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BACKGROUND: Clinical prediction models (CPM), such as the SCOAP-CERTAIN tool, can be utilized to enhance decision-making for lumbar spinal fusion surgery by providing quantitative estimates of outcomes, aiding surgeons in assessing potential benefits and risks for each individual patient. External validation is crucial in CPM to assess generalizability beyond the initial dataset. This ensures performance in diverse populations, reliability and real-world applicability of the results. Therefore, we externally validated the tool for predictability of improvement in oswestry disability index (ODI), back and leg pain (BP, LP). METHODS: Prospective and retrospective data from multicenter registry was obtained. As outcome measure minimum clinically important change was chosen for ODI with ≥ 15-point and ≥ 2-point reduction for numeric rating scales (NRS) for BP and LP 12 months after lumbar fusion for degenerative disease. We externally validate this tool by calculating discrimination and calibration metrics such as intercept, slope, Brier Score, expected/observed ratio, Hosmer-Lemeshow (HL), AUC, sensitivity and specificity. RESULTS: We included 1115 patients, average age 60.8 ± 12.5 years. For 12-month ODI, area-under-the-curve (AUC) was 0.70, the calibration intercept and slope were 1.01 and 0.84, respectively. For NRS BP, AUC was 0.72, with calibration intercept of 0.97 and slope of 0.87. For NRS LP, AUC was 0.70, with calibration intercept of 0.04 and slope of 0.72. Sensitivity ranged from 0.63 to 0.96, while specificity ranged from 0.15 to 0.68. Lack of fit was found for all three models based on HL testing. CONCLUSIONS: Utilizing data from a multinational registry, we externally validate the SCOAP-CERTAIN prediction tool. The model demonstrated fair discrimination and calibration of predicted probabilities, necessitating caution in applying it in clinical practice. We suggest that future CPMs focus on predicting longer-term prognosis for this patient population, emphasizing the significance of robust calibration and thorough reporting.
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Vértebras Lumbares , Fusión Vertebral , Humanos , Fusión Vertebral/métodos , Persona de Mediana Edad , Masculino , Femenino , Vértebras Lumbares/cirugía , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Evaluación de la Discapacidad , Degeneración del Disco Intervertebral/cirugía , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
Spinal cord injury (SCI) is a catastrophic condition that disrupts neurons within the spinal cord, leading to severe motor and sensory deficits. While current treatments can alleviate pain, they do not promote neural regeneration or functional recovery. Three-dimensional (3D) bioprinting offers promising solutions for SCI repair by enabling the creation of complex neural tissue constructs. This review provides a comprehensive overview of 3D bioprinting techniques, bioinks, and stem cell applications in SCI repair. Additionally, it highlights recent advancements in 3D bioprinted scaffolds, including the integration of conductive materials, the incorporation of bioactive molecules like neurotrophic factors, drugs, and exosomes, and the design of innovative structures such as multi-channel and axial scaffolds. These innovative strategies in 3D bioprinting can offer a comprehensive approach to optimizing the spinal cord microenvironment, advancing SCI repair. This review highlights a comprehensive understanding of the current state of 3D bioprinting in SCI repair, offering insights into future directions in the field of regenerative medicine.
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Bioimpresión , Impresión Tridimensional , Traumatismos de la Médula Espinal , Ingeniería de Tejidos , Andamios del Tejido , Traumatismos de la Médula Espinal/terapia , Humanos , Bioimpresión/métodos , Andamios del Tejido/química , Animales , Ingeniería de Tejidos/métodos , Medicina Regenerativa/métodos , Regeneración NerviosaRESUMEN
Damage to the central nervous system (CNS) often leads to irreversible neurological deficits, and there are currently few effective treatments available. However, recent advancements in regenerative medicine have identified CNS organoids as promising therapeutic options for addressing CNS injuries. These organoids, composed of various neurons and supporting cells, have shown potential for direct repair at injury sites. CNS organoids resemble the structure and function of actual brain tissue, which allows them to adapt and function well within the physiological environment when transplanted into injury sites. Research findings suggest that CNS organoids can replace damaged neurons, form new neural connections, and promote neural recovery. This review highlights the emerging benefits, evaluates preclinical transplantation outcomes, and explores future strategies for optimizing neuroregeneration using CNS organoids. With continued research and technological advancements, these organoids could provide new hope for patients suffering from neurological deficits.
