Functional Recovery Research Articles

Acute Opioid Administration Undermines Recovery after SCI: Adverse Effects Are Not Restricted to Morphine.

Previous studies have shown that administration of high doses of morphine in the acute phase of spinal cord injury (SCI) significantly undermines locomotor recovery and increases symptoms of chronic pain in a rat spinal contusion model. Similarly, SCI patients treated with high doses of opioid for the first 24 h postinjury have increased symptoms of chronic pain 1 year later. Whether these adverse effects are driven by morphine only or all opioids compromise recovery after SCI, however, is unknown. Based on our previous findings we hypothesized that activation of the kappa opioid receptor (KOR) is key in the morphine-induced attenuation of locomotor recovery after SCI. Thus, we posited that opioids that engage KOR-mediated signaling pathways (morphine, oxycodone) would undermine recovery, and clinically relevant opioids with less KOR activity (fentanyl and buprenorphine) would not. To test this, we compared the effects of the clinically relevant opioids on locomotor recovery and pain in a male rat spinal contusion model. Rats were given a moderate spinal contusion injury followed by 7 days of intravenous morphine, oxycodone, fentanyl, buprenorphine, or saline, and recovery was assessed for 28 days. All opioids produced analgesia on tests of thermal, mechanical, and incremented shock reactivity. However, tolerance developed rapidly with buprenorphine administration, particularly with daily administrations of 5 morphine milligram equivalent (MME) buprenorphine. Opioid-induced hyperalgesia (OIH) also developed across days following administration of higher doses (10 MME, 20 MME) of morphine and oxycodone. Fentanyl and buprenorphine did not produce OIH. Contrary to our hypothesis, however, we found that high doses of all opioids reduced recovery of locomotor function. Unlike the other opioids, the effects of buprenorphine on locomotor recovery appeared transient, but it also produced chronic pain. Morphine, oxycodone, and buprenorphine decreased reactivity thresholds on tests of mechanical and incremented shock stimulation. In sum, all opioids undermined long-term recovery in the rat model. Further interrogation of the molecular mechanisms driving the adverse effects is essential. This study provides critical insight into pain management strategies in the acute phase of SCI and potential long-term consequences of early opioid administration.

Effects of TTP-PECS Block Under Opioid-Sparing General Anesthesia on Postoperative Analgesia and Early Recovery Quality in Patients Undergoing Modified Radical Mastectomy.

Potent analgesics such as sufentanil and remifentanil play a pivotal role in general anesthesia, but these medications have disadvantages, including respiratory depression, nausea, vomiting, immune system suppression, and gastrointestinal function inhibition. This study aimed to evaluate the effects of the transversus thoracic muscle plane-pectoral nerves(TTP-PECS) block on postoperative analgesia, immune function and early postoperative recovery quality inpatients undergoingmodified radical mastectomy under opioid-sparing general anesthesia. A total of 100 patients scheduled for modified radical mastectomy under general anesthesia were randomly divided into the TTP-PECS block combined with opioid-sparing general anesthesia group (TO group, n=50) or the conventional general anesthesia group (GA group, n=50). The TO group underwent TTP-PECS block prior to induction, using oxycodone as the analgesic during induction instead of sufentanil, no additional continuous infusion of analgesic was performed intra-operatively. Visual analogue scale (VAS) scores at rest and during movement at different time points were recorded in both groups, and the levels of T cell subsets, natural killer (NK) cells were measured before the surgery and at 24h and 48h after the surgery. Quality of Recovery-40 (QoR-40) scores were assessed at 24h postoperatively, and the incidence of peri-operative adverse reactions was also observed in both groups. Except for 48h postoperatively, patients in the TO group had significantly lower VAS scores than those in the GA group at 2h, 6h, 12h, and 24h postoperatively at rest and during movement (P<0.05). At 24h and 48h postoperatively, the expression of CD4+ T cells and the CD4+/CD8+ ratio were significantly higher in the TO group than in the GA group (P<0.05). The QoR-40 scale, assessed at 24h postoperatively, showed that the TO group significantly outperformed the GA group in total scores as well as in sub-scores for emotional state, physical comfort, physical independence, psychological support, and pain (P<0.05). In addition, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were lower at time points T1-T4 than at T0 in both groups (P<0.05), but the differences between the two groups were not statistically significant(P>0.05). The incidence of cough reflex during induction and postoperative nausea and vomiting were significantly lower in the TO group than in the GA group (P<0.05). There was no statistically significant difference between the two groups in the incidence of other adverse reactions (P>0.05). The combination of TTP-PECS block and oxycodone-propofol opioid-sparing general anesthesia can provide superior postoperative analgesia and reduce the incidence of postoperative nausea and vomiting. It also alleviated the suppression of cellular immune function and improves the quality of early recovery in breast cancer patients. At the same time, opioid-sparing general anesthesia is a safe strategy for modified radical mastectomy. Chinese Clinical Trial Registry; ChiCTR2200066753.

