Developing core sets for persons following amputation based on the International Classification of Functioning, Disability and Health as a way to specify functioning

Amputation is a common late stage sequel of peripheral vascular disease and diabetes or a sequel of accidental trauma, civil unrest and landmines. The functional impairments affect many facets of life including but not limited to: Mobility; activities of daily living; body image and sexuality. Classification, measurement and comparison of the consequences of amputations has been impeded by the limited availability of internationally, multiculturally standardized instruments in the amputee setting. The introduction of the International Classification of Functioning, Disability and Health (ICF) by the World Health Assembly in May 2001 provides a globally accepted framework and classification system to describe, assess and compare function and disability. In order to facilitate the use of the ICF in everyday clinical practice and research, ICF core sets have been developed that focus on specific aspects of function typically associated with a particular disability. The objective of this paper is to outline the development process for the ICF core sets for persons following amputation. The ICF core sets are designed to translate the benefits of the ICF into clinical routine. The ICF core sets will be defined at a Consensus conference which will integrate evidence from preparatory studies, namely: (a) a systematic literature review regarding the outcome measures of clinical trails and observational studies, (b) semi-structured patient interviews, (c) international experts participating in an internet-based survey, and (d) cross-sectional, multi-center studies for clinical applicability. To validate the ICF core sets field-testing will follow. Invitation for participation: The development of ICF Core Sets is an inclusive and open process. Anyone who wishes to actively participate in this process is invited to do so

Muscle selection and dosing in patients undergoing treatment with abobotulinumtoxinA for lower limb spasticity in real world practice

ObjectiveDescribe abobotulinumtoxinA (aboBoNT-A) dosing parameters in the real-world management of lower limb spasticity (LLS).MethodsProspective, observational study (NCT04050527) following ambulatory adults with unilateral LLS treated with aboBoNT-A.Results The effectiveness population included 384 adults with LLS. The median total injected dose of aboBoNT-A was 600U [range 100–1475U], which was injected into a median of 4 muscles [range 1–8]. Across cycles 1 to 5, the most frequently injected lower limb muscles were the gastrocnemius medial (median of 100–150U injected in up to 84% of patients per cycle) and lateral (100–150U in up to 74%) heads, soleus (200U in up to 67%), tibialis posterior (150–200U in up to 50%), flexor digitorum longus (100–137.5U in up to 41%), and flexor hallucis longus (100U in up to 22%). Other lower limb muscles were injected in fewer than 15% of patients.ConclusionsIn this routine practice study, 6 muscles were identified as being most frequently injected for LLS. Injection practice was consistent with treatment of foot equinus and/or varus as the most common lower limb spasticity patterns. On average, total aboBoNT-A doses for the lower limb muscles were lower than approved.<br/

An impairment-specific hip exoskeleton assistance for gait training in subjects with acquired brain injury: a feasibility study

This study was designed to investigate the feasibility and the potential effects on walking performance of a short gait training with a novel impairment-specific hip assistance (iHA) through a bilateral active pelvis orthosis (APO) in patients with acquired brain injury (ABI). Fourteen subjects capable of independent gait and exhibiting mild-to-moderate gait deficits, due to an ABI, were enrolled. Subjects presenting deficit in hip flexion and/or extension were included and divided into two groups based on the presence (group A, n = 6) or absence (group B, n = 8) of knee hyperextension during stance phase of walking. Two iHA-based profiles were developed for the groups. The protocol included two overground gait training sessions using APO, and two evaluation sessions, pre and post training. Primary outcomes were pre vs. post-training walking distance and steady-state speed in the 6-min walking test. Secondary outcomes were self-selected speed, joint kinematics and kinetics, gait symmetry and forward propulsion, assessed through 3D gait analysis. Following the training, study participants significantly increased the walked distance and average steady-state speed in the 6-min walking tests, both when walking with and without the APO. The increased walked distance surpassed the minimal clinically important difference for groups A and B, (respectively, 42 and 57&nbsp;m &gt; 34&nbsp;m). In group A, five out of six subjects had decreased knee hyperextension at the post-training session (on average the peak of the knee extension angle was reduced by 36%). Knee flexion during swing phase increased, by 16% and 31%, for A and B groups respectively. Two-day gait training with APO providing iHA was effective and safe in improving walking performance and knee kinematics in ABI survivors. These preliminary findings suggest that this strategy may be viable for subject-specific post-ABI gait rehabilitation

Clinical Presentation of Patients with Lower Limb Spasticity Undergoing Routine Treatment with Botulinum Toxin: Baseline Findings from an International Observational Study