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Sistema Nervioso Central , Organoides , Humanos , Organoides/citología , Organoides/trasplante , Regeneración Nerviosa , Animales , Neuronas/citología , Neuronas/fisiología , Medicina Regenerativa/métodosRESUMEN
Osteoporotic vertebral compression fractures (OVCFs) are the most prevalent fractures among patients with osteoporosis, leading to severe pain, deformities, and even death. This study explored the use of ectopic embryonic calvaria derived mesenchymal stem cells (EE-cMSCs), which are known for their superior differentiation and proliferation capabilities, as a potential treatment for bone regeneration in OVCFs. We evaluated the impact of EE-cMSCs on osteoclastogenesis in a RAW264.7 cell environment, which was induced by the receptor activator of nuclear factor kappa-beta ligand (RANKL), using cytochemical staining and quantitative real-time PCR. The osteogenic potential of EE-cMSCs was evaluated under various hydrogel conditions. An osteoporotic vertebral body bone defect model was established by inducing osteoporosis in rats through bilateral ovariectomy and creating defects in their coccygeal vertebral bodies. The effects of EE-cMSCs were examined using micro-computed tomography (µCT) and histology, including immunohistochemical analyses. In vitro, EE-cMSCs inhibited osteoclast differentiation and promoted osteogenesis in a 3D cell culture environment using fibrin hydrogel. Moreover, µCT and histological staining demonstrated increased new bone formation in the group treated with EE-cMSCs and fibrin. Immunostaining showed reduced osteoclast activity and bone resorption, alongside increased angiogenesis. Thus, EE-cMSCs can effectively promote bone regeneration and may represent a promising therapeutic approach for treating OVCFs.
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Diferenciación Celular , Modelos Animales de Enfermedad , Células Madre Mesenquimatosas , Osteogénesis , Osteoporosis , Cráneo , Animales , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Ratas , Cráneo/patología , Ratones , Osteoporosis/patología , Osteoporosis/metabolismo , Osteoporosis/terapia , Femenino , Células RAW 264.7 , Osteoclastos/metabolismo , Regeneración Ósea , Ratas Sprague-Dawley , Trasplante de Células Madre Mesenquimatosas/métodos , Cuerpo Vertebral/metabolismo , Microtomografía por Rayos X , Fracturas Osteoporóticas/terapia , Fracturas Osteoporóticas/metabolismo , Fracturas Osteoporóticas/patologíaRESUMEN
The therapeutic potential of Mesenchymal stem cells (MSCs) for the treatment of Intervertebral disc (IVD) degeneration can be enhanced by amplifying specific cytokines and proteins. This study aimed to investigate the therapeutic potential of tetracycline-off system-engineered tonsil-derived mesenchymal stem cells (ToMSC-Tetoff-TGFß1-IGF1-BMP7) for treating intervertebral disc (IVD) degeneration. ToMSCs were isolated from a tonsillectomy patient and genetically modified with four distinct plasmids via CRISPR/Cas9-mediated knock-in gene editing. Transgene expression was confirmed through immunofluorescence, western blots, and an enzyme-linked immunosorbent assay for transforming growth factor beta 1 (TGFß1) protein secretion, and the effect of MSC-TetOff-TGFß1-IGF1-BMP7 on disc injury was assessed in a rat model. The ToMSC-Tetoff-TGFß1-IGF1-BMP7 treatment exhibited superior therapeutic effects compared to ToMSC-TGFß1, and ToMSC-SDF1α implantation groups, stimulating the regeneration of nucleus pulposus (NP) cells crucial for IVD. The treatment showed potential to restore the structural integrity of the extracellular matrix (ECM) by upregulating key molecules such as aggrecan and type II collagen. It also exhibited anti-inflammatory properties and reduced pain-inducing neuropeptides. ToMSC-Tetoff-TGFß1-IGF1-BMP7 holds promise as a novel treatment for IVD degeneration. It appears to promote NP cell regeneration, restore ECM structure, suppress inflammation, and reduce pain. However, more research and clinical trials are required to confirm its therapeutic potential.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Células Madre Mesenquimatosas , Núcleo Pulposo , Humanos , Ratas , Animales , Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Tetraciclina/farmacología , Antibacterianos/farmacología , Células Madre Mesenquimatosas/metabolismoRESUMEN
