Permanent Functional Disability Research Articles

Granular Hydrogels Improve Myogenic Invasion and Repair after Volumetric Muscle Loss.

Skeletal muscle injuries including volumetric muscle loss (VML) lead to excessive tissue scarring and permanent functional disability. Despite its high prevalence, there is currently no effective treatment for VML. Bioengineering interventions such as biomaterials that fill the VML defect to support cell and tissue growth are a promising therapeutic strategy. However, traditional biomaterials developed for this purpose lack the pore features needed to support cell infiltration. The present study investigates for the first time, the impact of granular hydrogels on muscle repair - hypothesizing that their flowability will permit conformable filling of the defect site and their inherent porosity will support the invasion of native myogenic cells, leading to effective muscle repair. Small and large microparticle fragments are prepared from photocurable hyaluronic acid polymer via extrusion fragmentation and facile size sorting. In assembled granular hydrogels, particle size and degree of packing significantly influence pore features, rheological behavior, and injectability. Using a mouse model of VML, it is demonstrated that, in contrast to bulk hydrogels, granular hydrogels support early-stage (satellite cell invasion) and late-stage (myofiber regeneration) muscle repair processes. Together, these results highlight the promising potential of injectable and porous granular hydrogels in supporting endogenous repair after severe muscle injury.

Abdominal versus pelvic gunshot injuries in terms of postoperative outcomes: A cohort representing the experience of 406 cases in seven years

Objective: Gunshot injuries have become a significant problem globally. This study aimed to assess the differences between abdominal versus pelvic gunshot injuries in terms of postoperative outcomes to determine which type of injury is more lethal. Material and Methods: This was a cohort study carried out to compare patients who had abdominal versus pelvic gunshot injuries, to analyse the differences in the impact of the anatomical site of injury on morbidity, mortality, and disabilities in all patients who had been admitted to the hospital due to torso gunshot injuries from February 2011 to December 2018. Results: During the study period, 406 patients suffered from torso gunshot injuries. 391 were males and 15 were females; 343 (84.4%) patients had abdominal gunshot wounds, which were considered the first group, while in the second group, there were 63 (15.6%) patients who had pelvic gunshot wounds In the first group, 328 (95.6%) patients required urgent explorative laparotomy, complications were observed in 83 (24.2%) patients, while re-operations were reported in 51 (14.9%) patients and 11 (3.2%) patients had permanent functional disabilities, and 46 (13.4%) patients passed away. In the second group, all patients were treated with urgent explorative laparotomy, 17 (27%) patients suffered from complications, re-operation occurred in 13 (20.6%) patients, permeant functional disability occurred in 17 (27%) patients, and mortality was seen in 16 (25.4%) patients. Conclusion: Our clinical experience has shown that mortality rates and long-term disability occur at a higher rate in pelvic gunshot injuries therefore early senior surgeon input is mandatory for the potential poor outcome to be minimized.

Talus osteomyelitis - tubercular or not?

Tuberculosis is a communicable infective disease caused by Mycobacterium tuberculosis (MTB). The most commonly involved organ is the lung (Pulmonary tuberculosis), however, MTB can affect any organ other than lungs; in this cases, it is known as Extrapulmonary Tuberculosis (EPTB), which can lead to significant morbidity and mortality. Patients with EPTB can rarely develop ankle or foot arthritis, which usually is either misdiagnosed or diagnosed very late, leading to complications. Early diagnosis and timely treatment are very important to prevent permanent functional disability, thus a high suspicion, even in the absence of specific symptoms, is a must. We report a rare case of osteoarthritis of talus which was tubercular, and in which the patient responded well to treatment.

The challenge of pharmacotherapy for musculoskeletal pain: an overview of unmet needs.

Musculoskeletal disorders are characterized by several impairments, including pain, affecting muscles, bones, joints and adjacent connective tissue, resulting in temporary or permanent functional limitations and disability. Musculoskeletal pain is particularly prevalent worldwide and greatly impacts the quality of life, social participation and economic burden. To date, several issues persist about the classification of musculoskeletal pain and its management strategies and resources. The treatment of musculoskeletal pain conditions is complex and often requires a multimodal approach, including pharmacological and non-pharmacological therapy that might be ineffective in many cases, resulting in poor patient satisfaction and controversial expectations about the potential benefits of available interventions. This manuscript provides an overview of unmet needs in managing musculoskeletal pain, particularly focusing on pharmacotherapeutic pitfalls in this context.