Idiopathic Mild Platelet Dysfunction: Baseline Characteristics and Clinical Courses.

The causes of nonsyndromic platelet storage pool disease are still unclear, and whether they are of genetic or acquired origin remains to be defined. The study aimed to describe the characteristics and natural history of this disorder. This mostly retrospective cohort enrolled adults presenting with bleeding from platelet dysfunction. Platelet glycoprotein defects, von Willebrand disease, syndromic inherited platelet disorders and known acquired platelet dysfunctions were excluded. Available patients were retested by lumiaggregometry (Chrono-Log) over 1 year after the initial diagnosis. There was a total of 56 patients; 91% female, with a median diagnostic age of 28 years (interquartile range [IQR]: 24.5-38.5). The subnormal responses to ADP, epinephrine, collagen, and arachidonate were found in 91%, 82%, 55%, and 34%, respectively. Nineteen patients had von Willebrand factor levels measured. Twenty-three subjects underwent repeat tests. Twenty-one of them were female (91%), with a median age and follow-up time of 37 years (IQR: 28-55) and 6 years (IQR: 3-12), respectively. Median ISTH-BAT bleeding scores at diagnosis and follow-up were 5 (IQR: 3-8) and 1 (IQR: 0-2), respectively. The common abnormalities were reduced responses to ADP combined with other agonists (83%). Twelve (52%) and five (22%) showed complete and partial platelet function recovery, respectively. None of the partial and non-recovery groups had a bleeding score over 4 at follow-up. Idiopathic mild platelet dysfunction was female-predominant and showed spontaneous symptom resolution after a long follow-up. Platelet function recovery was observed in most cases. Exogenous factors triggering this condition remain to be identified.

Freeze-Dried Porous Collagen Scaffolds for the Repair of Volumetric Muscle Loss Injuries.

Volumetric muscle loss (VML) injuries are characterized by the traumatic loss of skeletal muscle, resulting in permanent damage to both tissue architecture and electrical excitability. To address this challenge, we previously developed a three-dimensional (3D) aligned collagen-glycosaminoglycan (CG) scaffold platform that supported in vitro myotube alignment and maturation. In this work, we assessed the ability of CG scaffolds to facilitate functional muscle recovery in a rat tibialis anterior (TA) model of VML. Functional muscle recovery was assessed following implantation of either nonconductive CG or electrically conductive CG-polypyrrole (PPy) scaffolds at 4, 8, and 12 weeks postinjury by in vivo electrical stimulation of the peroneal nerve. After 12 weeks, scaffold-treated muscles produced maximum isometric torque that was significantly greater than nontreated tissues. Histological analysis further supported these reparative outcomes with evidence of regenerating muscle fibers at the material-tissue interface in scaffold-treated tissues that were not observed in nonrepaired muscles. Scaffold-treated muscles possessed higher numbers of M1 and M2 macrophages at the injury, while conductive CG-PPy scaffold-treated muscles showed significantly higher levels of neovascularization as indicated by the presence of pericytes and endothelial cells, suggesting a persistent wound repair response not observed in nontreated tissues. Finally, only tissues treated with nonconductive CG scaffolds displayed neurofilament staining similar to native muscle, further corroborating isometric contraction data. Together, these findings show that both conductive and nonconductive CG scaffolds can facilitate improved skeletal muscle function and endogenous cellular repair, highlighting their potential use as therapeutics for VML injuries.

Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury

BackgroundExercise rehabilitation therapy has garnered widespread recognition for its beneficial effects on the restoration of locomotor function in individuals with spinal cord injury (SCI). Notably, resistance exercise has demonstrated significant improvements in muscle strength, coordination, and overall functional recovery. However, to optimize clinical management and mimic exercise-like effects, it is imperative to obtain a comprehensive understanding of the molecular alterations that underlie these positive effects.MethodsWe conducted a randomized controlled clinical trial investigating the effects of resistance exercise therapy for incomplete SCI. We integrated the analysis of plasma proteomics and peripheral blood mononuclear cells (PBMC) transcriptomics to explore the molecular and cellular changes induced by resistance exercise. Subsequently, we established a weight-loaded ladder-climbing mouse model to mimic the physiological effects of resistance exercise, and we analyzed the plasma proteome and metabolome, as well as the transcriptomes of PBMC and muscle tissue. Lastly, to confirm the transmissibility of the neuroprotective effects induced by resistance exercise, we intravenously injected plasma obtained from exercised male mice into SCI female mice during the non-acute phase.ResultsPlasma proteomic and PBMC transcriptomic profiling underscored the notable involvement of the complement pathways and humoral immune response in the process of restoring locomotor function following SCI in the human trial. Moreover, it was emphasized that resistance exercise interventions could effectively modulate these pathways. Through employing plasma proteomic profiling and transcriptomic profiling of PBMC and muscle tissues in mice, our study revealed immunomodulatory responses that parallel those observed in human trials. In addition, our analysis of plasma metabolomics revealed an enhancement in lipid metabolism following resistance exercise. We observed that resistance exercise plasma exhibited significant effects in ameliorating locomotor disability after SCI via reducing demyelination and inhibiting neuronal apoptosis.ConclusionsOur investigation elucidates the molecular alterations associated with resistance exercise therapy promoting recovery of locomotor function following incomplete SCI. Moreover, we demonstrate the direct neuroprotective effects delivered via exercise plasma injection, which facilitates spinal cord repair. Mechanistically, the comprehensive multi-omics analysis involving both human and mice reveals that the principal constituents responsible for the observed neuroprotective effects within the plasma are predominantly immunoregulatory factors, warranting further experimental validation.Trial registrationThe study was retrospectively registered on 17 July, 2024, in Chinese Clinical Trial Registry (No.: ChiCTR2400087038) at https://www.chictr.org.cn/.

Outcome of Locking Compression Plate (LCP) Fixation of Diaphyseal Radius-Ulna fracture in Patients of 50 Years and Above

A prospective, observational study was conducted at National Institute of Traumatology and Orthopaedic Rehabilitation (NITOR), Dhaka, Bangladesh, from January 2018 to December 2019, to evaluate the effectiveness of locking compression plate (LCP) fixation in treating diaphyseal forearm fractures. A total of 34 adults aged 50 and above, a population with a high prevalence of osteoporosis, were selected for this study. With an average follow-up period of 25.27±1.39 weeks, the study found that older age and delayed surgery correlated with poorer outcomes, while motor vehicle accidents accounted for 52.94% of the injuries. The average time to radiological union was 12.18±1.53 weeks, with one case of nonunion and a complication rate of 11.76%. At the final follow-up, the mean range of motion for flexion-extension and supination-pronation was 133.53°±5.44° and 124.41°±11.19°, respectively, and the mean Quick DASH score was 14.6%±7.14%. According to the Anderson criteria, 50% of cases were rated as excellent, 47.06% as good, and 2.94% as poor. The study concludes that LCP fixation is an effective treatment for diaphyseal forearm fractures in this age group, demonstrating favorable outcomes regarding union rates, pain management, and functional recovery, with meticulous surgical technique being key to optimal results. Mugda Med Coll J. 2024; 7(2): 95-101

Clinical efficacy of THA with dual mobility cup vs. hemiarthroplasty in elderly patients with femoral neck fracture: a retrospective study

ObjectiveTo compare the clinical efficacy of total hip arthroplasty (THA) with or without dual mobility cup (DMC) vs. hemiarthroplasty (HA) in elderly Asian patients with acute femoral neck fracture (FNF).MethodsData of 284 elderly FNF patients treated at our institution from January 2017 to December 2021 were retrospectively collected. Patients were divided into the DMC-THA group (THA with DMC, n = 102), C-THA group (conventional THA without DMC, n = 88), and HA group (n = 94). The study assessed perioperative outcomes, hip functional recovery, treatment satisfaction, long-term prognosis, and quality of life.ResultsThe Harris Hip Scores in the DMC-THA group were significantly higher than those in the C-THA and HA groups at 3 months, 6 months, and 1 year postoperatively (P &amp;lt; 0.05). The satisfaction rate in the DMC-THA group (92.2%) was significantly higher compared to the C-THA (81.8%) and HA groups (80.9%) (P &amp;lt; 0.05). At 1 year post-surgery, the DMC-THA group demonstrated a significantly lower dislocation rate (2.0% vs. 9.1%) and superior mobility compared to the C-THA group (P &amp;lt; 0.05). Additionally, the DMC-THA group exhibited significantly better mobility and reduced pain/discomfort compared to the HA group (P &amp;lt; 0.05).ConclusionTHA with DMC offers superior joint function recovery, a lower dislocation rate, and improved quality of life compared to conventional THA and HA, positioning it as a preferred surgical option for elderly patients with acute FNF.

Single-Port Robotic Transvesical Partial Prostatectomy: A Novel Approach for Focal Treatment in Prostate Cancer.

