Full endoscopic surgery for calcium pyrophosphate deposition disease (CPPD) in the cervical ligamentum flavum: report of two cervical myelopathy cases.

Calcium pyrophosphate deposition disease (CPPD), known as pseudogout, is characterized by the accumulation of calcium pyrophosphate crystals in musculoskeletal structures, primarily joints. While CPPD commonly affects various joints, involvement in the cervical spine leading to myelopathy is rare. Surgical intervention becomes necessary when conservative measures fail, but reports on full endoscopic surgeries are extremely rare. We present two successful cases where full endoscopic systems were used for CPPD removal in the cervical spine. The surgical technique involved a full endoscopic approach, adapting the previously reported technique for unilateral laminotomy bilateral decompression. Full-endoscopic removal of cervical CPPD inducing myelopathy were successfully removed with good clinical and radiologic outcomes. The scarcity of endoscopic cases for cervical ligamentum flavum CPPD is attributed to the condition's rarity. However, our successful cases advocate for endoscopic surgery as a potential primary treatment option for CPPD-induced cervical myelopathy, especially in elderly patients or those with previous cervical operation histories. This experience encourages the consideration of endoscopic surgery for managing cervical ligamentum flavum CPPD as a viable alternative.

Lumbar fusion surgery in the era of an aging society: analysis of a nationwide population cohort with minimum 8-year follow-up.

BACKGROUND CONTEXT: Fusions for lumbar spine diseases are widely performed and have a growing incidence, especially in elderly population. PURPOSE: The goal of this study was to assess national trends of lumbar spinal fusions and examine the risk for re-operations after a lumbar fusion with a focus on 'epidemiologic transition' relating to age. STUDY DESIGN/SETTING: The prospectively collected Korean Health Insurance Review and Assessment Service (HIRA) nationwide cohort database was retrospectively reviewed. PATIENT SAMPLE: The total 278,815 patients who underwent lumbar spinal fusions for degenerative spine diseases between 2010 and 2018 were reviewed and used to assess trends in operative incidence. The 37,050 patients who underwent lumbar fusions between 1/2010 and 12/2011 were enrolled to determine 8-year reoperation rates. OUTCOME MEASURES: The overall number of lumbar spinal fusions were analyzed for the national annual trend. Demographic data, reoperation rates, and confounding clinical factors were evaluated. METHODS: The overall number of lumbar spinal fusions was analyzed to determine the national annual trend of operative incidence. For the reoperation rate analysis, the primary outcome measured was the cumulative incidence of revision operations within a minimum 8-year follow-up period. Additional outcomes included comparative analyses of the reoperation rate with respect to age, sex, or other underlying comorbidities. RESULTS: Over time, elderly patients comprised a larger portion of the cohort (2010:24.2%; 2018:37.6%), while operations in younger patients decreased over time (2010:40.3%; 2018:27.0%). In the cohort of patients with a minimum 8-year follow-up (n=37,050), rates of reoperation peaked in patients aged 60-69 years (17.6 per 1000 person-years [HR 2.20 compared to <40years]) and decreased for more elderly patients (14.3 per 1000 person-years [HR 1.80 compared to <40years]). Age was the most significant risk factor for reoperation. Osteoporosis was also a risk factor for reoperation in post-menopausal females. CONCLUSIONS: Increasing incidence of lumbar fusions in elderly patients was seen however the risk of reoperation decreased in patients aged 70 or more. Lumbar fusion for elderly patients should not be hesitated in the decision-making process because of concerns about reoperation.

Postoperative survival after lumbar instrumented surgery for metastatic spinal tumors: a nationwide population-based cohort analysis.

