Functional Recovery Research Articles

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

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.

Cardiomyocyte Foxp1‐Specific Deletion Promotes Post‐injury Heart Regeneration via Targeting Usp20‐HIF1ɑ‐Hand1 Signaling Pathway

AbstractThe adult mammalian heart has limited regenerative capacity to replace lost tissue after a major injury. Forkhead box P1 (Foxp1) regulates embryonic cardiomyocyte proliferation and heart development. However, whether Foxp1 participates in postnatal‐injury cardiomyocyte proliferation and heart regeneration remains unclear. This study demonstrates that Foxp1 is downregulated at border zone cardiomyocytes of both neonatal apical resection and adult myocardial infarction. Analysis of the Single‐cell transcriptome database reveals reduced Foxp1 expression in the cardiomyocyte population with high regenerative capacity. Cardiomyocyte‐Foxp1 loss‐of‐function significantly promotes, whereas cardiomyocytes‐Foxp1 gain‐of‐function suppresses cardiomyocyte proliferation. Mechanistically, Foxp1 directly regulates ubiquitin specific peptidase 20 (USP20), a de‐ubiquitinase that prevents hypoxia inducible factor 1ɑ (HIF1α) degradation. Thus, Foxp1 regulates HIF1α and downstream heart and neural crest derivatives expressed 1 (Hand1) to control the cardiomyocyte proliferation via metabolic transition from fatty acid oxidation to glycolysis. Finally, cardiac type troponin T2 (cTnT)‐promoter‐driven adeno‐associated virus 9 (AAV9) for Hand1 induction in cardiomyocytes significantly promoted cardiac regeneration and functional recovery. These findings may provide novel molecular strategies to promote heart regeneration and therapeutic interventions for heart failure.

GPx3 Promotes Functional Recovery after Spinal Cord Injury by Inhibiting Microglial Pyroptosis Through IRAK4/ROS/NLRP3 Axis.

Aim: Spinal cord injury (SCI) is a catastrophic injury characterized by oxidative stress. Glutathione peroxidase 3 (GPx3) is an antioxidant enzyme that protects against immune responses in various diseases. However, the effects of GPx3 in SCI remains unclear. This study aimed to investigate the role of GPx3 in SCI and its underlying mechanisms. Results: We injected adeno-associated viruses to overexpress GPx3 in mice. Primary microglia and BV2 cells were used as in vitro models. We knocked down or overexpressed GPx3 in BV2 cells. Additionally, BV2 cells transfected with siIRAK4 were used to perform rescue experiments. A series of histological and molecular biological analyses were used to explore the role of GPx3 in SCI. Overexpression of GPx3 inhibited oxidative stress in mice, improving functional recovery after SCI. Similarly, LPS+ATP stimulation decreased GPx3 expression in microglia. Silencing of GPx3 elevated the generation of reactive oxygen species, increased the expression of IRAK4 and pro-inflammatory factors, and promoted pyroptosis in microglia. However, overexpression of GPx3 reversed these results. Moreover, silencing of IRAK4 alleviated these phenomena, which were upregulated by GPx3 deficiency. Innovation and Conclusion: Our results demonstrated that GPx3 plays a critical role in SCI by inhibiting microglial pyroptosis via the IRAK4/ROS/NLRP3 signaling pathway. Antioxid. Redox Signal. 00, 000-000.

Effects of Teriparatide and Alendronate on Functional Recovery from Spinal Cord Injury and Postinjury Bone Loss