Introduction and Objective: Given the favorable cancer-specific survival rates in localized prostate cancer and the negative impact of whole-gland treatments on functional outcomes, the field is moving toward precision strategies such as focal therapy and organ-sparing surgery. We aim to report medium-term functional and oncologic outcomes for the initial Single-Port Robotic Transvesical Partial Prostatectomy (SP-TVRAPP) patient cohort. Materials and Methods: We analyzed a prospectively maintained database of 20 patients who underwent SP-TVRAPP between February 2021 and March 2024. Inclusion criteria were prostate-specific antigen (PSA) ≤10 ng/mL, clinical stage ≤ cT2b, ISUP Grade Group ≤3, unilateral lesions on multiparametric magnetic resonance imaging (mpMRI) with positive biopsy cores on the same side, and preoperative IIEF-5 ≥ 17. We also considered bilateral prostate cancer in the anterior zone and invisible mpMRI tumors confirmed by unilateral positive biopsies. Results: At baseline, patients had an average age of 61 years, a median PSA of 4.8 ng/mL (interquartile range [IQR]: 3.7-7.7), and a median Sexual Health Inventory for Men (SHIM) score of 24 (IQR: 18-25). All procedures were completed without complications, need for additional ports, or conversion. After a median hospital stay of 4.2 hours, 94% of cases were discharged without opioid prescriptions, and Foley catheters were removed after approximately 4 days. At 6 weeks, 3, 6, and 12 months postprocedure, potency rates, defined as a SHIM score ≥17, were 45.0%, 77.7%, 83.3%, and 87.5%, respectively. When potency was defined as having erections sufficient for penetration, the rates were 80.0%, 88.8%, 88.8%, and 93.7% for the same time intervals. Regarding urinary function, 60.0% were continent at 1 week, increasing to 85.0% by 6 weeks, 88.8% at both 3 and 6 months, and reaching 93.7% at 12 months postsurgery. Oncologically, 30.0% experienced upgrading and 40.0% upstaging within this cohort. Negative surgical margins were attained in 85.0% of the cases and the median PSA was 0.4 ng/mL 12 months after SP-TVRAPP. Two men were found to have residual GG1 cancer in the protocol biopsies and are currently on active surveillance. At a mean follow-up of 15.5 months (0.2-34.8) months, none of the patients has required secondary interventions, and all remain free of both clinically significant residual prostate cancer and metastatic disease. Conclusions: SP-TVRAPP represents a promising treatment for certain patients with localized prostate cancer. This targeted surgical method has been associated with faster postoperative recovery and has demonstrated high rates of early recovery in erectile function and urinary continence while ensuring oncologic safety.

Experimental evidence-based construction of electroacupuncture for ischemic stroke: a meta-analysis and systematic review

ObjectiveIschemic stroke represents a leading cause of disability and mortality worldwide, necessitating effective and complementary therapeutic strategies. Electroacupuncture (EA), a modern extension of traditional acupuncture, has garnered attention for its potential neuroprotective effects in ischemic stroke rehabilitation. This meta-analysis and systematic review aim to synthesize current experimental evidence on the efficacy of EA in ischemic stroke models, focusing on neurological outcomes, infarct volumes, and underlying molecular mechanisms.MethodsA comprehensive search was performed across four databases—Cochrane Library, EMBASE, PubMed, and Web of Science—to identify relevant experimental studies that utilized electroacupuncture (EA) as a therapeutic modality for ischemic stroke in animal models. This search encompassed all literature available from the inception of each library through December 2023. Studies were rigorously screened based on predefined inclusion and exclusion criteria. Data on cerebral infarction volume, neurological deficit scores, cellular apoptosis, and molecular pathways were extracted and analyzed.ResultsEleven eligible studies involving 302 animals (151 in EA treatment groups and 151 in control groups) were included. Meta-analysis revealed that EA significantly reduced cerebral infarction volumes [MD = −15.78, 95%CI (−21.40, −10.16), p &amp;lt; 0.05] and TUNEL-positive cells [MD = −26.46, 95%CI (−40.40, −12.51), p &amp;lt; 0.05], indicating reduced apoptosis. Improvements were also noted in neurological deficit scores [MD = −0.59, 95%CI (−0.92, −0.27), p &amp;lt; 0.05] and modified Neurological Severity Scores (mNSS) [MD = -5.68, 95%CI (−7.41, −3.95), p &amp;lt; 0.05], highlighting functional recovery. While the analysis showed no significant effect on caspase-3 densities [MD = −0.39, 95%CI (−0.79, 0.02), p &amp;gt; 0.05], a notable increase in Bcl-2 densities suggested an anti-apoptotic mechanism [MD = −0.73, 95%CI (−1.68, 0.21), p &amp;gt; 0.05]. The heterogeneity of the included studies points to complex underlying mechanisms, potentially involving modulation of apoptotic pathways and cerebral blood flow.ConclusionThis meta-analysis substantiates the neuroprotective potential of EA in ischemic stroke models, primarily through apoptosis modulation and possibly through improved cerebral perfusion. These findings advocate for the integration of EA into stroke rehabilitation protocols and underscore the need for clinical trials to validate its efficacy in human subjects. Our study not only reinforces the therapeutic value of EA but also prompts further investigation into its underlying mechanisms, potentially guiding more effective stroke recovery strategies.

