Functional Recovery Research Articles

Abstract 4118949: Factors Influencing Left Ventricular Function Recovery Following Left Ventricular Assist Device Implantation in Pediatric Dilated Cardiomyopathy: Insights from Single-Cell RNA Sequencing Analysis

Background and Objective: Heart transplantation is a recognized treatment for pediatric severe heart failure, but long-term issues necessitate alternative treatments. Some dilated cardiomyopathy (DCM) cases show left ventricular function recovery after LVAD implantation. This occurrence could lead to new treatments, but mechanisms are unclear. This study explores preoperative molecular factors interacting with LVAD's effects using single-cell transcriptomics on clinical samples. Methods: Twenty-five pediatric DCM patients underwent Berlin Heart EXCOR (BHE) implantation at our institution since 2013. Those with left ventricular ejection fraction (LVEF) improving by >20% were in the Recovery group (R), others in Non-Recovery (NR). Single-cell RNA-sequence was performed on myocardial tissue from six patients (three per group). Differential gene expression and pathway analysis were conducted for each cell type. Findings were validated by comparing them with histological evaluation or clinical examination in all 25 cases. Results: R: 10 patients; NR: 15. R's weight was 6.3 kg, NR's 9.9 kg (p=0.049); LVEF: R 23%, NR 16.5% (p=0.61). In pseudobulk analysis of cardiomyocytes, upregulated genes in R included NPPB, MYL7, PCDH9. KEGG analysis indicated activation of Tight Junction and ECM receptor pathways in R. In fibroblasts, major extracellular matrix proteins were higher in R, GSL gene expression in NR. Plasma Brain Natriuretic Peptide (BNP) at BHE implantation was significantly higher in R; 2913 [1836-3990 (95% CI)] vs 1278 [667-1888] pg/ml (Image1,2). No differences in tissue fibrosis rates were found between the groups. Conclusion: Alterations in gene expression patterns in some cell clusters, including cardiomyocytes, may contribute to left ventricular function recovery post-BHE implantation in pediatric DCM patients. Plasma BNP levels correlated with gene expression alterations, suggesting both a potentially protective effect on cardiomyocytes and a useful marker of LV functional recovery. Further validation of these candidate genes may elucidate intracellular molecular mechanisms.

Efferocytosis: A new therapeutic target for stroke.

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.

Advances in Bioceramics for Bone Regeneration: A Narrative Review

Large osseous defects resulting from trauma, tumor resection, or fracture render the inherent ability of the body to repair inadequate and necessitate the use of bone grafts to facilitate the recovery of both form and function of the bony defect sites. In the United States alone, a large number of bone graft procedures are performed yearly, making it an essential area of investigation and research. Synthetic grafts represent a potential alterative to autografts due to their patient-specific customizability, but currently lack widespread acceptance in the clinical space. Early in their development, non-autologous bone grafts composed of metals such as stainless steel and titanium alloys were favorable due to their biocompatibility, resistance to corrosion, mechanical strength, and durability. However, since their inception, bioceramics have also evolved as viable alternatives. This review aims to present an overview of the fundamental prerequisites for tissue engineering devices using bioceramics as well as to provide a comprehensive account of their historical usage and significant advancements over time. This review includes a summary of commonly used manufacturing techniques and an evaluation of their use as drug carriers and bioactive coatings—for therapeutic ion/drug release, and potential avenues to further enhance hard tissue regeneration.

Abstract 4134417: Cardiotoxicity Conundrum: Distinguishing Immune Checkpoint Inhibitor Myocarditis from Fluorouracil Cardiotoxicity in Concurrent Therapy

