Long-term outcomes of anterior cervical dynamic implants: motion-sparing or a delayed fusion?

BACKGROUND CONTEXT: Use of an anterior cervical dynamic implant (ACDI) is generally considered a non-fusion technique for treating cervical degenerative disorders. However, there is limited research focused on evaluating the long-term clinical and radiographic outcomes of ACDI. PURPOSE: To analyze the long-term clinical and radiographic outcomes of ACDI in the treatment of degenerative cervical disorders. STUDY DESIGN: A retrospective cohort study PATIENTS SAMPLE: Patients with degenerative cervical disorders who underwent anterior cervical discectomy and dynamic cervical implant (DCI) implantation between May 2012 and August 202 at our institution were included in this study. OUTCOME MEASURES: Clinical outcomes were assessed using the modified Japanese Orthopedic Association (mJOA), visual analog scale (VAS) scores and patient reported satisfaction rate. Imaging assessment parameters included intervertebral height (IH), intervertebral disc height (IDH), C2-7 range of motion (ROM), segmental ROM, the degree of DCI subsidence and anterior migration, heterotopic ossification (HO) as well as adjacent segment degeneration (ASD). METHODS: JOA and VAS scores were obtained through questionnaire. The patient reported satisfaction was rated as very satisfied, satisfied, less satisfied and dissatisfied at the final follow-up. The position of the implants, IDH and IH were evaluated on lateral radiographs. ROM at C2-7, ROM at operated level were measured on dynamic radiographs. Cervical three -dimensional computer tomography (CT) and magnetic resonance image (MRI) images were used to assess the presence of HO and ASD. The clinical and radiologic variables between the preoperative period and different follow-up time point were statistically analyzed by unpaired t-tests or chi-square tests. Statistical significance was defined as p<0.05. RESULTS: A total of 92 patients (51 males and 41 females) were included in this study. Among them, there were 36 cases of cervical spondylotic myelopathy, 26 cases of cervical radiculopathy, and 30 cases of myeloradiculopathy. The mean age was 55.1±12.6 years. The number of operated levels was single level in 57 patients, two levels in 31 patients, and three levels in 4 patients. The average follow-up period was 81.3 months (range: 35-135 months). The mean JOA scores showed a gradual increase at one month, one year, and the final follow-up (12.0±0.7,13.5±0.8, and14.4±1.1 respectively) compared to the preoperative score (9.1±0.9, p<0.01). VAS scores significantly decreased at one month, one year, and the final follow-up (4.1±0.7,2.3±0.9, and 2.0±0.8 respectively) compared to the preoperative score (7.2±l .2, p<0 .01). At the final follow-up, the patient reported satisfaction was rated as very satisfied, satisfied, less satisfied and dissatisfied (79%, 10%, 10%, 1% respectively). Revision surgery was not required for any of the patients during the follow-up period, either due to instrumentation failure or adjacent segmental diseases. In the radiographic assessment, there was a notable increase in IH and IDH after surgery compared to preoperative values (33.0±4.0mm vs 30.7±3.0mm, p<0.01 and 6.7±2.4mm vs 4.6±0.9mm, p<0.01 respectively), which gradually decreased at 1 year and the final follow-up (IH: 32.1±2.5 vs 30.9±3.5 p=0.024; IDH: 5.3±1.5 mm vs 4.3±0.6 mm, p=0.043 respectively). At the one-month postoperative follow-up, the segmental ROM exhibited a decrease compared with preoperative values (6.2±1.8° vs 7.5±2.0° p=0.044), followed by an increase at the one-year follow-up (6.2±1.8° vs 6.4±1.5° p=0 .078), but ultimately decreased at the final follow-up (6.4±1.5° vs 2.9±0.6°, p<0.01). HO was observed in approximately 81.5% of cases (75/92), while a great proportion (41.3%) of patients experienced varying degrees of prosthesis subsidence and anterior migration during the follow-up. CONCLUSION: At the long-term follow-up, a high incidence of HO, along with varying degrees of subsidence and migration of the prosthesis, were observed in most patients. As the motion preservation capability of the ACDI gradually diminishes, delayed intervertebral autofusion becomes a more likely outcome compared to motion sparing.

Exploiting Dual-Wavelength Depolarization of Skin-tissues for Camera-based Perfusion Monitoring.

Perfusion index (PI), the ratio between variable pulsatile (AC) and non-pulsatile (DC) components in a photoplethysmographic (PPG) signal, is an indirect and non-invasive measure of peripheral perfusion. PI has been widely used in assessing sympathetic block success, and monitoring hemodynamics in anesthesia and intensive care. Based on the principle of dual-wavelength depolarization (DWD) of skin tissues, we propose to investigate its opportunity in quantifying the skin perfusion contactlessly. The proposed method exploits the characteristic changes in chromaticity caused by skin depolarization and chromophore absorption. The experimental results of DWD, obtained with the post occlusive reactive hyperemia test and the local cooling and heating test, were compared to the PI values obtained from the patient monitor and photoplethysmography imaging (PPGI). The comparison demonstrated the feasibility of using DWD for PI measurement. Clinical trials conducted in the anesthesia recovery room and operating theatre further showed that DWD is potentially a new metric for camera-based non-contact skin perfusion monitoring during clinical operations, such as the guidance in anesthetic surgery.

