Functional Recovery Research Articles

Abstract TP107: Beyond Repair: Resurrecting Neurons through Stem Cell Therapy

Introduction: The intricate network of neurons orchestrates essential functions within the human body. Ischemic stroke, a major neurological disorder, challenges this network, leading to irreversible damage and functional impairment due to the limited regenerative capacity of neuronal tissues. Stem cells, with their unique properties of self-renewal and differentiation into various cell types, present a promising therapeutic avenue. This systematic review evaluates the efficacy and safety of stem cell therapies in treating ischemic stroke, aiming to restore neuronal structure and function. Objective: Our goal is to provide insights into the therapeutic potential of stem cell interventions for ischemic stroke, specifically their impact on clinical outcomes, functional recovery, and quality of life. This review synthesizes evidence from randomized clinical trials conducted between 2015 and 2024. Methods: A comprehensive search of databases such as PubMed, MEDLINE, and Cochrane Library identified relevant randomized clinical trials involving stem cell therapy for ischemic stroke. Results: Current data shows that various types of stem cell therapy are safe for treating neurological diseases, particularly ischemic stroke. While these therapies have enhanced motor recovery and neuroplasticity, their effectiveness in reducing scar size remains to be conclusively demonstrated. Notable improvements in patient outcomes include significant enhancements in the Modified Rankin Scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS). Additionally, imaging studies have shown increased neurogenesis and enhanced integrity of the corticospinal tract in the peri-infarct area. Conclusion: The review highlights a remarkable finding: a single administration of stem cells can yield measurable clinical improvements lasting at least 12 months post-treatment. This long-term effect is unprecedented among non-device or non-acute treatments for ischemic stroke, challenging current therapeutic approaches like thrombolysis. This systematic review underscores the transformative potential of stem cell therapy in addressing the challenges of ischemic stroke. Despite significant advancements, further research is essential to fully understand the mechanisms, optimize treatments, and fully harness the regenerative capabilities of stem cells, paving the way for innovative treatments that offer renewed hope for stroke patients.

C16 peptide and angiopoietin-1 alleviate the side effects of glucocorticoids in a rat multiple sclerosis model.

Natural glucocorticoids (GCs) have been widely used to treat acute multiple sclerosis (MS) attacks. However, they also cause significant side effects related to immunosuppression. Our previous study found that C16 peptide combined with angiopoietin-1 (Ang-1) inhibited inflammatory cell infiltration and protected blood vessels in animal models of inflammatory neurodegenerative diseases. An acute experimental autoimmune encephalomyelitis model was established in Lewis rats to explore the effects of these drugs on MS. One hundred rats were equally and randomly assigned into five groups: normal control, vehicle, low-dose methylprednisolone (MP), high-dose MP, and C16+Ang-1 (C+A). Histological examinations, behavioral tests, and high-throughput 16S rRNA gene sequencing were conducted to determine inflammation levels in the central nervous system, neuronal survival, functional recovery and gut microbiota. The results illustrated that C+A exerted a neuroprotective effect in MS rats, with fewer side effects observed in the C+A group than in the high-dose MP group. The abundance of Campylobacter was increased in vehicle-treated rats, indicating an imbalance of the gut microbiota after MS. The abundance of probiotic Lactobacillus plantarum was increased in the C+A group. Low-dose MP failed to reverse the gut microbiota imbalance, whereas both the C+A and high-dose MP groups exhibited gut microbiota profiles more similar to those of the normal controls, with C+A displaying superior efficacy. C16 plus Ang-1 might serve as a complement to GCs for the treatment of MS. Changes in the abundance of Campylobacter and L. plantarum suggest their essential roles in the pathogenesis of MS.

VNS facilitates the neurological function recovery after ischemia/reperfusion injury by regulating the A1/A2 polarization of astrocytes through the NMU-NMUR2 pathway.