Case Description: The patient is a 37-year-old male with metastatic gastroesophageal junction adenocarcinoma presenting with chest pain and dyspnea two days after initiation of leucovorin, fluorouracil, oxaliplatin (FOLFOX), and nivolumab therapy. He was tachycardic and hypotensive with elevated cardiac biomarkers and globally reduced left ventricular systolic function. Suspecting immune checkpoint inhibitor (ICI) myocarditis versus fluorouracil (5-FU) cardiotoxicity, he was treated simultaneously for both. After starting high-dose steroids and before uridine triacetate, he had improved symptoms, cardiac function, biomarkers, and invasive hemodynamics. Though his endomyocardial biopsy did not show inflammatory cell infiltrates, his CMR demonstrated increased T1 and T2 relaxation times consistent with myocarditis. Testing revealed normal dihydropyrimidine dehydrogenase (DPD) activity. He completed uridine triacetate and was discharged on a steroid taper. At follow-up, he remained clinically stable, tolerating oxaliplatin and docetaxel (FLOT) initiation and nivolumab rechallenge without 5-FU. Discussion: This case is challenging as the presentation does not conclusively identify a causative agent. The patient’s symptom severity suggests ICI myocarditis, while the early onset points to 5-FU cardiotoxicity. His quick recovery of cardiac function after medication cessation suggests 5-FU-associated Takotsubo cardiomyopathy. His improvement after steroids raises concern for an adverse immunologic response as in ICI myocarditis or idiosyncratic reactions to oxaliplatin with 5-FU. This patient received ICI therapy and chemotherapy, increasing his risk for cardiac immune-related adverse events. His protracted 5-FU infusion increased his risk for 5-FU cardiotoxicity, but his normal DPD activity mitigates this risk. Although his biopsy was negative, it cannot exclude ICI myocarditis. By the IC-OS 2021 consensus, he meets the criteria for ICI myocarditis presenting 48 hours after nivolumab exposure with cardiogenic shock, elevated cardiac biomarkers, decline in cardiac function, and CMR with elevated T1 and T2 relaxation times. Yet, his biomarkers remained normal with nivolumab rechallenge, arguing against ICI myocarditis and suggesting 5-FU as the culprit. Early recognition and differentiation of the culprit in concurrent therapies impact management and future treatment options. Rechallenge carries risk and requires interdisciplinary collaboration to ensure patient safety.

Abstract 4138546: From Nature’s Remedy to Cardiac Emergency: A Case of Takotsubo Cardiomyopathy Induced by High-Dose Berberine Supplementation

Introduction: Takotsubo cardiomyopathy (TCM) is a reversible cardiac condition often precipitated by emotional or physical stress. Certain medications have also been implicated. While prognosis is generally favorable, associated QTc prolongation and ventricular arrhythmias can be life threatening, necessitating identification of potential triggers. This report highlights TCM in a patient using high-dose berberine, a plant alkaloid known for its hypoglycemic properties. Case description: A 69-year-old female with a history of type 2 diabetes mellitus, and hyperlipidemia presented after a syncopal event. It was preceded by sudden onset of dizziness, nausea, and vomiting. She had been using berberine for a year to lower her blood sugar and had recently switched to a higher dose of a more potent formulation. Vitals were unremarkable. Initial evaluation revealed a prolonged QTc interval of 659 ms (Figure 1A) and elevated troponin-I levels. She was treated with intravenous magnesium, which improved her QTc to 540 ms and revealed new T-wave inversions in the precordial leads. Echocardiogram showed an ejection fraction (EF) of 35%, with LV apical akinesia and hypercontractile basal segments. Cardiac catheterization ruled out significant coronary artery disease, leading to a diagnosis of TCM. Berberine was discontinued, and guideline-directed medical therapy was initiated. Given the presentation with syncope and high suspicion of aborted sudden cardiac death (SCD), she was discharged with a wearable cardioverter-defibrillator (WCD) as a precaution due to the risk of ventricular arrhythmias during recovery. At her 8-week follow-up, QTc and EF had normalized (Figure 1B), prompting WCD removal. Conclusion: The pathophysiology of berberine-induced cardiomyopathy remains uncertain and requires further research. This case underscores the importance of recognizing the potential cardiotoxic effects of berberine, particularly when used in high doses. A thorough medication and supplement history is crucial in patients presenting with unexplained cardiac symptoms. The reversible nature of TCM, when promptly recognized and treated, highlights the need for comprehensive follow-up to ensure recovery of cardiac function.