Penile rehabilitation after radical prostatectomy using low-intensity shockwave therapy for erectile function: late results findings from a randomized clinical trial.

There is still few evidence to support the use of low-intensity extracorporeal shockwave therapy (LiESWT) in rehabilitation of erectile function after radical prostatectomy (RP). The aim of this study is to assess the long-term results of LiWEST as a penile rehabilitation method in patients who underwent RP. This is an assessment of the late results outcomes of our previous clinical trial registered in ReBEC (ensaiosclinicos.gov.br) RBR-85HGCG. Patients were randomized in two groups with two parallel arms and an allocation ratio of 1:1. The control group received tadalafil 5mg/day, while the experimental group received tadalafil 5mg/day and were submitted to 2400 shocks/session-week distributed on four different penile regions across 8weeks of treatment. Both groups started the penile rehabilitation after the removal of the transurethral catheter. Sexual function was assessed by International Index of Erectile Function (IIEF-5) score. A difference in IIEF-5 without statistical significance between the experimental and control groups. Among 77 patients included in our previous analysis, 35 patients were reassessed after a median follow-up of 45months (95% CI, 42-50months). Seventeen of them had to be excluded from the analysis for biochemical recurrence and/or new interventions. Remaining 7 and 11 patients in the experimental and control group, respectively. The final mean IIEF-5 score between experimental and control groups showed a difference in favor of the LiWEST group, not statistically significant (18.85, SD 5.66, 95% CI, 13.61-24.1 x 16.63, SD 5.48, 95%CI, 12.9- 20.31; respectively; P = 0.42). Subgroup analysis in patients still using IPDE5 there is a higher difference between mean IIEF5, however not statistically significantly (18.5, SD 6.12, 95%CI 12.07-24.92 x 15.85, SD 3.62, 95% CI, 12.50-19.20, P = 0.35). This study highlights that LiESWT may offer limited long-term benefit for erectile function recovery after RP. This study provides valuable long-term data on the use of LiESWT as a penile rehabilitation method after RP. The randomized design and parallel group structure strengthen the reliability Journal of Sexual Medicine Journal of Sexual Medicine For Peer Review of findings, with clear intervention protocols. However, limitations include a small final sample size due to patient exclusions, which likely impacted statistical power and the generalizability of results. Additionally, while differences in IIEF-5 scores favored the LiESWT group, the lack of statistical significance limits the ability to draw definitive conclusions about its effectiveness. The LiESWT showed no impact on long-term results of penile rehabilitation in patients submitted to RP.

A novel scoring system for better management of small bowel obstruction.

Due to the lack of a comprehensive evaluation of the prognosis of small bowel obstruction (SBO), recent clinical strategies have remained subjective and controversial. The recognition of pretreatment risk factors and tailored treatment could improve SBO outcomes. A series of posttreatment laboratory tests were integrated into a two-step clustering (TSC) analysis. The TSC outcome was determined according to different predictor importance (PI). A risk score (RS) system for the TSC outcome model was constructed by multivariable analysis. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were calculated to assess prediction accuracy. Of the 355 patients, 66 (18.6%) were sorted into the better prognosis group (BPG), 149 (42.0%) were sorted into the poor prognosis group (PPG), and 140 (39.4%) were sorted into the severe prognosis group (SPG) by TSC analysis. For the TSC outcome, four variables with higher PI were identified, namely, Ca (PI = 1), albumin (PI = 0.62), WBC count (PI = 0.5) and NE% (PI = 0.45). Compared with the SPG, the BPG presented better outcomes after surgery events. The TSC outcome model was efficient in distinguishing the duration of bowel function recovery and hospital stay by Kaplan‒Meier curves. Via multivariate analysis, a RS consisting of four risk factors, namely, constipation duration (OR = 1.002), APTT (OR = 0.923), PT (OR = 1.449) and PCT (OR = 1.540), was identified. The AUC of the RS on the TSC outcome model was 0.719 (95% CI, 0.635-0.804). A novel TSC outcome model and RS system was constructed to comprehensively reflect the tailored treatment, surgical events and posttreatment recovery for SBO patients.