Stroke is the second leading cause of death worldwide. Although conventional treatments such as thrombolysis and mechanical thrombectomy are effective, their narrow therapeutic window limits long-term neurological recovery. Previous studies have shown that vagus nerve stimulation (VNS) enhances neurological recovery after ischemia/reperfusion (I/R) injury, and neuromedin U (NMU) has neuroprotective effects. This study used a mouse model of cerebral I/R injury to investigate the potential mechanisms of NMU in VNS-mediated neurological improvement. The study consisted of two parts: first, assessing the dynamic expression of NMU and NMUR2, which peaked on day 14 post-I/R. NMUR2 was primarily localized in astrocytes, suggesting that the NMU-NMUR2 signaling pathway plays an important role in astrocyte regulation. Next, interventions with VNS, NMU, and R-PSOP+VNS were conducted to evaluate the role of this pathway in VNS-mediated recovery. The results showed that VNS significantly upregulated NMU and NMUR2 expression, which was blocked by the NMUR2 antagonist R-PSOP. VNS and NMU treatment increased the proportion of A2 astrocytes, reduced A1 astrocytes, and enhanced the expression of VEGF and BDNF, all of which were also blocked by R-PSOP. These findings indicate that the "VNS-NMU-NMUR2-astrocyte A1/A2 polarization-VEGF/BDNF pathway" plays a crucial role in promoting neurovascular remodeling, axonal and dendritic regeneration, and synaptic plasticity, thereby contributing to functional recovery.

Abstract TP95: Concurrent Recovery of Language and Motor Function during Inpatient Stroke Rehabilitation

Abstract TP95: Concurrent Recovery of Language and Motor Function during Inpatient Stroke Rehabilitation

Abstract TP116: Evaluation of the Clinical Efficacy of Rehabilitation Therapy Using the Complex Upper and Lower Limb Robot Gait Rehabilitation System (GTR-A) in Stroke Patient

Background and aims: Conventional approaches for stroke rehabilitation primarily involve static muscle strengthening exercises, weight bearing and shifting by therapists. Robot-assisted gait training facilitates the learning of reproducible symmetric gait patterns and reduces expenditure. The GTR-A (HUCASYSTEM, Korea), a robotic gait rehabilitation device for both upper and lower limbs, utilizes end-effector-based movement and provides training to enhance gait function. In this study, we aim to elucidate the clinical efficacy of rehabilitation therapy using GTR-A in subacute/chronic stroke patients. Methods: This study was a prospective, randomized, controlled clinical trial. There were 14 participants in total, with 7 in each of the experimental and control groups (table. 1). The gait abilities were evaluated using the berg balance scale (BBS), 6-minute walk test (6MWT) and cardiopulmonary exercise testing. Over period of 4 weeks, the experimental group underwent 10 sessions of robot-assisted rehabilitation for 30minutes/day, 3times/week in addition to conventional physical therapy for 30min/day, 5times/week. The control group received 10 sessions of only conventional physical therapy for 60minutes/day, 5times/week. Results: In the experimental group, significant improvements were observed in both BBS and 6MWT. However, there was no significant increase in maximal oxygen consumption. In contrast, the control group did not show significant functional improvements (table. 2). Conclusion: The combination of conventional rehabilitation therapy and robotic gait training using GTR-A showed superior outcomes in the recovery of gait function compared to conventional therapy alone.

Broad-spectrum downregulation of inflammatory cytokines by polydopamine nanoparticles to protect the injured spinal cord.

Acute neuroinflammation, which is notably characterized by a significant elevation in pro-inflammatory cytokines and chemokines, often rapidly develops following a traumatic spinal cord injury and exacerbates damage in the lesion area. This study addresses the limitations inherent in strategies that regulate only a single or a few cytokines, which are often insufficient to counteract the progression of secondary injuries. We explore the use of polydopamine nanoparticles as a broad-spectrum immunomodulator, capable of capturing by adsorption a wide range of cytokines and thereby effectively suppressing neuroinflammation. Leveraging their adhesive properties, these nanoparticles promptly reduce levels of various excessive cytokines, including IL-1α, IL-1β, IL-6, IL-10, IL-17A, IL-18, TNF-α, MCP-1, GRO/KC, M-CSF, MIP-3α, and IFN-γ, primarily through physical adsorption. This reduction in cytokine levels contributes to the subsequent inhibition of pro-inflammatory M1 microglia and A1 astrocyte activation, aiding in the recovery of motor functions in vivo. In summary, polydopamine nanoparticles represent a versatile and effective approach for modulating acute neuroinflammation in spinal cord injuries. By broadly down-regulating cytokines, polydopamine nanoparticles propose an innovative approach for treating spinal cord injuries. STATEMENT OF SIGNIFICANCE: The current study demonstrated the immunomodulatory potential of polydopamine nanoparticles in mitigating neuroinflammation following spinal cord injury. Both in vitro and in vivo analyses revealed significant downregulation of several key cytokines among a panel of 23 cytokines and chemokines. The potential underlying mechanisms governing these interactions were elucidated through comprehensive molecular dynamics simulations for the first time. Consequently, the downregulation of these cytokines and chemokines led to the inhibition of pro-inflammatory M1 microglia and A1 astrocyte activation in both in vitro and in vivo models. This inhibition protected neurons within the microenvironment, resulting in improved locomotor functions. Overall, this study underscores the prominent therapeutic efficacy of polydopamine nanoparticles in alleviating neuroinflammation, highlighting their potential as broad-spectrum regulators in intricate microenvironments.