Mesenchymal Stem Cell Therapy to Reduce the Neurological Deficit of Chronic Ischemic Stroke Patients: A Systematic Review

Current ischemic and hemorrhagic stroke treatments are limited by a narrow golden period and lack of regenerative benefits, so stem cell therapy emerges as an ideal candidate for functional recovery in stroke patients. Stem cell therapy, still being studied, is expected to repair ischemic areas damaged by stroke to restore their physiological functions and reduce neurological deficits in chronic stroke patients. This study aimed to determine the therapeutic efficacy of MSCs in reducing neurological deficits in chronic ischemic stroke patients. We conducted a systematic review. We searched PubMed, Cochrane Library, Science Direct, and Springer Link from inception until December 2022 for cohort studies dealing with mesenchymal stem cell therapy for patients with ischemic stroke. The citation-searching method in this study collected 1,038 articles using the advanced searching method and 8 articles using the citation-searching method, bringing the total number of articles to 1,046. The exclusion criteria used were articles with systematic reviews and meta-analyses and articles that were not accessible in full text. Based on the results of a systematic review study conducted, the conclusion that can be drawn is that MSCs therapy has proven effective in reducing neurological deficits in chronic ischemic stroke patients in terms of the decreased NIHSS score.

Pancreaticoduodenectomy for octogenarians under postoperative rehabilitation enhanced ERAS protocol.

Although pancreaticoduodenectomy (PD) for pancreatic or periampullary cancer is the gold standard treatment regardless of patient age, patients aged 80 years or older have poor postoperative short-term outcomes because of their poor functional status and many medical comorbidities. Postoperative rehabilitation in octogenarians could improve postoperative outcomes; however, its effect remains unclear. This retrospective study included patients who underwent PD at two institutions between January 2019 and December 2022. All patients were managed using the enhanced recovery after surgery (ERAS) protocol, and elderly patients or those with loss of muscle mass or frailty underwent additional perioperative rehabilitation. Postoperative short-term outcomes were compared between the octogenarians and non-octogenarians. We reviewed 251 patients including 44 octogenarians (17.5%). Octogenarians had higher rates of comorbidity (78.9% vs. 55.1%, P = 0.049) and sarcopenia (31.8% vs. 16.4%, P = 0.018) and a more impaired nutritional status than non-octogenarians and received postoperative rehabilitation more frequently (86.4% vs. 44.0%, P < 0.001, respectively). Under the rehabilitation-enhanced ERAS protocol, the postoperative major complication rate (25.0% vs. 24.6%, P = 0.960), the length of hospital stay (LOS) (P = 0.435), and the length of functional recovery (LOFR) (P = 0.110) did not differ between the two groups. In the multivariate analysis, age ≥ 80 years was not determined as a risk factor for major complications. Despite the poor functional and nutritional status of octogenarians, their postoperative major complication rates, LOS, and LOFR after PD were comparable with those of non-octogenarians under the rehabilitation-enhanced ERAS protocol.

The epidermal growth factor receptor inhibitor gefitinib enhances in vitro and in vivo sensory axon regeneration and functional recovery following transection in a mouse median nerve injury model.

The epidermal growth factor receptor (EGFR; ErbB1), a membrane bound receptor tyrosine kinase, is hypothesized to have an inhibitory influence on peripheral nerve regeneration. This study examines the impact of EGFR inhibition on nerve regeneration using the commercially available small molecule inhibitor gefitinib. In vitro assays included neurite outgrowth of cultured dorsal root ganglion (DRG) neurons from adult C57Bl/6 wildtype mice on immobilized chondroitin sulfate proteoglycans (CSPG). Following forelimb median nerve injury, EGFR expression, number of regenerated neurons (using retrograde labeling) and myelination of motor and sensory neurons were compared between mice that received either gefitinib or vehicle. Functional recovery was assessed using grip strength. EGFR expression on DRG and spinal motor neurons was confirmed. Gefitinib significantly increased neurite outgrowth in medium sized (30-50 μm) DRG neurons, resulting in longer neurites (183 ± 36 μm) compared with CSPG alone (49 ± 9 μm). After median nerve injury, significantly greater numbers of sensory neurons (638 ± 112 vs. 301 ± 81), but not motor neurons (31 ± 12 vs. 42 ± 13) regenerated in animals treated with gefitinib compared with controls. Regenerated axons in gefitinib treated animals displayed significantly greater diameter and increased g-ratio compared with controls. Grip strength recovered more quickly in animals receiving gefitinib compared with controls (27.6 vs. 19.1 g 18 days post-injury). This study provides data supporting the role of EGFR as a negative regulator of sensory but not motor neuron regeneration. Further, it demonstrates versatile potential uses of existing pharmaceuticals.

