Mitochondrial 'Birth-Death' coordinator: An intelligent hydrogen nanogenerator to enhance intervertebral disc regeneration.

Currently, mitochondrial dysfunction caused by oxidative stress is a growing concern in degenerative diseases, notably intervertebral disc degeneration (IVDD). Dysregulation of the balance of mitochondrial quality control (MQC) has been considered the key contributor, while it's still challenging to effectively harmonize different MQC components in a simple and biologically safe way. Hydrogen gas (H2) is a promising mitochondrial therapeutic molecule due to its bio-reductivity and diffusibility across cellular membranes, yet its relationship with MQC regulation remains unknown. Herein, we propose a mitochondrial 'Birth-Death' coordinator achieved by an intelligent hydrogen nanogenerator (Fe@HP-OD), which can sustainably release H2 in response to the unique microenvironment in degenerated IVDs. Both in vitro and in vivo results prove alleviation of cellular oxidative stress and restoration of nucleus pulposus cells function, thereby facilitating successful IVD regeneration. Significantly, this study for the first time proposes the mitochondrial 'Birth-Death' coordination mechanism: 1) attenuation of overactivated mitochondrial 'Death' process (UPRmt and unselective mitophagy); and 2) activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial 'Birth-Death' balance (mitochondrial biogenesis and controlled mitophagy). These pioneering findings can fill in the gaps in molecular mechanisms for H2 regulation on MQC homeostasis, and pave the way for future strategies towards restoring equilibrium of MQC system against degenerative diseases.

Identification and validation of ferroptosis-related biomarkers in intervertebral disc degeneration.

Introduction: Ferroptosis plays a significant role in intervertebral disc degeneration (IDD). Understanding the key genes regulating ferroptosis in IDD could reveal fundamental mechanisms of the disease, potentially leading to new diagnostic and therapeutic targets. Methods: Public datasets (GSE23130 and GSE70362) and the FerrDb database were analyzed to identify ferroptosis-related genes (DE-FRGs) involved in IDD. Single-cell RNA sequencing data (GSE199866) was used to validate the specific roles and expression patterns of these genes. Immunohistochemistry and Western blot analyses were subsequently conducted in both clinical samples and mouse models to assess protein expression levels across different tissues. Results: The analysis identified seven DE-FRGs, including MT1G, CA9, AKR1C1, AKR1C2, DUSP1, CIRBP, and KLHL24, with their expression patterns confirmed by single-cell RNA sequencing. Immunohistochemistry and Western blot analysis further revealed that MT1G, CA9, AKR1C1, AKR1C2, DUSP1, and KLHL24 exhibited differential expression during the progression of IDD. Additionally, the study highlighted the potential immune-modulatory functions of these genes within the IDD microenvironment. Discussion: Our study elucidates the critical role of ferroptosis in IDD and identifies specific genes, such as MT1G and CA9, as potential targets for diagnosis and therapy. These findings offer new insights into the molecular mechanisms underlying IDD and present promising avenues for future research and clinical applications.

Clinical Outcomes of Full-Endoscopic Visualized Foraminoplasty and Discectomy for Lumbar Disc Herniation with Bilateral Radiculopathy.

