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BACKGROUND: Pravastatin is a clinically effective drug for the treatment of hypercholesterolemia and is now found to play a beneficial role in the treatment of CNS injury; however, the mechanism remains unknown. OBJECTIVE: To ascertain the possible mechanism of action and whether pravastatin medication can expedite functional recovery following sciatic nerve crush injury. METHODS: Male Sprague-Dawley rats were randomly assigned into: pravastatin (sciatic nerve crush injury+pravastatin gavage), negative control (sciatic nerve crush injury+saline gavage), and sham operation (sciatic nerve exposure but no injury+saline gavage). While the other two groups received comparable amounts of saline gavage, the pravastatin group received postoperative pravastatin (5 mg/kg) by gavage for 1 week. The general conditions of the rats in each group were observed after operation. Sciatic function index was evaluated at the end of the 2nd, 4th, 6th, and 8th week after operation, and the wet mass ratio of the gastrocnemius muscle was measured at the end of the 8th week after operation. The levels of inflammatory cytokines in serum were measured using ELISA. Histomorphometrics was used to measure the number of myelinated nerve fibers, fiber diameter, axon diameter, and myelin sheath thickness. RT-qPCR assay was used to measure the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor, and western blot was used to measure the protein expression of growth-associated protein 43. RESULTS AND CONCLUSION: Compared with the negative control group, the sciatic function index in the pravastatin group recovered faster (P < 0.05) and was closer to the level of the sham operation group, the expression of tumor necrosis factor α and interleukin 6 in serum was lower (P < 0.05) and close to that of the sham operation group, and the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor in the sciatic nerve increased (P < 0.05 or P < 0.01), the relative protein expression of growth-associated protein 43 in the sciatic nerve was also significantly increased (P < 0.05), the number of myelinated nerve fibers was increased more, and the values of fiber diameter, axon diameter, and myelin sheath thickness were larger (P < 0.01) and closer to those of the sham operation group. To conclude, treatment with pravastatin accelerates functional recovery from sciatic nerve crush injury by a possible mechanism of inhibiting the expression of tumor necrosis factor α and interleukin 6 and promoting the secretion of neurotrophic factors nerve growth factor and brain-derived neurotrophic factor. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury (SCI) leads to severe inflammation and neuronal damage, resulting in permanent loss of motor and sensory functions. Zinc ions have shown potential in modulating inflammation and cellular survival, making them a promising therapeutic approach for SCI. This study investigates the mechanisms of zinc ion treatment in SCI, focusing on its effects on inflammation. Methods: We used transcriptomic analysis to identify key pathways and genes involved in the inflammatory response in a mouse model of SCI. In vitro studies assessed the impact of zinc ions on inflammation, cell polarization, and apoptosis. IKBα expression was evaluated as a potential target of zinc ions, both in cultured cells and in vivo. Results: Transcriptomic analysis revealed that zinc ions modulate inflammatory pathways through IKBα, which inhibits NF-κB activity. In vitro , zinc treatment upregulated IKBα expression, reducing inflammation, polarization, and apoptosis. These results were confirmed in the SCI mouse model, where zinc ions also reduced inflammation and cell death. Discussion: Our findings highlight a novel mechanism by which zinc ions regulate inflammation in SCI by upregulating IKBα and inhibiting NF-κB activation. This suggests potential therapeutic applications of zinc ions in SCI and other inflammatory conditions, warranting further investigation into their clinical benefits. [ABSTRACT FROM AUTHOR]

Earthquake reconnaissance trips often serve as the "tip of the spear" for assessing the real-world performance of buildings and infrastructure. Earthquakes are nature's laboratory experiments, exposing weaknesses and flaws by testing the structural integrity of each building. Traditional data collection approaches typically include documenting damage (or lack thereof) with photographs, taking measurements on structural characteristics (e.g., rebar cover, concrete cracking, residual drift, foundation settlement), and taking additional notes on qualitative damage (e.g., drywall cracking, stairway damage). The importance of incorporating recovery considerations into the design process has gained increased recognition to help maintain the health and vibrancy of the community after life safety measures have been assured. Though traditional activities remain valuable, the emphasis on systematically documenting building functionality, or predicting a return to functionality, during reconnaissance trips has been limited. The concept of functional recovery encompasses the readiness of a building to support its pre-earthquake uses, beyond providing shelter. The majority of research on building functional recovery has focused on fully defining the concept and identifying the most influential factors. Some studies have pushed further to quantify functional recovery targets for individual buildings, taking into account shaking intensity, building response, component damage, and other relevant factors. Though functional recovery concepts have historically been implicitly embedded in different areas of the model international building codes for decades (e.g., importance factors), explicit treatment of the topic has been absent. This paper presents an effort undertaken after the 2023 Türkiye earthquake to collect functional recovery information approximately two months following the event. It provides a summary of the challenges encountered when attempting to collect functional recovery data during the post-earthquake reconnaissance. Examples are given of a set of schools and hospitals, incorporating field observations and discussions with residents to glean any available information. By documenting these experiences, this paper highlights needed activities in the field of functional recovery and offers recommendations for further research. [ABSTRACT FROM AUTHOR]

Background: Disorders of consciousness (DoC) in non-traumatic ICU-patients are often treated with amantadine, although evidence supporting its efficacy is limited. Methods: This retrospective study analyzed non-traumatic DoC-patients treated with amantadine between January 2016 and June 2021. Data on patient demographics, clinical characteristics, treatment specifications, and outcomes were extracted from electronic medical records. Patients were classified as responders if their Glasgow Coma Scale (GCS) improved by ≥3 points within 5 days. Good outcome was defined as a modified Rankin Scale (mRS) of 0–2. Machine learning techniques were used to predict response to treatment. Results: Of 442 patients (mean age 73.2 ± 10.7 years, 41.0% female), 267 (60.4%) were responders. Baseline characteristics were similar between groups, except that responders had lower baseline GCS (7 [IQR 5–9] vs. 8 [IQR 5–10], p = 0.030), better premorbid mRS (2 [IQR 1–2] vs. 2 [IQR 1–3], p < 0.001) and fewer pathological cerebral imaging findings (45.7% vs. 61.1%, OR 0.56, 95% CI: 0.36–0.86, p = 0.008). Responders exhibited significantly lower mortality at discharge (13.5% vs. 27.4%, OR 0.41, 95% CI: 0.25–0.67, p < 0.001) and follow-up (16.9% vs. 32.0%, OR 0.43, 95% CI: 0.24–0.77, p = 0.002). Good outcomes were more frequent in responders at follow-up (4.9% vs. 1.1%, OR 6.14, 95% CI: 1.35–28.01, p = 0.004). In multivariate analysis higher premorbid mRS (OR 0.719, 95% CI 0.590–0.875, p < 0.001), pathological imaging results (OR 0.546, 95% CI 0.342–0.871, p = 0.011), and experiencing cardiac arrest (OR 0.542, 95% CI 0.307–0.954, p = 0.034) were associated with lower odds of response. Machine learning identified key predictors of response, with the Stacking Classifier achieving the highest performance (accuracy 64.5%, precision 66.6%, recall 64.5%, F1 score 61.3%). Conclusion: This study supports the potential benefits of intravenous amantadine in non-traumatic DOC-patients. Higher premorbid mRS, and pathological cerebral imaging were key predictors of non-response, offering potential avenues for patient selection and treatment customization. Findings from this study informed the design of our ongoing prospective study, which aims to further evaluate the long-term efficacy of amantadine. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the comprehensive impact of different exercise interventions on the quality of life in stroke patients through network meta-analysis, aiming to provide scientific evidence for developing more effective rehabilitation programs and improving patients' physical, psychological, and social functions. Methods: This systematic review, registered in PROSPERO (CRD42024541517) and following PRISMA guidelines, searched multiple databases (PubMed, Web of Science, EMbase, Cochrane, Ebsco) until November 1, 2024. Studies were selected based on the PICOS criteria, including RCTs on stroke and exercise. Methodological quality was assessed using RoB 2. Data analysis involved effect size calculations and network meta-analysis in Stata 17.0, with publication bias detected via funnel plots. Results: This meta-analysis included 41 studies (2,578 stroke patients) from 15 countries, published between 2002 and 2024. Participants aged 50–70 underwent interventions lasting 3 weeks to 6 months. DTOT (Dual-task oriented training)was most effective for Quality of Life, Mental Health, and Upper Limb Function; AQE (Aquatic Exercise) for Physical Health and Social Participation; ST(Strength Training) for Pain and Vitality; CIT(Constraint-Induced Therapy) for Mobility and Recovery; BCT for Memory and Thinking; ALCE(Aquatic and Land Combined Exercise) for Emotion and ADL; and ULT(Upper Limb Training) for Communication. No significant publication bias was found. Conclusion: This study indicates that different training methods have a significant impact on various dimensions of quality of life in stroke patients. Future research should focus on personalized rehabilitation programs, considering individual differences among patients, and explore multimodal integrated interventions to optimize outcomes. Long-term follow-up and outcome assessments should be strengthened to ensure the sustainability of interventions. Additionally, integrating mental health and social participation is essential to enhance overall quality of life. Emerging technologies such as VR, AI, and wearable devices can help optimize rehabilitation training. Interdisciplinary collaboration combining neuroscience, rehabilitation science, and psychology can provide more comprehensive rehabilitation solutions. [ABSTRACT FROM AUTHOR]

