Efficacy of focal muscular vibration in the treatment of upper limb spasticity in subjects with stroke outcomes: randomized controlled trial.

Focal muscular vibration (FMV) is a non-invasive technique that showed positive effects on spasticity of the upper limb in stroke subjects but different protocols have been proposed so the studies are not comparable and, to date, it is not clear which muscles should be treated, agonist, or antagonist muscles to obtain the better result on spasticity. The objective of this study is to evaluate the effects on spasticity of FMV on the upper limb flexor spastic muscles compared to the effects of FMV on the upper limb extensor muscles in subacute stroke patients. We treated 28 subacute stroke patients (mean age 64.28±13.79) randomized into two groups: Group A and Group B. Group A was treated by applying FMV to the flexor muscles of the upper limb, while Group B was treated by applying FMV to the extensor muscles of the upper limb. The effects on spasticity were assessed by Modified Ashworth Scale (primary outcome) and the upper limb motor function by instrumental robotic outcomes; moreover, muscle strength and pain were evaluated using Motricity Index and Numerical Rating Scale, respectively (secondary outcomes). Patients were subjected to FMV for three consecutive days and were evaluated three times: before treatment (T0), after a week (T1) and after a month (T2) from the end of treatment. Within group, analysis showed statistically significant changes over time of the MAS at the three joints (shoulder, elbow and wrist) in both groups, but post-hoc analysis showed that, only in Group A, MAS was significantly lower at T2, when compared with T0 at the shoulder and elbow. NRS, significantly changed over time only in the Group B. Motricity Index, did not change over time neither in the Group A, nor in the Group B. No statistically significant differences were detected in the between group analysis. Regarding the instrumental robotic outcomes, we detected a statistically significant reduction of the time required to complete the task (Duration) in both group a T2. In conclusion, this study highlighted how the same treatment protocol can determine an improvement in muscle tone and in the Duration to perform a task, regardless of the muscles treated, while the pain improves if we treat the agonist muscles.

Poststroke shoulder pain in subacute patients and its correlation with upper limb recovery after robotic or conventional treatment: A secondary analysis of a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Poststroke shoulder pain is a common complication. We aimed to investigate the prevalence of poststroke shoulder pain, with attention to the neuropathic component, and the relationship between poststroke shoulder pain and upper limb improvement in motor function, strength, disability, and quality of life after upper limb rehabilitation. METHODS: This is a secondary analysis of a multicenter randomized controlled trial to compare upper limb conventional or robotic rehabilitation on 224 patients enrolled in eight rehabilitation centers. We assessed poststroke shoulder pain (using the Numerical Rating Scale and the Douleur Neuropathique 4), and upper limb motor function, strength, disability, and quality of life at baseline (T0), after 30 rehabilitation sessions (T1), and three months after the end of rehabilitation (T2). RESULTS: A moderate/severe poststroke shoulder pain was reported by 28.9% of patients, while 19.6% of them showed a neuropathic component. At T0, the intensity of pain was higher in women and in patients with neglect syndrome, positively correlated with the time since stroke and disability and negatively correlated with motor function, strength, and the physical aspects of the quality of life.Moderate/severe pain and neuropathic component significantly reduced after both treatments and this reduction was maintained at T2. Finally, the intensity of pain at baseline was negatively correlated with the improvement of upper limb motor function. CONCLUSIONS: Poststroke shoulder pain negatively impact on motor performance, strength, disability, and physical aspects of the quality of life as well as on upper limb motor recovery; however, it can be reduced after a robotic or a conventional rehabilitation. Therefore, we suggest considering poststroke shoulder pain when planning the rehabilitation intervention.

Metabolomics signature improves the prediction of cardiovascular events in elderly subjects.

AIMS: Age is one of the most important determinants of cardiovascular health, therefore the management of cardiovascular diseases (CVD) in elderly people entails great challenge. A possible explanation of vascular senescence process is the mitochondrial damage and dysfunction. We hypothesized that metabolomic profiling would identify biomarkers predicting major cardiovascular events (MACEs) in elderly people, improving the clinical standard cardiovascular risk factors. METHODS AND RESULTS: Targeted-mass-spectrometry-based profiling of 49 metabolites was performed in a group of very old participants (n = 67, mean age = 85 ± 3 years) with a high rate of previous CVD (68%). Principal Component Analysis, Random Survival Forest analysis and Cox proportional hazards regression modeling were used to evaluate the relation between the metabolite factors and recurring MACEs. We tested discrimination ability and reclassification of clinical and metabolomic models. At follow-up (median = 3.5 years), 17 MACEs occurred (5 cardiovascular deaths, 1 nonfatal myocardial infarction, 7 nonfatal strokes and 4 peripheral artery surgeries) (incidence = 7.3% person-years). Metabolite factor 1, composed by medium- and long-chain acylcarnitines, and factor 7 (alanine) were independently associated with MACEs, after adjustment for clinical CV covariates [HR = 1.77 (95%CI = 1.11-2.81, p = 0.016) and HR = 2.18 (95%CI = 1.17-4.07, p = 0.014), respectively]. However, only factor 1 significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 7%, p = 0.01) and correctly reclassifying 41% of events and 37% of non-events resulting in a cNRI = 0.79 (p = 0.005). CONCLUSIONS: Aging mitochondrial dysfunction evaluated by metabolomic profiling is associated with MACEs, independently of standard predictors.

Expression of tissue inhibitor of metalloprotease 3 is reduced in ischemic but not neuropathic ulcers from patients with type 2 diabetes mellitus.

Diabetic foot ulceration remains one of the most common and most serious consequences of diabetes. Persistently high levels of matrix metalloproteases (MMPs) contribute to wound chronicity. Our aim was to assess the concentrations of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in neuropathic and ischemic diabetic foot ulcers by analyzing biopsy samples. In this study, biopsies were taken from 35 diabetic foot ulcers of type 2 diabetes mellitus patients and distinguished in neuropathic (n = 14) or ischemic (n = 21). Zymography assay was utilized for the analysis of MMP-2 and MMP-9 activity. TACE activity was evaluated by a specific fluorimetric assay. mRNA levels of MMPs as well as TIMPs were detected using quantitative real-time polymerase chain reaction. The activity of MMP9 and A Disintegrin and A MetalloProtease Domain 17/TNF-Alpha Converting Enzyme (ADAM17/TACE) was significantly increased in ischemic compared to neuropathic biopsies. No differences were detected between both groups for the mRNA levels of MMPs as well as of ADAMs. However, TIMP3 mRNA expression was decreased in ischemic samples. The combination of increased activity of MMP9 and ADAM17/TACE with decreased concentrations of TIMP-3 mRNA expression in ischemic diabetic foot ulcers compared to neuropathic samples suggests that the increased proteolytic environment may represent a causative factor in the ulcer progression. New treatment strategies for healing diabetic foot ulcers could be directed toward increasing levels of TIMP3.