Axillary web syndrome in women after breast cancer surgery referred to an Oncological Rehabilitation Unit: which are the main risk factors? A retrospective case-control study.

OBJECTIVE: Axillary web syndrome (AWS) is a complication of surgical procedures in breast cancer (BC) patients. This condition with poorly understood incidence and etiology is characterized by the locoregional development of scar tissue, leading to subcutaneous cording, motion impairment and pain. The early identification of patients at risk for AWS would improve their clinical management. Here, we sought to characterize the prevalence of and the risk factors associated with AWS in BC women after surgery. PATIENTS AND METHODS: All patients with BC that underwent axillary surgery referred to an Outpatient Service for Oncological Rehabilitation were retrospectively collected. These women were assessed two weeks after the surgical procedure for their clinicopathologic features, type of therapeutic interventions, and AWS presence, laterality, pain, localization, cords type, and number of cords. RESULTS: Altogether, 177 patients (mean aged 60.65 ± 12.26 years) were included and divided into two groups: AWSPOS (n=52; 29.4%) and AWSNEG (n=125; 70.6%). Patients with tumor N ≥1 (OR=3.7; p<0.001), subjected to mastectomy, axillary lymph node dissection (ALND) and chemotherapy showed significant correlations with AWS onset (p<0.05). The range of shoulder motion limitation (OR=11.2; p<0.001) and the presence of breast cancer related lymphedema (OR=3.5; p=0.020) were associated with AWS. CONCLUSIONS: Mastectomy, ALND, chemotherapy, low staging tumors, shoulder range of motion limitations, and BCRL represent risk factors for AWS onset. Realizing new strategies for assessing the individual risk of AWS is a crucial clinical need to improve the health-related quality of life of BC survivors.

Three-dimensional laser scanning as a reliable and reproducible diagnostic tool in breast cancer related lymphedema rehabilitation: a proof-of-principle study.

OBJECTIVE: In this study, we aimed to assess the reproducibility and reliability of a three-dimensional laser scanner (3DLS) in measuring the upper limb volume of BRCL women undergoing a 2-week complete decongestive therapy (CDT). PATIENTS AND METHODS: 3DLS and CM were used to measure the upper limb volume in a cohort of BCRL women before (T0) and after (T1) a 2-week CDT. We evaluated: a) correlation between 3DLS and CM at both time points; b) level of agreement and the consistency of the different measurements at both time points; c) correlation between the inter-rater operator analysis in terms of total limb volume differences before and after rehabilitative treatment of both circumferential method and laser scanning 3D in breast cancer related lymphedema patients. RESULTS: Taken together, 43 BCRL women (age 51.1 ± 5.4 years) were included. Both 3DLS and CM showed a significant inter and intra-operator correlation in the arm volume measurement at both time-points (T0: r2=0.99, p<0.0001; T1: r2=0.99, p<0.0001). 3DLS showed a strong correlation with CM (r2=0.99, p<0.0001) in terms of volume measurement and provided greater intra-operator correlation (r2=0.92 vs. 0.62) in detecting volume variations after the treatment (T1-T0). CONCLUSIONS: 3DLS confirmed to be highly sensitive, cheap and easy-to-use in the evaluation of the upper limb volume in BCRL women before and after a rehabilitative treatment. These findings suggest that augmented reality technologies might be very useful in oncological rehabilitation.

Low back pain related to a sacral insufficiency fracture: role of paravertebral oxygen-ozone therapy in a paradigmatic case of nociplastic pain.

We describe the case of a 68-year-old woman with an acute episode of severe low back pain (LBP) resistant to opioids, who had experienced a sacral insufficiency fracture (SIF) two years earlier. At clinical examination, patient reported constant, dull, non-localizable pain at lumbar and sacral level, exacerbated by paravertebral palpation, particularly at L4-L5 and the sacroiliac joint, with a concomitant and remittent neuropathic component, difficult to localize at lumbar and sacral level. The latest magnetic resonance imaging study revealed disc herniations at L3-L4, L4-L5, and L5-S1 levels. The patient was treated with intramuscularparavertebral injections of oxygen-ozone (O2O3) mixture for 4 weeks (once a week), using a O3 concentration of 20 mcg/mL (5 mL in L4-L5 zone and 5 mL in L5-S1 zone, bilaterally). At 1 week after the first injection, the pain (assessed by Numerical Pain Rating Scale and Brief Pain Inventory) was considerably reduced and the patient's health-related quality of life (assessed by Short Form 12-Item Health Survey and European Quality of Life Index) had improved; these findings were confirmed at follow-up 1 month after the last injection. This paradigmatic case of nociplastic pain successfully treated by paravertebral O2O3 therapy might be a starting point for further studies on the effects of this treatment in terms of decreasing pain and improving HRQoL in patients affected by opioid-resistant LBP.