OBJECTIVE: The treatment of lumbar disc herniation (LDH) with bilateral radiculopathy using transforaminal endoscopic lumbar discectomy (TELD) remains challenging, especially at the L5/S1 level with narrow foramen or high iliac crest. Full-endoscopic visualized foraminoplasty and discectomy (FEVFD) is a newly developed technique for LDH and lumbar stenosis. However, there is limited evidence on the efficacy of FEVFD technique in the treatment of LDH with bilateral radiculopathy. This study was to assess the clinical outcomes and safety of using FEVFD in the treatment of LDH with bilateral radiculopathy. METHODS: This retrospective study enrolled 63 patients with LDH presenting with bilateral radiculopathy between January 2018 and January 2022. Patients enrolled before January 2020 were treated using a conventional transforaminal endoscopic surgical system (TESSYS) technique (TESSYS, n = 33) and treated using a FEVFD technique after that (FEVFD, n = 30). The total operation time and the number of intraoperative fluoroscopies were recorded. The Oswestry Disability Index (ODI) and visual analog scale (VAS) were evaluated preoperatively and postoperatively (at 1-month, 3-month, 6-month, and final follow-ups). Global outcomes at final follow-up were assessed using modified MacNab criteria. RESULTS: Compared with TESSYS, patients in FEVFD group had a shorter operation time (92.9 vs. 78.0 min). The intraoperative fluoroscopies in FEVFD group were significantly lower than those in TESSYS group (18.7 vs. 4.9). After the operation, the VAS and ODI scores at all follow-ups in the two groups were significantly lower than those before operation. For the L5/S1 level, the values of VAS and ODI scores in FEVFD group were significantly lower than those of in TESSYS group at 3-month, 6-month, and final follow-up. For the L4/5 level, however, no significant difference was found in VAS and ODI scores between these two groups at the follow-ups. According to the modified MacNab criteria, the excellent-to-good rate in TESSYS and FEVFD groups was 84.8% and 90.0%, respectively. CONCLUSION: For LDH with bilateral radiculopathy, using the FEVFD technique could not only reduce the operation time and radiation, but also improve the clinical outcomes at the L5/S1 level.

How global spine sagittal alignment and spinal degeneration affect locomotive syndrome risk in the elderly.

BACKGROUND: The aim of this study was to delineate the features of the locomotive syndrome (LS) risk stage in the elderly population, encompassing global spine sagittal alignment, visible spinal degenerative changes on plain radiographs, muscle strength, physical capabilities, and low back pain (LBP). METHODS: The study enrolled 232 subjects, evaluated using plain radiographs. The evaluation included measurements of lumbar lordosis (LLA), thoracic kyphosis (TKA), spinal inclination (SIA) angles, and sagittal vertical axis. Assessments included lumbar osteophyte formation (LOF) and lumbar disc height (LDH) to examine spinal degenerative changes. LS evaluation used the locomotive syndrome risk test based on LS risk criteria, classifying participants into no risk, stage 1 LS, and stage 2 LS groups. Using a visual analogue scale (VAS), we investigated the prevalence of low back pain (LBP) and assessed physical performances across these groups. RESULTS: There were 132 participants with no LS risk, 71 with stage 1 LS risk, and 29 with stage 2 LS risk. As LS risk increased, LBP prevalence and VAS scores rose, physical abilities, and back muscle strength decreased. TKA showed no variation across groups, while LLA decreased with advancing LS risk stage. Except for L1-L2 and L5-S1, lumbar disc height (LDH) decreased with higher LS risk stages. LOF occurrence increased notably with higher LS risk stages. Spinal inclination angle (SIA) significantly increased with advancing LS risk stages. CONCLUSION: Participants diagnosed with LS exhibited an increased incidence of spinal degeneration, reduced LLA, and global spinal imbalance characterized by anterior spinal inclination.

Spontaneous regression of lumbar disc herniation: four cases report and review of the literature.

Spontaneous regression of lumbar disc herniation refers to shrinkage or disappearance of herniated nucleus pulposus without invasive surgical treatments. This phenomenon has been reported and is supported by improved clinical symptoms and radiographic after conservative treatment, but the underlying mechanism remains unclear. This article reports 4 cases of disc reabsorption and reviews the distribution of several clinical and radiographic factors of disc herniation reabsorption of total 46 patients, including the four from our study, gathered from 28 recent publications. Some of these factors are present with anomalous distributions. But some factors have similar deviations in patients with lumbar disc herniation. Therefore, more research is needed to explore the correlation between those factors and disc reabsorption.

Sequential Targeted Enzyme-Instructed Self-Assembly Supramolecular Nanofibers to Attenuate Intervertebral Disc Degeneration.