Functionally enhanced mesenchymal stromal cells participate in the repair of intervertebral disc. This study aimed to assess the safety and tolerability of intradiscal administration of matrilin-3-primed adipose-derived stromal cell (ASC) spheroids with hyaluronic acid (HA) in patients with chronic discogenic low back pain (LBP). In this single-arm, open-label phase I clinical trial, eight patients with chronic discogenic LBP were observed over 6 months. Each patient underwent a one-time intradiscal injection of 1 mL of 6.0 × 106 cells/disc combined with HA under real-time fluoroscopic guidance. Safety and feasibility were gauged using Visual Analogue Scale (VAS) pain and Oswestry Disability Index (ODI) scores and magnetic resonance imaging. All participants remained in the trial, with no reported adverse events linked to the procedure or stem cells. A successful outcome-marked by a minimum 2-point improvement in the VAS pain score and a 10-point improvement in ODI score from the start were observed in six participants. Although the modified Pfirrmann grade remained consistent across all participants, radiological improvements were evident in four patients. Specifically, two patients exhibited reduced high-intensity zones while another two demonstrated decreased disc protrusion. In conclusion, the intradiscal application of matrilin-3-primed ASC spheroids with HA is a safe and feasible treatment option for chronic discogenic LBP.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Dolor de la Región Lumbar , Células Madre Mesenquimatosas , Humanos , Proteínas Matrilinas , Dolor de la Región Lumbar/terapia , Estudios de Factibilidad , Resultado del Tratamiento , Degeneración del Disco Intervertebral/tratamiento farmacológico , ObesidadRESUMEN
BACKGROUND: Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. METHODS: Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. RESULTS: Models were developed and integrated into a web-app ( https://neurosurgery.shinyapps.io/fuseml/ ) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59-0.74], back pain (0.72, 95%CI: 0.64-0.79), and leg pain (0.64, 95%CI: 0.54-0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. CONCLUSIONS: Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk-benefit estimation, truly impacting clinical practice in the era of "personalized medicine" necessitates more robust tools in this patient population.
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Fusión Vertebral , Dolor de Espalda/diagnóstico , Dolor de Espalda/etiología , Dolor de Espalda/cirugía , Femenino , Humanos , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Fusión Vertebral/métodos , Resultado del TratamientoRESUMEN
Synaptic cell adhesion molecules (SynCAMs) play an important role in the formation and maintenance of synapses and the regulation of synaptic plasticity. SynCAM3 is expressed in the synaptic cleft of the central nervous system (CNS) and is involved in the connection between axons and astrocytes. We hypothesized that SynCAM3 may be related to the astrocytic scar (glial scar, the most important factor of CNS injury treatment) through extracellular matrix (ECM) reconstitution. Thus, we investigated the influence of the selective removal of SynCAM3 on the outcomes of spinal cord injury (SCI). SynCAM3 knock-out (KO) mice were subjected to moderate compression injury of the lower thoracic spinal cord using wild-type (WT) (C57BL/6JJc1) mice as controls. Single-cell RNA sequencing analysis over time, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and immunohistochemistry (IHC) showed reduced scar formation in SynCAM3 KO mice compared to WT mice. SynCAM3 KO mice showed improved functional recovery from SCI by preventing the transformation of reactive astrocytes into scar-forming astrocytes, resulting in improved ECM reconstitution at four weeks after injury. Our findings suggest that SynCAM3 could be a novel therapeutic target for SCI.