Management of spasticity with onabotulinumtoxinA: practical guidance based on the italian real-life post-stroke spasticity survey.

The present paper provides practical guidance on the management of adult spasticity with OnabotulinumtoxinA. Advisory Board members reviewed the available evidence and discussed their personal experiences in order to address the unmet needs in the management of spasticity with botulinum toxin type A identified by the recent Italian Real-Life Post-Stroke Spasticity Survey. Stroke patients should be referred to spasticity services that have adequate facilities and multidisciplinary teams with the necessary training, competence and expertise. The current literature shows a strong correlation between the development of post-stroke spasticity and the degree of central sensorimotor system destruction/disorganization. Use of tools such as the Poststroke Checklist may help clinicians in the long-term follow-up of stroke patients. The maximum dose of onabotulinumtoxinA - according to the current literature this ranges from 300U to 400U for upper limb and from 500U to 600U for lower limb aggregate postures - should be re-considered. In addition, there is a need for future consensus (also based on pharmacoeconomic considerations) on consistent clinical care models for the management of patients with post-stroke spasticity.

From paper to informatics: the Post Soft Care-App, an easy-to-use and fast tool to help therapists identify unmet needs in stroke patients.

Even after rehabilitation, post stroke patients remain disabled. The Post Stroke Checklist (PSC) was developed to highlight unmet needs of community-dwelling stroke patients. The present study set out to validate Post Soft Care-App, designed to administer the PSC using smartphones and tablets, in order to monitor unmet needs in chronic patients. Fifty-three patients and fifteen physiotherapists were enrolled. The therapists administered the PSC to patients using the app, and then completed a structured questionnaire on its usability and utility. The Post Soft Care-App highlighted the following unmet needs: increased spasticity (56.6%), reduced independence in activities of daily living (47.2%), reduced mobility (45.3%), absence of secondary prevention (45.3%). Therapists positively evaluated Post Soft Care-App as useful, practical, quick to complete (96.2%), and effective in helping improve communication with patients (75.5%). The Post Soft Care-App can be considered a valid assessment tool for helping therapists to monitor functional outcomes in chronic patients.

Post Soft Care: Italian implementation of a post-stroke checklist software for primary care and identification of unmet needs in community-dwelling patients.

The needs of community-dwelling stroke patients are often not fully addressed. The Global Stroke Community Advisory Panel had developed the Post Stroke Checklist (PSC) with the aim of standardizing long-term stroke assessment and consequently care of patients. PSC has been validated for UK and Singapore, and an Italian version has been proposed. The aim of this study is to assess the needs of community-dwelling Italian stroke patients using an online version of PSC. Secondary aim is to assess utility of PSC for patients and clinicians. The PSC was administered to a sample of 64 patients with stroke in Italy by general practioners. PSC is a questionnaire formed by 11 questions, each one covering a domain identified as important for patients' health. After administration of PSC, patient and clinician satisfaction with the PSC was assessed by a specific questionnaire. The PSC identified specific problems for patients related to a worsening from the last examination not evaluated by any specialist. The online PSC highlighted problems related to mood, (in 50% of sample), mobility (53.1%), spasticity (42.2%), and pain (37.5%). Both patients and clinicians provided good results about the utility of online PSC. The PSC was confirmed to be a useful tool for identifying the needs of community-dwelling patients with stroke. Particular attention should be deserved to problems related to mood, mobility, and hence participation to social life, pain, and spasticity. For taking into account these aspects, the online PSC can be a useful portable tool for clinicians.

Recovery from vegetative state of patients with a severe brain injury: a 4-year real-practice prospective cohort study.