Comparing the performance of a femoral shaft fracture fixation using implants with biodegradable and non-biodegradable materials.

Orthopedic injuries, such as femur shaft fractures, often require surgical intervention to promote healing and functional recovery. Metal plate implants are widely used due to their mechanical strength and biocompatibility. Biodegradable metal plate implants, including those made from magnesium, zinc, and iron alloys, offer distinct advantages over non-biodegradable materials like stainless steel, titanium, and cobalt alloys. Biodegradable implants gradually replace native bone tissue, reducing the need for additional surgeries and improving patient recovery. However, non-biodegradable implants remain popular due to their stability, corrosion resistance, and biocompatibility. This study focuses on designing an implant plate for treating transverse femoral shaft fractures during the walking cycle. &#xD;The primary objective is to conduct a comprehensive finite element analysis (FEA) of a fractured femur's stabilization using various biodegradable and nonbiodegradable materials. The study assesses the efficacy of different implant materials, discusses implant design, and identifies the optimal materials for femoral stabilization. Results indicate that magnesium alloy is superior among biodegradable materials, while titanium alloy is preferred among non-biodegradable options. The findings suggest that magnesium alloy is the recommended material for bone implants due to its advantages over non-degradable alternatives.&#xD.

Robotic surgery versus laparoscopic surgery for rectal cancer: a comparative study on surgical safety and functional outcomes.

This study aims to evaluate the clinical efficacy and functional outcomes of DA Vinci (Xi)-assisted surgery compared to conventional laparoscopic surgery for middle and low rectal cancer, focusing on oncologic cure and functional preservation. Between December 2020 and June 2021, 102 patients with middle and low rectal cancer (tumour lower margin ≤10 cm) were enrolled at the affiliated Hospital of Xuzhou Medical University. Participants were divided into two groups: robot-assisted (n = 51) and laparoscopy-assisted (n = 51). Each group underwent a radical resection using their assigned method. Clinical and functional outcomes were analysed post-surgery. Preoperative data did not differ significantly between groups (P > 0.05). All surgeries were successfully completed without conversion to open surgery. The robotic group experienced significantly less intraoperative blood loss (55.2 ± 29.8 mL vs. 109.5 ± 58.5 mL) and faster recovery in gastrointestinal function (35.1 ± 9.4 h vs. 40.7 ± 1.9 h), diet recovery (2.1 ± 0.8 days vs. 2.9 ± 0.4 days), and catheter removal (2.9 ± 2.7 days vs. 5.3 ± 2.1 days). The robotic group also dissected more lymph nodes (23 ± 6 vs. 15 ± 4). However, they had longer operative times (239.8 ± 29.6 min vs. 141.1 ± 18.5 min) and higher hospital costs. Satisfaction levels regarding defecation, voiding, and sexual functions were notably higher in the robotic group. No significant differences in surgical safety or immediate postoperative outcomes were observed between robotic and laparoscopic approaches. However, robotic surgery demonstrated superior lymph node dissection, anal function preservation, and gastrointestinal recovery, enhancing overall functional outcomes.

Therapeutic potential of mackerel-derived peptides and the synthetic tetrapeptide TVGF for sleep disorders in a light-induced anxiety zebrafish model