LOCAL AND SYSTEMIC MEDIATORS OF SKELETAL MUSCLE WASTING IN HUMANS FOLLOWING ACUTE TRAUMA

AbstractIntroductionSkeletal muscle wasting is an important clinical issue following acute traumatic injury, and can delay recovery and cause permanent functional disability particularly in the elderly. However, the fundamental mechanisms involved in trauma-induced muscle wasting remain poorly defined and therapeutic interventions are limited.ObjectivesTo characterise local and systemic mediators of skeletal muscle wasting in elderly patients following acute trauma.MethodsExperiments were approved by a local NHS Research Ethics Committee and all participants provided written informed consent. Vastus lateralis biopsies and serum samples were taken from human male and female patients shortly after acute trauma injury in lower limbs (n=6; mean age 78.7±4.4 y) and compared to age-matched controls (n=6; mean age 72.6±6.3 y). Atrogenes and upstream regulators (MuRF1; MAFbx; IL6, TNFα, PGC-1α) mRNA expression was assessed in muscle samples via RT-qPCR. Serum profiling of inflammatory markers (e.g. IL6, TNFα, IL1β) was further performed via multiplex assays. To determine whether systemic factors induced by trauma directly affect muscle phenotype, differentiated primary human myotubes were treated in vitro with serum from controls or trauma patients (pooled; n=3 each) in the final 24 hours of differentiation. Cells were then fixed, stained for myogenin and imaged to determine minimum ferret diameter. Statistical significance was determined at P<0.05.ResultsThere was an increase in skeletal muscle mRNA expression for E3 ligase MAFbx and inflammatory cytokine IL-6 (4.6 and 21.5-fold respectively; P<0.05) in trauma patients compared to controls. Expression of myogenic determination factor MyoD and regulator of mitochondrial biogenesis PGC-1α was lower in muscle of trauma patients vs controls (0.5 and 0.39-fold respectively; P<0.05). In serum, trauma patients showed increased concentrations of circulating pro-inflammatory cytokines IL-6 (14.5 vs. 0.3 pg/ml; P<0.05) and IL-16 (182.7 vs. 85.2 pg/ml; P<0.05) compared to controls. Primary myotube experiments revealed serum from trauma patients induced atrophy (32% decrease in diameter) compared to control serum-treated cells (P<0.001).ConclusionSkeletal muscle from patients following acute trauma injury showed greater expression of atrophy and inflammatory markers. Trauma patient serum exhibited higher circulating pro-inflammatory cytokine concentrations. Primary human myotubes treated with serum from trauma patients showed significant atrophy compared to healthy serum-treated controls. We speculate a mechanism(s) acting via circulating factors may contribute to skeletal muscle pathology following acute trauma.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Advancements in Diffusion MRI Tractography for Neurosurgery.

Diffusion magnetic resonance imaging tractography is a noninvasive technique that enables the visualization and quantification of white matter tracts within the brain. It is extensively used in preoperative planning for brain tumors, epilepsy, and functional neurosurgical procedures such as deep brain stimulation. Over the past 25 years, significant advancements have been made in imaging acquisition, fiber direction estimation, and tracking methods, resulting in considerable improvements in tractography accuracy. The technique enables the mapping of functionally critical pathways around surgical sites to avoid permanent functional disability. When the limitations are adequately acknowledged and considered, tractography can serve as a valuable tool to safeguard critical white matter tracts and provides insight regarding changes in normal white matter and structural connectivity of the whole brain beyond local lesions. In functional neurosurgical procedures such as deep brain stimulation, it plays a significant role in optimizing stimulation sites and parameters to maximize therapeutic efficacy and can be used as a direct target for therapy. These insights can aid in patient risk stratification and prognosis. This article aims to discuss state-of-the-art tractography methodologies and their applications in preoperative planning and highlight the challenges and new prospects for the use of tractography in daily clinical practice.

Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far?

Traumatic brain injury (TBI) is one of the leading causes of long-lasting morbidity and mortality worldwide, being a devastating condition related to the impairment of the nervous system after an external traumatic event resulting in transitory or permanent functional disability, with a significant burden to the healthcare system. Harmful events underlying TBI can be classified into two sequential stages, primary and secondary, which are both associated with breakdown of the tissue homeostasis due to impairment of the blood-brain barrier, osmotic imbalance, inflammatory processes, oxidative stress, excitotoxicity, and apoptotic cell death, ultimately resulting in a loss of tissue functionality. The present study provides an updated review concerning the roles of brain edema, inflammation, excitotoxicity, and oxidative stress on brain changes resulting from a TBI. The proper characterization of the phenomena resulting from TBI can contribute to the improvement of care, rehabilitation and quality of life of the affected people.