Patients who have suffered severe traumatic or nontraumatic brain injuries can show a progressive recovery, transitioning through a range of clinical conditions. They may progress from coma to a vegetative state (VS) and/or a minimally conscious state (MCS). A longer duration of the VS is known to be related to a lower probability of emergence from it; furthermore, the literature seems to lack evidence of late improvements in these patients. This real-practice prospective cohort study was conducted in inpatients in a VS following a severe brain injury, consecutively admitted to a vegetative state unit (VSU). The aim of the study was to assess their recovery in order to identify variables that might increase the probability of a VS patient transitioning to MCS. Rehabilitation treatment included passive joint mobilisation and helping/placing patients into an upright sitting position on a tilt table. All the patients underwent a specific assessment protocol every month to identify any emergence, however late, from the VS. Over a 4-year period, 194 patients suffering sequelae of a severe brain injury, consecutively seen, had an initial Glasgow Coma Scale score ≤ 8. Of these, 63 (32.5%) were in a VS, 84 (43.3%) in a MCS, and 47 (24.2%) in a coma; of the 63 patients admitted in a VS, 49 (57.1% males and 42.9% females, mean age 25.34 ± 19.12 years) were transferred to a specialist VSU and put on a slow-to-recover brain injury programme. Ten of these 49 patients were still in a VS after 36 months; of these 10, 3 recovered consciousness, transitioning to a MCS, 2 died, and 5 remained in a VS during the last 12 months of the observation. Univariate analysis identified male sex, youth, a shorter time from onset of the VS, diffuse brain injury, and the presence of status epilepticus as variables increasing the likelihood of transition to a MCS. Long-term monitoring of patients with chronic disorders of consciousness should be adequately implemented in order to optimise their access to rehabilitation services.

The Italian real-life post-stroke spasticity survey: unmet needs in the management of spasticity with botulinum toxin type A.

The present national survey seeking to identify unmet needs in the management of spasticity with botulinum toxin type A focused on the use of OnabotulinumoxinA, since this is the brand with the widest range of licensed indications in Italy. Physicians from twenty-four Italian neurorehabilitation units compiled a questionnaire about "real-life" post-stroke spasticity management. OnabotulinumtoxinA was reported to be used in the following average doses: upper limb 316.7 ± 79.1 units; lower limb 327.8 ± 152.3; upper and lower limb 543.7 ± 123.7 units. Of the physicians surveyed, 37.5% felt that increasing the frequency of OnabotulinumtoxinA injection would improve its efficacy; 70.8% use electrical stimulation/electromyography guidance (one fourth of injections with no instrumental guidance). Instrumental evaluation was used by 41.7% of the physicians. The participants expressed the view that early identification of post-stroke spasticity would be facilitated by the availability of a post-stroke checklist, and that this should be used by physiotherapists (91.7%), physiatrists (58.3%), family doctors (50%), stroke unit physicians (25%), patients and caregivers (79.2%). According to our findings, the management of poststroke spasticity has several unmet needs that, were they addressed, might improve these patients' clinical outcomes and quality of life. These needs concern patient follow-up, where a clearly defined pathway is lacking; furthermore, there is a need to use maximum doses per treatment and to ensure early intervention on post-stroke spasticity.

Mini invasive skeletal muscle biopsy technique with a tri-axial end cut needle.

OBJECTIVE: Skeletal Muscle Biopsy is a minor surgical procedure for the diagnosis of different neuromuscular pathological conditions and has recently gained popularity also in the research field of age-related muscular modifications and sarcopenia. Few studies focused on the application of mini-invasive muscular biopsy in both normal and pathological conditions. The aim of our study was to describe a mini invasive ultrasound-guided skeletal muscular biopsy technique in complete spinal cord injured (SCI) patients and healthy controls with a tri-axial end-cut needle. PATIENTS AND METHODS: Skeletal muscle biopsies were collected from 6 chronic SCI patients and 3 healthy controls vastus lateralis muscle with a tri-axial end cut needle (Biopince© - Angiotech). Muscle samples were stained for ATPase to determine fibers composition, moreover, gene expression of cyclooxygenase-1 (COX-1) and prostaglandin E2 receptor has been analyzed by Real Time RT-PCR. RESULTS: All the procedures were perfomed easily without failures and complications. Control tissue was macroscopically thicker than SCI one. Control specimen displayed an equal distribution of type I and type II fibers, while SCI sample displayed a prevalence of type II fibers SCI specimen displayed a significant reduction in COX-1 gene expression. This mini-invasive approach was easy, accurate and with low complication rate in performing skeletal muscle biopsy in both SCI patients and controls. CONCLUSIONS: This technique could be useful in conditions in which the overall quantity of specimen required is small like for molecular biology analysis. For histological diagnostic purposes and/or conditions in which the original tissue is already pathologically modified, this technique should be integrated with more invasive techniques.

Evaluation of serum myostatin and sclerostin levels in chronic spinal cord injured patients.