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Gliosis , Traumatismos de la Médula Espinal , Animales , Astrocitos/metabolismo , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Cicatriz/patología , Gliosis/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/metabolismoRESUMEN
Neuropathic pain (NP) is a complex, debilitating, chronic pain state, heterogeneous in nature and caused by a lesion or disease affecting the somatosensory system. Its pathogenesis involves a wide range of molecular pathways. NP treatment is extremely challenging, due to its complex underlying disease mechanisms. Current pharmacological and nonpharmacological approaches can provide long-lasting pain relief to a limited percentage of patients and lack safe and effective treatment options. Therefore, scientists are focusing on the introduction of novel treatment approaches, such as stem cell therapy. A growing number of reports have highlighted the potential of stem cells for treating NP. In this review, we briefly introduce NP, current pharmacological and nonpharmacological treatments, and preclinical studies of stem cells to treat NP. In addition, we summarize stem cell mechanisms-including neuromodulation in treating NP. Literature searches were conducted using PubMed to provide an overview of the neuroprotective effects of stem cells with particular emphasis on recent translational research regarding stem cell-based treatment of NP, highlighting its potential as a novel therapeutic approach.
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Tratamiento Basado en Trasplante de Células y Tejidos , Inflamación/terapia , Neuralgia/terapia , Trasplante de Células Madre , Dolor Crónico/patología , Dolor Crónico/terapia , Humanos , Inflamación/patología , Neuralgia/patología , Manejo del Dolor , Células Madre/citologíaRESUMEN
Whitlockite (WH) is the second most abundant inorganic component of human bone, accounting for approximately 25% of bone tissue. This study investigated the role of WH in bone remodeling and formation in a mouse spinal fusion model. Specifically, morphology and composition analysis, tests of porosity and surface area, thermogravimetric analysis, an ion-release test, and a cell viability test were conducted to analyze the properties of bone substitutes. The MagOss group received WH, Group A received 100% beta-tricalcium phosphate (ß-TCP), Group B received 100% hydroxyapatite (HAp), Group C received 30% HAp/70% ß-TCP, and Group D received 60% HAp/40% ß-TCP (n = 10 each). All mice were sacrificed 6 weeks after implantation, and micro-CT, hematoxylin and eosin (HE) staining, and Masson trichome (MT) staining and immunohistochemistry were performed. The MagOss group showed more homogeneous and smaller grains, and nanopores (<500 nm) were found in only the MagOss group. On micro-CT, the MagOss group showed larger fusion mass and better graft incorporation into the decorticate mouse spine than other groups. In the in vivo experiment with HE staining, the MagOss group showed the highest new bone area (mean: decortication group, 9.50%; A, 15.08%; B, 15.70%; C, 14.76%; D, 14.70%; MagOss, 22.69%; p < 0.0001). In MT staining, the MagOss group demonstrated the highest new bone area (mean: decortication group, 15.62%; A, 21.41%; B, 22.86%; C, 23.07%; D, 22.47%; MagOss, 26.29%; p < 0.0001). In an immunohistochemical analysis for osteocalcin, osteopontin, and CD31, the MagOss group showed a higher positive area than other groups. WH showed comparable bone conductivity to HAp and ß-TCP and increased new bone formation. WH is likely to be used as an improved bone substitute with better bone conductivity than HAp and ß-TCP.