Epicardial fat tissue, a hidden enemy against the early recovery of left ventricular systolic function after transcatheter aortic valve implantation.

Epicardial fat tissue (EFT) is an active organ that can affect cardiac function and structure through endocrine, paracrine, and proinflammatory mechanisms. We hypothesized that greater thickness of EFT may harm the recovery of left ventricular (LV) systolic function in patients with severe aortic stenosis (AS) and reduced LV ejection fraction (EF≤50%) undergoing transcatheter aortic valve implantation (TAVI). A sixty six patients with severe AS and 20% ≥ LVEF≤50% who underwent TAVI were included. Patients were categorized into two groups based on LV systolic function recovery 30days after TAVI defined by≥20% relative increase in LV Global longitudinal strain (GLS) from baseline. EFT was determined by ECG-gated contrast-enhanced multidetector computed tomography (MDCT). Forty-five patients (68.0%) showed LV systolic function recovery. EFT showed no significant correlation with the baseline LV-GLS but was associated with less likelihood of LV systolic function recovery (OR 0.7, 95% CI 0.50 - 0.98, P = 0.04). In the multivariate analysis, higher LVMI (OR 1.05, 95% CI 1.00-1.10, P = 0.02), lower LV-GLS (OR 0.55, 95% CI 0.40-0.82, P = 0.002), and thinner EFT (OR 0.38, 95% CI 0.20-0.73, P = 0.003) were independently associated with LV systolic function recovery after TAVI. EFT extent is associated with LV systolic function recovery in AS patients with impaired LVEF undergoing TAVI and therefore may help in risk stratification and management of these patients.

Effect of electroacupuncture on vascular remodeling in rats with cerebral ischemia by regulating irisin based on VEGF/Akt/eNOS signaling pathway.

This study aimed to explore the cumulative effects and expression patterns of electroacupuncture (EA) on irisin secretion, observe the effects of EA on the recovery of neurobehavioral function and vascular remodeling after cerebral ischemia, and elucidate the mechanism by which EA promotes vascular remodeling by regulating irisin expression. A rat model of left middle cerebral artery occlusion (MCAO) was prepared, and EA was performed. Tissue distribution and expression of irisin were determined by immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Type III fibronectin domain protein 5-silenced adeno-associated virus (rAAV-shFNDC5) was injected into the lateral ventricle as a control. Neurobehavioral function was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and behavioral experiments, while vascular remodeling was evaluated using laser speckle blood flow imaging, and the expressions of irisin and vascular remodeling-related factors were measured by ELISA and Western blotting. The number of FNDC5-positive neurons, fluorescence intensity, and irisin expression reached their maximum increase after 7 days of EA treatment. In addition, the EA group exhibited a significant reduction in cerebral infarct volume and impairment of neurobehavioral function, an increase in cerebral blood flow and microvascular diameter on the ischemic side, and significantly higher expression levels of FNDC5, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS). However, rAAV-shFNDC5 significantly weakened the therapeutic effects of EA. EA upregulated irisin expression, reaching a peak after 7 days of EA and then stabilizing. EA facilitated vascular remodeling after cerebral ischemia, and this might be associated with the activation of the irisin-mediated VEGF/Akt/eNOS signaling pathway.