Are There Any Differences in Road Traffic Injury Outcomes between Older and Younger Adults? Setting the Grounds for Posttraumatic Senior Personal Injury Assessment Guidelines

Injury outcomes seem to be more severe in older than younger persons. This may make personal injury assessment (PIA) particularly difficult, mainly because of seniors' previous health frailties. To set the grounds for seniors' PIA guidelines, we compared an older with a younger adult population of trauma victims and, secondarily, identified differences between the groups regarding three-dimensional and medico-legal damage parameters assessment. Using a retrospective study of victims of road traffic accidents, we compared the groups (n = 239 each), assuring similar acute injury severity (ISS standardised difference = 0.01): G1 (older adults); G2 (younger adults). Logistic regression was used to estimate the odds ratio. G1 revealed higher negative consequences when considering the three-dimensional damage assessment, with more frequent and severe outcomes, being a cause of further difficulties in daily living activities, with a loss of independence and autonomy. Nevertheless, regarding the medico-legal damage parameters, permanent functional disability did not show significant differences. This study generates evidence that reveals the need to rethink the traditional methodology of PIA in older persons, giving more relevance to the real-life contexts of each person. It is essential to: obtain complete information about previous physiologic and health states, begin the medico-legal assessment as early as possible, make regular follow-ups, and perform a multidisciplinary evaluation.

Therapeutic Sources of Skeletal Muscle Regeneration from Volumetric Muscle Loss: A Narrative Review

PURPOSE: Minor skeletal muscle injuries can be repaired, but more extensive volumetric muscle loss (VML) leads to a permanent functional disability with ambiguous therapeutic outcomes, and reconstructive surgical procedures are constrained by donor tissue scarcity. This review assessed the considerable attention paid to biomaterials in healing damaged skeletal muscle.METHODS: A comprehensive search in PubMed, Web of Science, Google Scholar, and Wiley Online Library was conducted to obtain previous studies exploring the state of biocompatible tissue scaffolds for VML recovery.RESULTS: By regenerating the function of damaged skeletal muscle, tissue-engineered skeletal muscle construction could revolutionize the treatment of VML. However, transporting cells into the wounded muscle location presents a significant challenge because it may result in unfavorable immunological reactions. The development and validation of several biomaterials with varying physical and chemical natures to treat various muscle injuries have recently been undertaken to overcome this problem. This review discusses the relative benefits of satellite cells (SC), the most prevalent skeletal muscle stem cells employed to seed scaffolds.CONCLUSIONS: Biomaterials can be used with skeletal muscle stem cells and growth factors to repair VML because of their customizable and desirable physicochemical qualities. Owing to the capacity of SCs for self-renewal and their undifferentiated state, these cells are excellent candidates for cell therapy. A large gap exists between understanding SC behavior and how it can be used to repair and regenerate human skeletal muscle tissue. Thus, this review sought to portray the current knowledge on the lifespan of SCs and their involvement in exercise-induced muscle regeneration and hypertrophy.

Assessment of informational needs in Behcet’s patients

Behçet’s disease (BD) is one of the rare rheumatologic diseases which affects most commonly young adults in the third or fourth decade of life. Inspite of the multi system nature of the disease can lead to temporary or permanent functional disability, informational needs of BD patients is still unknown as no studies has investigated such issue, hence the aim is to assess the informational needs among patients with Behçet’s disease. A cross-sectional descriptive design on a convenient sample of 68 adult BD patients was utilized. Data was collected using the following tools: (a) structured interview questionnaire and (b) the Arabic version of Toronto Informational Needs Questionnaire (TINQ) adapted for BD. The highest percentage of the study sample was male (82.40%) came from rural area (61.80%) and aged 31-42 (58.00%) with a mean age of (38±7.01 years). The study results showed the information related to treatment, disease characteristics, investigative tests and psychosocial items are highly important needs among BD patients. Age, gender and education are influencing factors for informational needs in the sample of the study. Further replication of the study is recommended from different geographical areas.

Safety and efficacy of an injectable nerve-specific hydrogel in a rodent crush injury model.

While the peripheral nervous system has the inherent ability to recover following injury, results are often unsatisfactory, resulting in permanent functional deficits and disability. Therefore, methods that enhance regeneration are of significant interest. The present study investigates an injectable nerve-tissue-specific hydrogel as a biomaterial for nerve regeneration in a rat nerve crush model. Nerve-specific hydrogels were injected into the subepineurial space in both uninjured and crushed sciatic nerves of rats to assess safety and efficacy, respectively. The animals were followed longitudinally for 12 wk using sciatic functional index and kinematic measures. At 12 wk, electrophysiologic examination was also performed, followed by nerve and muscle histologic assessment. When the hydrogel was injected into an uninjured nerve, no differences in sciatic functional index, kinematic function, or axon counts were observed. A slight reduction in muscle fiber diameter was observed in the hydrogel-injected animals, but overall muscle area and kinematic function were not affected. Hydrogel injection following nerve crush injury resulted in multiple modest improvements in sciatic functional index and kinematic function with an earlier return to normal function observed in the hydrogel treated animals as compared to untreated controls. While no improvements in supramaximal compound motor action potential were observed in hydrogel treated animals, increased axon counts were observed on histologic assessment. These improvements in functional and histologic outcomes in a rapidly and fully recovering model suggest that injection of a nerve-specific hydrogel is safe and has the potential to improve outcomes following nerve injury.