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Remodelación Ósea , Sustitutos de Huesos/uso terapéutico , Fosfatos de Calcio/uso terapéutico , Fusión Vertebral , Animales , Huesos/diagnóstico por imagen , Huesos/ultraestructura , Femenino , Ratones Endogámicos C57BL , Microtomografía por Rayos XRESUMEN
Recently, a bioactive glass ceramic (BGC) has been developed for use as intervertebral cages for anterior cervical discectomy and fusion (ACDF). However, the effectiveness and safety of BGC cages remain to be evaluated. We completed a retrospective comparison of the radiological and clinical outcomes of 36 patients (52 levels) who underwent ACDF with a BGC cage and 35 patients (54 levels) using allograft bone. The following variables were compared between the two groups: the visual analog (VAS) neck and arm pain score and the neck disability index (NDI), measured before surgery and 1 year after; the change in Cobb's angle, between the C2 and C7 vertebrae, the global sagittal angle, and disc height compared from before surgery to 1 year after; and the rate of spinal fusion and cage subsidence at 1 and 2 years after surgery. The VAS and NDI scores were not different between the two groups. Similarly, the spinal fusion rate was not different between the BGC and allograft bone group at 1 year (73% and 87%, respectively; p = 0.07) and 2 years (94% and 91%, respectively; p = 0.54) after surgery. However, the rate of cage subsidence was higher in the allograft bone (43%) than the BGC (19%) group (p = 0.03), as was the rate of instrument-related failure (p = 0.028), with a specifically higher incidence of implant fracture or failure in the allograft bone group (p = 0.025). Overall, our findings indicate that BGC cages provide a feasible and safe alternative to allograft bone for ACDF.
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Placas Óseas , Trasplante Óseo/métodos , Cerámica , Vértebras Cervicales/cirugía , Discectomía/métodos , Fusión Vertebral/métodos , Adulto , Anciano , Trasplante Óseo/efectos adversos , Vértebras Cervicales/diagnóstico por imagen , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor de Cuello/cirugía , Dimensión del Dolor , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Cortical bone trajectory (CBT) technique has a theoretical benefit for patients with osteoporosis, and leads to reduce screw loosening. However, there are no reports of complications and outcomes of CBT. METHODS: Consecutive patients (n = 34) with degenerative lumbar spines who underwent PLIF between December 2013 and December 2015 and were followed up for at least six months were analyzed in this study. Bone mineral density, fusion rate, cage subsidence, C-arm, screw loosening, screw violation, trajectory angle of the screw, Hounsfield unit and extent of facetectomy were examined. Outcome assessments were obtained in all patients preoperatively and postoperatively. RESULTS: There were 34 patients and 73 screw levels. After the surgery with cortical screw fixation and PLIF, patients had good clinical outcomes. However, ten of the 34 patients had problems with cortical screw fixation such as screw loosening or cage migration. In the patients with screw loosening, two underwent revision surgery due to cage migration, and one had an infection. Incorrect trajectory angles of the screw were significantly related with screw loosening. Low BMD and HU at screw fixation level were associated with screw loosening. Cage subsidence was statistically related with clinical outcomes. CONCLUSION: The cortical screw offers improved clinical outcomes since it requires minimal muscle dissection. However, we have experienced some early complications using this technique. To reduce complications such as screw loosening, an exact insertion angle of the screw and osteoporotic bone quality should be considered carefully.
