent AKI (OR 2.711; 95%CI 2.667–2.755, p < 0.001), WE admission (OR 1.113; 95%CI 1.100–1.126, p < 0.001), and mEI (OR 1.056; 95% CI 1.055–1.057, p < 0.001). Discussion: Italian elderly patients admitted during WE with AKI are exposed to a higher risk of IHM, especially if they need dialysis treatment and have high comorbidity burden.

We assessed whether muscle metabolism biomarkers (MMb) identified by near-infrared spectroscopy (NIRS) are valid for determining adaptations following revascularization or exercise training in peripheral artery disease (PAD). Eighteen patients (males n = 13; 69 ± 7 years) were randomized to receive revascularization (Rev = 6) or pain-free home-based exercise (Ex = 12). MMb were safely collected via a NIRS-assisted treadmill test as area-under-curve for the spectra of oxygenated (-oxy), deoxygenated (-deoxy), differential (-diff) and total (-tot) hemoglobin traces. MMb, ankle–brachial index (ABI), pain-free (PFWD) and 6-min (6MWD) walking distances were assessed at baseline and after four months. MMb were correlated at baseline with ABI (MMb-oxy r = 0.46) and 6MWD (MMb-tot r = 0.51). After treatments, MMb-oxy showed an expected increase, which was more relevant for Rev group than the Ex (56% vs. 20%), with trends towards normalization for the other MMb. These changes were significantly correlated with variations in ABI (MMb-oxy r = 0.71; p = 0.002) and 6MWD (MMb-tot r = 0.58; p = 0.003). The MMb-diff in Rev group and MMb-deoxy in Ex group at baseline predicted clinical outcomes being correlated with PFWD improvements after 4-month (r = −0.94; p = 0.005 and r = −0.57; p = 0.05, respectively). A noninvasive NIRS-based test, feasible in a clinical setting, identified muscle metabolism biomarkers in PAD. The novel MMb were associated with validated outcome measures, selectively modified after different interventions and able to predict long-term functional improvements after surgery or exercise training.

Restless leg syndrome (RLS) disrupts sleep, affecting the quality of life of patients with various chronic diseases. We assessed the prevalence of RLS in peripheral artery disease (PAD) patients and the effects of a pain-free exercise program. A total of 286 patients with claudication were enrolled in a home-based low-intensity exercise program prescribed at the hospital. RLS was determined through standardized questions. Hemodynamics, degree of calf deoxygenation, and mobility were assessed using the ankle-brachial-index, a treadmill test assisted by near-infrared spectroscopy and the 6-min walk test, respectively. During hospital visits, persistence of RLS, adherence to exercise, hemodynamics, and mobility were assessed. At the enrollment, 101 patients (35%) presented RLS, with higher prevalence among females (p = 0.032). Compared to RLS-free patients, they showed similar hemodynamics but more severe calf deoxygenation (p < 0.001) and lower mobility (p = 0.040). Eighty-seven RLS patients (83%) reported the disappearance of symptoms after 39 (36−70) days of exercise. This subgroup, compared to nonresponders, showed higher adherence (p < 0.001), hemodynamic (p = 0.041), and mobility improvements (p = 0.003). RLS symptoms were frequent in PAD but were reduced by a pain-free walking exercise aimed at inducing peripheral aerobic adaptations. The concomitant recovery of sleep and mobility may represent a synergistic action against the cardiovascular risk in PAD.

The study retrospectively evaluated the association between rehabilitative outcomes and risk of peripheral revascularizations in elderly peripheral artery disease (PAD) patients with claudication. Eight-hundred thirty-five patients were enrolled. Ankle-brachial index (ABI) and maximal walking speed (Smax) were measured at baseline and at discharge from a structured home-based rehabilitation program. For the analysis, patients were divided according to a baseline ABI value (severe: ≤0.5; moderate: ≥0.5) and according to hemodynamic or functional rehabilitative response (responder: ABI ≥ 0.10 and/or Smax > 0.5 km/h). Three-year outcomes were collected from the regional registry. According to the inclusion criteria (age 60⁻80, ABI < 0.80; program completion) 457 patients, 146 severe and 311 moderate, were studied. The whole population showed significant functional and hemodynamic improvements at discharge, with 56 revascularizations and 69 deaths at follow-up. Compared to the moderate group, the severe group showed a higher rate of revascularizations (17% vs. 10%, p < 0.001) and deaths (29% and 8%, respectively; p < 0.001). However, patients with severe PAD who were ABI responders after rehabilitation showed less revascularizations than non-responders (13% vs. 21%; hazard ratio (HR): 0.52) and were not different from patients with moderate disease (9%). Superimposable rates were observed for Smax responders (13% vs. 21%; HR: 0.55; moderate 10%). In conclusion, elderly patients with severe PAD empowered by better rehabilitation outcomes showed lower rates of peripheral revascularizations and deaths that were comparable to patients with moderate PAD.