Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain

Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment of BTcP. Light-activated drugs offer a novel potential strategy for the rapid control of pain without the typical adverse effects of systemic analgesic drugs. mGlu5 metabotropic glutamate receptor antagonists display potent analgesic activity, and light-induced activation of one of these compounds (JF-NP-26) in the thalamus was found to induce analgesia in models of inflammatory and neuropathic pain. We used an established mouse model of BTcP based on the injection of cancer cells into the femur, followed, 16 days later, by systemic administration of morphine. BTcP was induced by injection of endothelin-1 (ET-1) into the tumor, 20 min after morphine administration. Mice were implanted with optic fibers delivering light in the visible spectrum (405 nm) in the thalamus or prelimbic cortex to locally activate systemically injected JF-NP-26. Light delivery in the thalamus caused rapid and substantial analgesia, and this effect was specific because light delivery in the prelimbic cortex did not relieve BTcP. This finding lays the groundwork for the use of optopharmacology in the treatment of BTcP.This work was supported by the Italian Ministry of Health (Project code: GR-2016-02362046).Peer reviewe

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Early predictors of ventricular remodeling after myocardial infarction

These data confirm the association between VR and survival. Surprisingly, no independent predictors identify Pts who will develop R. Interestingly markers linked with the biohumoral mechanisms currently related with the pathophysiology of VR, are not predictors of VR

La responsabilità sanitaria tra continuità e cambiamento

Il volume raccoglie una serie di scritti che si prefiggono di indagare nelle varie prospettive l'impatto della l. 24/2017 sulla responsabilità dei sanitari e delle strutture di diagnosi e cura

What is the impact of robotic rehabilitation on balance and gait outcomes in people with multiple sclerosis? A systematic review of randomized control trials

Introduction: In recent years, robot-assisted gait training (RAGT) has been proposed as therapy for balance and gait dysfunctions in people with multiple sclerosis (PwMS). Through this systematic review, we aimed to discuss the impact of RAGT on balance and gait outcomes. Furthermore, characteristics of the training in terms of robots used, participants characteristics, protocols and combined therapeutic approaches have been described. Evidence acquisition: As part of the Italian Consensus on robotic rehabilitation "CICERONE" a systematic search was provided in PubMed, the Cochrane Library and PEDro to identify relevant studies published before December 2019. Only randomized control trials (RCT) involving RAGT for PwMS were included. PEDro scale was used to assess the risk of bias and the Oxford Center for Evidence-Based Medicine (OCEBM) was used to assess level of evidence of included studies. Evidence synthesis: The search on databases resulted in 336 records and, finally, 12 studies were included. RAGT was provided with Exoskeleton in ten studies (6-40 session, 2-5 per week) and with end-effector in two studies (12 sessions, 2-3 per week) with large variability in terms of participants' disability. All the exoskeletons were combined with bodyweight support treadmill and movement assistance varied from 0% to 100% depending on participants' disability, two studies combined exoskeleton with virtual reality. The end-effector speed ranged between 1.3 and 1.8 km/h, with bodyweight support starting from 50% and progressively reduced. In seven out of twelve studies RAGT was provided in a multimodal rehabilitation program or in combination with standard physical therapy. There is level 2 evidence that RAGT has positive impact in PwMS, reaching the minimally clinically importance difference in Berg Balance Scale, six-minute walking test and gait speed. Conclusions: In available RCT, RAGT is mostly provided with exoskeleton devices and improves balance and gait outcomes in a clinically meaningful way. Considering several advantages in terms of safety, motor assistance and intensity of training provided, RAGT should be promoted for PwMS with severe disability in a multimodal rehabilitation context as an opportunity to maximize recovery

A multi-centric observational study on heterotopic ossification in severely brain injured patients with disorders of consciousness: preliminary data