Introduction: Cycloastragenol (CAG) has a wide range of pharmacological effects, including anti-inflammatory, antiaging, antioxidative, and antitumorigenic properties. In addition, our previous study showed that CAG administration can promote axonal regeneration in peripheral neurons. However, whether CAG can activate axon regeneration central nervous system (CNS) remains unknown. Methods: Here, we established a novel mouse model for visualizing spinal cord dorsal column axon regeneration involving the injection of AAV2/9-Cre into the lumbar 4/5 dorsal root ganglion (DRG) of Rosa-tdTomato reporter mice. We then treated mice by intraperitoneal administration of CAG. Results: Our results showed that intraperitoneal CAG injections significantly promoted the growth of vitro -cultured DRG axons as well as the growth of dorsal column axons over the injury site in spinal cord injury (SCI) mice. Our results further indicate that CAG administration can promote the recovery of sensory and urinary function in SCI mice. Conclusion: Together, our findings highlight the therapeutic potential of CAG in spinal cord injury repair. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) causes prominent deposition of extracellular matrix molecules, particularly the chondroitin sulphate proteoglycan (CSPG) member neurocan. In tissue culture, neurocan impedes the properties of oligodendrocytes. Whether therapeutic reduction of neurocan promotes oligodendrogenesis and functional recovery in ICH is unknown. Methods: Mice were retro-orbitally injected with adeno-associated virus (AAV-CRISPR/Cas9) to reduce neurocan deposition after ICH induction by collagenase. Other groups of ICH mice were treated with vehicle or a drug that reduces CSPG synthesis, 4-4-difluoro-N-acetylglucosamine (difluorosamine). Rota-rod and grip strength behavioral tests were conducted over 7 or 14 days. Brain tissues were investigated for expression of neurocan by immunofluorescence microscopy and western blot analysis. Brain cryosections were also stained for microglia/macrophage phenotype, oligodendrocyte lineage cells and neuroblasts by immunofluorescence microscopy. Tissue structural changes were assessed using brain magnetic resonance imaging (MRI). Results: The adeno-associated virus (AAV)-reduction of neurocan increased oligodendrocyte numbers and functional recovery in ICH. The small molecule inhibitor of CSPG synthesis, difluorosamine, lowered neurocan levels in lesions and elevated numbers of oligodendrocyte precursor cells, mature oligodendrocytes, and SOX2+ nestin+ neuroblasts in the perihematomal area. Difluorosamine shifted the degeneration-associated functional state of microglia/macrophages in ICH towards a regulatory phenotype. MRI analyses showed better fiber tract integrity in the penumbra of difluorosamine mice. These beneficial difluorosamine results were achieved with delayed (2 or 3 days) treatment after ICH. Conclusion: Reducing neurocan deposition following ICH injury is a therapeutic approach to promote histological and behavioral recovery from the devastating stroke. [ABSTRACT FROM AUTHOR]

Background: Bimalleolar fractures of the ankle are complex injuries that involve both bone and ligamentous structures, affecting joint stability and function. This prospective study examines the functional outcomes of surgical management for bimalleolar fractures treated at a tertiary care center. Aims and Objectives: This study aims to evaluate the functional outcomes of surgical management in patients with bimalleolar ankle fractures, with a focus on post-surgical complications, recovery rates, and factors influencing prognosis. The primary objectives include assessing post-operative range of motion, the incidence of complications, and overall functional outcomes based on established scoring systems. Materials and Methods: Thirty patients, aged 6-60 years with closed bimalleolar fractures, underwent surgical fixation using various techniques, including malleolar screws, K-wires, and plate fixation. Functional outcomes were assessed over 24 months using clinical evaluations, radiographic analysis, and patient-reported scoring systems. Results: The results showed that 80% of patients achieved good to excellent outcomes, with minimal complications. Complications, such as infection and nonunion, were observed in 40% of cases. Conclusion: The findings suggest that surgical management of bimalleolar fractures using internal fixation techniques leads to favorable outcomes, restoring ankle stability and function in most patients. Early intervention, accurate anatomical reduction, and appropriate rehabilitation are essential to optimizing recovery and minimizing complications. [ABSTRACT FROM AUTHOR]

Background and Purpose: Social determinants of health (SDOH), including social networks, impact disability and quality of life post-stroke, yet the direct influence of SDOH on functional change remains undetermined. We aimed to identify which SDOH predict change on the modified Rankin Scale (mRS) within 90 days after stroke hospitalization. Methods: Stroke patients from the Transitions of Care Stroke Disparities Study (TCSDS) were enrolled from 12 hospitals in the Florida Stroke Registry. TCSDS aims to identify disparities in hospital-to-home transitions after stroke. SDOH were collected by trained interviewers at hospital discharge. The mRS was assessed at discharge, 30- and 90-day post-stroke. Multinomial logistic regression models examined contributions of each SDOH to mRS improvement or worsening (compared to no change) from discharge to 30- and 90-day, respectively. Results: Of 1190 participants, median age was 64 years, 42% were women, 52% were non-Hispanic White, and 91% had an ischemic stroke. Those with a limited social support network had greater odds of functional decline at 30 days (aOR = 1.39, 1.17–1.66), adjusting for age and onset to arrival time and at 90 days (aOR = 1.50, 1.10–2.05) after adjusting for age. Results were consistent after further adjustment for additional SDOH and participant characteristics. Individuals living with a spouse/partner had reduced odds of functional decline at 90 days (aOR = 0.74, 0.57–0.98); however, results were inconsistent with more conservative modeling approaches. Conclusion: The findings highlight the importance of SDOH, specifically having a greater number of individuals in your social network in functional recovery after stroke. [ABSTRACT FROM AUTHOR]