IntroductionAnxiety-like insomnia is a known risk factor for the onset and worsening of certain neurological diseases, including Alzheimer’s disease. Due to the adverse effects of current anti-insomnia medications, such as drug dependence and limited safety, researchers are actively exploring natural bioactive compounds to mitigate anxiety-like insomnia with fewer side effects. Mackerel (Pneumatophorus japonicus), a traditional Chinese medicine, is known for its tonic effects and is commonly used to treat neurasthenia. The use of mackerel protein extract has been shown to effectively improve symptoms of light-induced anxiety-like insomnia in a zebrafish model.MethodsThis study examines the effects of mackerel bone peptides (MW &amp;lt; 1 kDa, MBP1) and the synthetic peptide Thr-Val-Gly-Phe (TVGF) on light-induced anxiety-like insomnia in zebrafish. The evaluation is conducted through behavioral observation, biochemical marker analysis, and gene transcriptome profiling.ResultsMBP1 significantly alleviated abnormal hyperactivity and restored neurotransmitter levels (dopamine and γ-aminobutyric acid) to normal. Moreover, it mitigated oxidative stress by reducing reactive oxygen species production and malonaldehyde levels, while enhancing antioxidant enzyme activities (superoxide dismutase and catalase). This was further attributed to the regulation of lipid accumulation and protein homeostasis. Furthermore, MBP1 ameliorated sleep disturbances primarily by restoring normal expression levels of genes involved in circadian rhythm (per2 and sik1) and visual function (opn1mw2, zgc:73075, and arr3b). Molecular docking analysis indicated that TVGF exhibited good affinity for receptors linked to sleep disturbances, including IL6, HTR1A, and MAOA. TVGF exhibited sedative effects in behavioral assays, mainly mediated by regulating the normal expression of genes associated with circadian rhythm (cry1bb, cry1ba, per2, per1b and sik1), visual function (opn1mw1, gnb3b, arr3b, gnat2), purine metabolism (pnp5a), and stress recovery (fkbp5).DiscussionThese findings suggest that MBP1 and TVGF could be promising therapies for light-induced anxiety-like insomnia in humans, offering safer alternatives to current medications. Additionally, the regulation of genes related to circadian rhythm and visual perception may be a key mechanism by which MBP1 and TVGF effectively relieve anxiety-like insomnia.

Trojan Horse Strategy for Wireless Electrical Stimulation-Induced Zn2+ Release to Regulate Neural Stem Cell Differentiation for Spinal Cord Injury Repair.

Due to the uncertain differentiation of neural stem cells (NSCs), replenishing lost neurons by endogenous neural differentiation to repair spinal cord injury (SCI) remains challenging. The electrical stimulation-induced drug release is a promising approach for the localized and controlled release of drugs to regulate the differentiation of NSCs into neurons. Here, we developed Zn-PDA@BT nanoparticles acted as Trojan Horse to enter cells through endocytosis for Zn2+-controlled release therapy by the potentials generated by the piezoelectric effect. Due to the presence of polydopamine (PDA), under ultrasound stimulation, the electrical signal derived from the piezoelectric effect of barium titanate nanoparticles can be attracted to the surface of Trojan Horse nanoparticles to facilitate the controlled release of Zn2+. And Zn2+ bonded with PDA can increase the intracellular Zn2+ concentration within mouse-derived NSCs (mNSCs) to regulate the differentiation of mNSCs, which could enhance excitatory neuronal differentiation and inhibit astrocyte differentiation of mNSCs by activating the TGF-β and p53 pathways. More importantly, this Trojan Horse therapy allowed mNSCs to differentiate into mature neurons in 5 days, while the natural differentiation process took 10 days. Moreover, the transplantation of mNSC-ingested Zn-PDA@BT nanoparticles effectively replenished lost neurons at the damaged site and promoted function recovery after SCI in vivo, demonstrating the great potential of electrical stimulation-induced Zn2+ release for SCI repair.

Prognostic impact of a 3-week multimodal prehabilitation program on frail elderly patients undergoing elective gastric cancer surgery: a randomized trial.