STUDY DESIGN: Case-control study. OBJECTIVES: To assess serum myostatin levels, bone mineral density (BMD), appendicular skeletal muscle mass (ASMM) and serum sclerostin levels in chronic spinal cord injured (SCI) patients and healthy controls. SETTING: SCI centre in Italy. METHODS: Blood samples, whole-body bioelectrical impedance analysis and BMD measurement with the ultrasound technique at the calcaneus level were taken from patients suffering from chronic SCI (both motor complete and incomplete) and healthy control subjects. RESULTS: A total of 28 SCI patients and 15 healthy controls were enrolled. Serum myostatin levels were statistically higher (P<0.01) in SCI patients compared with healthy controls. Similar results were found comparing both the motor complete and the motor incomplete SCI subgroups to healthy controls. Serum sclerostin was significantly higher in patients with SCI compared with healthy controls (P<0.01). BMD, stiffness and mean T-score values in SCI patients were significantly lower than those in healthy controls. Serum myostatin concentrations in the motor complete SCI subgroups correlated only with serum sclerostin levels (r(2)=0.42; P=0.001) and ASMM (r(2)=0.70; P=0.002) but not in healthy controls. DISCUSSION: Serum myostatin and serum sclerostin are significantly higher in chronic SCI patients compared with healthy controls. They are potential biomarkers of muscle and bone modifications after SCI. This is the first study reporting an increase in serum myostatin in patients suffering from chronic SCI and a correlation with ASMM.

Heart Rate Variability (HRV) modifications in adult hemiplegic patients after botulinum toxin type A (nt-201) injection.

BACKGROUND: The most important adverse effect of BoNT-A is the systemic diffusion of the toxin. There is some evidence that the administration of high doses can increase the risk of systemic diffusion and the development of clinically evident adverse effects, however an international consensus does not exist about its maximum dose. AIM: The aim of this study was to evaluate changes in autonomic heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA injection in spastic stroke patients. Moreover, the treatment safety by monitoring adverse events occurrence was assessed. DESIGN: Case control study. POPULATION: Eleven stroke survivors with spastic hemiplegia. METHODS: Patients were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12 units/Kg. Each patient underwent an ECG recording before injection and 10 days after treatment. Linear and non-linear Heart Rate variability (HRV) measures were derived from ECGs with a dedicated software. RESULTS: None of the variable considered showed statistically significant changes after BoNT-A injection. CONCLUSION: The use of incobotulinumtoxinA in adult patients at doses up to 12 units/kg seems to be safe regarding autonomic heart drive. CLINICAL REHABILITATION IMPACT: The use of IncobotulinumtoxinA up to 600 units could be a safe therapeutic option in spastic hemiplegic stroke survivors.

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment.

Osteoporotic fractures are a public health problem and their incidence and subsequent economic and social costs are expected to rise in the next future. Different drugs have been developed to reduce osteoporosis and the risk of osteoporotic fractures, and among them, antiresorptive agents, and in particular oral alendronate, are the most widely utilized. However, one of the most common problems with antiresorptive drugs is poor adherence to treatment, which is associated with a high fracture incidence and with an increase in hospitalization costs. One of the main reasons of poor adherence to these treatments is the occurrence of adverse events, mainly at gastrointestinal (GI) level, including dyspepsia, dysphagia, and esophageal ulcers. In light of these considerations the aim of this paper is to perform a literature review to show the pathophysiologic bases of GI alendronate-induced adverse events and how new bisphosphonate formulations like effervescent alendronate can improve compliance and persistence to treatment and decrease the fracture rate incidence in osteoporotic patients.

Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways.

CONTEXT: Recently, vitamin D (VitD) has been recognized as increasingly importance in many cellular functions of several tissues and organs other than bone. In particular, VitD showed important beneficial effects in the cardiovascular system. Although the relationship among VitD, endothelium, and cardiovascular disease is well established, little is known about the antioxidant effect of VitD. OBJECTIVE: Our objective was to study the intracellular pathways activated by VitD in cultured human umbilical vein endothelial cells undergoing oxidative stress. DESIGN: Nitric oxide production, cell viability, reactive oxygen species, the mitochondrial permeability transition pore, membrane potential, and caspase-3 activity were measured during oxidative stress induced by administration of 200 µM hydrogen peroxide for 20 minutes. Experiments were repeated in the presence of specific vitamin D receptor ligand ZK191784. RESULTS: Pretreatment with VitD alone or in combination with ZK191784 is able to reduce the apoptosis-related gene expression, involving both intrinsic and extrinsic pathways. At the same time, it has been shown the activation of pro-autophagic beclin 1 and the phosphorylation of ERK1/2 and Akt, indicating a modulation between apoptosis and autophagy. Moreover, VitD alone or in combination with ZK191784 is able to prevent the loss of mitochondrial potential and the consequent cytochrome C release and caspase activation. CONCLUSIONS: The present study shows that VitD may prevent endothelial cell death through modulation of the interplay between apoptosis and autophagy. This effect is obtained by inhibiting superoxide anion generation, maintaining mitochondria function and cell viability, activating survival kinases, and inducing NO production.