Cumulative experience meets modern science: Remarkable effects of TongXieYaoFang formula on facilitating intestinal mucosal healing and secretory function.

TongXieYaoFang (TXYF), a classical formula used in Traditional Chinese Medicine, is renowned for its efficacy in treating chronic abdominal pain and diarrhoea. Modern research suggests that fundamental relief from these symptoms depends on complete intestinal mucosal healing, which normalises gut secretory functions. Consensus between traditional and modern medical theories indicates that TXYF is particularly suitable for treating the remission phase of ulcerative colitis (UC). Unfortunately, its potential in the remission phase has not received sufficient attention, and its use has been largely limited to a supportive role during the acute phase. This study aimed to elucidate the efficacy of TXYF in promoting intestinal mucosal healing and enhancing gut secretory function during the non-acute damage phase, as well as to identify the underlying mechanisms contributing to its effects. A mouse model of dextran sulphate sodium salt (DSS)-induced colitis was optimised to specifically evaluate the effects of TXYF on mucosal healing during the repair phase. The effects of TXYF on murine colon function were assessed by measuring faecal pellet count and water content, and further evaluated through immunohistochemical analyses. The underlying mechanisms of action of TXYF were elucidated using mouse intestinal organoid cultures, intestinal stem cell (ISCs) transplantation, immunofluorescence, and western blotting. Active components of TXYF were identified via LC-MS/MS analysis and integrated with network pharmacology for bioinformatics assessment. TXYF significantly promoted mucosal healing, as reflected by reduced disease activity scores, increased colon length, enhanced epithelial proliferation, and decreased histological damage. Furthermore, TXYF enhanced the recovery of critical intestinal functions, including barrier integrity, absorption, secretion, and motility. Notably, the improvement in the secretory function was particularly pronounced. Mechanistically, these therapeutic effects were mediated by the upregulation of the Atonal homolog 1/SAM pointed domain containing ETS transcription factor/Mucin 2 pathway, which facilitates the differentiation and maturation of ISCs into goblet cells, thereby contributing to both mucosal repair and enhanced secretory function. Our study demonstrated that TXYF significantly promotes intestinal mucosal healing and enhances secretory function. These findings offer a solid basis for exploring the potential applications of TXYF in UC management during the remission phase.

Prospective analysis on possible changes of cognitive functions in children on follow-up for brain tumor.

This study was aimed at evaluating cognitive functioning in children with brain tumors before and after surgery and at the end of all adjunctive treatments. All newly diagnosed children with primary brain tumor were prospectively assessed. Neurocognitive evaluations were performed before surgery (T0), within 7-10days from surgery (T1) and 18-24months after the end of all treatments (T2). Language, memory, attention, executive functions, visual-constructional, and sensorimotor skills were evaluated at T0, T1, and T2, whereas intelligent quotient (IQ) was explored at T0 and T2. Twenty-five patients (M:F = 15:10, mean age 10.9 ± 3.4years) were enrolled between January 2019 and December 2022. At baseline, patients showed major deficits in narrative memory (6.6 ± 3.7, p < 0.001) and visuo-spatial memory (copy design tasks: general 6.8 ± 3.9, p < 0.001; specific 6.2 ± 3.3, p < 0.001; and motor 5.2 ± 3.2, p < 0.001). In the post-surgery phase (T1), significant deficits remained in narrative memory (6.2 ± 3.3, p < 0.001) and visual-motor coordination (copy design tasks: specific 5.9 ± 3.0, p < 0.001; motor 4.8 ± 4.3 p < 0.001), while attention and visual-constructional abilities significantly improved (p = 0.04 and p = 0.001 respectively). Nine out of 25 patients (36%) reached the T2 evaluation: persistency of deficits in the area of visuo-spatial processing and a possible decline in median IQ values in comparison to T0 evaluation (93 vs 100, p = 0.05) were shown. Children with brain tumors may present several neuropsychological impairments since diagnosis. Surgery may have a positive impact in relation to the recovery of some cognitive functions. However, cognitive decline may worsen over time. Baseline and periodic neurocognitive evaluations should be encouraged to indicate targets for cognitive monitoring, to early detect functional difficulties.