Research indicates that prehabilitation is effective in optimizing physical status before surgery, although this method may be considered "aggressive" for frail elderly patients. This study aimed to evaluate whether multimodal prehabilitation decreases postoperative complications and improves functional recovery in frail elderly patients undergoing gastric cancer surgery, in comparison to usual clinical care. This study was a single-center, single-blind, randomized controlled trial. Patients over 65 years old with a Fried Frailty Index of 2 or higher, scheduled for gastric cancer surgery, were considered for inclusion. Eligible participants were randomized in a 1:1 ratio to either the intervention or control group. The intervention group underwent a 3-week multimodal prehabilitation program prior to surgery, in addition to perioperative care guided by ERAS protocols. The control group received only the latter. The primary outcome was the comprehensive complications index (CCI) measured at 30 days after surgery. Secondary outcomes included 30-day overall complications, functional walking capacity as assessed by 6-minute walking distance (6MWD) at 4 weeks postoperatively, and 3-month postoperative quality of life. This study was registered at ClinicalTrials.gov (No. NCT06510088). Among the 112 eligible patients, the median age was 74 years, with 58 (52.7%) being female.No between-group difference was found in the primary outcome measure, 30-day CCI. The Median (Q1-Q3) CCI for the intervention and control groups was 0 (0-12.2) and 0 (0-22.6) (P = 0.082), while the mean (SD) CCI was 6.1 (15.8) and 9.8 (12.7), respectively (P = 0.291). Notably, the incidence of severe complications (CCI > 20) was significantly lower in the intervention group compared to the control group (11.1% vs. 25.9%, P = 0.046), particularly in terms of medical complications (12.3% vs. 29.3%, P = 0.025). Preoperatively, 27 patients (47.4%) in the intervention group exhibited an increase in the 6MWD of at least 20m, compared to 16 patients (27.6%) in the control group (P = 0.028). At 4 weeks postoperatively, more patients in the intervention group returned to their baseline 6MWD levels (63.2% vs. 43.1%, P = 0.031). Secondary parameters of functional capacity in the postoperative period generally favored the multimodal prehabilitation approach. In frail elderly patients undergoing elective gastric cancer surgery, a prehabilitation program did not affect the 30-day postoperative complication rate or CCI but reduced severe complications and improved perioperative functional capacity. [ClinicalTrials.gov], [NCT06510088], [07/15/2024], [Retrospectively registered].

Using Extracorporeal Shockwave Therapy in Patients with Orthopedic Conditions

Background: Among other non-invasive procedures, Extracorporeal Shockwave Treatment (ESWT) has been used to resolve many musculoskeletal ailments. The authors completed a systematic review to study articles that reported the effectiveness of focused shockwave therapy in patients with orthopedic conditions. Methods: A comprehensive search was conducted across reputable databases including Pub Med, The Cochrane Library, Science Direct, PEDro, Clinicaltrials.gov, and Google Scholar, ensuring a thorough review of the literature until October 10, 2022. Original articles of any design reporting on the use of ESWT in orthopedic patients were meticulously selected. Information related to study design, sample size, participants, intervention, and key findings of the study were extracted. The PEDro classification scale, a recognized tool, was used to evaluate the quality of the studies, further enhancing the credibility of findings. Results: Nineteen research articles (including 1157 participants) were retrieved and included for qualitative analysis. The sample size ranged from twenty-one to one hundred fifteen subjects, and the articles were published between 2001 and 2022. Out of 19 studies published, five were conducted in China, three in Germany, two in Iran and Turkey, and one in the United States, Canada, Italy, Denmark, Spain, Taiwan, and Saudi Arabia. The risk of bias was either moderate or low among the included studies. In patients with various orthopedic conditions, considerable moderate evidence of ESWT’s effectiveness and success in lowering pain levels, increasing treatment success rates, promoting patient-reported functional recovery, and raising performance-based functional outcomes was seen in the results. Conclusion: The systematic literature review provided compelling evidence of the successful application of ESWT in treating a wide range of musculoskeletal problems. These positive outcomes were achieved without severe complications and morbidities, offering a promising outlook for the future of orthopedic treatment.

Sheffield Adaptive Patterned Electrical Stimulation (SHAPES) Therapy for Post Stroke Arm spasticity: study protocol for a 3-arm, a partially blinded, randomised controlled trial