Possible synergism of physical exercise and ghrelin-agonists in patients with cachexia associated with chronic heart failure.

The occurrence of cachexia of multifactorial etiology in chronic heart failure (CHF) is a common and underestimated condition that usually leads to poor outcome and low survival rates, with high direct and indirect costs for the Health Care System. Recently, a consensus definition on cachexia has been reached, leading to a growing interest by the scientific community in this condition, which characterizes the last phase of many chronic diseases (i.e., cancer, acquired immunodeficiency syndrome). The etiology of cachexia is multifactorial and the underlying pathophysiological mechanisms are essentially the following: anorexia and malnourishment; immune overactivity and systemic inflammation; and endocrine disorders (anabolic/catabolic imbalance and resistance to growth hormone). In this paper, we review the main pathophysiological mechanisms underlying CHF cachexia, focusing also on the broad spectrum of actions of ghrelin and ghrelin agonists, and their possible use in combination with physical exercise to contrast CHF cachexia.

NSAIDs and opioids in management of fragility fractures.

Fragility fractures and their care are a major burden on individuals, health systems, and social care systems in industrialized countries. Fragility fracture can lead to long lasting painful and disabling condition. The level of pain is a major determinant for the outcome of any treatment of these fractures regardless of its location. The treatment of pain in patient with fragility fracture is rarely considered a priority in the care pathway.

Sarcopenia or muscle modifications in neurologic diseases: a lexical or patophysiological difference?

Sarcopenia is a condition characterized by a decrease in muscle mass and function (strength and mobility) that is frequently observed in the elderly. In people with paresis and altered mobility due to central nervous system (CNS) diseases, this definition then may not be applicable. In CNS diseases, mainly stroke and spinal cord injury, different and specific patterns of muscle loss and muscle changes have been described, due to denervation, disuse atrophy, spasticity and myosteatosis. The main observations available about these phenomena in CNS diseases are reviewed, and a broad view on the specific physiopathological mechanisms is also described. Moreover, a description of the potential pharmacological targets and treatment strategies (physical and nutritional) is provided. Since sarcopenia of the elderly and muscle modifications and muscle atrophy in CNS diseases have different mechanisms, it is probable that they do not respond equally to the same treatments.

The value of adding mirror therapy for upper limb motor recovery of subacute stroke patients: a randomized controlled trial.

BACKGROUND: Upper limb paresis remains a relevant challenge in stroke rehabilitation. AIM: To evaluate if adding mirror therapy (MT) to conventional therapy (CT) can improve motor recovery of the upper limb in subacute stroke patients. DESIGN: Prospective, single-center, single-blind, randomised, controlled trial. SETTING: Subacute stroke patients referred to a Physical and Rehabilitation Medicine Unit between October 2009 and August 2011. POPULATION: Twenty-six subacute stroke patients (time from stroke <4 weeks) with upper limb paresis (Motricity Index ≤ 77). METHODS: Patients were randomly allocated to the MT (N.=13) or to the CT group (N.=13). Both followed a comprehensive rehabilitative treatment. In addition, MT Group had 30 minutes of MT while the CT group had 30 minutes of sham therapy. Action Research Arm Test (ARAT) was the primary outcome measures. Motricity Index (MI) and the Functional Independence Measure (FIM) were the secondary outcome measures. RESULTS: After one month of treatment patients of both groups showed statistically significant improvements in all the variables measured (P<0.05). Moreover patients of the MT group had greater improvements in the ARAT, MI and FIM values compared to CT group (P<0.01, Glass's Δ Effect Size: 1.18). No relevant adverse event was recorded during the study. CONCLUSION: MT is a promising and easy method to improve motor recovery of the upper limb in subacute stroke patients. CLINICAL REHABILITATION IMPACT: While MT use has been advocated for acute patients with no or negligible motor function, it can be usefully extended to patients who show partial motor recovery. The easiness of implementation, the low cost and the acceptability makes this therapy an useful tool in stroke rehabilitation.