Objectives: This study evaluated the efficacy of teriparatide (TPTD) and alendronate (ALN) in mitigating bone loss, enhancing bone structure, and facilitating motor function recovery following spinal cord injury (SCI). Methods: All the rats were allocated into four groups: a sham surgery group (SHAM group), a normal saline group (SCI + NS group), a TPTD treatment group after SCI (SCI + TPTD group), and an ALN treatment group after SCI (SCI + ALN group). The Basso, Beattie, and Bresnahan (BBB) scores and gait analyses were used to assess the motor abilities of rats following SCI and the effects of treatment. HE staining, Masson’s trichrome staining, and LFB staining were performed to evaluate the extent of spinal cord tissue damage. Micro-CT was used to measure 12 bone-related parameters of the proximal tibia and create 3D images, and structural changes in the proximal tibial bone tissue were observed under a light microscope after HE staining. Results: After 12 weeks of treatment, the micro-CT data indicated that TPTD significantly increased key bone indicators, such as bone mineral density, after SCI (p &lt; 0.01), whereas ALN did not significantly improve these indicators (p &gt; 0.05). Compared with the SCI + NS group, the SCI + TPTD group presented significantly greater BBB scores and near-normal gait parameters (p &lt; 0.05). Analyses of pathological sections revealed that TPTD significantly reduced the cavity area in the spinal cord after SCI, decreased the proportion of scar tissue, and increased the retention of neural myelin (p &lt; 0.05). However, ALN had no significant effect on these indicators (p &gt; 0.05). Conclusions: TPTD was more effective than ALN at mitigating bone loss and promoting motor function recovery after SCI, and it demonstrated significant advantages in reducing spinal cord damage and improving tissue structure.

Long-Term in vivo Observation of Maize Leaf Xylem Embolism, Transpiration and Photosynthesis During Drought and Recovery.

Plant water transport is essential to maintain turgor, photosynthesis and growth. Water is transported in a metastable state under large negative pressures, which can result in embolism, that is, the loss of function by the replacement of liquid xylem sap with gas, as a consequence of water stress. To avoid experimental artefacts, we used an optical vulnerability system to quantify embolism occurrence across six fully expanded maize leaves to characterize the sequence of physiological responses (photosynthesis, chlorophyll fluorescence, whole-plant transpiration and leaf inter-vein distance) in relation to declining water availability and leaf embolism during severe water stress. Additionally, we characterize the recovery of leaf function in the presence of sustained embolism during a 6-day recovery period. Embolism formation occurred after other physiological processes were substantially depressed and were irreversible upon rewatering. Recovery of transpiration, net CO2 assimilation and photosystem II efficiency were aligned with the severity of embolism, whereas these traits returned to near pre-stress levels in the absence of embolism. A better understanding of the relationships between embolism occurrence and downstream physiological processes during stress and recovery is critical for the improvement of crop productivity and resilience.

Surgical outcomes of non-fovea-sparing internal limiting membrane peeling using a double-staining technique for symptomatic myopic foveoschisis: a retrospective study.

To investigate the incidence of postoperative macular hole (MH), visual acuity, and anatomical recovery in patients who underwent a non-fovea-sparing technique using a double-staining method for symptomatic myopic foveoschisis without pre-existing macular holes. A retrospective study. We evaluated 39 eyes from 39 consecutive patients diagnosed with myopic foveoschisis from May 2017 to September 2022 at Fujita Health University Hospital. All patients underwent non-fovea-sparing internal limiting membrane peeling using a double-staining method and were monitored for 6 months postoperatively. Best-corrected visual acuity (BCVA) as measured by the logarithm of the minimum angle of resolution (logMAR), central retinal thickness (CRT), and the presence of foveoschisis were assessed using optical coherence tomography (OCT) preoperatively (pre) and at 1 month (1M), 3 months (3M), and 6 months (6M) postoperatively. No cases of postoperative rhegmatogenous retinal detachment were observed. A postoperative MH developed in one eye. The mean logMAR values at pre, 1M, 3M, and 6M were 0.38 ± 0.37, 0.23 ± 0.33, 0.18 ± 0.25, and 0.13 ± 0.29, respectively (all P < 0.001). The mean CRTs at pre, 1M, 3M, and 6M were 384.6 ± 177.2, 262.2 ± 84.4, 200.3 ± 64.9, and 185.6 ± 61.0μm, respectively (all P < 0.001). Foveoschisis was observed in all 39 eyes (100%) preoperatively and in 17 eyes (43.6%) at 1M, nine eyes (34.6%) at 3M, and zero eyes (0%) at 6M postoperatively. The non-fovea-sparing double-staining technique was effective in treating myopic foveoschisis without MH, leading to significant improvements in both visual function and anatomical recovery. This method may be a promising surgical option for managing myopic foveoschisis.