Functional Recovery After 18 Sessions of Radio Electric Asymmetric Conveyor Tissue Optimization Reparative Protocol for Hill-Sachs Lesion in a Post-traumatic Shoulder Dislocation

Functional Recovery After 18 Sessions of Radio Electric Asymmetric Conveyor Tissue Optimization Reparative Protocol for Hill-Sachs Lesion in a Post-traumatic Shoulder Dislocation

Editorial: Nervous regeneration and functional recovery in the central and peripheral nervous systems: diagnostic methods, gene/cell therapies, and interventions

Editorial: Nervous regeneration and functional recovery in the central and peripheral nervous systems: diagnostic methods, gene/cell therapies, and interventions

Functional outcome of displaced clavicle fractures treated with locking compression plate

Clavicle fractures, common in young, active individuals, often occur due to trauma or repetitive stress and account for about 2.6% to 5% of all fractures. These fractures typically happen in the midshaft and are often displaced. Historically, they were treated conservatively, but this approach often led to malunion and poor shoulder function. Recent studies show that surgical interventions, particularly with locking compression plates (LCP), improve healing, shoulder function, and reduce complications like non-union and malunion. Surgical treatments, such as open reduction internal fixation (ORIF) or closed reduction internal fixation (CRIF), are especially beneficial for displaced fractures or those with additional complications. LCPs provide better stability, especially in osteoporotic patients, although potential complications include screw loosening and infection. Overall, evidence supports surgical treatment with LCPs for better functional outcomes and fewer complications compared to nonoperative methods. This study is being done to assess functional outcome of clavicle fractures managed with open reduction with LCP. A prospective interventional study was conducted to assess functional outcome of clavicle fractures managed with ORIF with LCP. Constant-Murley score was evaluated before the treatment and were repeated after 6 weeks (T1), 12 weeks (T2) and 24 weeks (T3). The study involved 30 participants with an average age of 31.23 years, consisting of 80% males and 20% females. Of these, 53% had right-sided clavicular fractures, and 47% had left-sided fractures. Most surgeries were performed within 2-3 days of admission, with 93.33% of fractures showing union within 12 weeks. The constant Murley’s score, which measures functional outcomes, improved significantly over time: from 5.28 before surgery to 91.09 after 24 weeks. The functional outcome was graded excellent in 90% of patients. Statistical analysis showed significant improvement in scores post-surgery (p&lt;0.001). Age had a weak positive correlation with better outcomes, while time from admission to surgery and time to union had strong negative correlations with functional outcomes. These findings suggest that faster surgery and quicker union lead to better functional recovery, and age has a slight impact on outcomes.

Identifying Biomarkers for Remyelination and Recovery in Multiple Sclerosis: A Measure of Progress

Background: Multiple sclerosis (MS) pathology is characterized by acute and chronic inflammation, demyelination, axonal injury, and neurodegeneration. After decades of research into MS-related degeneration, recent efforts have shifted toward recovery and the prevention of further damage. A key area of focus is the remyelination process, where researchers are studying the effects of pharmacotherapy on myelin repair mechanisms. Multiple compounds are being tested for their potential to foster remyelination in different clinical settings through the application of less or more complex techniques to assess their efficacy. Objective: To review current methods and biomarkers to track myelin regeneration and recovery over time in people with MS (PwMS), with potential implications for promyelinating drug testing. Methods: Narrative review, based on a selection of PubMed articles discussing techniques to measure in vivo myelin repair and functional recovery in PwMS. Results: Non-invasive tools, such as structural Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), are being implemented to track myelin repair, while other techniques like evoked potentials, functional MRI, and digital markers allow the assessment of functional recovery. These methods, alone or in combination, have been employed to obtain precise biomarkers of remyelination and recovery in various clinical trials on MS. Conclusions: Combining different techniques to identify myelin restoration in MS could yield novel biomarkers, enhancing the accuracy of clinical trial outcomes for remyelinating therapies in PwMS.

Risk factors for motor decline following parasagittal and falx meningioma resection in the middle third

ObjectiveThe resection of parasagittal and falx meningiomas in the middle third superior sagittal sinus (SSS) is associated with a high risk of postoperative motor deficits. This study discusses the risk factors affecting postoperative motor decline and recovery of motor function after follow-up.MethodsThe results of a single-institution retrospective cohort study of parasagittal and falx meningioma resection in the middle third between 2016 and 2023 were reviewed, and parameters were screened as potential predictors. Variables of interest included postoperative motor decline and outcome after follow-up. Univariate and multivariate analyses were performed to identify risk factors.ResultsAmong 87 patients who underwent resection of parasagittal (63.2%) or falx (36.8%) middle third meningiomas, 14.9% (13/87) experienced postoperative motor decline. Among the 36 patients (41.4%) with preoperative motor deficits, 66.3% improved, 17.0% unchanged, and 16.7% (6/36) worsened following surgery. Among the 51 patients without preoperative motor deficits, 13.7% (7/51) developed new weakness. The predictors of postoperative motor decline were major venous involvement (p = 0.022), falx meningioma (p = 0.031), loss of the brain-tumor interface (p=0.033) and WHO grade II-III (p = 0.032).ConclusionsThe resection of parasagittal and falx meningiomas in the middle third carries a high rate of postoperative morbidity and deserves perioperative planning. Alternative surgical strategies, such as preserving the brain-tumor arachnoid interface and minority residual tumors, may prevent motor decline in a subset of high-risk patients.