Punicalagin inhibits neuron ferroptosis and secondary neuroinflammation to promote spinal cord injury recovery.

Spinal cord injury (SCI) represents a severe type of central nervous system damage, with no effective treatment currently available, partly due to neuronal ferroptosis and subsequent neuroinflammation. Punicalagin, an anti-inflammatory compound extracted from pomegranate peel, has exhibited therapeutic potential for inflammatory diseases. In this study, we present evidence that punicalagin facilitates the recovery of neurological function following SCI by mitigating neuronal ferroptosis. Mechanistically, this effect involves the upregulation of nuclear factor E2-related factor 2 (Nrf2) and the activation of the Nrf2- Solute Carrier Family 7 Member 11 (SLC7A11)- Glutathione Peroxidase 4 (GPX4) signaling pathway. Furthermore, punicalagin aids in the resolution of secondary neuroinflammation by modulating the M1/M2 polarization of microglia, thereby promoting SCI recovery. Collectively, these findings suggest that punicalagin enhances functional recovery after SCI by inhibiting neuronal ferroptosis and reducing microglial M1 polarization. Consequently, punicalagin may represent a promising therapeutic agent for the treatment of spinal cord injury.

Proportional recovery in mice with cortical stroke.

The proportional Recovery Rule (PRR) has been frequently used to predict recovery of lost motor function in acute stroke patients. However, it still needs to be explored whether the same concept applies to preclinical, i.e. animal models of stroke recovery. To address this question, we investigated behavioral data from 125 adult male C57Bl/6 J mice with photothrombotic strokes in the sensorimotor cortex. Lesion size and location were determined in the first week using in vivo T2-weighted MRI. Motor recovery was evaluated repeatedly over four weeks using the cylinder, grid walk, and rotating beam test. Recovery trajectories were analyzed using a newly formulated Mouse Recovery Rule (MRR), comparing it against the traditional PRR. Initial findings indicated variable recovery patterns, which were separated using a stepwise linear regression approach resulting in two clusters: 47 % PRR and 53 % MRR. No significant correlation was found between recovery patterns and lesion size or location, suggesting that other biological factors drive individual differences in recovery. Of note, in the MRR cluster, animals recovered to 90 % of their initial behavioral state within the first four weeks post-stroke, which is higher than the 70 % recovery usually reported in human PRR studies. This study demonstrates the complexity of translating the PRR to stroke recovery models in mice and underscores the need for species-specific recovery models. Our findings have implications for designing and interpreting therapeutic strategies for stroke recovery in preclinical settings, with the potential to improve the predictive accuracy of stroke recovery assessments.

Antibiotic-Induced dysbiosis of the ocular microbiome affects corneal circadian rhythmic activity in mice.

The ocular surface microbiota plays a critical role in maintaining corneal homeostasis, but its disruption and subsequent effects on corneal functions remain poorly understood. This study investigates how antibiotic-induced microbial depletion affects the corneal circadian transcriptome in C57BL/6J mice. Dysbiosis was induced using a topical antibiotic cocktail, and RNA sequencing was employed to analyze gene expression across eight time points over 24 h. Antibiotic treatment disrupted corneal circadian rhythms, eliminating rhythmicity in 1,812 genes and introducing rhythmicity in 1,928 previously arrhythmic genes. Furthermore, epithelial adhesion was impaired, inflammation was elevated, and neural sensitivity was reduced. More than 50 % of ocular microbial genera exhibited daily oscillations, with six genera showing significant correlations with corneal rhythmic transcripts. Additionally, the administration of TLR agonists restored circadian gene expression patterns, with partial recovery of corneal barrier function and immune homeostasis, further highlighting the potential of microbiota-targeted therapies in treating ocular surface disorders. These findings underscore the critical role of the ocular microbiota in regulating corneal health and suggest that restoring microbial balance via TLR activation may offer new therapeutic avenues for eye diseases.

Effect of Whey Protein Supplementation on Postoperative Outcomes After Gynecological Cancer Surgery: A Randomized Controlled Trial.