Comprehensive Insights into De Quervain’s Tenosynovitis: From Etiology to Rehabilitation

De Quervain's tenosynovitis, a common condition affecting the first dorsal compartment of the wrist, is characterized by pain, swelling, and restricted tendon mobility, often resulting from repetitive manual tasks or biomechanical strain. This review integrates insights from three recent studies, emphasizing the multifactorial etiology, advanced diagnostic techniques, and evolving treatment modalities. Etiological factors include mechanical strain, anatomical variations, and degenerative changes, with ultrasonography emerging as a critical tool for enhancing diagnostic accuracy and guiding therapeutic strategies. Conservative treatments such as splinting, corticosteroid injections, and occupational therapy remain the cornerstone of management, while surgical decompression offers definitive relief for refractory cases. Emerging rehabilitative approaches, including graded tendon-loading protocols, and innovations in imaging and therapy, highlight a shift toward more precise and patient-centered care. Despite advancements, challenges persist in optimizing treatment protocols and addressing long-term functional recovery. Further research is essential to refine diagnostic and therapeutic strategies, reduce recurrence rates, and improve patient outcomes.

Effect of nursing process-based nursing decision implementation on emergency patients with acute ST-segment elevation myocardial infarction

BackgroundThis article aimed to assess the impact of nursing decision interventions based on the nursing process on the clinical outcomes and quality of life (QoL) of patients with ST-segment elevation myocardial infarction (STEMI). The main research question was whether nursing decision-making interventions can improve clinical outcomes in patients with acute STEMI (ASTEMI), including time management, cardiac function recovery, and QoL. It was hypothesized that patients receiving nursing process-based interventions would demonstrate significant improvements in clinical outcomes, recovery time, incidence of adverse cardiac events, and QoL compared to those receiving standard care.MethodsA retrospective analysis was conducted, including 205 patients with ASTEMI as the study sample, 125 cases in the intervention group (IG) and 80 cases in the control group (CG). Data on time management indicators, major cardiac adverse events, QoL scores, left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) levels were collected.ResultsThrough intervention, the IG suggested visibly shorter rescue time, vein opening time, intervention procedure time, and hospital stay compared to the CG; the probability of heart failure (HF), cardiac arrest, and death in the IG was visibly lower than in the CG; the physical health, mental health, social relationships, and environmental scores in the IG were visibly higher than in the CG. Further comparison of post-intervention outcomes between the IG and CG showed no statistically significant differences in serum BNP and cardiac troponin I levels (P > 0.05), with the confidence intervals (CIs) indicating that the changes between the two groups were comparable. However, when comparing post-intervention LVEF between the groups, the IG showed a significantly higher LVEF than the CG (P < 0.05), with a CI of (P = 0.03, 95% CI [0.05, 0.18]).ConclusionImproved nursing decision-making based on the nursing process not only demonstrates advantages in time management but also visibly enhances the QoL of patients with ASTEMI in the emergency setting, reduces the risk of serious cardiac adverse events, and has a positive impact on cardiac function recovery.

Subacute Neurological Improvement Predicts Favorable Functional Recovery After Intracerebral Hemorrhage: INTERACT2 Study.