How Do the Timing of Early Rehabilitation Together with Cognitive and Functional Variables Influence Stroke Recovery? Results from the CogniReMo Italian Multicentric Study

Background: The time lapse between the acute event and the beginning of rehabilitation seems to play a significant role in determining the effectiveness of rehabilitation together with the severity of neurological deficits and impairments of motor and cognitive functions. The present study aims to further explore the prognostic role of cognitive and motor functions, concerning the different times of the beginning of neurorehabilitation. Methods: A secondary examination was conducted by applying a cluster analysis on the data of 386 stroke patients in the subacute phase who were enrolled in the Cognitive and Recovery of Motor Functions (CogniReMo) study. Results: The Barthel Index at the admission predicts clinical outcome: if BI was 0, it was on average 28.7 ± 24.1 at discharge. For patients with Barthel Index &lt;15 at discharge, the discriminant was unaltered executive functions having an average output of 61.3 instead of 45.5. In the range of BI at admission between 16 and 45, the discriminant variable was to have an NIHSS ≤ 5 to obtain a high outcome (BI = 75.4 instead of BI = 61.9). Subjects with a BI at admission &gt;45 were the best responders to rehabilitation, with a mean BI at discharge of 85 if they have alteration in spatial attention, and 95.3 if they have no deficits in spatial attention. Also, for inpatients hospitalized in a period ranging from the 20th to the 37th day after stroke, spatial attention was a discriminant variable to have a poor outcome (BI = 34.3) vs. a good one (BI = 76.7). Conclusions: The algorithm identified a hierarchical decision tree that might assume a significant role for clinicians in defining an appropriate rehabilitation pathway, depending on the time of rehabilitation beginning and the severity of motor and cognitive deficits.

Intranasal delivery of hMSC-derived supernatant for treatment of ischemic stroke by inhibiting the pro-inflammatory polarization of neutrophils

BackgroundStem cells utilized for ischemic stroke treatment often display unstable homing capabilities and diminished activity in vivo, limiting their neuroprotective efficacy. Furthermore, the optimal delivery route for stem cells remains undetermined. While the cytokines secreted by stem cells show promise in modulating post-stroke inflammation, the direct application of these supernatants in ischemic stroke treatment and the underlying mechanisms are still unclear.MethodsSecretory supernatants (hMSC-L) and cell lysate products (hMSC-M) from primary human umbilical cord mesenchymal stem cells-cultured medium were administered intranasally to mice with cerebral ischemia. The neuroprotective effects of hMSC-L and hMSC-M were assessed with TTC staining, behavioral tests and pathological staining. Flow cytometry and qPCR evaluated the expression of immune cells and cytokines in the CNS and peripheral immune organs. In vitro, flow cytometry and ELISA measured the effects of hMSC-L and hMSC-M on N2 polarization and inflammatory cytokines expression in primary murine neutrophils. Western blot analysis determined the impact of hMSC-L and hMSC-M on the PPAR-γ/STAT6/SOCS1 pathway, which is crucial for N2 neutrophil polarization.ResultsTTC staining, behavioral experiments, and pathological assessments reveal intranasal delivery of hMSC-L and hMSC-M significantly reduces the infarct volume of mice with cerebral ischemia, improves neurological function scores, and promotes motor function recovery. Higher concentrations of hMSC-M contributed a more pronounced effect on neuropathological improvements in ischemic mice. Intranasal delivery of hMSC-L and hMSC-M significantly reduces neutrophil infiltration in the brain post-stroke and increases the proportion of anti-inflammatory N2-subtype neutrophils, boosting the expression levels of IL-10 and TGF-β. In vitro experiments demonstrate that hMSC-L and hMSC-M promote nuclear translocation of PPAR-γ in neutrophils stimulated with PMA, activating the downstream STAT6/SOCS1 signaling pathway to encourage N2-subtype neutrophil polarization.ConclusionsIntranasal delivery of hMSC-L and hMSC-M effectively ameliorates cerebral ischemic injury in mice, comparable to traditional administration routes like intravenous delivery. Treatment with hMSC-L and hMSC-M enhances the PPAR-γ/STAT6/SOCS1 pathway and improves the neuroinflammatory response post-stroke by increasing N2 neutrophil infiltration. These results provide a theoretical basis for a deeper understanding of the mechanisms of stem cell therapy and for exploring suitable delivery pathways of stem cell treatment.

