Transforming the Management of Articular Fractures in the Foot: A Critical Examination of Current Methods and Future Directions: A Review.

This study provides a comprehensive examination of the current methodologies and potential strategies for the treatment of articular fractures of the foot. In the field of orthopedic healthcare, these fractures present a significant challenge due to their complex nature and the fact that they affect the routines of patients. The motivation behind this study is based on two main concepts. The first one is represented by the use of emerging medical technologies and personalized medicine to bring a significant transformation in the management of foot fractures and give a better quality of treatment that is accepted by the patient. However, because there are inequities in the availability of the necessary medical care and equipment, as well as uneven incorporation in clinical settings, new technologies cannot be used to treat these types of fractures. Regarding the second concept behind this study, it is indicated that although current treatment methods are essential, they have a number of shortcomings when it comes to properly addressing these types of injuries. An approach is needed that takes into account the biomechanical points of view and the particularities of each patient. This approach could be applied in all hospital settings. Through this study, we want to highlight the progress made in recent years in surgical techniques such as 3D printing, minimally invasive surgery (MIS), and biological products. However, in the application of this new discovery, new obstacles have been discovered that prevent the efficient treatment of these types of injuries. This study examines the effectiveness and limitations of current treatments, as well as how differences in healthcare, such as available equipment, training of medical staff, and technological advances, affect patient outcomes in everyday life. This research wishes to emphasize that continuous innovation, interdisciplinary collaboration, and the use of an optimal approach that is appropriate for each patient, are essential. This study aims to provide new insights and useful recommendations for future research and clinical practice. The main role of this research is to improve the quality of life of patients and increase the standards of care in this complex field, which is in permanent evolution.

Changes in pNFH Levels in Cerebrospinal Fluid and Motor Evolution after the Loading Dose with Nusinersen in Different Types of Spinal Muscular Atrophy.

Aim and Objectives: The objective of our retrospective study was to investigate the changes in pNFH levels in cerebrospinal fluid, which is a reliable marker of neuronal damage, after the loading dose of nusinersen in different types of spinal muscular atrophy. Materials and Methods: We analyzed the spinal muscular atrophy types, the number of copies of the SMN2 gene, and the progression of the motor status using specific motor function scales in a group of 38 patients with spinal muscular atrophy types 1, 2, and 3. Results: We found a significant inverse correlation between pNFH levels and patient age, progress on functional motor scales, and nusinersen administration. Our results also revealed that the neurofilament levels in the cerebrospinal fluid were higher in patients with 2 SMN2 copies than those with more than 2 copies, although the association was not statistically significant due to the abnormal distribution of the values. Conclusions: We identified several predictors of favorable evolution under nusinersen treatment, including spinal muscular atrophy type 1, children aged ≤ 30 months, and the presence of only 2 copies of SMN2. Our study provides important insights into the use of pNFH as a biomarker to monitor disease progression and responses to treatment in patients with spinal muscular atrophy.

Clinical and Electrophysiological Changes in Pediatric Spinal Muscular Atrophy after 2 Years of Nusinersen Treatment.

In the new therapeutic era, disease-modifying treatment (nusinersen) has changed the natural evolution of spinal muscular atrophy (SMA), creating new phenotypes. The main purpose of the retrospective observational study was to explore changes in clinical evolution and electrophysiological data after 2 years of nusinersen treatment. We assessed distal compound motor action potential (CMAP) on the ulnar nerve and motor abilities in 34 SMA patients, aged between 1 and 16 years old, under nusinersen treatment, using specific motor scales for types 1, 2 and 3. The evaluations were performed at treatment initiation and 26 months later. There were registered increased values for CMAP amplitudes after 2 years of nusinersen, significantly correlated with motor function evolution in SMA type 1 patients (p < 0.005, r = 0.667). In total, 45% of non-sitters became sitters and 25% of sitters became walkers. For SMA types 1 and 2, the age at the treatment initialization is highly significant (p < 0.0001) and correlated with treatment yield. A strong negative correlation (r = −0.633) was observed for SMA type 1 and a very strong negative correlation (r = −0.813) for SMA type 2. In treated SMA cases, the distal amplitude of the CMAP and motor functional scales are important prognostic factors, and early diagnosis and treatment are essential for a better outcome.

Physical Therapy and Nusinersen Impact on Spinal Muscular Atrophy Rehabilitative Outcome.