BACKGROUND: It is difficult to predict the expected survival after lumbar instrumented surgery for metastases owing to the difference among different cancer origins and the relatively short survival after surgery. AIMS: The aim of this study is to analyze the postoperative survival period of lumbar spinal metastasis patients who underwent lumbar instrumented surgery. METHODS: Data were collected from the Korean National Health Insurance Review and Assessment Service database. Patients who underwent lumbar spinal surgery with instrumentation between January 2011 and December 2015 for metastatic lumbar diseases were reviewed. The mean postoperative survival period of patients with metastatic lumbar cancer according to each primary cancer type was evaluated. RESULTS: A total of 628 patients were enrolled and categorized according to primary cancer type. The overall median survival rate was 1.11±1.30 years. The three most prevalent primary cancer groups were lung, hepatobiliary, and colorectal cancers, presenting relatively short postoperative survival rates (0.93±1.25, 0.74±0.75 and 0.74±0.88 years, respectively). The best postoperative survival period was observed in breast cancer (2.23±1.83 years), while urinary tract cancer showed the shortest postoperative survival period (0.59±0.69 years). CONCLUSION: The postoperative survival period of patients with lumbar metastatic spinal tumors according to different primary cancers after instrumented fusion was ˃1 year overall, with differences according to different primary origins. This result may provide information regarding the expected postoperative survival after instrumented surgery for lumbar spinal metastases.

A quantitative analysis of surgical smoke-derived particulate matter and formaldehyde exposure during spine surgery: a possible occupational hazard.

OBJECTIVE: Since its introduction, electrocautery has served as a valuable surgical tool, enabling precise tissue cutting and effective hemostasis in spine surgery. While there have been numerous efforts to elucidate the possible hazardous effects of surgical smoke in various surgical fields, there has been very little discussion in the context of spine surgery. The objective of this study was to measure and conduct a quantitative analysis of the particulate matter (PM) of different sizes and of formaldehyde (HCHO) generated by smoke during spine surgeries. METHODS: This study included a consecutive series of patients who underwent 1- or 2-level lumbar spinal fusion surgery between June and November 2021. Particle counts were measured using a particle counter, specifically focusing on six different sizes of PM (0.3, 0.5, 1, 2.5, 5, and 10 µm). Additionally, measurements were taken for HCHO in parts per million (ppm). Monopolar cautery was used in the surgical setting. Systematic measurements were conducted at specific time points during the surgical procedures to assess the levels of PM and HCHO. Furthermore, the efficacy of surgical smoke suction was evaluated by comparing the PM levels with and without adjacent placement of suction. RESULTS: This study involved 35 patients, with measurements of both PM and HCHO taken in 27 cases. The remaining 8 cases had measurements only for PM. In this study, statistically significant quantitative changes in various PM sizes were observed when electrocautery was used during spine surgery (12.3 ± 1.7 vs 1975.7 ± 422.8, 3.4 ± 0.5 vs 250.1 ± 45.7, and 1.9 ± 0.2 vs 78.1 ± 13.3, respectively, for 2.5-, 5-, and 10-µm PM; p < 0.05). The level of HCHO was also significantly higher (0.085 ± 0.006 vs 0.131 ± 0.014 ppm, p < 0.05) with electrocautery use. Utilization of adjacent suction of surgical smoke during electrocautery demonstrated a statistically significant reduction in PM levels. CONCLUSIONS: The findings of this study highlight the potential surgical smoke-related hazards that spine surgeons may be exposed to in the operating room. Implementing simple interventions, such as utilizing nearby suction, can effectively minimize the amount of toxic surgical smoke and mitigate these risks.

Intervertebral disc organ-on-a-chip: an innovative model to study monocyte extravasation during nucleus pulposus degeneration.

Degenerative cascades of the intervertebral disc (IVD) are characterized by the presence of immune cells like monocytes, macrophages, and leukocytes, which contribute to inflammation. Previous in vitro studies on monocyte chemotaxis in the presence of chemical or mechanical stimulation were unable to establish the effects of endogenous stimulating factors from resident IVD cells, or fully understand macrophage and monocyte differentiation pathways in IVD degeneration. Our study simulates monocyte extravasation using a fabricated microfluidic chemotaxis IVD organ-on-a-chip (IVD organ chip), which models the geometry of IVD, chemoattractant diffusion, and infiltration of immune cells. Additionally, the fabricated IVD organ chip mimics stepwise monocyte infiltration and differentiation into macrophages in the degenerative nucleus pulposus (NP) induced by IL-1ß. We find that naïve NP cells do not recruit THP-1 monocyte-like cells, but degenerative NP cells recruit and accumulate macrophages through chemo-gradient channels. Furthermore, the differentiated and migrated THP-1 cells show phagocytic activity around inflammatory NP cells. Our in vitro model of monocyte chemotaxis with degenerative NP on an IVD organ chip depicts the sequential processes of monocyte migration/infiltration, monocyte-to-macrophage differentiation, and accumulation. Using this platform to gain a deeper understanding of monocyte infiltration and differentiation processes can provide insights into the pathophysiology of the immune response in degenerative IVD.