Whey protein's biochemical properties make it an ideal nutritional supplement for patients with cancer, especially in perioperative care. Thus, the present study aims to assess the efficacy of whey protein supplementation (WPS) compared to standard care in enhancing postoperative outcomes for patients undergoing comprehensive surgical staging for gynecological cancer. In an open-label, randomized controlled trial conducted at Rajavithi Hospital between November 28, 2023 and July 8, 2024, 61 patients scheduled for comprehensive surgical staging were enrolled. Participants were randomized in a 1:1 ratio to either the WPS group (n = 30) or the control group (n = 31). The WPS group received isolated whey protein powder (20 g of protein per serving), administered at 6 pm before surgery and 6 am on the first postoperative day. The control group received standard postoperative care. The primary endpoint was the length of hospital stay (LOHS), with secondary outcomes including gastrointestinal function recovery, postoperative analgesic use, complications, and potential WPS-related adverse events such as transaminitis, acute kidney injury, and electrolyte imbalances. The WPS group had a significantly shorter LOHS than the control group (79.0 ± 6.7 vs. 93.3 ± 28.4 h, P = 0.021). Additionally, the WPS group demonstrated significant improvements in gastrointestinal function, with shorter times to first flatus (P < 0.001), first defecation (P = 0.013), and first ambulation (P = 0.043). No significant differences were observed between the groups regarding postoperative analgesic use or complications, including fever, nausea/vomiting, wound infection, and readmission (P > 0.05). Furthermore, no WPS-related adverse events were reported. The use of WPS in the perioperative operative management of gynecological cancer surgery yields promising results by significantly reducing the LOHS and accelerating the recovery of gastrointestinal function while maintaining a favorable safety profile.

Nanosphere hydrogel-mediated delivery of miR-34a-5p improves achilles tendon function in rat model.

Restoring motor function and preventing re-rupture and adhesion during Achilles tendon healing remain significant clinical challenges. Increasing evidence suggests that miRNA plays a crucial role in tendon healing and regeneration. The previously designed nanosphere hydrogel sustained-release system enables targeted, controlled release of drugs. In this study, we developed a version of this system loaded with miR-34a-5p for localized delivery to an acute Achilles tendon injury model. The results of the Achilles functional index and Catwalk behavior analysis in rats indicated that miR-34a-5p mimic promoted early recovery of motor function following Achilles tendon injury. Although gross observation suggested that the miR-34a-5p mimic group had a minimal inhibitory effect on the adhesion of Achilles tendon tissue, tension analysis demonstrated that it effectively increased the maximum tensile strength. Additionally, in vitro experiments showed that miR-34a-5p mimic could increase tendon cells proliferation and improve tendon cells viability. This study confirmed the efficacy of the miR-34a-5p nanosphere hydrogel sustained-release system in tendon injury repair, presenting it as a promising treatment strategy for clinical practice.

Dynamic in vivo monitoring of granum structural changes of Ctenanthe setosa (Roscoe) Eichler during drought stress and subsequent recovery.

Investigating the effects of drought stress and subsequent recovery on the structure and function of chloroplasts is essential to understanding how plants adapt to environmental stressors. We investigated Ctenanthe setosa (Roscoe) Eichler, an ornamental plant that can tolerate prolonged drought periods (40 and 49 days of water withdrawal). Conventional biochemical, biophysical, physiological and (ultra)structural methods combined for the first time in a higher plant with in vivo small-angle neutron scattering (SANS) were used to characterize the alterations induced by drought stress and subsequent recovery. Upon drought stress, no significant changes occurred in the chloroplast ultrastructure, chlorophyll content, 77K fluorescence emission spectra and maximal quantum efficiency of PSII (Qy dark), but the actual quantum efficiency of PSII (Qy light) decreased, the amounts of PSI-LHCII complexes and PSII monomers declined, and that of PSII supercomplexes increased. Thickness of the leaf and of the adaxial hypodermis, chloroplast length and granum repeat distance (RD) values decreased upon drought stress, as shown by light microscopy and SANS, respectively. Because of the very slight (nm-range) changes in RD values, the large biological variability (significant differences in RD values among the leaves and studied leaf regions) and the invasive sampling required for this method, transmission electron microscopy (TEM) hardly showed significant differences. On the other side, in situ SANS analyses provided a unique insight in vivo into the fast structural recovery of the granum structure of drought-stressed leaves, which happened already 18 h after re-watering, while functional and biochemical recovery took place on a longer time scale.