525 - Anger expression among survivors after stroke in Greek elderly

Introduction:Individuals may consider stroke complications as a threat to their well-being and self- esteem. Anger often occurs in patients after stroke and can disrupt the course of patient’s recovery.The aim of the present study was to investigate anger expression and degree of functionality in patients after stroke. Additionally, the relationship between the above parameters, as well as their correlation with socio-demographic characteristics and clinical factors of these patients were explored.Method:A total of 110 patients after stroke (69 men and 41 women) with a mean age of 69.3 ± 13.7 years were recruited and completed (a) a sociodemographic-clinical questionnaire, (b) the State - Trait Anger Expression Inventory and (c) Barthel Index.Results:76.4% of the participants had ischemic stroke; while the 60% were retired. and the 20% of the sample showed severe to total dependence on self-care of basic parameters such as mobility, personal hygiene, feeding, incontinence and standing alone using the toilet. There was a positive statistically significant correlation between the degree of functionality and anger control. Patient, who were more independent and functional, exhibited more control of their anger. Women had statistically significant lower functionality/ independence score (BI) and anger-in score than men. Finally, patients with a history of prior stroke had higher anger-out score compared to patients with no previous history.Conclusions:People with a previous history were more likely to suffer from greater and/or permanent functional impairment, disability, dependence, and experience emotional distress for longer periods of time. Women usually take care of other family members. Their inability to fulfill their role as well as their own dependence make the situation even more stressful, resulting in expressing anger. The results can be exploited by health professionals in order to recognize patients’ difficulties in rehabilitation programs.

Monitoring of Gait Parameters in Post-Stroke Individuals: A Feasibility Study Using RGB-D Sensors.

Stroke is one of the most significant causes of permanent functional impairment and severe motor disability. Hemiplegia or hemiparesis are common consequences of the acute event, which negatively impacts daily life and requires continuous rehabilitation treatments to favor partial or complete recovery and, consequently, to regain autonomy, independence, and safety in daily activities. Gait impairments are frequent in stroke survivors. The accurate assessment of gait anomalies is therefore crucial and a major focus of neurorehabilitation programs to prevent falls or injuries. This study aims to estimate, using a single RGB-D sensor, gait patterns and parameters on a short walkway. This solution may be suitable for monitoring the improvement or worsening of gait disorders, including in domestic and unsupervised scenarios. For this purpose, some of the most relevant spatiotemporal parameters, estimated by the proposed solution on a cohort of post-stroke individuals, were compared with those estimated by a gold standard system for a simultaneous instrumented 3D gait analysis. Preliminary results indicate good agreement, accuracy, and correlation between the gait parameters estimated by the two systems. This suggests that the proposed solution may be employed as an intermediate tool for gait analysis in environments where gold standard systems are impractical, such as home and ecological settings in real-life contexts.

A Systematic Review of the Value of a Bladder Scan in Cauda Equina Syndrome Diagnosis.

Cauda equina syndrome (CES) is one of the emergency conditions that can lead to devastating permanent functional disabilities, if misdiagnosed. Multiple studies have questioned the reliability of clinical assessment in diagnosing CES, whether some of the features should be considered to be potential red flags. Bladder dysfunction can reflect CE compromise. The post-void residual (PVR) volume bladder scan is useful in CES diagnosis, but to date there has been no single systematic review supporting its use. Furthermore, there is no clear cut-off point to consider PVR statistically significant. The aim of the study is to perform a systematic review of the current evidence behind the use of the PVR bladder scan as a diagnostic tool for CES diagnosis. This was a comprehensive search using Medline, PubMed and Embase. All articles included post-void bladder scans with the mentioned clear cut-off volume as a diagnostic parameter. A total of five study articles from 1955 fit with our inclusion and exclusion criteria. The total number of patients who had a bladder scan was 531. CES was confirmed in 85 cases. Bladder scan diagnosed 70 cases and excluded 327. The best results for both sensitivity and specificity in correlation with the sample of the study were for PVR more than 200 ml. Measuring the post-void urine volume using a bladder scan is an essential tool in the diagnosis of CES. There is a significant correlation between the PVR volume more than 200 ml and higher sensitivity and specificity.