Introduction: Recovery of lower urinary tract (LUT) and lower gastrointestinal tract (LGIT) is a high priority for people with lived experience following spinal cord injury (SCI). A universally accepted validated patient‐reported outcome (PRO) measure of the individual sensory and motor components of LGIT and LUT function, which allows tracking of recovery is lacking. To address this literature gap, the SCI Bladder and Bowel Control Questionnaire (SCI‐BBC‐Q) was developed. Methods: The SCI‐BBC‐Q was developed as a direct assessment of the micturition and defecation experiences of an individual with SCI with possible neurogenic LUT and LGIT dysfunction. The SCI‐BBC‐Q development process consisted of two phases, measure development and evaluation. Measure development was guided by a conceptual framework, review of existing instruments and literature, and an iterative process of item incorporation, review, feedback, and consensus revision. Evaluation included cognitive interviewing, and assessments of feasibility, reliability, and content validity. Results: The final 6‐item SCI‐BBC‐Q is a PRO, which assesses motor and sensory function related to micturition and defecation, requiring ~5 min to complete. Assessments of clarity of the instrument components with regard to understanding of what is being asked in the questionnaire, feasibility of administration, reliability, internal consistency, and agreement with proxy measures have demonstrated that the SCI‐BBC‐Q provides consistent, stable, and reproducible data. Significant correlations were found between SCI‐BBC‐Q scores and the anorectal motor and sensory components of the International Standards for the Neurological Classification of SCI. Conclusion: The SCI‐BBC‐Q is a practical and reliable method for baseline and ongoing evaluation of patients with neurogenic LUT and LGIT dysfunction, especially in the acute and subacute period when function is changing due to neurological plasticity. It is also appropriate for use in monitoring response to treatments related to neurological recovery. [ABSTRACT FROM AUTHOR]

Remyelination refers to myelin regeneration, which reestablishes metabolic supports to axons. However, remyelination often fails in multiple sclerosis (MS), leading to chronic demyelination and axonal degeneration. Therefore, pharmacological approaches toward enhanced remyelination are highly demanded. Recently, deferiprone (DFP) was reported to exert neuroprotective effects, besides its iron-chelating ability. Since DFP exerts protective effects through various mechanisms, which share several factors with myelin formation process, we aimed to investigate the effects of DFP treatment on remyelination. Focal demyelination was induced by injection of lysolecithin, into the optic nerve of male C57BL/6J mice. The animals were treated with DFP/vehicle, starting from day 7 and continued during the myelin repair period. Histopathological, electrophysiological, and behavioral studies were used to evaluate the outcomes. Results showed that DFP treatment enhanced remyelination, decreased g-ratio and increased myelin thickness. At the mechanistic level, DFP enhanced oligodendrogenesis and ameliorated gliosis during the remyelination period. Furthermore, our results indicated that enhanced remyelination led to functional recovery as evaluated by the electrophysiological and behavioral tests. Even though the exact molecular mechanisms by which DFP-enhanced myelin repair remain to be elucidated, these results raise the possibility of using deferiprone as a therapeutic agent for remyelination therapy in MS. [ABSTRACT FROM AUTHOR]

Functional recovery from brain damage, such as stroke, is a plastic process in the brain. The excitatory glutamate α -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) plays a crucial role in neuronal functions, and the synaptic trafficking of AMPAR is a fundamental mechanism underlying synaptic plasticity. We recently identified a collapsin response mediator protein 2 (CRMP2)-binding compound, edonerpic maleate, which augments rehabilitative training-dependent functional recovery from brain damage by facilitating experience-driven synaptic delivery of AMPARs. In animals recovering from cryogenic brain injury, a potential compensatory area adjacent to the injured region was observed, where the injection of CNQX, an AMPAR antagonist, significantly attenuated functional recovery. In the compensatory brain area of animals recovering from cryogenic injury, the administration of edonerpic maleate enhanced both excitatory and inhibitory synaptic inputs at pyramidal neurons. In contrast, recovered animals that did not receive the drug exhibited augmentation of only excitatory synaptic input. The threshold of picrotoxin-induced epileptic seizure in recovered animals without edonerpic maleate treatment was lower than in intact animals and recovered animals with edonerpic maleate. Thus, edonerpic maleate enhances motor function recovery from brain damage by balancing excitatory and inhibitory synaptic inputs, which helps prevent epileptic seizures during recovery. [ABSTRACT FROM AUTHOR]

Spinal cord injuries (SCIs) often result in secondary damage; therefore, interventions beyond current cell transplantation methods must be explored. The innate phagocytic propensity of macrophages are exploited for artificially aged erythrocytes and developed a delivery system fusing erythrocytes with reactive oxygen species (ROS)‐reactive nanoparticles prepared from a diselenide‐bond cross‐linked organic compound. The system targets peripheral blood macrophages, delivering anti‐glutamate drug‐loaded nanoparticles to the SCI site, releasing the drug upon ROS stimulation. This efficiently enables targeted drug delivery and reprograms peripheral macrophages through synergistic action with erythrocytes and encapsulated nucleic acids, effectively modulating the immune microenvironment in the SCI zone (significantly reduces neuronal apoptosis and alters the macrophage phenotype in the SCI region). The approach effectively addresses glutamate toxicity and immune inflammation by effectively regulating the lesion microenvironment, providing protection to neurons and creating favorable conditions for regeneration. Departing from the conventional "red blood cell backpack" model, the "chocolate chip cookie" concept is paradigm‐altering, enabling multifaceted erythrocyte functions. Collectively, the system comprehensively enhances the post‐SCI microenvironment. Its efficacy in SCI treatment and innovative drug delivery approach open new possibilities for neural function recovery. By laying the groundwork for future clinical applications, the research pioneers a transformative path toward advancing SCI therapeutics. [ABSTRACT FROM AUTHOR]

Purpose: Identify patient subgroups with different functional outcomes after SCI and study the association between functional status and initial ISNCSCI components. Methods: Using CART, we performed an observational cohort study on data from 675 patients enrolled in the Rick-Hansen Registry(RHSCIR) between 2014 and 2019. The outcome was the Spinal Cord Independence Measure (SCIM) and predictors included AIS, NLI, UEMS, LEMS, pinprick(PPSS), and light touch(LTSS) scores. A temporal validation was performed on data from 62 patients treated between 2020 and 2021 in one of the RHSCIR participating centers. Results: The final CART resulted in four subgroups with increasing totSCIM according to PPSS, LEMS, and UEMS: 1)PPSS < 27(totSCIM = 28.4 ± 16.3); 2)PPSS ≥ 27, LEMS < 1.5, UEMS < 45(totSCIM = 39.5 ± 19.0); 3)PPSS ≥ 27, LEMS < 1.5, UEMS ≥ 45(totSCIM = 57.4 ± 13.8); 4)PPSS ≥ 27, LEMS ≥ 1.5(totSCIM = 66.3 ± 21.7). The validation model performed similarly to the original model. The adjusted R-squared and F-test were respectively 0.556 and 62.2(P-value <0.001) in the development cohort and, 0.520 and 31.9(P-value <0.001) in the validation cohort. Conclusion: Acknowledging the presence of four characteristic subgroups of patients with distinct phenotypes of functional recovery based on PPSS, LEMS, and UEMS could be used by clinicians early after tSCI to plan rehabilitation and establish realistic goals. An improved sensory function could be key for potentiating motor gains, as a PPSS ≥ 27 was a predictor of a good function. IMPLICATIONS FOR REHABILITATION: After a traumatic Spinal Cord Injury (SCI), early neurological examination using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is recommended to determine initial injury severity and prognosis. This study identified three initial ISNCSCI components defining four subgroups of SCI patients with different expectations in functional outcomes, namely the initial pinprick sensory score, the Lower Extremity Motor Score, and the Upper Extremity Motor Score. Clinicians could use these subgroups early after tSCI to plan rehabilitation and set realistic therapeutic goals regarding functional outcomes. In clinical practice, careful and accurate assessment of pinprick sensation early after the SCI is crucial when predicting function or stratifying patients based on the expected function. [ABSTRACT FROM AUTHOR]