Intensified dietetic care during and up to three months after hospital admission in older patients at risk of malnutrition, a randomised controlled trial.

Inadequate protein intake is associated with poor physical functioning and suboptimal recovery in hospitalised older adults. Despite standard dietetic care, dietary protein intakes falls well below the recommended levels. To address this problem, we developed an intensified trans-sectorial dietetic intervention that targets hospitalised older adults. This study aims to evaluate its impact on physical functioning and dietary protein intake during and post hospitalisation. This multicentre individually randomised controlled trial was conducted in five hospitals from January 2021 until December 2022. Hospitalised older adults, aged ≥55 years and at risk of malnutrition were randomised to receive regular care (CON) or intensive dietetic intervention (INT). The intervention consisted of personalized, intensive care, including trans-sectorial guidance by trained dietitians, increased consultations, and supportive materials focused on protein intake. Additionally, the intervention emphasized engagement in dietary behaviour and physical activity during hospitalisation and continued for three months post-discharge. The primary outcome was change in physical functioning measured by the Short Physical Performance Battery (SPPB) from admission to three months post-discharge, analysed with linear mixed models for repeated measures. Secondary outcomes included protein intake, body composition, muscle strength, physical activity, activities of daily living, fear of falling, pain, fatigue, appetite and quality of life. A total of 76 hospitalised older adults were included in the study of which 38 were in CON and 38 received INT. The overall drop-out was 30% (CON 26%; INT 34%). The participants had a median age 73y (Inter Quartile Range: 62-78y) with 50% females. Overall, Physical functioning improved from 6 points (IQR: 1-9 points) at baseline to 9 points (IQR: 7-11) at three months post-discharge (p<0.0001). Likewise, protein intake increased from 0.8g/kg bodyweight (IQR: 0.6-1.0) to 1.0g/kg bodyweight (IQR: 0.8-1.2) (p<0.0001). There were no significant differences between intervention and control group. All secondary outcomes improved over time, except for fear of falling, leg extension strength, and body composition, with no significant differences between intervention and control group. Hospitalised older patients improved their physical functioning and protein intake after three months post-discharge, although the majority not to recommended levels. No effects of the intensive dietetic treatment could be detected due to low intervention adherence and a small sample size. Future research should be conducted with an intervention consisting of a strong combination of nutritional support and exercise with a successful implementation and a flexible study design catered to the needs of the older patient. Landelijk Trial Register (NL8041; NL72069.029.19) www.onderzoekmetmensen.nl; registered 2019-09-23; covering all WHO Trial Registration Data Set items.

Assessment of photoreceptor recovery and visual function utilizing adaptive optics and microperimetry in patients with surgically closed macular holes.

This study investigated the association between photoreceptor structural restoration and visual function outcomes in patients undergoing surgery for closed macular holes (MHs). Using adaptive optics scanning laser ophthalmoscopy (AOSLO) and microperimetry, we aimed to provide a more detailed understanding of photoreceptor recovery and visual improvement in closed MHs. We conducted a retrospective observational study of 31 eyes of 28 patients who underwent vitrectomy with internal limiting membrane (ILM) peeling to treat idiopathic MHs. Visual and structural outcomes were monitored 3 months to 2 years postoperatively: best-corrected visual acuity (BCVA), MH diameter and duration, optical coherence tomography (OCT) images, 4° retinal mean sensitivity (RMS), fixation rates, 68.2 % BCEA (binary contour ellipse area) of microperimetry, and cone density as measured by AOSLO. Based on the OCT findings, the patients were categorized into two groups: type 1 (closed MH with no neurosensory defect at the fovea) and type 2 (closed MH with a foveal neurosensory defect). The analysis revealed that type 1 closures resulted in significantly better photoreceptor recovery, with cone cells migrating toward the fovea and forming dense islets, consistent with the integrity of the inner segment/outer segment layer on OCT. These patients also had better postoperative BCVA and higher RMS rather than fixation improvement, aligning with the improved cone density. In contrast, type 2 closures exhibited sparse cone distribution and a prevalence of large, high-density cells, possibly indicating glial cell proliferation and exposed retinal pigment epithelium (RPE). MH size, rather than duration or preoperative BCVA, was a key determinant of type 1 closure outcomes. AOSLO is a valuable tool for evaluating microstructural healing in MHs and reveals that type 1 closure, characterized by cone migration, leads to greater neuroretinal repair and improved BCVA and retinal sensitivity. Meanwhile, type 2 closures, marked by less photoreceptor recovery and higher glial proliferation, correspond to poorer visual function outcomes. This study highlights the role of photoreceptor density and migration in achieving optimal visual function post-surgery for MH closure.