As an age-related disease, intervertebral disc degeneration is closely related to inflammation and aging. Inflammatory cytokines and cellular senescence collectively contribute to the degradation of intervertebral disc. Blocking this synergy reduces disc extracellular matrix damage caused by inflammation and aging. In this study, drug-loaded nanofibers with sequential targeting functions are constructed through intelligent response, hydrophilicity, and in situ self-assembly empowerment of flurbiprofen. The peptide precursor responds to the cleavage of overexpressed MMP-2 in the degenerative intervertebral disc microenvironment (intracellular and extracellular), resulting in the formation of self-assembled nanofibers that enable the on-demand release of flurbiprofen and COX-2 response. In vitro, Comp. 1 (Flurbiprofen-GFFYPLGLAGEEEERGD) reduces the expression of inflammation-related genes and proteins and the polarization of M1 macrophages by competitively inhibiting COX-2 and increases the expression of extracellular matrix proteins COL-2 and aggrecan. Additionally, it can reduce the expression of Senescence-Associated Secretory Phenotype and DNA damage in aged nucleus pulposus cells and promote the recovery of proliferation and cell cycle. In vivo, drug-loaded nanofibers delay intervertebral disc degeneration by inhibiting inflammation and preventing the accumulation of senescent cells. Therefore, the sequentially targeted self-assembled drug-loaded nanofibers can delay intervertebral disc degeneration by blocking the synergistic effect of inflammatory cytokines and cellular senescence.

Psoas muscle sequestered disc mimicking an intramuscular abscess: A rare case report.

This report documents a rare case of a sequestered disc in the psoas muscle mimicking an intramuscular abscess, notable for its lack of systemic infection indicators and resolution without surgical intervention. Such cases emphasize the need for accurate differential diagnosis and highlight potential conservative management pathways for sequestered disc herniations. A 57-year-old male presented with acute low back pain following minor weight lifting, unresponsive to NSAIDs. MRI and CT imaging, followed by CT-guided aspiration and cultures, were employed to investigate a nodular structure within the right psoas muscle. Initial imaging suggested an infectious etiology; however, aspiration yielded no material, and cultures were negative. Follow-up MRIs demonstrated improvement and eventual resolution of the lesion, supporting a diagnosis of sequestered disc herniation. This case underscores the importance of considering differential diagnoses for psoas abscess-like presentations and suggests that conservative management may be sufficient in certain cases of sequestered disc fragments.

The influence of preoperative 12-item veterans rand physical component scores on outcomes following cervical disc replacement.

PURPOSE: To evaluate the influence of preoperative VR-12 physical component scores (PCS) on outcomes following cervical disc replacement (CDR). METHODS: Patients undergoing elective CDR were retrospectively identified. Patient-reported outcomes (PROs) of interest included VR-12 PCS/VR-12 Mental Component Score (MCS)/9-Item Patient Health Questionnaire (PHQ-9)/Short Form-12 (SF-12) PCS and MCS/Patient-Reported Outcome Measurement Information System-Physical Function (PROMIS-PF)/Visual Analog Scale-Neck Pain (VAS-NP)/VAS-Arm Pain (VAS-AP)/Neck Disability Index (NDI). Baseline up to two-year postoperative scores were obtained (average follow-up: 9.2 ± 6.8months). Two cohorts were created: VR-12 PCS < 35 or VR-12 PCS ≥ 35. Improvements in scores from baseline to six weeks postoperatively and to final follow-up were calculated. Changes in scores were compared to previously reported thresholds to determine rates of minimum clinically important difference (MCID). RESULTS: Of 127 patients, 64 were in the worse VR-12 PCS group. Patients with better VR-12 PCS were more likely to have private insurance (p = 0.034). When accounting for insurance differences, the worse VR-12 PCS group reported inferior NDI/VAS-NP/PHQ-9/PROMIS-PF/VR-12 PCS/SF-12 PCS at six weeks and final follow-up (p ≤ 0.015, all). The worse VR-12 PCS group reported greater improvements in VAS-AP and VR-12 PCS by six weeks and in NDI/VR-12 MCS/VR-12 PCS/SF-12 PCS by final follow-up (p ≤ 0.026, all). Patients with worse VR-12 PCS reported greater MCID achievement for VR-12 MCS and SF-12 PCS (p ≤ 0.034, both). CONCLUSION: Following surgery, patients with worse VR-12 PCS report greater improvements in PROs, highlighting the increased relative impact of surgery for patients with worse baseline physical function. These findings can be used to optimize patient experience perioperatively and inform postoperative expectations.