Aims: to identify occurrence of neurogenic heterotopic ossification (NHO) in patients with prolonged disorder of consciousness (DoC) and possible risk factors. Design: Multi-center observational study. Setting: twenty-three intensive neurorehabilitation units. Subjects: two hundred and seventy-eight patients with prolonged disorder of consciousness (DoC; 150 in vegetative state and 128 in minimally conscious state) of different aetiology (vascular 125, traumatic=83; anoxic=56 brain injury and other brain aetiologies=14). Main Measures: at study entry: clinical evaluation by the Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS), Early Rehabilitation Barthel Index (ERBI), Clinical Feature Scale (CFS); presence of ventilator support, spasticity, bone fractures. Within 3 months after admission: clinical evidence of NHO (i.e. limited range of motion and/or joint pain and/or local inflammation) confirmed by standard radiological and/or sonographic evaluation and presence of paroxysmal sympathetic hyperactivity (PSH). Results: Thirty-one patients (11.2%) developed NHO. Presence of abnormal ossifications was significantly higher in patients in VS than in patients in MCS and in patients with traumatic brain injury. Moreover patients with NHO showed higher DRS category and total score, higher occurrence of limb spasticity and bone fractures at study entry than patients without NHO. Patients with NHO did not differ from patients without NHO for sex, age, time post-injury, CRS-R and ERBI total scores, presence of non-invasive ventilator support at study entry and presence of PSH. Conclusions: Our findings suggest a relation between development of NHO and clinical diagnosis, functional disability status and aetiology in patients with DoC. Moreover, we identified spasticity and bone fractures as possible risk factors for occurrence of NHO in patients with severe brain injury and DoC

Early rehabilitation for severe acquired brain injury in intensive care unit: multicenter observational study

The increased survival after a severe acquired brain injury (sABI) raise the problem of making most effective the treatments in Intensive Care Unit (ICU)/Neurointensive Care Unit (NICU), also integrating rehabilitation care. Despite previous studies reported that early mobilization in ICU was effective in preventing complications and reducing hospital stay, few studies addressed the rehabilitative management of sABI patients in ICU/NICU

Effects of robot-assisted gait training on postural instability in Parkinson's disease: a systematic review

INTRODUCTION: Postural instability is a cardinal feature of Parkinson's disease, together with rest tremor, rigidity and bradykinesia. It is a highly disabling symptom that becomes increasingly common with disease progression and represents a major source of reduced quality of life in patients with Parkinson's disease. Rehabilitation aims to enable patients with Parkinson's disease to maintain their maximum level of mobility, activity and independence. To date, a wide range of rehabilitation approaches has been employed to treat postural instability in Parkinson's disease, including robotic training. Our main aim was to conduct a systematic review of current literature about the effects of robot-assisted gait training on postural instability in patients with Parkinson's disease.EVIDENCE ACQUISITION: A systematic search using the following MeSH terms (Parkinson disease; postural balance; robotics; rehabilitation) and string {("robotics [mh]" OR "robot-assisted" OR "electromechanical") and ("rehabilitation [mh]" OR "training") and ("postural balance [mh]")} was conducted on PubMed, Cochrane Library and PEDro electronic databases. Full text articles in English published up to December 2020 were included. Data about patient characteristics, robotic devices, treatment procedures and outcome measures were considered. Every included article got checked for quality. Level of evidence was defined for all studies.EVIDENCE SYNTHESIS: Three authors independently extracted and verified data. In total, 18 articles (2 systematic reviews, 9 randomized controlled trials, 4 uncontrolled studies and 3 case series/case reports) were included. Both end-effector and exoskeleton devices were investigated as to robot-assisted gait training modalities. No clear relationship between treatment parameters and clinical conditions was observed. We found a high level of evidence about the effects of robot-assisted gait training on balance and freezing of gait in patients with Parkinson's disease.CONCLUSIONS: This systematic review provides to the reader a complete overview of current literature and levels of evidence about the effects of robot-assisted gait training on postural instability issues (static and dynamic balance, freezing of gait, falls, confidence in activities of daily living and gait parameters related to balance skills) in patients with Parkinson's disease