Background: Irrespective of the severity, survival of a stroke has become commonplace, but many experience long-term physical, cognitive, and emotional difficulties, with walking difficulties being a frequent challenge. The community-based model of gait training is an innovative and holistic approach to neurorehabilitation that focuses on restoring mobility and enhancing the overall quality of life of stroke survivors. Aims: To assess the impact of community-based stroke rehabilitation programs from existing literatures. Objectives: To identify community-based stroke rehabilitation programs that are effective in improving function in stroke survivors. Methods: We conducted a scoping review of peer-reviewed articles to understand the impact of the community-based rehabilitation model of mobility training after stroke. We searched five different databases: PsycINFO, PubMed, CINAHL complete, Embase, and SCOPUS using topic-specific keywords. Only studies published in the English language from 2013 to 2023 were included. Results: Thirty-five articles met the inclusion criteria. Mobility training using either a treadmill or overground surfaces improved mobility. Orthotics use improved gait and balance among stroke survivors. Adapted video games for rehabilitation improved gait speed, balance, and mobility while the use of transcutaneous electrical nerve stimulation (TENS) aided functional recovery. The use of music or sound incorporated with exercises improved mobility, gait speed, and balance. Engaging in group exercises improved walking capacity, balance, walking speed, cardiovascular function, and community integration. Conclusion: Some community-based rehabilitation programs are effective in improving the physical and social recovery of stroke survivors. This concept can be considered when planning a recovery program for stroke survivors who do not have the ability to access a hospital rehabilitation setting. [ABSTRACT FROM AUTHOR]

Active physiotherapy (APT) embraces a patient-centered approach, prioritizing self-management within the biopsychosocial model and involving active patient movements. Beyond structured exercise, APT incorporates pain neuroscience education, Mulligan Mobilization (MWM), and active myofascial release techniques to integrate sensory-motor information for functional recovery and pain relief. This study aims to rigorously compare the effectiveness of APT versus conventional physical therapy (CPT) on pain and functional outcomes in patients with chronic knee pain. Eighty-seven patients with symptomatic and radiographically confirmed knee pain were included in this 12-month follow-up of a randomized controlled trial, conducted at a national institute and a rehabilitation clinic. Patients were randomized to either APT (n = 44) or CPT (n = 43). The APT protocol integrated pain neuroscience education, MWM, active myofascial release techniques, and structured exercises focusing on flexibility, stability, neuromuscular control, and coordination. The CPT protocol included health education, laser therapy, ultrasound therapy, and exercise. Both interventions were performed for 60 min twice a week for 3 months. The primary outcome was the Knee Injury and Osteoarthritis Outcome Score-4 domain version (KOOS4). Secondary outcomes included pain intensity (VAS), KOOS-pain, activities of daily living (ADL), function in sport and recreation (Sports/Rec), knee-related quality of life, global rating of change (GROC), quality of life (SF-36), Tampa Scale for Kinesiophobia (TSK), and functional performances measured at different intervals. Intention-to-treat analyses were performed. Of the 87 patients, 70 (80.5%) completed the 12-month follow-up. KOOS4 improved more in the APT group (16.13; 95% CI, 10.39–21.88) than in the CPT group (11.23; 95% CI, 5.42–17.04). APT showed additional improvement in KOOS4 compared to CPT (2.94; 95% CI: 0.04 to 5.85, p = 0.047). The VAS difference was −3.41 mm (95% CI: −6.40 to −0.43, p = 0.025), favoring APT. APT also showed more improvements in KOOS-pain, KOOS-ADL, KOOS-Sports/Rec, and TSK (p < 0.05). No differences between groups were observed in GROC and SF-36. APT significantly improved most functional performance variables compared to CPT (p < 0.05). Active Physiotherapy outshines conventional physical therapy by delivering more substantial reductions in pain intensity and marked enhancements in function among patients with knee pain. This distinctive efficacy underscores the invaluable role of APT in the management of chronic knee pain. By actively involving patients in their recovery journey, APT not only fosters superior results but also emphasizes the critical need to integrate these advanced therapeutic strategies into everyday clinical practices. [ABSTRACT FROM AUTHOR]

Background: VR (Virtual Reality) has emerged as a recent treatment approach in neurorehabilitation. The feasibility of VR-guided therapy in the acute phase after stroke has not been assessed. Methods: This was a cohort study of consecutive patients with suspected stroke who were admitted to the Essen University Hospital Stroke Unit between March 2022 and May 2022. All patients who had an indication for physical or occupational therapy due to upper extremity sensorimotor, cognitive or perceptual deficits were included and considered for VR-guided treatment. We excluded patients with predominant deficits in lower extremity function, since these could not be targeted with our VR system. A multidimensional approach was used to assess the feasibility of VR-guided therapy, which included characterization of eligible patients, resource utilization as well as treatment acceptance. For this purpose, we analyzed baseline and clinical characteristics, causes for withholding the treatment as well as qualitative and quantitative treatment metrics in patients who received VR-guided therapy. Results: Out of 326 patients admitted with suspected stroke, n = 172 were included in our final analysis. Of these, n = 37 (21.5%) received VR-guided therapy. The most common cause for withholding treatment were neuropsychological limitations (22.9%), followed by physical impairment, comorbidity and level of consciousness alterations (all 17.8%). Patients who received VR-guided therapy tended to have better functional status and less severe neurological deficits. VR-guided sessions had a median duration of 20 min (IQR 17–29) with additional 13 min (IQR 9–17) of preparation time. In the majority of patients who received VR-guided therapy, motivation was rated equal or higher as compared with conventional treatment (76%) and therapists considered VR-guided therapy well feasible (65%). Conclusions: Despite important treatment barriers, VR may provide additional opportunities to enhance functional recovery in the acute phase after stroke for selected patients. Our findings could aid in planning further randomized controlled trials which are required to refine approaches and assess the effectiveness of VR-guided therapy in the acute setting. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: We investigated the relationship between physical activity and functional recovery in post-acute rehabilitation units. Findings: Decreased sedentary behavior time and increased total physical activity time were associated with high functional recovery. Message: Interventions for physical activity duration may be effective in improving activities of daily living in post-acute and subacute older patients. Purpose: The effect of increased physical activity duration on functional recovery in older inpatients in subacute settings is not well established. This study aimed to investigate the relationship between physical activity and functional recovery in older patients receiving post-acute and subacute care. Methods: We analyzed cohort data of hospitalized older patients (age ≥ 65 years) in the post-acute rehabilitation units. The main outcome was functional independence measure (FIM) gain. Physical activity was measured using a triaxial accelerometer. Changes in sedentary behavior and total physical activity time from admission to discharge were measured as changes in each physical activity time. Logistic regression analysis was performed to examine the relationship between changes in physical activity and FIM gain. Results: A total of 210 patients were eligible for analysis. The mean age of the study patients was 83.6 ± 7.2 years, and 63.8% (n = 134) were female. According to the multivariate regression analysis, changes in sedentary behavior time were significantly associated with high recovery of FIM gain (odds ratio [OR] 0.996, 95% confidence interval [CI]: 0.993–1.000; p = 0.026), and changes in total physical activity time also showed a similar association (OR 1.006, 95% CI 1.000–1.011; p = 0.041). Conclusion: Decreased sedentary behavior time and increased total physical activity time were significantly associated with high functional recovery in post-acute rehabilitation units. These results suggest that interventions for physical activity duration may be effective in improving activities of daily living in older post-acute and subacute patients. [ABSTRACT FROM AUTHOR]