Optic Disc Infiltration as a Sign of Multiple Myeloma Recurrence.

Multiple myeloma is a plasma cell dyscrasia with an age-standardized incidence of 3 - 4 per 100,000 in the Caucasian population. It is the second most common hematological malignancy after non-Hodgkin lymphoma, representing 1% of all cancers. Herein, we present a case report of multiple myeloma with ocular involvement as a sign of recurrence. A 62-year-old woman, with a known history of lambda light chain multiple myeloma, presented with reduced visual acuity in both eyes while on maintenance chemotherapy. The patient also had mild unsteadiness and fatigue. Fundus examination revealed bilateral optic disc swelling and hemorrhages of the posterior pole. Magnetic resonance imaging disclosed no abnormalities. Although no biopsy of the optic nerve was possible, intracranial pressure was elevated and cerebrospinal fluid was riddled with neoplastic cells, affirming the diagnosis. After 2 months of chemotherapy, visual function and the appearance of the posterior pole returned to normal. In cases of multiple myeloma, mechanisms, such as hyperviscosity syndrome, microvascular impairment and optic nerve and meningeal infiltration on a cellular level may have played a pivotal role in the ocular involvement, which can be the first sign of recurrence.

Percutaneous plasma disc decompression through a lower surgical approach for the treatment of cervicogenic headache in patients with cervical spondylotic radiculopathy: A retrospective cohort study.

Cervical spondylotic radiculopathy (CSR) is the most common type of cervical spondylosis, frequently accompanied by cervicogenic headache (CEH). Percutaneous plasma disc decompression (PPDD) and pulsed radiofrequency (PRF) are minimally invasive techniques targeting cervical intervertebral discs or cervical nerves, and have been proven to be effective methods for treatment of CSR and CEH. The present study aimed to evaluate clinical efficacy and practicality of percutaneous plasma disc decompression (PPDD) via a lower surgical approach for the treatment of cervicogenic headache (CEH) and upper extremity radicular pain by analyzing clinical outcomes of patients with cervical spondylotic radiculopathy (CSR) undergoing PPDD and pulsed radiofrequency (PRF). Clinical data of patients with CSR who received PPDD (n=79) or PRF (n=92) at Shanghai Traditional Chinese Medicine Hospital (Shanghai, China) and Jiashan County People's Hospital (Jiaxing, China) from January 2022 to December 2022 were retrospectively collected and analyzed. The surgical site and procedure, bleeding volume, preoperative analgesic use and upper extremity symptoms, history of nerve block treatment and duration of disease were recorded, as well as relevant postoperative complications (infection, hematoma, nerve injury). The therapeutic effects [NRS (numeric rating scale) and NDI (neck disability index) score, and CEH remission rate at 1, 3 and 6 months after treatment] of both surgical methods were investigated using the telephone follow-up. CEH remission rates at 1, 3 and 6 months after surgery in the PPDD group were significantly higher than in the PRF group (78.8 vs. 43.5, P=0.016; 84.8 vs. 34.8, P=0.003 and 75.8 vs. 26.1%, P=0.005, respectively). The PPDD group showed higher NRS scores than the PRF group at 1 month after surgery (3 vs. 2, P<0.0001) and lower NRS scores than the PRF group at 6 months after surgery (2 vs. 3, P<0.0001). NDI scores in the PPDD group were significantly lower than those in the PRF group at 1, 3 and 6 months after surgery (15.49 vs. 20.05, P=0.002; 16.06 vs. 20.10, P=0.003 and 9.90 vs. 13.80, P=0.001, respectively). There was no significant difference in postoperative complication rate between the two groups (P>0.999). PPDD could significantly relieve CEH symptoms and upper extremity radicular pain in patients with CSR treated via a lower surgical approach and PPDD was more effective than PRF for long-term CEH remission and pain alleviation.

Melatonin mitigates matrix stiffness-induced disc degenetation by inhibiting reactive oxygen species and melatonin receptor mediated-PI3K/AKT/NF-κB pathway.