Abstract TP127: Isolation and Stroke: A Retrospective Analysis of Outcomes Amidst Solitude

Introduction: Stroke is the leading cause of long-term disability and fifth leading cause of death in the United States. Social isolation (SI) and loneliness are known risk factors for stroke and may be linked to worse functional outcomes. Previous animal studies have demonstrated enhanced outcomes associated with socialization. The impact of SI following stroke may be clinically relevant for therapeutic intervention. Hypothesis: Stroke patients experiencing social isolation will exhibit worse outcomes compared to those with social support networks. Aim: This retrospective analysis aims to compare stroke outcomes during the COVID-19 visitation restrictions with outcomes during the preceding years when visitation was permitted. Methods: Data were collected from the Patient Cohort Explorer, a de-identified database within our institution’s Research Data Warehouse. Patients were divided into two groups based on date: the isolation group and the control group. The control group included patients admitted from December 1, 2018, to January 1, 2019, during normal visitation policies, while the isolation group comprised patients admitted from December 1, 2020, to January 1, 2021, during visitation restrictions. Two-proportion Z-tests were conducted to analyze differences in demographic data, and two-sample T-tests were used to assess outcomes, including length of stay and discharge disposition. Results: A total of 725 unique patients met the inclusion criteria, with demographic characteristics such as sex and race well-matched between the isolated and control groups, except for a notable age difference (p-value .011). Significant differences in mortality rates were observed, with the control group showing a higher likelihood of returning home (p-value &lt; .001) and the isolation group having a greater proportion of deaths (p-value .003). Additionally, there was a statistically significant difference in hospital stay length, with the control group able to discharge earlier (p-value .001). Conclusion: Social isolation can result in longer hospital stays, poorer outcomes, and increased mortality for patients with acute infarcts. Since the data was gathered during the COVID-19 pandemic, it's challenging to eliminate the virus as a confounding factor in these outcomes. However, the findings suggest that patients lacking social support may face worse functional recovery and different recovery trajectories compared to those with support.

Stem Cell–Based Therapies via Different Administration Route for Stroke: A Meta-analysis of Comparative Studies

Stroke, a neurological condition from compromised cerebral blood perfusion, remains a major global cause of mortality and disability. Conventional therapies like tissue plasminogen activator are limited by narrow therapeutic windows and potential adverse effects, highlighting the urgency for novel treatments. Stem cell–based therapies, with their neuroprotective and regenerative properties, present a promising yet highly diverse alternative. By conducting literature search and data extraction from the PubMed, Embase, and Cochrane databases, this meta-analysis assessed the clinical efficacy and safety of stem cell–based therapies administered via intravenous (IV) and non-IV routes in 17 studies with stroke patients. Primary outcomes included the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS), while secondary outcomes included mortality and adverse events. Results demonstrated significant improvements in NIHSS, BI, and mRS scores, particularly in non-IV groups within 6- and 12-month follow-ups, suggesting delayed but enhanced therapeutic efficacy. Mortality was reduced in both IV and non-IV groups, indicating treatment safety. Adverse events, categorized into neurological and systemic complications, showed no significant differences between intervention and control groups, further emphasizing the safety of stem cell therapies. Non-IV routes showed more long-term benefits, potentially due to enhanced cell delivery and integration. These findings demonstrate the potential of stem cell therapies to improve functional recovery and survival in stroke patients, regardless of administration route. However, the delayed response underscores the need for extended follow-up in clinical applications. Further research is required to standardize treatment protocols, optimize cell types and doses, and address patient-specific factors to integrate stem cell therapies into routine clinical practice.