Botulinum Toxin—A High-Dosage Effect on Functional Outcome and Spasticity-Related Pain in Subjects with Stroke

Stroke patients can develop spasticity and spasticity-related pain (SRP). These disorders are frequent and can contribute to functional limitations and disabling conditions. Many reports have suggested that higher doses than initially recommended of BTX-A can be used effectively and safely, especially in the case of severe spasticity; however, whether the treatment produces any benefit on the functional outcome and SRP is unclear. Studies published between January 1989 and December 2022 were retrieved from MEDLINE/PubMed, Embase, and Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA, (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term “high dosage” indicates ≥600 U. Nine studies met the inclusion criteria. Globally, 460 subjects were treated with BTX-A high dose, and 301 suffered from stroke. Studies had variable method designs, sample sizes, and aims. Only five (55.5%) reported data about the functional outcome after BTX-A injection. Functional measures were also variable, and the improvement was observed predominantly in the disability assessment scale (DAS). SRP pain was quantified by visual analog scale (VAS) and only three studies reported the BTX-A effect. There is no scientific evidence that this therapeutic strategy unequivocally improves the functionality of the limbs. Although no clear-cut evidence emerges, certain patients with spasticity might obtain goal-oriented improvement from high-dose BTX-A. Likewise, data are insufficient to recommend high BTX dosage in SRP

Electromagnetic Field Therapy: A Rehabilitative Perspective in the Management of Musculoskeletal Pain - A Systematic Review

: Electromagnetic fields (EMFs) provide a non-invasive, safe, and easy method to treat pain with respect to musculoskeletal diseases. The purpose of this systematic review was to describe the use of electromagnetic therapy in the rehabilitation field by investigating the efficacy in acute and chronic pain in the musculoskeletal disorders. A database search was conducted using the following resources: PubMed, Cochrane, PEDro, SCOPUS, and WoS. The following MESH terms were used: [Electromagnetic field AND/OR Rehabilitation], [Electromagnetic field AND/OR Pain], [Pulsed Magnetic field AND/OR Rehabilitation] and [Pulsed Magnetic field AND/OR Pain], [Pulsed Electromagnetic field AND/OR Rehabilitation] and [Pulsed Electromagnetic field AND/OR Pain], per the guidelines of the PRISMA statement. Articles published between January 1, 2009 and December 31, 2018 were included as assessment of musculoskeletal pain conditions, randomized clinical trial including crossover and prospective design studies, full English text available, population age > 18 years; instead were excluded neurological randomized clinical trials, transcranial magnetic stimulation application, neuropathic pain, animal/in vitro studies, and articles without English abstract or English full text. Three independent investigators (AMC, NG, and LP) retrieved all the information. Twenty-one RTC (N=21) were considered for the inclusion and exclusion criteria. The results showed as pulsed magnetic fields at low intensity and frequency (from 1 Hz up to 100 Hz) are commonly used with efficacy in resolving musculoskeletal pain. EMFs therapy is a well tolerated, effective with no negative side effects, which can be integrated with rehabilitation for the treatment of chronic and acute pain in musculoskeletal diseases, but further studies are needed to examine the use of more standardized protocols

Frequent NRG1 fusions in caucasian pulmonary mucinous adenocarcinoma predicted by Phospho-ErbB3 expression

NRG1 fusions were recently reported as a new molecular feature of Invasive Mucinous Adenocarcinoma (IMA) of the lung. The NRG1 chimeric ligand acts as a strong inductor of phosphorylation and tyrosine kinase activity of the ErbB2/ErbB3 heterodimer, thus enhancing the PI3K-AKT/MAPK pathways. The NRG1 fusions were widely investigated in Asian IMA cohorts, whereas just anecdotal information are available about the occurrence of NRG1 fusions in IMA Caucasian population. Here we firstly explored a large Caucasian cohort of 51 IMAs and 34 non- IMA cases for the occurrence of NRG1 rearrangements by fluorescent in situ hybridization (FISH) and RNA target sequencing. FISH results were correlated to the immunohistochemical expression of phosphorylated-ErbB3 (pErbB3) receptor and the mutational status of KRAS, EGFR and ALK genes. The NRG1 rearrangements were detected in 31% IMAs and 3% non-IMAs and the CD74-NRG1 fusion transcript variant was characterized in 4 NRG1-positive IMAs. Moreover, pErbB3 expression was found to be strictly associated to the mucinous pattern (p = 0.012, Chi-square test) and all IMA cases showing aberrant expression of pErbB3 demonstrated NRG1 rearrangements. No significant correlation between NRG1 rearrangements and EGFR, KRAS or ALK mutations respectively, was observed. We report for the first time that NRG1 fusions are driver alterations clearly associated with mucinous lung adenocarcinoma subtype of Caucasian patients and not exclusive of Asiatic population. pErbB3 immunostaining may represent a strong predictor of NRG1 fusions, pointing out the detection of pErbB3 by IHC as a rapid and effective pre-screening method to select the NRG1-positive patients