Intervertebral disc degeneration (IVDD) may lead to an increase in extracellular matrix (ECM) stiffness, contributing to the progression of the disease. Melatonin reportedly mitigates IVDD; while its potential to attenuate elevated matrix stiffness-induced IVDD remains unexplored. Therefore, we aimed to investigate whether melatonin can alleviate the progression of IVDD triggered by increased matrix stiffness and elucidate its mechanisms. Nucleus pulposus (NP) tissues were collected from patients, and ECM stiffness, reactive oxygen species (ROS) levels, apoptosis rates, and p65 expression in these tissues with varying Pfirrmann scores were determined. In vitro experiments were conducted to investigate the effects of melatonin on the NP cells cultured on soft substrate with differing stiffness levels. Our findings revealed a positive correlation between ECM stiffness in human NP tissue and degree of IVDD. Additionally, phosphorylation of P65 exhibited a strong association with matrix stiffness. Enhanced levels of ROS and cellular apoptosis were observed within degenerated intervertebral discs. In vitro experiments demonstrated that melatonin significantly inhibited catabolism and apoptosis induced by stiff matrices, along with elevated ROS levels. Furthermore, we observed that melatonin inhibited NP cell catabolism and apoptosis by reducing the melatonin receptors mediated activation of the PI3K/AKT and NF-κB pathways. Also, we found that the reduction of ROS by melatonin can assist in inhibiting the activation of the NF-κB pathway. The outcomes of the in vivo experiments corroborated the results of the in vitro experiments. Collectively, melatonin can potentially alleviate high matrix stiffness-induced IVDD by reducing intracellular ROS levels and inhibiting the PI3K/AKT/NF-κB pathway.

The footprint mismatch of cervical disc arthroplasty comes from degenerative factor besides ethnic factor.

A mismatch in footprints of cervical total disc arthroplasty (CTDA) implants occasionally occurred in Asian population and it had been attributed solely to ethnic factor. Yet, cervical degeneration process may play a role. Our purpose was to compare the cervical vertebra morphometric data with and without degeneration. The study included patients with CT scans of cervical spine from our hospital between January, 2019, and September, 2021. The total cervical degenerative index (TCDI) of each patient were collected by adding CDI score for 5 disc-levels. Patients were categorized into normal (TCDI 0-5) and degeneration groups (TCDI 6-60). Various measurements of the C3-C7 vertebral body and endplate were taken. Forty-nine patients in the normal group and 55 in the degeneration group were included. No significant difference was noted in gender, BH, BW, or BMI except age and TCDI (p < .001). During degeneration, disproportional endplate size changes were observed, with an increment ratio of 12-20% in the anteroposterior and 5-17% in the mediolateral plane throughout C3-C7, while vertebral body height remained constant. In conclusion, degeneration process, besides ethnic factor, causes the endplate size and shape mismatch. This information can help spine surgeon choose appropriate implants in CTDA surgery.

"Advancements in minimally invasive treatment for lumbar disc herniation: insights into condoliase and chondroitin sulfate ABC endolyase".

This study examines the efficacy and safety of condoliase chemonucleolysis (CC) in treating lumbar disc herniation (LDH) and highlights emerging alternatives like chondroitin sulfate ABC endolyase. Research indicates that condoliase, an enzyme used to degrade glycosaminoglycans in the nucleus pulposus, provides effective and prompt relief of leg pain, with significant reductions observed within a day of treatment. Studies reveal that a lower pretreatment straight leg raising (SLR) angle may predict early symptom relief, and condoliase is generally effective at doses up to 1.25 U, balancing efficacy and safety. Despite promising results, concerns about long-term safety, including disc height reduction and imaging changes, persist. Additionally, chondroitin sulfate ABC endolyase shows potential as a safer and more effective alternative, though further research is needed to optimize treatment protocols and assess long-term outcomes. Future investigations should address current limitations, such as small sample sizes and short follow-up periods, to better understand the long-term benefits and risks of these treatments.

Surgical management of herniated intervertebral disc in children: Running title: Pediatric disc herniation.