OBJECTIVE: Describe how people with lower limb spasticity present for treatment in routine clinical practice. METHODS: Prospective, observational study (Clinicaltrials.gov: NCT04050527) of ambulatory adult patients (≥ 18 years) with unilateral lower limb spasticity (able to take ≥ 5 steps with or without assistance) presenting for routine spasticity management, including treatment with abobotulinumtoxinA. RESULTS: The study population included 430 adults with lower limb spasticity. Despite their relatively young age (mean ± standard deviation 53.7 ± 13.9 years), only 20% of patients were employed. Most patients had an acquired brain injury due to cerebrovascular disease; 84.1% reported having concomitant upper limb spasticity. Using the Leg Activity Measure, most patients reported no or only mild difficulties in performing hygiene/positioning tasks, while 80.7% had at least mild difficulty with indoor ambulation and 90.5% had at least mild difficulty with walking outdoors. Sensory, communication and/or cognitive impairments were also common. At the first treatment cycle, 50.7% of patients set active function primary goals, including locomotion transferring or standing. CONCLUSION: These observations highlight the complexity of presentation that must be considered when setting treatment goals for lower limb spasticity and emphasize the types of impairment and activity (functional) limitations that treating teams may expect to encounter in their patients and should cover in their initial and follow-up assessments

Adult Spasticity International Registry Study: methodology and baseline patient, healthcare provider, and caregiver characteristics

Objective: The main aim of this study was to determine the utilization patterns and effectiveness of onabotulinumtoxinA (Botox®) for treatment of spasticity in clinical practice. Design: An international, multicentre, prospective, observational study at selected sites in North America, Europe, and Asia. Patients: Adult patients with newly diagnosed or established focal spasticity, including those who had previously received treatment with onabotulinum-toxin A. Methods: Patients were treated with onabotulinumtoxinA, approximately every 12 weeks, according to their physician’s usual clinical practice over a period of up to 96 weeks, with a final follow-up interview at 108 weeks. Patient, physician and caregiver data were collected. Results: Baseline characteristics are reported. Of the 745 patients enrolled by 75 healthcare providers from 54 sites, 474 patients had previously received onabotulinumtoxinA treatment for spasticity. Lower limb spasticity was more common than upper limb spasticity, with stroke the most common underlying aetiology. The Short-Form 12 (SF-12) health survey scores showed that patients’ spasticity had a greater perceived impact on physical rather than mental aspects. Conclusion: The data collected in this study will guide the development of administration strategies to optimize the effectiveness of onabotulinumtoxinA in the management of spasticity of various underlying aetiologies

Assessment of Glioblastoma Response in the Era of Bevacizumab: Longstanding and Emergent Challenges in the Imaging Evaluation of Pseudoresponse

Glioblastoma is the deadliest primary malignant brain neoplasm, and despite the availability of many treatment options, its prognosis remains somber. Enhancement detected by magnetic resonance imaging (MRI) was considered the best imaging marker of tumor activity in glioblastoma for decades. However, its role as a surrogate marker of tumor viability has changed with the appearance of new treatment regimens and imaging modalities. The antiangiogenic therapy created an inflection point in the imaging assessment of glioblastoma response in clinical trials and clinical practice. Although BEV led to the improvement of enhancement, it did not necessarily mean tumor response. The decrease in the enhancement intensity represents a change in the permeability properties of the blood brain barrier, and presumably, the switch of the tumor growth pattern to an infiltrative non-enhancing phenotype. New imaging techniques for the assessment of cellularity, blood flow hemodynamics, and biochemistry have emerged to overcome this hurdle; nevertheless, designing tools to assess tumor response more accurately, and in so doing, improve the assessment of response to standard of care (SOC) therapies and to novel therapies, remains challenging

Superior Neuroprotective Efficacy of LAU-0901, a Novel Platelet-Activating Factor Antagonist, in Experimental Stroke