INTRODUCTION: Spinal muscular atrophy (SMA) is a progressive neurological disease with autosomal recessive transmission that affects motor neurons, causing their loss and resulting in muscle waste and motor deficiency. Nusinersen, the first SMN2 pre-mRNA targeted therapy approved by the Food and Drug Administration and the European Medicines Agency, has demonstrated high efficacy in improving motor function, as well as respiratory and nutritional statuses. MATERIALS AND METHODS: We observed 55 patients (children/adolescents) diagnosed with spinal muscular atrophy (SMA), who received nusinersen therapy. To investigate the benefits of physical therapy on rehabilitation outcomes, we compared the motor evolution of patients who received nusinersen and performed daily physical therapy (study group) to those of the control group, who received only nusinersen therapy. RESULTS: Motor skill improvements were statistically significantly (p < 0.001) higher in the study group, being almost four times better (12.66%), effect size, in comparison to the control group (3.18%). CONCLUSIONS: Physical therapy has provided superior results for those who receive it on a regular basis. These results include the correction of posture, reduction in stiffness, expansion of the range of motion and strengthening of muscles, thus allowing patients to do more movements and boosting their ability to perform everyday tasks.

Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I.

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular progressive disease, characterized by decreased amounts of survival motor neuron (SMN) protein, due to an autosomal recessive genetic defect. Despite recent research, there is still no cure. Nusinersen, an antisense oligonucleotide acting on the SMN2 gene, is intrathecally administered all life long, while onasemnogene abeparvovec-xioi, a gene therapy, is administered intravenously only once. Both therapies have proven efficacy, with best outcomes obtained when administered presymptomatically. In recent years, disease-modifying therapies such as nusinersen and onasemnogene abeparvovec-xioi have changed the natural history of SMA. METHODS: We observed seven SMA type I patients, who received both therapies. We compared their motor function trajectories, ventilation hours and cough assist sessions to a control group of patients who received one therapy, in order to investigate whether combination therapy may be more effective than a single intervention alone. RESULTS: Patients who received both therapies, compared to the monotherapy cohort, had the same motor function trajectory. Moreover, it was observed that the evolution of motor function was better in the 6 months following the first therapy than in the first 6 months after adding the second treatment. CONCLUSIONS: Our results suggest that early treatment is more important than combined therapy.

Clinical features and genetics in non-5q spinal muscular atrophy caused by acid ceramidase deficiency.

Spinal muscular atrophy (SMA) is a spectrum of genetically and clinically heterogeneous diseases leading to the progressive degeneration of peripheric motor neurons with subsequent muscle weakness and atrophy. More than 95% of the cases of SMA are represented by homozygous mutations of the SMN1 gene (5q-SMA). Because this disease represents the leading cause of death due to a genetic cause and due to the availability of genetic therapies which can now save the life of the patient and stop the progress of the disease, early diagnosis is crucial. This report presents the case of a 13-year-old patient admitted to our hospital in 2018 who presented a phenotype typical to 5q-SMA. Next-generation sequencing (NGS) and Sanger sequencing of the SMN1 gene were performed, and a negative result was obtained. Consequently, we continued testing using whole-exome sequencing and discovered three mutations in the ASAH1 gene (one pathogenic and two variants of uncertain significance). Pathogenic mutations in the ASAH1 gene are responsible for spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and Farber disease, which overlapped with our patient's phenotype. Currently, there are 45 SMA cases caused by mutations in the ASAH1 gene reported worldwide; however, the present case is the first reported in Romania.

Mobile Mechatronic/Robotic Orthotic Devices to Assist-Rehabilitate Neuromotor Impairments in the Upper Limb: A Systematic and Synthetic Review.

This paper overviews the state-of-the-art in upper limb robot-supported approaches, focusing on advancements in the related mechatronic devices for the patients' rehabilitation and/or assistance. Dedicated to the technical, comprehensively methodological and global effectiveness and improvement in this inter-disciplinary field of research, it includes information beyond the therapy administrated in clinical settings-but with no diminished safety requirements. Our systematic review, based on PRISMA guidelines, searched articles published between January 2001 and November 2017 from the following databases: Cochrane, Medline/PubMed, PMC, Elsevier, PEDro, and ISI Web of Knowledge/Science. Then we have applied a new innovative PEDro-inspired technique to classify the relevant articles. The article focuses on the main indications, current technologies, categories of intervention and outcome assessment modalities. It includes also, in tabular form, the main characteristics of the most relevant mobile (wearable and/or portable) mechatronic/robotic orthoses/exoskeletons prototype devices used to assist-rehabilitate neuromotor impairments in the upper limb.