The frequency and prognostic significance of subacute neurological improvement (SNI) on 90-day outcomes after acute intracerebral hemorrhage are unknown. Secondary analyses of participant data from the INTERACT2 trial (second Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trial). SNI included any, moderate, significant, and substantial neurological improvement defined as ≥1, ≥2, ≥3, and ≥4 points decrease, respectively, on the National Institutes of Health Stroke Scale from 24 hours to 7 days after intracerebral hemorrhage. Logistic regression models were used to assess associations of SNI and death or major disability (modified Rankin Scale score of 3-6), major disability (modified Rankin Scale scores, 3-5), and death alone at 90 days. Data are reported as odds ratios and 95% CIs. Of 2571 patients included in analyses, 1492 (58.0%), 1057 (41.1%), 731 (28.4%), and 490 (19.1%) patients experienced any, moderate, significant, and substantial SNI (24 hours to 7 days) after intracerebral hemorrhage, respectively. After adjustment for key confounders, any SNI was associated with 49%, 25%, and 65% reduced odds of death or major disability (odds ratio, 0.51 [95% CI, 0.42-0.63]), major disability alone (odds ratio, 0.75 [95% CI, 0.63-0.90]), and death (odds ratio, 0.35 [95% CI, 0.24-0.50]), respectively. Moderate, significant, and substantial SNI were also significantly associated with decreased odds of death or major disability at 90 days. The relationship between any SNI and study outcomes was consistent in most subgroups, including age and baseline hematoma volume. Early intensive blood pressure-lowering treatment did not increase the odds of SNI. SNI from 24 hours to 7 days is common after intracerebral hemorrhage and predicts a lower likelihood of death or major disability. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00716079.

Resting-state connectivity enhancement in Aphasia patients post-speech therapy: a localization model.

Resting-state functional connectivity has become a valuable tool in studying post-stroke aphasia (PSA). However, the specific distribution of increased functional connectivity areas (IFCAs) in PSA patients after speech-language therapy (SLT) remains unclear, particularly compared with the intrinsic brain network (IBN) observed in healthy controls. This study aimed to explore the effects of SLT and spontaneous recovery on functional connectivity changes in the brain. We recruited twenty healthy controls and twelve PSA patients, each of whom underwent one month of SLT. The Chinese version of the Western Aphasia Battery (WAB) was administered to assess language function recovery. The Dice coefficients were calculated between each patient's lesion and the reference lesion, which showed moderate to high intensity. The results revealed a close association between the spatial distribution of IFCAs and improvements in specific language functions. Our findings indicate that the distribution pattern of IFCAs may serve as a significant marker of recovery in PSA patients.

Tacrolimus and mycophenolate mofetil in corticosteroid-resistant hepatitis secondary to tislelizumab: a case report

Tislelizumab is a monoclonal antibody with high binding affinity for programmed death-1 (PD-1) receptors. In patients with extensive-stage small-cell lung cancer (ES-SCLC), the first-line use of tislelizumab combined with chemotherapy has shown significant efficacy. However, with the widespread use of PD-1 inhibitors, there are increasing reports of immune-related adverse events (irAEs) in clinical practice, with immune-related hepatitis (IRH) being particularly common. This article reports a case of an ES-SCLC patient (cT3N3M0 cStage IIIB) who developed corticosteroid-resistant hepatitis and recovered through dual immunosuppressant therapy. The patient was a 67-year-old male, diagnosed with ES-SCLC, who received a combination therapy of etoposide, cisplatin, and tislelizumab. Three weeks after the fourth treatment cycle, the patient experienced symptoms, such as decreased appetite, itching, yellow urine, and jaundice, and was diagnosed with IRH, manifested as “Grade 3 total bilirubin increase,” “Grade 3 alanine transaminase increase,” and “Grade 3 aspartate transaminase increase.” Despite intravenous injection of methylprednisolone (MP) 100 mg/day (2 mg/kg) and oral administration of mycophenolate mofetil (MMF) 1 g twice daily, liver function continued to be impaired. In this context, tacrolimus (TAC) (5 mg, twice daily) was added to the therapy, and the IRH level was reduced from Grade 3 to normal. Subsequently, TAC and MMF were gradually reduced and eventually discontinued. Unfortunately, after discontinuing immunosuppressants, IRH recurred. Although the patient still responded to TAC combined with MMF, liver function recovery took a longer time. Due to persistent liver dysfunction, the patient failed to receive second-line chemotherapy and ultimately passed away due to disease progression. Through this case, we hope to emphasize the importance of reasonably extending the use of immunosuppressants to avoid the recurrence of IRH and reduce the premature discontinuation of immunosuppressants. Besides, when tumor progression and IRH recurrence occur simultaneously, providing effective immunosuppressive therapy and reasonably arranging systemic anti-tumor therapy may bring clinical benefits to patients.