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STUDY DESIGN: Heterogeneous data collection via a mix of prospective, retrospective, and ambispective methods. OBJECTIVE: To evaluate the effect of biological sex on patient-reported outcomes after spinal fusion surgery for lumbar degenerative disease. SUMMARY OF BACKGROUND DATA: Current literature suggests sex differences regarding clinical outcome after spine surgery may exist. Substantial methodological heterogeneity and limited comparability of studies warrants further investigation of sex-related differences in treatment outcomes. METHODS: We analyzed patients who underwent spinal fusion with or without pedicle screw insertion for lumbar degenerative disease included within a multinational study, comprising patients from 11 centers in 7 countries. Absolute values and change scores (change from pe-operative baseline to post-operative follow-up) for 12-month functional impairment (Oswestry disability index [ODI]) and back and leg pain severity (numeric rating scale [NRS]) were compared between male and female patients. Minimum clinically important difference (MCID) was defined as > 30% improvement. RESULTS: Six-hundred-sixty (59%) of 1115 included patients were female. Female patients presented with significantly baseline ODI (51.5 ± 17.2 vs. 47.8 ± 17.9, P<0.001) and back pain (6.96 ± 2.32 vs. 6.60 ± 2.30, P=0.010) and leg pain (6.49 ± 2.76 vs. 6.01 ± 2.76, P=0.005). At 12-months, female patients still reported significantly higher ODI (22.76 ± 16.97 vs. 20.50 ± 16.10, P=0.025), but not higher back (3.13 ± 2.38 vs. 3.00 ± 2.40, P=0.355) or leg pain (2.62 ± 2.55 vs. .34 ± 2.43, P=0.060). Change scores at 12 months did not differ significantly among male and female patients in ODI (∆ 1.31, 95% CI -3.88-1.25, P=0.315), back (∆ 0.22, 95% CI -0.57-0.12, P=0.197) and leg pain (∆ 0.16, 95% CI -0.56-0.24, P=0.439). MCID at 12-months was achieved in 330 (77.5%) male patients and 481 (76.3%) female patients (P=0.729) for ODI. CONCLUSION: Both sexes experienced a similar benefit from surgery in terms of relative improvement in scores for functional impairment and pain. Although female patients reported a higher degree of functional impairment and pain preoperatively, at 12 months only their average scores for functional impairment remained higher than those for their male counterparts, while absolute pain scores were similar for female and male patients.
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Degeneration of fibrocartilaginous tissues is often associated with complex pro-inflammatory factors. These include reactive oxygen species (ROS), cell-free nucleic acids (cf-NAs), and epigenetic changes in immune cells. To effectively control this complex inflammatory signaling, it developed an all-in-one nanoscaffold-based 3D porous hybrid protein (3D-PHP) self-therapeutic strategy for treating intervertebral disc (IVD) degeneration. The 3D-PHP nanoscaffold is synthesized by introducing a novel nanomaterial-templated protein assembly (NTPA) strategy. 3D-PHP nanoscaffolds that avoid covalent modification of proteins demonstrate inflammatory stimuli-responsive drug release, disc-mimetic stiffness, and excellent biodegradability. Enzyme-like 2D nanosheets incorporated into nanoscaffolds further enabled robust scavenging of ROS and cf-NAs, reducing inflammation and enhancing the survival of disc cells under inflammatory stress in vitro. Implantation of 3D-PHP nanoscaffolds loaded with bromodomain extraterminal inhibitor (BETi) into a rat nucleotomy disc injury model effectively suppressed inflammation in vivo, thus promoting restoration of the extracellular matrix (ECM). The resulting regeneration of disc tissue facilitated long-term pain reduction. Therefore, self-therapeutic and epigenetic modulator-encapsulated hybrid protein nanoscaffold shows great promise as a novel approach to restore dysregulated inflammatory signaling and treat degenerative fibrocartilaginous diseases, including disc injuries, providing hope and relief to patients worldwide.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Humanos , Ratas , Animales , Especies Reactivas de Oxígeno/metabolismo , Porinas , Porosidad , Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Estrés OxidativoRESUMEN