Despite advancements in acute medical management, poststroke rehabilitation (PsR) remains a critical aspect in maximizing recovery and quality of life (QOL) for stroke survivors. In the present case report, poststroke survivor was administered a 90-day tailored integrated yoga and naturopathy (IYN) intervention including daily neutral arm bath, partial massage, and yoga therapy. Following interventions, clinically significant improvement in the range of motion of joints, handgrip strength (Lt. 2.7 kg vs. 14.9 kg), improvement in mid-arm circumference, gait, and cognition (Montreal Cognitive Assessment scores 16 vs. 29) was achieved. In QOL, there was an improvement in each domain of the Short Form 36 questionnaire except for role limitations due to the physical health domain. Improvement in blood pressure (150/60 mmHg vs. 118/70 mmHg) led to a reduction in need of medication. Notably, there was improvement in depression (19 vs. 08), anxiety (18 vs. 08), and stress (21 vs. 07) scores. This case report underscores the potential of IYN intervention in PsR.

Abstract Background Irrespective of the severity, survival of a stroke has become commonplace, but many experience long-term physical, cognitive, and emotional difficulties, with walking difficulties being a frequent challenge. The community-based model of gait training is an innovative and holistic approach to neurorehabilitation that focuses on restoring mobility and enhancing the overall quality of life of stroke survivors. Aims To assess the impact of community-based stroke rehabilitation programs from existing literatures. Objectives To identify community-based stroke rehabilitation programs that are effective in improving function in stroke survivors. Methods We conducted a scoping review of peer-reviewed articles to understand the impact of the community-based rehabilitation model of mobility training after stroke. We searched five different databases: PsycINFO, PubMed, CINAHL complete, Embase, and SCOPUS using topic-specific keywords. Only studies published in the English language from 2013 to 2023 were included. Results Thirty-five articles met the inclusion criteria. Mobility training using either a treadmill or overground surfaces improved mobility. Orthotics use improved gait and balance among stroke survivors. Adapted video games for rehabilitation improved gait speed, balance, and mobility while the use of transcutaneous electrical nerve stimulation (TENS) aided functional recovery. The use of music or sound incorporated with exercises improved mobility, gait speed, and balance. Engaging in group exercises improved walking capacity, balance, walking speed, cardiovascular function, and community integration. Conclusion Some community-based rehabilitation programs are effective in improving the physical and social recovery of stroke survivors. This concept can be considered when planning a recovery program for stroke survivors who do not have the ability to access a hospital rehabilitation setting.

Abstract Background VR (Virtual Reality) has emerged as a recent treatment approach in neurorehabilitation. The feasibility of VR-guided therapy in the acute phase after stroke has not been assessed. Methods This was a cohort study of consecutive patients with suspected stroke who were admitted to the Essen University Hospital Stroke Unit between March 2022 and May 2022. All patients who had an indication for physical or occupational therapy due to upper extremity sensorimotor, cognitive or perceptual deficits were included and considered for VR-guided treatment. We excluded patients with predominant deficits in lower extremity function, since these could not be targeted with our VR system. A multidimensional approach was used to assess the feasibility of VR-guided therapy, which included characterization of eligible patients, resource utilization as well as treatment acceptance. For this purpose, we analyzed baseline and clinical characteristics, causes for withholding the treatment as well as qualitative and quantitative treatment metrics in patients who received VR-guided therapy. Results Out of 326 patients admitted with suspected stroke, n = 172 were included in our final analysis. Of these, n = 37 (21.5%) received VR-guided therapy. The most common cause for withholding treatment were neuropsychological limitations (22.9%), followed by physical impairment, comorbidity and level of consciousness alterations (all 17.8%). Patients who received VR-guided therapy tended to have better functional status and less severe neurological deficits. VR-guided sessions had a median duration of 20 min (IQR 17–29) with additional 13 min (IQR 9–17) of preparation time. In the majority of patients who received VR-guided therapy, motivation was rated equal or higher as compared with conventional treatment (76%) and therapists considered VR-guided therapy well feasible (65%). Conclusions Despite important treatment barriers, VR may provide additional opportunities to enhance functional recovery in the acute phase after stroke for selected patients. Our findings could aid in planning further randomized controlled trials which are required to refine approaches and assess the effectiveness of VR-guided therapy in the acute setting.

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Background. The participants of the breakout session "Role of nutritional support in the process of recovery of patients with acute cerebral circulatory failure", organised with the support of Nutricia Company within the framework of the II All-Russian Neurocongress with international participation, held on 10-12 October 2024 in Moscow, discussed the problems and approaches to the recovery of patients with acute cerebral circulatory failure.Conclusion. Close attention of the participants was focused on the issues of adequate replenishment of nutritional needs of the patients' organism, without which rehabilitation is impossible.

Abstract Background While shared decision making is a cornerstone of orthopedic care, orthopedic surgeons face challenges in tailoring their advice and expectation management to individual shoulder arthroplasty patients due to the lack of systematically summarized evidence-based knowledge. This systematic review aims to provide an overview of current knowledge on independent predictive effects of patient-related factors on functional and pain-related outcomes after shoulder arthroplasty. Methods We included longitudinal cohort studies including patients receiving total or reverse shoulder arthroplasty or hemiarthroplasty for primary osteoarthritis or cuff tear arthropathy. Studies with only univariable analyses were excluded. MEDLINE, Embase, and CINAHL databases were last searched on June 27, 2023. Risk of bias was evaluated using the QUIPS tool. For the analyses, we divided outcomes into three domains (Functional Recovery, Pain, and Functional Recovery & Pain) and four time points (short term, medium-short term, medium-long term and long term). When appropriate, meta-analyses were conducted to pool regression coefficients or odds ratios. Otherwise, results were summarized in a qualitative analysis. We used the GRADE approach to rate the certainty of the evidence. Results Thirty-three studies analyzing over 6900 patients were included; these studied 16 PROMs and 52 prognostic factors. We could perform meta-analyses for six combinations of prognostic factor, domain, and time point. Only the meta-analysis for medium-long term poor ASES scores indicated worse outcomes for previous shoulder surgery (OR (95%CI) of 2.10 (1.33–3.33)). The majority of reported factors showed unclear or neutral independent effects on functional outcomes. Conclusions Methodological heterogeneity and selective/incomplete reporting prevented us from pooling most results, culminating in a largely qualitative analysis. Depression, preoperative opioid use, preoperative ASES and SST scores, surgery on the dominant side, previous surgery, male gender, no. of patient-reported allergies, back pain, living alone, CTA vs OA, diabetes, and greater preoperative external ROM predicted neutral to worse or worse outcomes. In contrast, higher electrical pain threshold on the operative side, OA/RCA vs other diagnosis, and private insurance vs Medicaid/Medicare predicted neutral to better or better outcomes. These results can help orthopedic surgeons tailor their advice and better manage expectations. Systematic review registration PROSPERO CRD42021284822.