AI prediction model for endovascular treatment of vertebrobasilar occlusion with atrial fibrillation

Endovascular treatment (EVT) for vertebrobasilar artery occlusion (VBAO) with atrial fibrillation presents complex clinical challenges. This comprehensive multicenter study of 525 patients across 15 Chinese provinces investigated nuanced predictors beyond conventional metrics. While 45.1% achieved favorable outcomes at 90 days, our advanced machine learning approach unveiled subtle interaction effects among clinical variables not captured by traditional statistical methods. The predictive model distinguished high-risk subgroups by integrating multiple parameters, demonstrating superior prognostic precision compared to standard NIHSS-based assessments. Novel findings include nonlinear relationships between dyslipidemia, stroke severity, and functional recovery. The developed predictive algorithm (AUC 0.719 internally, 0.684 externally) offers a more sophisticated risk stratification tool, potentially guiding personalized treatment strategies in high-complexity VBAO patients with atrial fibrillation.

Loss and Downtime Assessment of RC Dual Wall–Frame Office Buildings Toward Resilient Seismic Performance

This study quantitatively assesses the impact of seismic design strategies on the performance of reinforced concrete (RC) dual wall–frame office buildings by comparing direct and indirect economic losses and downtime in life-cycle terms. A high-rise archetype building located in Santiago, Chile, on stiff soil was evaluated as a benchmark case study. Three design strategies to potentially enhance the seismic performance of a building designed conventionally were explored: (i) incorporating fluid viscous dampers (FVDs) in the lateral load-resisting structure; (ii) replacing conventional non-structural components with enhanced ones (ENCs); and (iii) a combination of the previous two strategies. First, probabilistic structural responses were estimated through incremental dynamic analyses using three-dimensional nonlinear models of the archetypes subjected to a set of hazard-consistent Chilean ground motions. Second, FEMA P-58 time-based assessment was conducted to estimate expected annual losses (EALs) for economic loss estimation. Finally, for downtime assessment, a novel probabilistic framework, built on the FEMA P-58 methodology and the REDi guidelines, was employed to estimate the expected annual downtimes (EADs) to achieve specific target recovery states, such as reoccupancy (RO) and functional recovery (FR). Results revealed that seismically enhancing RC dual wall–frame buildings with FVDs significantly improves resilience by reducing loss and downtime. For example, the enhanced building with FVDs achieved an EAL of 0.093% and EAL of 8.6 days for FR, compared to the archetype base building without design improvements, which exhibited an EAL of 0.125% and an EAD of 9.5 days for FR. In contrast, the impact of ENCs alone was minor, compared to the effect of FVDs, with an EAL of 0.106% and an EAD of 9.1 days for FR. With this detailed recovery modeling, probabilistic methods, and a focus on intermediate recovery states, this framework represents a significant advancement in resilience-based seismic design and recovery planning.

Abstract TMP77: Robotic-Guided Implantation of 3D-Printed Hydrogel Scaffolds to Enhance Axonal Regeneration and Functional Recovery After Stroke: A Novel Minimally Invasive Surgical Approach