Intervertebral disc (IVD) degeneration (IVDD) is a leading cause of chronic low back pain. There is a strong clinical demand for more effective treatments for IVDD as conventional treatments provide only symptomatic relief rather than arresting IVDD progression. This study shows that senolytic therapy with local drug delivery can inhibit IVDD and restore IVD integrity. ABT263, a senolytic drug, is loaded in poly(lactic-co-glycolic acid) nanoparticles (PLGA-ABT) and intradiscally administered into injury-induced IVDD rat models. The single intradiscal injection of PLGA-ABT may enable local delivery of the drug to avascular IVD, prevention of potential systemic toxicity caused by systemic administration of senolytic drug, and morbidity caused by repetitive injections of free drug into the IVD. The strategy results in the selective elimination of senescent cells from the degenerative IVD, reduces expressions of pro-inflammatory cytokines and matrix proteases in the IVD, inhibits progression of IVDD, and even restores the IVD structure. This study demonstrates for the first time that local delivery of senolytic drug can effectively treat senescence-associated IVDD. This approach can be extended to treat other types of senescence-associated degenerative diseases.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Animales , Sistemas de Liberación de Medicamentos , Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Preparaciones Farmacéuticas , Ratas , SenoterapéuticosRESUMEN
The degenerative changes in the spine of the frail elderly gradually exacerbate the alignment of the spine as the degeneration progresses. This study was conducted to assess the relationship between frailty and spine sagittal alignment measured in terms of global, cervical, thoracic, and lumbo-pelvic parameters. In total, 101 patients aged 75 years and older hospitalized for spine surgery were prospectively enrolled. We evaluated spinal sagittal parameters by dividing them into global (C7 sagittal vertical axis [SVA] and T1 pelvic angle [T1PA]), cervical (the C2-7 Cobb angle, Jackson line, and C2-7 plumb line), thoracic (thoracic kyphosis [TK]), and lumbo-pelvic (pelvic tilt [PT] and pelvic incidence minus lumbar lordosis value [PI-LL]). Patient characteristics; the Fatigue, Resistance, Ambulation, Illness, Loss of Weight (FRAIL) scale; and sagittal spinal parameters were included in the analysis. Multiple regression analysis was performed to identify associations between the FRAIL scale and sagittal spinal parameters. The FRAIL scale showed correlations with global sagittal parameters (C7 SVA [ß = 0.225, p = 0.029] and T1PA [ß = 0.273, p = 0.008]) and lumbo-pelvic parameters (PT [ß = 0.294, p = 0.004] and PI-LL [ß = 0.323, p = 0.001). Cervical and thoracic parameters were not directly associated with the FRAIL scale. LL and PI-LL were associated with TK, and TK was associated with cervical parameters (the C2-7 Cobb angle, Jackson line and C2-7 plumb line). In conclusion, frailty status could be an important factor that influences sagittal spinal alignment in the elderly. In this study, it was found that frailty mainly affected the balance of lumbo-pelvic alignment, and consequently affected the balance of the whole spine.
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Fragilidad , Cifosis , Lordosis , Anciano , Humanos , Cifosis/diagnóstico por imagen , Lordosis/diagnóstico por imagen , Vértebras Lumbares , Pelvis/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/cirugíaRESUMEN
OBJECTIVE: To evaluate the relationship between prevalence of osteoporosis and risk factors, medical costs, reoperation, and readmission in patients after spine surgery. METHODS: Patients >50 years old with thoracic or lumbar spine diseases who underwent spine surgery between 2005 and 2008 were selected from the Korean National Health Insurance Service databases for analysis. There were 147,676 patients selected, who were divided into 2 groups (osteoporosis and non-osteoporosis) and followed for 8 years. Multiple logistic regressions were performed to examine the effect of osteoporosis following spine surgery. RESULTS: Patients with osteoporosis showed significant increases in readmission rates (odds ratio = 1.26, P < 0.001). Osteoporosis was found to be significantly associated with longer hospital stays and increased medical costs regardless of the cause of spine disease. For readmission, there was a 62-day difference in hospitalization time and U.S. dollars $2040 difference in medical costs between the osteoporosis group and non-osteoporosis group. Total medical costs of the osteoporosis group were about U.S. dollars $310 million more than total medical costs of the non-osteoporosis group. Osteoporosis increased the risk of reoperation in fusion surgery, particularly in the first 3 months postoperatively (odds ratio = 1.34, P < 0.001). CONCLUSIONS: Osteoporosis was significantly associated with higher readmission rates, longer hospitalization, and greater medical costs during the 8-year follow-up. It also increased the risk of reoperation in fusion surgery. Proper management of osteoporosis is essential before spine surgery, particularly fusion surgery, to help reduce patients' socioeconomic burden and produce more satisfactory surgical outcomes.