Tumour distribution and characteristics associated with poor surgical outcomes in patients with sporadic spinal schwannomas

PurposeSpinal schwannomas are benign tumours that can compress the spinal cord or nerve roots, causing neurological symptoms. Despite successful surgical resection, some patients experience suboptimal functional recovery. Several risk factors for poor prognosis have been identified, but limited research has explored the influence of tumour distribution and characteristics. In this study, we aimed to identify prognostic variables associated with residual neurological deficit in patients undergoing surgical resection for sporadic spinal schwannomas.MethodsClinical and radiological data of consecutive patients who underwent surgery for spinal schwannomas at Saitama Medical Centre between January 2010 and March 2024 were retrospectively reviewed. Patients with neurofibromatosis type 2 or foraminal and paravertebral schwannomas were excluded. Data collected included patient demographics, radiological features, and surgical complications. Residual neurological deficit was defined as a Modified McCormick scale grade of II–V, persistent neurogenic pain, or bladder/bowel dysfunction.ResultsGross total resection was achieved in 55 cases (76.4%). Postoperative complications occurred in 6 cases (8.3%), including cerebrospinal fluid fistula and vascular injury. At a median follow-up of 26.4 months, 20 patients (27.8%) had residual neurological deficits. Univariable and multivariable logistic regression identified thoracic spine involvement (odds ratio [OR], 5.03; 95% confidence interval [CI], 1.47–18.6; p = 0.01) and dumbbell-shaped tumours (OR, 0.15; 95% CI, 0.02–1.28; p = 0.04) as significantly associated with residual neurological deficits. Moreover, thoracic spinal schwannomas were associated with a significantly higher incidence of persistent postoperative neurogenic pain than that associated with cervical or lumbosacral tumours (p = 0.001).ConclusionsThoracic spine involvement and tumours that are not dumbbell-shaped were identified as significant risk factors for residual neurological deficits in patients undergoing surgical treatment for spinal schwannomas. Awareness of tumour distribution and characteristics may assist in refining preoperative assessments, guiding strategic decisions, and potentially improving surgical management for better patient care.

Autologous bone grafting combined with spheroid-based matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: Good clinical outcomes alongside abnormal postoperative gait patterns.

This study aimed to evaluate the clinical and functional outcomes of autologous bone grafting with spheroid-based matrix-induced autologous chondrocyte implantation (MABCI) for osteochondral defects of the knee by analysing pre- and postoperative patient-reported outcome measures (PROMs). Postoperative gait analysis was conducted and compared with a matched healthy control group to investigate biomechanical deviations. A total of 35 patients (m: 21, f: 14; mean defect size: 4.2 ± 2.4 cm², localisation: femoral condyle: 31, patellofemoral: 5) were analysed. The mean follow-up was 42.6 ± 22.8 months. International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), PROMIS 29 profile, and a questionnaire on patient perception of treatment success were assessed to evaluate PROMs. 3D-instrumented gait analysis (GRAIL, Motek) was used to assess lower extremity kinematics, kinetics and vertical ground reaction forces, compared to sex-, age- and body mass index-matched healthy controls. All clinical scores showed significant improvement compared to the preoperative condition (IKDC: 73.1 ± 10.1 vs. 56.6 ± 17.2, p < 0.01; KOOS subcategories: pain 82.0 [±12.7] vs. 70.7 [±16.7] [p < 0.01], symptoms 79.1 [±20.3] vs. 68.9 [±13.9] [p < 0.01], activities of daily living 90.1 [±11.2] vs. 80.5 [±15.6] [p < 0.01], sport and recreational function: 65.3 [±19.3] vs. 51.3 [±26.29] [p < 0.01], quality of life 52.2 [±18.6] vs. 42.6 [±18.6] [p < 0.01]; numeric pain rating scale: 2.7 ± 2.0 vs. 5.0 ± 2.5, p < 0.01). The analysed patients reported a high satisfaction rate (94.3%). Self-selected walking speed was significantly lower than in healthy controls (1.17 ± 0.17 m/s vs. 0.98 ± 0.18 m/s, p < 0.01). Peak knee flexion angle (PKA) during loading response was significantly smaller (9.6° ± 7.0 vs. 17.7° ± 4.6, p < 0.01), and knee extension moment was significantly reduced (0.1 Nm/kg ± 0.2 vs. 0.4 Nm/kg ± 0.2, p < 0.01). MABCI is an effective treatment for osteochondral knee defects, showing significant improvements in all evaluated PROMs. Postoperative gait analysis revealed abnormal gait patterns, including reduced PKA and lower knee extension moment, suggesting a need for further rehabilitation to optimise functional recovery. Level III.