IntroductionPost stroke elbow spasticity (PSES) affects over a third of individuals following stroke and negatively impacts on functional recovery, comfort and quality of life. Drug therapies have limited efficacy and unwanted side effects, botulinum toxin, although effective, is costly, and conventional electrical stimulation therapies are limited long term by habituation. We aim to investigate the efficacy of Sheffield Adaptive Patterned Electrical Stimulation (SHAPES), that delivers temporally and spatially varying pattern of electrical stimulation, against transcutaneous electrical stimulation (TENS) and standard care at reducing PSES.Methods and designOverall, 297 people with PSES will be randomised (1:1:1) to one of 3 arms: Standard care (no electrical stimulation), TENS (conventional patterned electrical stimulation) or SHAPES (adaptive patterned electrical stimulation). Both SHAPES and TENS are delivered using a specially designed electrical stimulation sleeve used for 60 min each day for 6-weeks. Outcome measures are completed at baseline, end of treatment (EOT 6 weeks) and then 6-weeks, 12-weeks and 24-weeks after the end of treatment. Efficacy will be determined based on the proportion of participants experiencing meaningful improvement (18%) in the 7-day Numerical Rating Scale (NRS-S) for PSES, compared between both intervention arms and standard care, and between the two intervention groups. Measures of arm motor function (Action Research Arm Test, MRC scale), and quality of life (SQoL-6D, EQ-5D) will also be measured along with a parallel health economic evaluation.DiscussionThe results of the SHAPES trial will inform management of elbow spasticity after stroke. The SHAPES intervention is a low cost, self-administered intervention for the management of spasticity that can be used repeatedly, and if found to be more effective than TENS or control has the potential to be widely implemented in the UK NHS healthcare setting. Furthermore, despite the wide use of TENS in the management of spasticity, this study will provide critically required evidence regarding its efficacy. The trial has been registered with the ISRCTN registry (ISRCTN26060261).

Enhancing Recovery in Fracture Management: An Evidence-Based Approach to Early Mobilization

●Background: Traditionally, fracture management has centered around prolonged immobilization, based on the belief that restricting movement allows bone tissue the stability needed to heal effectively. This approach, while protective, can often lead to complications such as muscle atrophy, joint stiffness, and delayed return to function. In recent years, however, early mobilization has emerged as a promising alternative, with the potential to not only speed recovery but also to enhance functional outcomes. ●Aim and Objectives: This study examines the effects of early mobilization on recovery and complications in fracture patients, aiming to identify optimal techniques for varying fracture types and patient demographics. ●Methods: A systematic review and comparative study were conducted, analyzing outcomes across patients managed with early mobilization and those treated with standard immobilization. ●Results: Patients undergoing early mobilization experienced faster recovery times, lower rates of complications, and higher satisfaction scores. Enhanced quality of life and functional recovery were observed, with significant reductions in joint stiffness and muscle loss. ●Conclusion: Early mobilization shows significant benefits in fracture management, particularly when tailored to individual patient needs. Future studies are recommended to explore long-term impacts and protocol optimization.

Chitosan-Modified Hydrogel Microsphere Encapsulating Zinc-Doped Bioactive Glasses for Spinal Cord Injury Repair by Suppressing Inflammation and Promoting Angiogenesis.

Spinal cord injury (SCI) is a common nerve injury caused by external force, resulting in sensory and motor impairments. Previous studies demonstrated that inhibiting the neuroinflammation promoted SCI repair. However, these approaches are low efficient, and lack targeting specificity, and even require repeated and high doses of systemic administration. To address such issues, in the present study, chitosan-modified hydrogel microspheres encapsulating with zinc-doped bioactive glasses (CS-MG@Zn/BGs) is constructed for targeted repair of SCI. In vitro, the CS-MG@Zn/BGs effectively inhibited the acute inflammatory response initiated by microglia and promoted angiogenic activities. In vivo, CS-MG@Zn/BGs targeted the injured site, and attenuated neuroinflammation by inhibiting microglia infiltration and modulating microglia polarization toward M2 type. Furthermore, it facilitated vascular reconstruction, neuronal differentiation, axonal regeneration and remyelination at the injured site, and thereby promoted motor function recovery of SCI mice. The in vitro and in vivo results implied that CS-MG@Zn/BGs may be a promising alternative for the rehabilitation of SCI.

Segmental phase angles as predictors of functional recovery and activities of daily living in patients after stroke.