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Osteoporosis/complicaciones , Readmisión del Paciente/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Enfermedades de la Columna Vertebral/complicaciones , Anciano , Femenino , Humanos , Masculino , Osteoporosis/epidemiología , Readmisión del Paciente/economía , Prevalencia , Reoperación/economía , República de Corea/epidemiología , Enfermedades de la Columna Vertebral/cirugíaRESUMEN
Cognitive status has been reported to affect the peri-operative and post-operative outcomes of certain surgical procedures. This prospective study investigated the effect of preoperative cognitive impairment on the postoperative course of elderly patients (n = 122, >65 years), following spine surgery for degenerative spinal disease. Data on demographic characteristics, medical history, and blood analysis results were collected. Preoperative cognition was assessed using the mini-mental state examination, and patients were divided into three groups: normal cognition, mild cognitive impairment, and moderate-to-severe cognitive impairment. Discharge destinations (p = 0.014) and postoperative cardiopulmonary complications (p = 0.037) significantly differed based on the cognitive status. Operation time (p = 0.049), white blood cell count (p = 0.022), platelet count (p = 0.013), the mini-mental state examination score (p = 0.033), and the Beck Depression Inventory score (p = 0.041) were significantly associated with the length of hospital stay. Our investigation demonstrated that improved understanding of preoperative cognitive status may be helpful in surgical decision-making and postoperative care of elderly patients with degenerative spinal disease.
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OBJECTIVE: Cervical surgery in patients with cervical spondylotic myelopathy (CSM) and cerebral palsy (CP) is challenging owing to the complexities of the deformity. We assessed factors affecting postoperative complications and outcomes after CSM surgery in patients with CP. METHODS: Thirty-five consecutive patients with CP and CSM who underwent cervical operations between January 2006 and January 2014 were matched to 35 non-cerebral palsy (NCP) control patients. Postoperative complications and radiologic outcomes were compared between the groups. In the CP group, the Japanese Orthopaedic Association score; Oswestry neck disability index; modified Barthel index; and values for the grip and pinch, Box and Block, and Jebsen-Taylor hand function tests were obtained preand postoperatively and compared between those with and without postoperative complications. RESULTS: Sixteen patients (16/35%) in the CP group and seven (7/35%) in the NCP group (p=0.021) had postoperative complications. Adjacent segment degeneration (p=0.021), postoperative motor weakness (p=0.037), and revisions (p=0.003) were significantly more frequent in the CP group than in the NCP group; however, instrument-related complications were not significantly higher in the CP group (7/35 vs. 5/35, p=0.280). The number of preoperative fixed cervical deformities were significantly higher in CP with postoperative complications (5/16 vs. 1/19, p=0.037). In the CP group, clinical outcomes were almost similar between those with and without postoperative complications. CONCLUSION: The occurrence of complications during the follow-up period was high in patients with CP. However, postoperative complications did not significantly affect clinical outcomes.
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BACKGROUND: We assessed pedicle screw accuracy utilizing a novel navigation-based spine surgery robotic system by comparing planned pathways with placed pathways in a porcine model. METHODS: We placed three mini screws per vertebra for accuracy evaluation and used a reference frame for registration in four pigs (46 screws in 23 vertebrae). We planned screw paths and performed screw insertion under robot guidance. Using C-arm and CT images, we evaluated accuracy by comparing the 3D distance of the placed screw head/tip from the planned screw head/tip and 3D angular offset. RESULTS: Mean registration deviation between the preoperative 3D space (C-arm) and postoperative CT scans was 0.475 ± 0.119 mm. The average offset from preoperative plan to final placement was 4.8 ± 2.0 mm from the head (tail), 5.3 ± 2.3 mm from the tip and 3.9 ± 2.4 degrees of angulation. CONCLUSIONS: Our spine surgery robot showed good accuracy in executing an intended planned trajectory and screw path. This faster and more accurate robotic system will be applied in future studies, first in cadavers and subsequently in the clinical field.