Ischemic strokes often disrupt white matter (WM) microstructure, particularly affecting the corticospinal tract (CST) in the internal capsule (IC), leading to significant motor deficits. While evidence shows that axon sprouting occurs post-stroke, it often follows erratic paths, limiting functional recovery. Recent advances in 3D-printed hydrogel scaffolds have shown promise in guiding axon regeneration in spinal cord injury models. We hypothesize that implanting these scaffolds at white matter sites affected by stroke, aligned with CST fibers, will enhance functional axonal regeneration and motor recovery. Our aim is to develop and validate a precise and clinically applicable scaffold delivery system for future human studies. We have developed a novel, minimally invasive stereotaxic method for the precise deployment of 1.3 mm diameter scaffolds within the IC of non-human primates (NHPs). Our approach utilizes a clinically available stereotactic robot (ROSA, ZimmerBiomet) combined with a linear cannula system (AlphaOmega) to plan scaffold placement. Then, we attempted to deploy scaffolds devices into thermally coagulated lesions in NHPs (n=2) and simulated lesions within hydrogel phantoms (n=2). Post-implant MRI, co-registered with high-resolution diffusion tensor imaging were applied to check for scaffold placement accuracy (n=4). We further complement the scaffold placement method by using a novel neurosurgical microrobot (Robeauté) designed for navigation along 3D nonlinear curves, with accuracy confirmed by CBCT imaging in phantom tests. Our implantation methods accurately placed scaffolds in the intended locations and orientations, aligning with CST fibers in both phantom models and NHP brains. The deviation angle between the scaffold and CST fibers was 17.83° (SD 6.71°, n=3). The scaffolds were precisely positioned within the IC, validating our approach. Our robot-guided method accurately steered them to their intended position, demonstrating minimal errors in targeted white matter regions. The methods described are poised for clinical translation, potentially extending the applicability of scaffold technology for improving motor function post-stroke. We are preparing NHPs for behavioral and upper limb motor assessments to evaluate the impact of scaffold implantation on axon regeneration, recovery, and performance. This research aims to enhance our understanding of ischemic stroke and develop innovative therapies to restore motor function in patients.

Abstract TMP61: Ixodes ricinus-Contact Phase Inhibitor (Ir-CPI) reduces neutrophil-mediated injury and promotes recovery following intracerebral hemorrhage in a mouse model

Introduction: Secondary brain injury following intracerebral hemorrhage (ICH) is largely driven by neuroinflammation, which is exacerbated by neutrophil infiltration and their release of neutrophil extracellular traps (NETs). This process disrupts the blood-brain barrier and increases neuronal death. The present study investigates the efficacy of Ir-CPI, an inhibitor of neutrophil-mediated thromboinflammation, in reducing neutrophil-driven damage and promoting functional recovery post-ICH. Methods: ICH was induced in mice via bacterial collagenase injection into the right striatum. Mice were then treated with either PBS, Ir-CPI or enoxaparin. Treatments were administered intravenously immediately after stroke. Cerebral lesion and hemorrhage volumes were assessed up to 14 days by MRI. Neutrophil infiltration, NET release, and neuronal degeneration were evaluated histologically. Functional recovery was assessed using the Corner test and the Bederson’s scale. Results: After ICH induction, Ir-CPI did not increase cerebral lesion or hemorrhage volumes compared to PBS. Ir-CPI resulted in lower hemorrhage volumes than the enoxaparin group on Day 1. By Day 14, the volume of hemorrhage in the Ir-CPI group was significantly reduced in comparison to Day 1. Additionally, Ir-CPI decreased neutrophil infiltration and NETs release in the hemorrhagic area, along with a reduction in neuronal degeneration. In contrast, enoxaparin had no significant impact on reducing neutrophils or neuronal damage. Functional recovery was superior in the Ir-CPI group, with the Corner test showing a significant improvement from Day 1 to Day 5 compared to the PBS and enoxaparin groups. By Day 14, the Ir-CPI group's performance did not significantly differ from baseline, indicating enhanced long-term motor function and spatial awareness. The Bederson’s score also demonstrated a significant improvement in the Ir-CPI group, with lower scores between Day 1 and Day 5 compared to the other groups, thereby highlighting Ir-CPI's effectiveness in reducing neurological deficits. Conclusions: Ir-CPI is a promising therapeutic agent for patients suffering from ICH, exhibiting both safety and efficacy in reducing neutrophil-driven brain damage and enhancing functional recovery. These findings indicate that Ir-CPI may be beneficial in mitigating secondary brain injury and improving patient outcomes following ICH. The potential of Ir-CPI is currently being evaluated in the Phase IIa BIRCH trial (NCT05970224).