Savings of loss-of-life expectancy and lifetime medical costs from prevention of spinal cord injuries: analysis of nationwide data followed for 17 years

BackgroundThe objectives of this research were to determine the savings of loss-of-life expectancy (LE) and lifetime medical costs (LMC) from prevention of spinal cord injuries (SCI) in Taiwan.MethodsFrom the claims...

Cortical Laminar Recording of Multi-unit Response to Distal Forelimb Electrical Stimulation in Rats.

Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brain's poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. In this protocol, we describe how to perform recordings to quantify the neuroprotective and regenerative effect of implanted engineered CS-GAG hydrogel (eCS) on brain tissue. This experiment was performed in rats under three conditions: healthy without injury (Sham), controlled cortical impact (CCI) injury on the rostral forelimb area (RFA), and CCI-RFA with eCS implants. This protocol describes the procedure used to perform the craniotomy, the positioning of the cortical recording electrode, the positioning of the stimulation electrode (contralateral paw), and the recording procedure. In addition, a description of the exact electrical setup is provided. This protocol details the recordings in the brain of injured animals while preserving most of the uninjured tissue intact, with additional considerations for intralesional and laminar recordings of multi-unit response. Graphic abstract: Sensorimotor response to paw stimulation using cortical laminar recordings.

Laser-induced ocular injury: a narrative review

There is an increasing trend of reported laser-induced ocular injury. We aimed to review theliterature on the basic principles of laser, clinical management and safety precaution of laser-induced ocular injury. A literature search on the PubMed database was conducted to include articles dated up to April 2020. One example case of laser-induced ocular injury is provided. Clinical presentation of laser-induced ocular injury is variable. The clinical features can be transient and subtle. Appropriate investigations are useful to establish a diagnosis and to evaluate the severity of the injury. Laser-induced ocular injury most commonly involves the macula, which can be complicated by intraocular haemorrhage, macular hole, epiretinal membrane, and choroidal neovascularization. There are currently no evidence-based or well-recognized treatments for laser-induced retinopathy. Surgical intervention might be considered if there is significant intraocular hemorrhage or macular hole. Laser-induced ocular injury may cause permanent visual sequelae and functional disability. Diagnosis of an eye injury should be supported by objective clinical findings and/or appropriate investigations. As medical and surgical treatment options are currently limited, the key to combat laser ocular injuries lies in prevention and awareness of the general public should be reinforced.

Delayed Diagnosis in a Case of Smoldering Sporotrichal Monoarthropathy

We present the clinical, imaging, and laboratory findings of a 41-year-old male with culture proven Sporothrix schenckii osteoarticular infection of the right knee. Fungal arthropathies are a rare and indolent form of septic arthritis, which often leads to a delayed diagnosis. Early diagnosis and treatment of fungal arthropathies is critical to preventing permanent functional disability.

Association of depression and chronic lower-back pain

Aims: To study the frequency of major depressive disorder, assess sleep quality, permanent functional disability and association of major depressive disorder with the permanent disability, quality of life and quality of sleep in patients of chronic low backache. Materials and Methods: Hundred consecutive patients visiting orthopedic OPD with chronic low backache in a tertiary hospital were included, patients with a past history of psychiatric illness were excluded. The interview was taken for diagnosis of major depressive disorder using DSM 5 and assessed for severity of depression, health-related quality of life and sleep quality by Hamilton depression rating scale, SF 36 health questionnaire, Pittsburg Quality of Sleep Index respectively. The proportion was compared by using chi-square test, scores of scales were compared using Mann Whitney test and Kruskal-Wallis test followed by Dunn’s post-hoc multiple comparisons. Statistical data were analyzed by Graph Pad InStat version 3.06. (San Diego, California, US).A p value of <0.05 was considered statistically significant. Results: The frequency of major depressive disorder, poor quality of sleep in patients of chronic low backache was 74 and 81 respectively. Patients having MDD had a poorer quality of sleep, quality of life and a higher functional disability.Severe functional disability due to a low backache had severe depressive symptoms, poorer quality of sleep and life. The severity of depression is positively correlated with functional disability. Conclusions: patients with chronic low backache had a high frequency of depression, poor quality of sleep and life and higher functional disability.

Disturbed Glucose Metabolism in Rat Neurons Exposed to Cerebrospinal Fluid Obtained from Multiple Sclerosis Subjects.

Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS). In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF) that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO) patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s) expression and suggest that MS appears to be linked with metabolic deformity.