STUDY DESIGN: Retrospective literature review analysis OBJECTIVE: Analyze the risk factors, characteristics, outcome, and follow up of surgical management of disc herniation in children ≤15 years old (y.o) through a review of the literature. BACKGROUND: Disc herniation is a rare disease in the pediatric population. While conservative treatment if very often tried, some cases require surgical treatment. METHODS: A literature search was conducted using PubMed data base using the terms 'pediatric/children/adolescent disc herniation' and 'surgical management' as key words. Significant manuscripts i.e: case reports, case series, reviews were identified and analyzed. The exclusion criteria were: series and cases with patients >15 y.o, results non-individualizable and medical management. RESULTS: 49 studies were identified, 28 were retained. 69 children <15 y.o were identified with a median age of 13 y.o (SD 1-15). The mean FU was 3.3 years. Trauma and repeated micro traumatism were identified as the main causes of disc herniation in this population. It is mostly a lumbar disease, with very anecdotic cases of thoracic or cervical herniation described. In the absence of neurological deficit, conservative treatment should be tried. Different types of surgery exist (open, endoscopic, tubular), with no difference in outcome or complications. The post-operative outcome was very satisfactory, with no neurological sequalae described with excellent recovery. CONCLUSIONS: Pediatric disc herniation is often caused by precipitating factors such as trauma. In the absence of resolution with conservative treatment, surgical options yield favorable short term clinical outcomes with minimal complications and no neurological sequalae.

Physical therapy and non-surgical manual disc reduction combined with anterior repositioning splint for acute disc displacement without reduction of the temporomandibular joint in adolescents.

OBJECTIVES: Current studies on the treatment of adolescent patients with disc displacement without reduction (DDWOR) are limited by short follow-up periods and small sample sizes, and there are few comparative studies on the efficacy of conservative treatment with and without disc reduction for acute DDWOR. This study compared the therapeutic effects of two conservative treatment methods: physical therapy alone and physical therapy combined with non-surgical manual disc reduction and anterior repositioning splints (ARS), in adolescent patients with acute DDWOR. MATERIALS AND METHODS: This retrospective study included adolescent patients with DDWOR who underwent physical therapy at the Temporomandibular Joint Rehabilitation Department of the Shanghai Ninth People's Hospital from January 2018 to December 2021. Patient assessment data were collected before and after treatment. Patients were followed up through telephone and online questionnaires from March to August 2023. RESULTS: The results indicate that compared to physical therapy alone, the combination of physical therapy and non-surgical manual disc reduction with ARS showed better short-term efficacy, improved mouth opening, and better long-term pain control. Also, it may be effective in preventing degenerative joint disease. CONCLUSIONS: This combination therapy is recommended for clinical application in adolescent patients with acute DDWOR. CLINICAL RELEVANCE: The present research demonstrates the superior efficacy of physical therapy and non-surgical manual disc reduction combined with anterior repositioning splint in adolescent patients with acute DDWOR.

Neural network segmentation of disc volume from magnetic resonance images and the effect of degeneration and spinal level.

Background: Magnetic resonance imaging (MRI) noninvasively quantifies disc structure but requires segmentation that is both time intensive and susceptible to human error. Recent advances in neural networks can improve on manual segmentation. The aim of this study was to establish a method for automatic slice-wise segmentation of 3D disc volumes from subjects with a wide range of age and degrees of disc degeneration. A U-Net convolutional neural network was trained to segment 3D T1-weighted spine MRI. Methods: Lumbar spine MRIs were acquired from 43 subjects (23-83 years old) and manually segmented. A U-Net architecture was trained using the TensorFlow framework. Two rounds of model tuning were performed. The performance of the model was measured using a validation set that did not cross over from the training set. The model version with the best Dice similarity coefficient (DSC) was selected in each tuning round. After model development was complete and a final U-Net model was selected, performance of this model was compared between disc levels and degeneration grades. Results: Performance of the final model was equivalent to manual segmentation, with a mean DSC = 0.935 ± 0.014 for degeneration grades I-IV. Neither the manual segmentation nor the U-Net model performed as well for grade V disc segmentation. Compared with the baseline model at the beginning of round 1, the best model had fewer filters/parameters (75%), was trained using only slices with at least one disc-labeled pixel, applied contrast stretching to its input images, and used a greater dropout rate. Conclusion: This study successfully trained a U-Net model for automatic slice-wise segmentation of 3D disc volumes from populations with a wide range of ages and disc degeneration. The final trained model is available to support scientific use.