Acute kidney injury in critically ill COVID-19 patients in a tertiary hospital: short and long-term kidney and patient outcomes.

Acute kidney injury (AKI) in the setting of COVID-19 is associated with worse clinical and renal outcomes, with limited long-term data. To evaluate critically ill COVID-19 patients with AKI that required nephrologist consultation (NC-AKI) in a tertiary hospital. Prospective single-center cohort of critically ill COVID-19 adult patients with NC-AKI from May 1st, 2020, to April 30th, 2021. Kidney replacement therapy (KRT), recovery of kidney function, and death at 90-day and 1-year follow-up were evaluated. 360 patients were included, 60.6% were male, median age was 66.0 (57.0-72.0) years, 38.1% had diabetes, and 68.6% had hypertension. AKI stages 1, 2, and 3 were detected in 3.6%, 5.6%, and 90.8% of patients, respectively. KRT was indicated in 90% of patients. At the 90-day follow-up, 88.1% of patients died and 10.0% had recovered kidney function. Female gender (p = 0.047), older age (p = 0.047), AKI stage 3 (p = 0.005), requirement of KRT (p < 0.0001), mechanical ventilation (p < 0.0001), and superimposed bacterial infection (p < 0.0001) were significantly associated death within 90 days. At 1 year, mortality was 89.3%. Amongst surviving patients, 72% recovered kidney function, although with significantly lower eGFR compared to baseline (85.5 ± 23.6 vs. 65.9 ± 24.8 mL/min, p = 0.003). Critically ill COVID-19 patients with NC-AKI presented a high frequency of AKI stage 3 and KRT requirement, with a high 90-day mortality. Surviving patients had high rates of recovery of kidney function, with a lower eGFR at one-year follow-up compared to baseline.

Examining the Efficacy, Safety, and Future Prospects of Tirofiban in Managing Myocardial Infarction among Diabetic Patients.

Myocardial infarction (MI) is a leading cause of death worldwide, particularly in patients with diabetes mellitus (DM). Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, has shown promise as adjunctive therapy in the emergency management of MI in diabetic patients. However, a comprehensive understanding of its use, efficacy, safety, and limitations in this patient population is necessary to optimize treatment strategies and improve patient outcomes. This review article utilized a systematic approach to gather relevant research articles, clinical trials, and studies on the use of tirofiban in the therapy of MI in diabetic patients. Databases, such as PubMed and Google Scholar, were extensively searched using specific keywords related to tirofiban, MI, DM, STEMI, and antiplatelet therapy. The collected data were carefully examined, summarized, and analyzed to provide an extensive overview of using tirofiban in the management of MI in diabetic individuals. The analysis of the gathered literature revealed that tirofiban has demonstrated efficacy in improving clinical outcomes, reducing myocardial ischemia-reperfusion injury, and promoting early recovery of heart function in diabetic patients with MI undergoing percutaneous coronary intervention. The fast on- and off-rate and dose-dependent effect of the drug on platelet aggregation contribute to its effectiveness. However, caution should be exercised due to the potential risk of tirofiban-associated thrombocytopenia. Clinical trials and studies have provided evidence- based dosing guidelines, enabling the safe and effective administration of tirofiban in this patient population. Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, shows promise as adjunctive therapy in the emergency management of MI in diabetic patients. It has demonstrated efficacy in improving clinical outcomes, reducing myocardial ischemia-reperfusion injury, and promoting early recovery of heart function. However, healthcare providers should be cautious regarding the potential risk of tirofiban-associated thrombocytopenia. Further research is needed to optimize dosing guidelines, evaluate long-term safety, and fully understand the benefits and limitations of tirofiban in this patient population. The comprehensive insights provided in this review aim to enhance treatment strategies and improve patient outcomes in the emergency management of MI in diabetic individuals.