Radiologic risk factors associated with development of myelopathy in patients with ossification of the posterior longitudinal ligament of the cervical spine.

STUDY DESIGN: Retrospective Cohort Study OBJECTIVE: Myelopathy following ossification of the posterior longitudinal ligament (OPLL) is one of the devastating clinical features in these patients, while we still know little about which factors are associated with development of myelopathy. We evaluated the difference of radiologic measurements between OPLL patients with or without myelopathy and searched for the clinical significance with emphasis on the impact of dynamic motion. METHODS: 305 patients diagnosed of OPLL were enrolled for retrospective review. They were divided into two groups according to the coexistence of radiographic evidence of myelopathy. Demographic data as well as radiologic measures including the presence of disc degeneration (DD), anterior-posterior diameter (APD) of central canal, canal compromise (CC) ratio, global and segmental range of motion (gROM and sROM), OPLL type (morphologic classification) and K-line were collected. RESULTS: APD (odds ratio (OR); 0.411), CC ratio (OR; 1.100) and sROM (OR; 1.371) were significantly associated with the presence of myelopathy in the multivariate analysis. While the statistically significant factors were same in OPLLs with CC larger than 50%, presence of DD (OR; 4.509) and sROM (OR; 1.295) were significantly associated with myelopathy but not the CC itself in OPLLs with CC smaller than 50%. CONCLUSIONS: We discovered that the APD, CC ratio and sROM had significant association with development of myelopathy in OPLLs. And the presence of dynamic factors had significant association with myelopathy in OPLLs with smaller CC ratios. This observation and its clinical significance on development of myelopathy might enhance our understanding of OPLL.

Use of prophylactic perioperative antibiotics for lumbar spinal fusions: A nationwide population-based cohort study.

BACKGROUND: Perioperative prophylactic antibiotic (PPA) use in spine surgery is known to reduce the rate of surgical site infections. In the past decade, several evidence-based guidelines have been published and surveillance systems to monitor the proper use of antimicrobials had been adapted by many institutes. OBJECTIVE: To report the trends of PPA prescription in lumbar fusion surgeries nationwide in the Republic of Korea. METHODS: This is a nationwide registry study. Using the population-based data from the Republic of Korea provided by the Korean Health Insurance Review and Assessment Service, data of all lumbar spinal fusion surgeries performed between 2010 and 2018 in adult patients (age ≥19 years) were reviewed. RESULTS: The most frequently used antibiotics were first-generation cephalosporins, which accounted for 38.2 % of total PPA prescriptions and were prescribed in 58.96 % of lumbar fusion surgeries. A gradual increase in prescription trends was observed. The second most frequently used PPAs were second-generation cephalosporins, which showed decrease in use from 2016. The frequency of vancomycin prescriptions gradually increased over the observation period and showed an almost four-fold increase in 2018 compared to 2010. First- and second-generation cephalosporins were prescribed less frequently to patients with renal disease. CONCLUSION: The pattern of PPA use has changed remarkably over the observation period. Furthermore, specific differences in PPA prescriptions were observed among patients with certain co-morbidities.

Elucidating the effect of mechanical stretch stress on the mechanism of ligamentum flavum hypertrophy: Development of a novel in vitro multi-torsional stretch loading device.