Platelet-activating factor (PAF) accumulates during cerebral ischemia, and inhibition of this process plays a critical role in neuronal survival. Recently, we demonstrated that LAU-0901, a novel PAF receptor antagonist, is neuroprotective in experimental stroke. We used magnetic resonance imaging in conjunction with behavior and immunohistopathology to expand our understanding of this novel therapeutic approach. Sprague–Dawley rats received 2 h middle cerebral artery occlusion (MCAo) and were treated with LAU-0901 (60 mg/kg) or vehicle 2 h from MCAo onset. Behavioral function, T2-weighted imaging (T2WI), and apparent diffusion coefficients were performed on days 1, 3, and 7 after MCAo. Infarct volume and number of GFAP, ED-1, and NeuN-positive cells were conducted on day 7. Behavioral deficit was significantly improved by LAU-0901 treatment compared to vehicle on days 1, 3, and 7. Total lesion volumes computed from T2WI were significantly reduced by LAU-0901 on days 1, 3, and 7 (by 83%, 90%, and 96%, respectively), which was consistent with decreased edema formation. Histopathology revealed that LAU-0901 treatment resulted in significant reduction of cortical and subcortical infarct volumes, attenuated microglial infiltration, and promoted astrocytic and neuronal survival. These findings suggest LAU-0901 is a promising neuroprotectant and provide the basis for future therapeutics in patients suffering ischemic stroke

Downregulation of PHEX in multibacillary leprosy patients: observational cross-sectional study

BACKGROUND: Peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. The phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) encodes a homonymous protein (PHEX) implicated in bone metabolism. PHEX/PHEX alterations may result in bone and cartilage lesions. PHEX expression is downregulated by intracellular Mycobacterium leprae (M. leprae) in cultures of human Schwann cells and osteoblasts. M. leprae in vivo effect on PHEX/PHEX is not known. METHODS: Cross-sectional observational study of 36 leprosy patients (22 lepromatous and 14 borderline-tuberculoid) and 20 healthy volunteers (HV). The following tests were performed: PHEX flow cytometric analysis on blood mononuclear cells, cytokine production in culture supernatant, 25-hydroxyvitamin D (OHvitD) serum levels and (99m)Tc-MDP three-phase bone scintigraphy, radiography of upper and lower extremities and blood and urine biochemistry. RESULTS: Significantly lower PHEX expression levels were observed in lepromatous patients than in the other groups (χ(2) = 16.554, p < 0.001 for lymphocytes and χ(2) = 13.933, p = 0.001 for monocytes). Low levels of 25-(OHvitD) were observed in HV (median = 23.0 ng/mL) and BT patients (median = 27.5 ng/mL) and normal serum levels were found in LL patients (median = 38.6 ng/mL). Inflammatory cytokines, such as TNF, a PHEX transcription repressor, were lower after stimulation with M. leprae in peripheral blood mononuclear cells from lepromatous in comparison to BT patients and HV (χ(2) = 10.820, p < 0.001). CONCLUSION: Downregulation of PHEX may constitute an important early component of bone loss and joint damage in leprosy. The present results suggest a direct effect produced by M. leprae on the osteoarticular system that may use this mechanism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0651-5) contains supplementary material, which is available to authorized users

Localization of Secondary Metabolites in Marine Invertebrates: Contribution of MALDI MSI for the Study of Saponins in Cuvierian Tubules of H. forskali

BACKGROUND: Several species of sea cucumbers of the family Holothuriidae possess a particular mechanical defense system called the Cuvierian tubules (Ct). It is also a chemical defense system as triterpene glycosides (saponins) appear to be particularly concentrated in Ct. In the present study, the precise localization of saponins in the Ct of Holothuria forskali is investigated. Classical histochemical labeling using lectin was firstly performed but did not generate any conclusive results. Thus, MALDI mass spectrometry Imaging (MALDI-MSI) was directly applied and completed by statistical multivariate tests. A comparison between the tubules of relaxed and stressed animals was realized. RESULTS: These analyses allowed the detection of three groups of ions, corresponding to the isomeric saponins of the tubules. Saponins detected at m/z 1287 and 1303 were the most abundant and were apparently localized in the connective tissue of the tubules of both relaxed and stressed individuals. Saponins at m/z 1125 and 1141 were detected in lower amount and were present in tissues of relaxed animals. Finally, saponin ions at 1433, 1449, 1463 and 1479 were observed in some Ct of stressed holothuroids in the outer part of the connective tissue. The saponin group m/z 14xx seems therefore to be stress-specific and could originate from modifications of the saponins with m/z of 11xx. CONCLUSIONS: All the results taken together indicate a complex chemical defense mechanism with, for a single organ, different sets of saponins originating from different cell populations and presenting different responses to stress. The present study also reflects that MALDI-MSI is a valuable tool for chemical ecology studies in which specific chemical signalling molecules like allelochemicals or pheromones have to be tracked. This report represents one of the very first studies using these tools to provide a functional and ecological understanding of the role of natural products from marine invertebrates