Unlocking the potential of LHPP: Inhibiting glioma growth and cell cycle via the MDM2/p53 pathway.

The recurrence of glioma after treatment has remained an intractable problem for many years. Recently, numerous studies have explored the pivotal role of the mouse double minute 2 (MDM2)/p53 pathway in cancer treatment. Lysine phosphate phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a newly discovered tumor suppressor, has been confirmed in numerous studies on tumors, but its role in glioma remains poorly understood. Expression matrices in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were analyzed using gene set enrichment analysis (GSEA), revealing significant alterations in the p53 pathway among glioma patients with high LHPP expression. The overexpression of LHPP in glioma cells resulted in a reduction in cell proliferation, migration, and invasive ability, as well as an increase in apoptosis and alterations to the cell cycle. The present study has identified a novel inhibitory mechanism of LHPP against glioma, both in vivo and in vitro. The results demonstrate that LHPP exerts anti-glioma effects via the MDM2/p53 pathway. These findings may offer a new perspective for the treatment of glioma in the clinic.

Enhancing the autologous fascial sling procedure: A novel fixation method for treating stress urinary incontinence in female patients.

BACKGROUND: Synthetic mid-urethral sling surgery has long been the standard surgical treatment for stress urinary incontinence (SUI) worldwide. Using an autologous fascial sling is an alternative to reduce adverse events. We evaluated the treatment outcomes of a novel fixation method applied to the autologous transobturator fascial (TOF) sling procedure for female patients with SUI. METHODS: A retrospective study was conducted between 2017 and 2020, including 33 patients with SUI who underwent mid-urethral TOF sling surgery with the novel fixation method. We used a self-locking feature (V-LOC™) that was fixed to each side of skin layer above the obturator foramen, and the tension of the fascia sling was adjusted by manipulating the V-LOC™ suture. We analyzed all data collected through questionnaires, including Urinary Distress Inventory-Short Form (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7), Overactive Bladder Symptom Score (OABSS), and Clinical Global Impressions of Improvement (CGI-I). Adverse events were also recorded. RESULTS: This study included 33 female patients aged 39-79 (mean 59.76 years). Following the procedure, there was a significant reduction in the total scores of UDI-6, IIQ-7, and OABSS (preoperative 9.73±4.35, 10.21±5.79, 6.06±4.03 and postoperative 3.52±3.41, 0.85±3.67, 3.06±2.90, respectively) (p < 0.001). Further analysis of each sub-score of the questionnaires revealed significant improvement in certain symptoms. The mean total score of CGI-I was 2.00 ± 0.80. The maximum flow rate was documented for 18 patients, and no significant reduction was observed after the procedure (p = 0.804). Complications reported included voiding dysfunction in two patients (6.1 %), inguinal pain in one patient (3.0 %), and mild delayed wound healing in one patient (3.0 %). CONCLUSION: This modified TOF sling surgery with a novel fixation method by V-LOC™ suture offers feasibility and adjustability as its main advantages. Our study demonstrated significant improvements in patient outcomes.

The role of ALDH1A1 in glioblastoma proliferation and invasion.

High-grade gliomas, including glioblastoma multiforme (GBM), continue to be a leading aggressive brain tumor in adults, marked by its rapid growth and invasive nature. Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), an enzyme, plays a significant role in tumor progression, yet its function in high-grade gliomas is still poorly investigated. In this study, we evaluated ALDH1A1 levels in clinical samples of GBM. We also assessed the prognostic significance of ALDH1A1 expression in GBM and LGG (low grade glioma) patients using TCGA (The Cancer Genome Atlas) database analysis. The MTT and transwell assays were utilized to examine cell growth and the invasive capability of U87 cells, respectively. We quantitatively examined markers for cell proliferation (Ki-67 and cyclin D1) and invasion (MMP2 and 9). A Western blot test was conducted to determine the downstream signaling of ALDH1A1. We found a notable increase in ALDH1A1 expression in high-grade gliomas compared to their low-grade counterparts. U87 cells that overexpressed ALDH1A1 showed increased cell growth and invasion. We found that ALDH1A1 promotes the phosphorylation of AKT, and inhibiting AKT phosphorylation mitigates the ALDH1A1's effects on tumor growth and migration. In summary, our findings suggest ALDH1A1 as a potential therapeutic target for GBM treatment.

The Emerging Role of Herbal Medicines in Cancer by Interfering with Posttranslational Modifications.