Abstract Background Walking impairment after stroke is associated with substantial limitations in functional independence, quality of life, and long-term survival. People in the subacute phase after stroke who are unable to walk are most likely to benefit the greatest from use of overground robotic gait training (RGT). This study will provide preliminary evidence regarding the clinical use and efficacy of RGT during the subacute phase of stroke recovery as well as observational findings associated with the safety, tolerability, feasibility, and cost of delivering RGT during inpatient stroke rehabilitation. Methods This prospectively registered randomized controlled trial will enroll 54 patients admitted to inpatient rehabilitation within six months of stroke. Admitted patients will be screened at admission to inpatient rehabilitation for eligibility. Consented patients will be randomized based on stroke severity to receive either RGT or usual care for 90 minutes per week of gait training intervention during inpatient rehabilitation length of stay. Patients will complete assessments on walking and health outcomes at admission and discharge from inpatient rehabilitation and at 1- and 3-month follow-up. Intent-to-treat and per protocol analysis will be performed to evaluate safety [rate of adverse events, visual analog scale, and treatment completion rate], walking function [gait speed via 10-Meter Walk Test, Functional Ambulation Category, gait endurance via 6-Minute Walk Test] and health outcomes [Modified Rankin Scale, Stroke Rehabilitation Assessment of Movement, Continuity Assessment Record and Evaluation Tool, 5 Times Sit-to-Stand Test, Berg Balance Scale, and Stroke Impact Scale–16], and cost-analysis. Discussion This study will provide foundational evidence regarding the clinical use and efficacy of a RGT program during the subacute phase of stroke recovery with specific findings associated with the safety, tolerability, feasibility, and cost-analysis of delivering RGT during inpatient stroke rehabilitation. Trial registration NCT06430632.

Introduction Avascular necrosis of the femoral head (ANFH) is a phenomenon vascular supply disruption lead to death of bone cells around the femoral head. The disease is a severe health issue all over the world. Within 2 years about 80 % to 85 % of symptomatic cases will result in collapse of the femoral head. Recovery of hip function after total hip arthroplasty (THA) may be influenced by many factors that vary among different racial/ethnic groups. Most findings in this field have been from Western developed nations, and not much information from developing Asian countries is available. This study aimed to determine the six-month functional outcome and patient–related factors that predict functional recovery in patients with avascular necrosis of the femoral head (ANFH) undertaking total hip arthroplasty (THA). Methods Between January 2022 and December 2023 there were 143 patients participating in this prospective study. Demographic, medical history and clinical findings were collected from their medical records. The six‑month functional outcome was evaluated using the Harris hip score (HHS). The mean age of the participants was 55.90 ± 11.49 years, and the majority (86.7 %) were male. Most patients had excellent (43.4 %) or good outcome (51.7 %). Discussion Our study had some limitations: the length of the follow-up after surgery is short (6 months), that hospital-related factors like the type and volume of the hospital have not been analyzed. Nonetheless, previous observations suggest that most of the improvement in physical function occurs during the first six months following surgery and remains the same for a long time. However, our sample has typical demographic and clinical characteristics of patients with THA for ANFH, suggesting that determinants of the 6-month functional outcome in the current study could apply to other patients undergoing this surgery. Results The determinants of excellent outcome were a higher preoperative HHS (odds ratio (OR): 4.369, 95 % confidence interval (CI) =1.854 – 10.299; p < 0.001) and absence of comorbidity (OR: 2.440, 95 % CI = 1.071 – 5.557, p = 0.034). No demographic (age, gender, body mass index), medical history (using of steroids, alcohol consumption or smoking), or any other clinical parameter (stage or side of the affected hip, time until surgery) had a significant influence on functional outcome. Conclusion Earlier surgery during functional decline and better management of comorbidity may help improve THA outcomes for patients with avascular necrosis of the femoral head.

Abstract Background Osteoporotic vertebral compression fractures (OVCF) severely affect the quality of life in the aged population. Percutaneous vertebroplasty (PVP) alleviates pain and stabilizes vertebrae, but suboptimal bone cement distribution can cause complications. Hence, this study aimed to clarify whether a new technique for PVP, using a curved guide wire, enhances the distribution of bone cement and improves clinical outcomes in patients with OVCF. Methods Patients with single-segment OVCF underwent PVP or curved guide wire percutaneous vertebroplasty (C-PVP). Propensity score matching (PSM) was employed to balanced the baseline characteristics. The primary outcomes were the visual analog scale (VAS) and Oswestry disability index (ODI) scores. The secondary outcomes included assessments of bone cement distribution, bone cement injection volume, radiological parameters, and general clinical results. Additionally, Complications and adverse events were documented. Results After PSM analysis, each group comprised 54 patients, which significantly reduced baseline differences. The C-PVP group showed better clinical outcomes compared to the traditional PVP group. One month after surgery, the C-PVP group had significantly lower VAS and ODI scores (p

Spinal cord injury (SCI) often results in irreversible loss of sensory and motor functions, and most SCIs are incurable with current medical practice. One of the hardest challenges in treating SCI is the development of a dysfunctional pathological microenvironment, which mainly comprises excessive inflammation, deposition of inhibitory molecules, neurotrophic factor deprivation, glial scar formation, and imbalance of vascular function. To overcome this challenge, implantation of functional biomaterials at the injury site has been regarded as a potential treatment for modulating the dysfunctional microenvironment to support axon regeneration, remyelination at injury site, and functional recovery after SCI. This review summarizes characteristics of dysfunctional pathological microenvironment and recent advances in biomaterials as well as the technologies used to modulate inflammatory microenvironment, regulate inhibitory microenvironment, and reshape revascularization microenvironment. Moreover, technological limitations, challenges, and future prospects of functional biomaterials to promote efficient repair of SCI are also discussed. This review will aid further understanding and development of functional biomaterials to regulate pathological SCI microenvironment.

Introduction: This study aimed to compare the effectiveness of endoscopic carpal tunnel release (ECTR) versus open carpal tunnel release (OCTR) in treating carpal tunnel syndrome (CTS), focusing on symptom relief, functional recovery and post-operative complications. Methods: A retrospective analysis was conducted on 44 patients diagnosed with CTS, randomly assigned to undergo either ECTR (n=23) or OCTR (n=21). Parameters evaluated included post-operative pain, grip strength, functional status using the Disability of the Arm, Shoulder and Hand (DASH) score and time to return to work. Results: Patients who underwent ECTR demonstrated superior functional recovery and quicker return to daily and work activities compared to those in the OCTR group. Grip strength improvement post-surgery showed no significant difference between the groups. However, ECTR patients reported significantly lower DASH scores and faster return to work, indicating better outcomes. There were fewer reports of post-operative complications and scar sensitivity in the ECTR group. Conclusion: ECTR provides an effective alternative to OCTR for CTS treatment, with advantages in functional recovery speed, reduced post-operative discomfort and faster return to work. These findings support the adoption of ECTR as a preferred surgical approach for CTS, highlighting its potential to improve patient outcomes with minimal complications.