Research Progress on the Role of Cartilage Endplate in Intervertebral Disc Degeneration.

Low back pain significantly impacts individuals' quality of life, with intervertebral disc degeneration (IDD) being a primary contributor to this condition. Currently, IDD treatment primarily focuses on symptom management and does not achieve a definitive cure. The cartilage endplate (CEP), a crucial nutrient-supplying tissue of the intervertebral disc, plays a pivotal role in disc degeneration. This review examines the mechanisms underlying CEP degeneration, summarizing recent advancements in understanding the structure and function of CEP, the involvement of various signaling pathways, and the roles of cartilage endplate stem cells (CESCs) and exosomes (Exos) in this process. The aim of this review is to provide a comprehensive reference for future research on CEP. Despite progress in understanding the role of CEP in IDD, the mechanisms underlying CEP degeneration remain incompletely elucidated. Future research poses significant challenges, necessitating further investigations to elucidate the complexities of CEP.

Validating the Accuracy of a Patient-Facing Clinical Decision Support System in Predicting Lumbar Disc Herniation: Diagnostic Accuracy Study.

BACKGROUND: Low back pain (LBP) is a major cause of disability globally, and the diagnosis of LBP is challenging for clinicians. OBJECTIVE: Using new software called Therapha, this study aimed to assess the accuracy level of artificial intelligence as a Clinical Decision Support System (CDSS) compared to MRI in predicting lumbar disc herniated patients. METHODS: One hundred low back pain patients aged ≥18 years old were included in the study. The study was conducted in three stages. Firstly, a case series was conducted by matching MRI and Therapha diagnosis for 10 patients. Subsequently, Delphi methodology was employed to establish a clinical consensus. Finally, to determine the accuracy of the newly developed software, a cross-sectional study was undertaken involving 100 patients. RESULTS: The software showed a significant diagnostic accuracy with the area under the curve in the ROC analysis determined as 0.84 with a sensitivity of 88% and a specificity of 80%. CONCLUSIONS: The study's findings revealed that CDSS using Therapha has a reasonable level of efficacy, and this can be utilized clinically to acquire a faster and more accurate screening of patients with lumbar disc herniation.

Inhibition of KDM2/7 Promotes Notochordal Differentiation of hiPSCs.

Intervertebral disc disease (IDD) is a debilitating spine condition that can be caused by intervertebral disc (IVD) damage which progresses towards IVD degeneration and dysfunction. Recently, human pluripotent stem cells (hPSCs) were recognized as a valuable resource for cell-based regenerative medicine in skeletal diseases. Therefore, adult somatic cells reprogrammed into human induced pluripotent stem cells (hiPSCs) represent an attractive cell source for the derivation of notochordal-like cells (NCs) as a first step towards the development of a regenerative therapy for IDD. Utilizing a differentiation method involving treatment with a four-factor cocktail targeting the BMP, FGF, retinoic acid, and Wnt signaling pathways, we differentiate CRISPR/Cas9-generated mCherry-reporter knock-in hiPSCs into notochordal-like cells. Comprehensive analysis of transcriptomic changes throughout the differentiation process identified regulation of histone methylation as a pivotal driver facilitating the differentiation of hiPSCs into notochordal-like cells. We further provide evidence that specific inhibition of histone demethylases KDM2A and KDM7A/B enhanced the lineage commitment of hiPSCs towards notochordal-like cells. Our results suggest that inhibition of KDMs could be leveraged to alter the epigenetic landscape of hiPSCs to control notochord-specific gene expression. Thus, our study highlights the importance of epigenetic regulators in stem cell-based regenerative approaches for the treatment of disc degeneration.