This study investigated the association between segmental phase angles and functional outcomes in patients after stroke, hypothesizing that increased segmental phase angle correlates with improved functional status. A retrospective cohort study of 1012 patients after stroke was conducted. Whole body and segmental phase angles were measured using bioelectrical impedance analysis within 3 days of admission. Our exposure of interest was segmental phase angle measured via a multifrequency bioelectrical impedance analyzer and calculated as phase angle = arctangent (Xc/R) × (180/π), where R is the resistance of the right half of the body and Xc is the reactance measured at 50 kHz. The primary outcomes were the motor subscale of the functional independence measure (FIM) at discharge and FIM change between admission and discharge. Secondary outcomes included FIM scores for specific activities. Multiple linear regression analysis was performed to assess associations. Phase angles of the healthy upper and lower limbs demonstrated stronger associations with discharge FIM motor scores (β = 0.175 and β = 0.105, respectively) and FIM motor gain (β = 0.242 and β = 0.092, respectively) compared with whole body or paretic limb phase angles. Upper limb phase angles were more closely related to grooming and toileting abilities, whereas lower limb phase angles were associated with both toileting and locomotion at discharge. Segmental phase angles, particularly those of the nonparetic limbs, are promising predictors of functional outcomes in patients after stroke. Assessing segmental phase angles may guide targeted interventions and rehabilitation strategies for improving specific activities of daily living.

Elevated plasma progranulin levels in the acute phase are correlated with recovery of left ventricular function in the chronic phase in patients with acute myocardial infarction.

Progranulin is a secreted glycoprotein that regulates inflammation and wound healing. However, plasma progranulin levels in the acute phase and their clinical significance in patients with acute myocardial infarction (AMI) remain to be elucidated. We aimed to investigate the relationship between the increase in plasma progranulin levels in the acute phase and the recovery of left ventricular function in the chronic phase in AMI patients. Eighteen AMI patients were followed up for 6 months. Blood samples were collected from the antecubital vein on day 0 (on admission) and day 7 in the acute phase. The control group consisted of patients without significant coronary artery stenosis, as assessed by cardiac catheterization (n = 16). Plasma progranulin levels were measured by enzyme-linked immunosorbent assay. Echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI to evaluate left ventricular ejection fraction using the modified Simpson's method. Plasma progranulin levels in the AMI group on day 0 (69.5 ± 24.6 ng/mL) were similar to those in the control group (84.2 ± 47.1 ng/mL). There was a significant increase in progranulin levels in the AMI group on day 7 (104.2 ± 52.0 ng/mL) compared with day 0. The increase in plasma progranulin levels in the acute phase was positively correlated with the increase in left ventricular ejection fraction between the acute and chronic phases. Among various factors, only plasma progranulin levels were favorably correlated with left ventricular functional recovery in the chronic phase. The increase in plasma progranulin levels in the acute phase may serve as a predictive biomarker and a contributer for the recovery of left ventricular function in the chronic phase in patients with AMI.

Pericapsular nerve group block reduces opioid use and pain after hip surgery: A systematic review and meta-analysis of randomized controlled trials.

While the pericapsular nerve group (PENG) block has become increasingly popular for managing pain after hip surgery, its efficacy remains controversial. We systematically searched Pubmed, Web of Science, Embase, and the Cochrane Library for randomized controlled trials to assess current evidence about the efficacy of the PENG block. Patients who received PENG block were compared to those who received sham/no block in terms of opioid consumption and pain within 24h after surgery, time to first opioid requirement, functional recovery, risk of nausea and vomiting, and patient dissatisfaction. The quality of evidence was assessed using the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) system. We meta-analyzed six trials involving 416 patients who received preoperative PENG block and 415 who received sham/no block. Patients did not receive any other type of multimodal analgesia. Within 24 h after hip surgery, PENG block significantly reduced postoperative opioid consumption (MD = -12.03, 95% CI: -21.47 to -2.59, P < 0.01, I2 = 97%), particularly in subpopulations undergoing hip replacement, hip fracture, or who had spinal anesthesia, and it significantly decreased dynamic pain scores, but not static scores, without increasing risk of nausea or vomiting or patient dissatisfaction. Individual studies suggested that the PENG block can prolong the time to the first opioid requirement and can improve functional recovery. Most meta-analyses provided evidence of moderate quality according to the GRADE system. The available evidence indicates that preoperative PENG block can significantly decrease opioid consumption and pain early after hip surgery, and it may also promote early functional rehabilitation. However, the limited number of included studies and sample size make it difficult to draw firm conclusions. The decision on whether to apply the PENG block should take into account the patient's age and the type of surgery and anesthesia.