Background: Distal end radius fractures are common injuries treated in orthopedic practice, with varying treatment modalities influencing outcomes. Aims and Objectives: The study was designed to compare the outcomes between open reduction and internal fixation (ORIF) with plating and K-wires plus casting in patients treated for distal end radius fractures. Materials and Methods: One hundred patients with distal end radius fractures were included and divided into two groups: Group A (ORIF with plating) and Group B (K-wires plus casting), with 50 patients in each group. Parameters included were healing time, complication rates, functional recovery, patient satisfaction scores, pain levels during recovery, and the time to return to daily activities. Results: Group A demonstrated a shorter average healing time (8 weeks) compared to Group B (9 weeks). Complication rates showed 5% malunion and 4% delayed union in Group A, against 12% and 6%, respectively, in Group B. Functional recovery was higher in Group A, with 93% grip strength and 88% range of motion recovery. Patient satisfaction was also higher in Group A (8.5 out of 10) compared to Group B (7.5 out of 10). Pain levels during recovery were lower in Group A, and the time to return to daily activities was shorter (8 weeks for Group A versus 10 weeks for Group B). Conclusion: The study suggests that ORIF with plating offers better outcomes in terms of healing time, complication rates, functional recovery, patient satisfaction, pain management, and quicker return to daily activities than K-wires plus casting for distal end radius fractures.

Abstract Background Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI. Methods We generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology. Results PNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis. Conclusion Our findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery.

Abstract Background Despite progress in stroke therapy (e.g., revascularisation interventions by thrombolysis and/or thrombectomy, organised stroke care), many stroke survivors will have impairment of neurological function. We aimed to compare the cost-effectiveness of an oral natural formulation, MLC601, versus placebo in functional recovery among subjects receiving standard of care after an ischemic stroke of intermediate severity assessed with NIH Stroke Scale at baseline (b-NIHSS 8–14). Methods A Markov cohort model with a 2-year time horizon was developed to simulate patients from a published randomised placebo-controlled clinical trial of MLC601 in their post-stroke functional recovery assessed by modified Rankin Score (mRS), from a health system perspective. Transition probabilities were derived from a multi-centre clinical trial in South East Asia. As cost and utility data were not collected in the trial, therefore we extracted them from the published literature. The main outcomes were incremental cost, incremental quality-adjusted life-year (QALY) gained, and incremental cost-effectiveness ratio (ICER). Besides base-case and sensitivity analyses, we performed subgroup analyses to explore the heterogeneity of patients with poor-prognosis factors (b-NIHSS 10–14, stroke onset to treatment time > 48 h, rehabilitation during first 3 month). All costs are expressed in 2022 Euro and USD, with an annual discount rate of 3% applied to costs and QALYs. Results Base-case analysis showed that MLC601 was cost-effective compared with placebo, with €5,080 saved and 0.45 QALY gained, resulting in an ICER of -€11,352.50 per QALY gained. Similarly, results from subgroup analyses indicated that the use of MLC601 was a dominant strategy in all subgroups with poor-prognosis factors. Sensitivity analyses revealed the results were robust. Conclusion Compared with placebo on top of standard stroke care, MLC601 was cost-effective in post-stroke functional recovery over two years. Due to the lack of cost and utility data from the study population, the results might not be generalizable to other settings. Further studies with country-specific data are needed to confirm the results of this study. Trial registration URL http://www.clinicaltrials.gov . Unique identifier NCT00554723 November 7, 2007.

Objective Spinal cord injury (SCI), one of the major disabilities concerning central nervous system injury, results in permanent tissue loss and neurological impairment. The existing therapeutic options for SCI are limited and predominantly consist of chemical compounds. In this study, we delved into the neuroprotective effects of myricetin, a natural flavonoid compound, and the underlying mechanisms, specifically in the context of SCI, utilizing an in vivo model. Previously, our investigations revealed an elevation in the phosphorylated form of Lin-11, Isl-1, and Mec-3 kinase1 (LIMK1) at chronic time points postinjury, coinciding with neuronal loss and scar formation. Our primary objective here was to assess the potential neuroprotective properties of myricetin in SCI and to ascertain if these effects were linked to LIMK inhibition, a hitherto unexamined pathway to date. Methods Computational docking and molecular dynamics simulation studies were performed to assess myricetin’s potential to bind with LIMK. Then, using a rat contusion model, SCI was induced and different molecular techniques (Western blot, Evans Blue assay, quantitative reverse transcription polymerase chain reaction and immunohistochemistry) were performed to determine the effects of myricetin. Results Remarkably, computational docking models identified myricetin as having a better interaction profile with LIMK than standard. Subsequent to myricetin treatment, a significant downregulation in phosphorylated LIMK expression was observed at chronic time points. This reduction correlated with a notable decrease in glial and fibrotic scar formation, and enhanced neuroprotection indicating a positive outcome in vivo. Conclusion In summary, our findings underscore myricetin’s potential as a bioactive compound capable of attenuating SCI-induced injury cascades by targeting the LIMK pathway.

Objective Patients and Methods Results Conclusions To evaluate the impact of prolonged ischaemia during partial nephrectomy (PN), which remains understudied despite its potential clinical relevance.Of 1371 patients managed with on‐clamp PN (2011–2014), 759 (55%) had imaging and assessment of serum creatinine levels before and after PN within the appropriate timeframes necessary for inclusion. This timeframe was chosen to allow for a robust analysis of both warm and cold ischaemia. Recovery from ischaemia (Recischaemia) was defined as ipsilateral glomerular filtration rate (GFR) preserved, normalized by percentage of parenchymal volume preserved (PPVP), and would be 100% if all nephrons recovered completely from ischaemia. Pearson correlation and multivariable linear regression models were used to assess associations between Recischaemia and ischaemia type and duration.Of 759 patients, 525 (69%) were managed with warm ischaemia. The median warm/cold ischaemia times were 22 and 30 min, respectively. Overall, the median percent ipsilateral GFR preserved, PPVP and Recischaemia were 79%, 83% and 96%, respectively. Segmented regression analysis demonstrated substantially greater decline in Recischaemia, beginning at approximately 30 min for warm ischaemia, which was not observed for hypothermia. Prolonged ischaemia (defined as >30 min) occurred in 197 patients (26%; 88 warm/109 cold). For limited ischaemia (≤30 min), hypothermia was often used for tumours with increased tumour size and complexity (P < 0.01), while for prolonged ischaemia, the warm/cold subgroups had similar patient and tumour characteristics. For limited ischaemia and prolonged hypothermia, median Recischaemia remained >95%, independent of ischaemia time. Differences in Recischaemia between the warm and cold cohorts became significant only after 30 min (P < 0.05). On multivariable analysis, prolonged warm ischaemia was associated with reduced Recischaemia (P = 0.02), which fell 3.9% for every additional 10 min beyond 30 min.Our data suggest that Recischaemia begins to decline significantly after 30 min during PN, although hypothermia was protective. Avoidance of prolonged warm ischaemia should be prioritized in patients with solitary kidneys and/or significant pre‐existing chronic kidney disease. [ABSTRACT FROM AUTHOR]