Significance: Herbal medicines have a long history of comprehensive cancer treatment through various posttranslational modifications (PTMs). Recently, emerging evidence revealed that dysregulation of reactive oxygen species (ROS) and ROS-regulated signaling pathways influence cancer initiation, growth, and progression in a paradoxical role with either low levels or increasing levels of basal ROS. However, ROS-triggered modifications of target proteins in the face of ROS-mediated signal transduction are not fully understood in the anticancer therapies of herbal medicines. In this review, we briefly introduce the PTM-dependent regulations of herbal medicines, and then focus on the current ideals that targeting ROS-dependent PTMs via antioxidant and redox signaling pathways can provide a promising strategy in herbal-based anticancer effects. Recent Advances: Advanced development in highly sensitive mass spectrometry-based techniques has helped utilize ROS-triggered protein modifications in numerous cancers. Accumulating evidence has been achieved in laboratory to extensively ascertain the biological mechanism of herbal medicines targeting ROS in cancer therapy. Two general mechanisms underlining ROS-induced cell signaling include redox state and oxidative modification of target protein, indicating a new perspective to comprehend the intricate dialogues between herbal medicines and cancer cellular contexts. Critical Issues: Complex components of herbal medicines limit the benefits of herbal-based cancer therapies. In this review, we address that ROS-dependent PTMs add a layer of proteomic complexity to the cancer through altering the protein structure, expression, function, and localization. Elaborating ROS-triggered PTMs implicated in cell signaling, apoptosis, and transcriptional regulation function, and the possible cellular signaling, has provided important information about the contribution of many ROS targeting herbal therapies in anticancer effects. Continued optimization of proteomic strategies for PTM analysis in herbal medicines is also briefly discussed. Future Directions: Rigorous evaluations of herbal medicines and proteomic strategies are necessary to explore the aberrant regulation of ROS-triggered antioxidant and redox signaling contributing to the novel protein targets and herbal-associated pharmacological issues. These efforts will eventually help develop more herbal drugs as modern therapeutic agents.

Merging metabolic modeling and imaging for screening therapeutic targets in colorectal cancer.

Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved a novel machine learning-based method to computationally screen, in a high-throughput manner, the effects of enzyme perturbations predicted by a computational model of CRC metabolism. This approach reveals the network-wide effects of metabolic perturbations. Our results highlighted hexokinase (HK) as the crucial target, which subsequently became our focus for experimental validation using patient-derived tumor organoids (PDTOs). Through metabolic imaging and viability assays, we found that PDTOs cultured in CAF-conditioned media exhibited increased sensitivity to HK inhibition, confirming the model predictions. Our approach emphasizes the critical role of integrating computational and experimental techniques in exploring and exploiting CRC-CAF crosstalk.

Diagnostic values and relevant factors of lumbar posterior lesions in axial spondyloarthritis.

OBJECTIVES: To compare the lumbar posterior lesions between axial spondyloarthritis (axSpA) and lumbar disc herniation (LDH) patients, then their diagnostic value and related factors were evaluated. METHODS: This cross-sectional study included axSpA patients from January 2020 to September 2023. They were classified as ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) individuals. Canada-Denmark (CANDEN) magnetic resonance imaging (MRI) scoring system was used to assess the defects of the lumbar spine. Receiver operating characteristic curve analysis was utilized to determine the value of distinguishing nr-axSpA. Linear regression analyses were adopted to find the relevant factors for lumbar posterior lesions. RESULTS: Ninety-six AS, 98 nr-axSpA, and 108 LDH patients were included. The CANDEN scores were greater in axSpA patients, AS in particular. Furthermore, lumbar posterior lesions can distinguish AS, nr-axSpA, and LDH. Besides, lumbar posterior lesions were positively related to the similar MRI changes in their adjacent structures, but were inversely associated with the other abnormalities. CONCLUSIONS: Lumbar posterior lesions were more serious in axSpA patients. These alterations had value in distinguishing axSpA. Lumbar posterior defects were related to their adjacent components, and they may not fully follow the MRI changing pattern of vertebral bodies and sacroiliac joints.

Albumin to globulin ratio (AGR) in systemic lupus erythematosus: correlation with disease activity.

OBJECTIVE: To investigate the role of albumin-to-globulin ratio (AGR) in systemic lupus erythematosus (SLE) and its relationship with disease activity. METHODS: This retrospective study consecutively selected patients with SLE and healthy controls. Patients were divided into three groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K): group 1 (mild disease activity, SLEDAI-2K ≤ 6), group 2 (moderate disease activity, SLEDAI-2K 7-12) and group 3 (severe disease activity, SLEDAI-2K > 12). Predictors of SLE disease activity were analysed by ordinal logistical regression. RESULTS: A total of 101 Chinese patients with SLE and 75 healthy Chinese controls were included. Patients with SLE had lower AGR values than healthy individuals, and group 3 patients with SLE displayed lower AGR values than those in group 1, but similar values to group 2. AGR was inversely correlated with SLEDAI-2K (r = -0.543). Ordinal logistic regression analysis showed that lower AGR (ß = -1.319) and lower complement C4 (ß = -1.073) were independent risk factors for SLE disease activity. CONCLUSIONS: AGR was decreased in patients with SLE and may be utilized as a useful inflammatory biomarker for monitoring SLE disease activity.