IntroductionMethodsResultsConclusionDodecafluoropentane emulsion (DDFPe) administration has previously demonstrated improved gas exchange in single-organ perfusion models. This could translate to prevention of brain injury in cardiac arrest.We induced cardiac arrest in 12 pigs, performing CPR after 5-minute downtime. Pigs were randomly assigned to DDFPe (n = 7) or saline placebo (n = 5) groups. Neurologic injury biomarkers were measured at baseline, after return of spontaneous circulation (ROSC), and every 24 hours in survivors. Blinded Neurological Alertness Score, Neurological Dysfunction Score, and Overall Performance Score was performed in addition to histopathological scoring of parietal and hippocampal sections.One placebo and four DDFPe pigs survived the 96-hour observation period. The odds ratio for ROSC was 7.2 (p = 0.22). Survival odds ratio was 4.6 (p = 0.29). All surviving animals had impaired motor responses that recovered by 72 hours. DDFPe animals showed better neuro-behavioral scores than placebo.The findings of this novel study provide a proof of concept and early signal toward efficacy of intravenous DDFPe in cardiac arrest. The trend toward improved ROSC and functional survival may reflect improved microcirculatory gas exchange in DDFPe animals. Improving gas exchange in brain microcirculation during resuscitation from cardiac arrest may provide a significant therapeutic benefit. [ABSTRACT FROM AUTHOR]

Background: While shared decision making is a cornerstone of orthopedic care, orthopedic surgeons face challenges in tailoring their advice and expectation management to individual shoulder arthroplasty patients due to the lack of systematically summarized evidence-based knowledge. This systematic review aims to provide an overview of current knowledge on independent predictive effects of patient-related factors on functional and pain-related outcomes after shoulder arthroplasty. Methods: We included longitudinal cohort studies including patients receiving total or reverse shoulder arthroplasty or hemiarthroplasty for primary osteoarthritis or cuff tear arthropathy. Studies with only univariable analyses were excluded. MEDLINE, Embase, and CINAHL databases were last searched on June 27, 2023. Risk of bias was evaluated using the QUIPS tool. For the analyses, we divided outcomes into three domains (Functional Recovery, Pain, and Functional Recovery & Pain) and four time points (short term, medium-short term, medium-long term and long term). When appropriate, meta-analyses were conducted to pool regression coefficients or odds ratios. Otherwise, results were summarized in a qualitative analysis. We used the GRADE approach to rate the certainty of the evidence. Results: Thirty-three studies analyzing over 6900 patients were included; these studied 16 PROMs and 52 prognostic factors. We could perform meta-analyses for six combinations of prognostic factor, domain, and time point. Only the meta-analysis for medium-long term poor ASES scores indicated worse outcomes for previous shoulder surgery (OR (95%CI) of 2.10 (1.33–3.33)). The majority of reported factors showed unclear or neutral independent effects on functional outcomes. Conclusions: Methodological heterogeneity and selective/incomplete reporting prevented us from pooling most results, culminating in a largely qualitative analysis. Depression, preoperative opioid use, preoperative ASES and SST scores, surgery on the dominant side, previous surgery, male gender, no. of patient-reported allergies, back pain, living alone, CTA vs OA, diabetes, and greater preoperative external ROM predicted neutral to worse or worse outcomes. In contrast, higher electrical pain threshold on the operative side, OA/RCA vs other diagnosis, and private insurance vs Medicaid/Medicare predicted neutral to better or better outcomes. These results can help orthopedic surgeons tailor their advice and better manage expectations. Systematic review registration: PROSPERO CRD42021284822. [ABSTRACT FROM AUTHOR]

Background: Motor impairments limit the functional abilities of patients after stroke; it is important to identify low-cost rehabilitation avenues. The aim of this study is to determine the effectiveness of thermal stimulation in addition to conventional therapy for functional recovery in post-stroke patients. Methods: An electronic search was performed in the MEDLINE, Scopus, Web of Science, EMBASE, CINAHL, SPORTDiscus, Epistemonikos, LILACS, and PEDro databases. The eligibility criterion was randomized clinical trials that analyzed the clinical effects of thermal stimulation plus conventional therapy. Two authors independently performed the search, study selection, data extraction, and risk of bias assessment. Results: Eight studies met the eligibility criteria, and six studies were included in the quantitative synthesis. For thermal stimulation plus conventional therapy versus conventional therapy alone, the mean difference (MD) for function was 6.92 points (95% CI = 4.36–9.48; p < 0.01), for motor function was 6.31 points (95% CI = 5.18–7.44; p < 0.01), for balance was 4.41 points (95% CI = −2.59–11.4; p = 0.22), and for walking was 1.01 points (95% CI = 0.33–1.69; p < 0.01). For noxious thermal stimulation versus innocuous thermal stimulation, the MD for activities of daily living was 1.19 points (95% CI = −0.46–2.84; p = 0.16). Conclusions: In the short term, adding thermal stimulation to conventional therapy showed statistically significant differences in functional recovery in post-stroke patients. The quality of evidence was high to very low according to GRADE rating. The studies included varied in the frequency and dosage of thermal stimulation, which may affect the consistency and generalizability of the results. A larger quantity and a better quality of clinical studies are needed to confirm our findings. PROSPERO registration: CRD42023423207. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (OA) is a prevalent and disabling condition often managed with physiotherapy or intra-articular injections. However, the comparative effectiveness of these treatments remains unclear. This systematic review aimed to evaluate and compare the efficacy of physiotherapy and intra-articular injections in managing knee OA. Methods: A systematic search of PubMed, Scopus, Web of Science, PEDro, and Cochrane Library was conducted. Randomized controlled trials (RCTs) comparing physiotherapy and intra-articular injections in knee OA patients were included. Key outcomes included pain (VAS), function (WOMAC, KOOS), range of motion (ROM), and quality of life. Data from five studies with a total of 552 participants were analyzed. Results: Intra-articular injections, particularly botulinum toxin and hyaluronic acid, were found to provide rapid pain relief, outperforming physiotherapy in short-term pain management. However, physiotherapy contributed significantly to long-term functional improvements, particularly in early-stage OA. Combination therapy of injections and physiotherapy yielded the best short-term pain relief and functional outcomes. Heterogeneity in study designs and follow-up periods limited the generalizability of findings. Conclusions: Intra-articular injections are effective for immediate pain control, while physiotherapy plays a crucial role in maintaining joint function, especially for long-term management. Combining both interventions may offer the most comprehensive benefits. Further research is needed to determine the long-term efficacy of these treatments. [ABSTRACT FROM AUTHOR]

Stroke and traumatic brain injury leave many survivors with permanent neurological disabilities, and the development of therapeutics to enhance functional recovery is needed. Both residential and infiltrating immune cells participate in the acute inflammation after brain injury, exacerbating functional outcomes; however, some immune cells have been reported to alter their characteristic to a reparative phenotype. This review focused on the recent findings of the reparative immunity of myeloid cells. Functional recovery after injury is achieved through the combination of resolution of inflammation, reorganization of neuronal network, white matter repair, angiogenesis and extracellular matrix reorganization. In each process, myeloid cells play vital roles in leading to functional recovery. Further research on the diversity of immune cells implicated in neural repair will be promising to develop therapeutics enhancing functional recovery after brain tissue injuries. [ABSTRACT FROM AUTHOR]