OBJECTIVE: We developed a novel multi-torsional mechanical stretch stress loading device for ligamentum flavum cells and evaluated its influence on the development of ligamentum flavum hypertrophy, a common cause of lumbar spinal canal stenosis. MATERIALS AND METHODS: Stretch strength of the device was optimized by applying 5% and 15% MSS loads for 24, 48, and 72 h. A cytotoxicity assay of human ligamentum flavum cells was performed and the results were compared to control (0% stress). Inflammatory markers (interleukin [IL]-6, IL-8), vascular endothelial growth factor [VEGF], and extracellular matrix (ECM)-regulating cytokines (matrix metalloproteinase [MMP]-1, MMP-3 and MMP-9, and tissue inhibitor of metalloproteinase [TIMP]-1 and TIMP-2) were quantified via enzyme-linked immunosorbent assay. RESULTS: Using our multi-torsional mechanical stretch stress loading device, 5% stress for 24 hour was optimal for ligamentum flavum cells. Under this condition, the IL-6 and IL-8 levels, VEGF level, and MMP-1, MMP-3, and TIMP-2 were significantly increased, compared to the control. CONCLUSION: Using the novel multi-torsional mechanical stretch stress loading device we confirmed that, mechanical stress enhances the production of inflammatory cytokines and angiogenic factors, and altered the expression of ECM-regulating enzymes, possibly triggering ligamentum flavum hypertrophy.

Adipokine human Resistin promotes obesity-associated inflammatory intervertebral disc degeneration via pro-inflammatory cytokine cascade activation.

Adipokine human Resistin (hResistin), is known to be associated with insulin resistance and secrete low-grade pro-inflammatory cytokines in obesity. Although studies on low-grade inflammation of adipokine hResistin are known, studies on the effects and mechanisms of intervertebral disc degeneration (IVDD) are still lacking. Thus, we investigated the adipokine hResistin with or without pro-inflammatory cytokine IL-1ß in intervertebral disc (IVD) cells such as human annulus fibrosus (hAF) and nucleus pulposus (hNP). The protein expression changes in IL-1ß, IL-6, IL-8, MMP-1, MMP-3, and MMP-13, induced by the combined-hResistin and IL-1ß stimulation on hAF cells, was significantly greater than that of the same induced by mono-IL-1ß stimulation. Similarly, in the case of the protein expression change of inflammatory mediators induced by the combined-hResistin and IL-1ß stimulation on hNP cells was also significantly greater than that of the same induced by mono-IL-1ß stimulation. These results improve understanding of hResistin on inflammatory IVDD but also with other obesity-related inflammatory diseases.

Characteristics of Sagittal Spinopelvic Alignment Changes After Symptom Relief After Simple Lumbar Decompression.

BACKGROUND: Sagittal spinopelvic alignment (SSPA) parameters are essential for the diagnosis of adult spinal deformities (ASDs) and their progression. Certain clinical symptoms that occur in patients with lumbar spinal stenosis (LSS) and herniated nucleus pulposus (HNP) may distort the SSPA and mimic ASD. OBJECTIVE: To differentiate SSPA in symptomatic patients from asymptomatic patients within 10 minutes in the standing position. METHODS: This retrospective cohort study evaluated changes in SSPA after simple lumbar decompression surgery in patients with LSS and HNP. Relative sagittal alignment (RSA), relative pelvic version, relative lumbar lordosis (RLL), Lordosis Distribution Index (LDI), and global alignment and proportion (GAP) values were calculated using the conventional Schwab classification method. First, the preoperative and postoperative SSPA parameters were compared. Second, patients were subgrouped into symptomatic within 10 minutes of standing (SP group) and other symptoms of LSS and HNP as controls. Changes in SSPA parameters after symptom relief after simple lumbar decompression surgery were compared between the two groups. RESULTS: Overall, all SSPA parameters improved after surgery. However, after subgrouping, patients in the control group did not show significant SSPA alterations, except for LDI, whereas patients in the SP group significantly improved in terms of their RSA, RLL, LDI, and GAP values after symptom relief after surgery. CONCLUSION: Patients with pain on standing within 10 minutes showed significant correction in RSA, RLL, and GAP values after simple lumbar decompression. Therefore, it is important to observe such clinical symptoms to avoid misdiagnosis of ASD.

Current Knowledge and Future Therapeutic Prospects in Symptomatic Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration is the main source of intractable lower back pain, and symptomatic IVD degeneration could be due to different degeneration mechanisms. In this article, we describe the molecular basis of symptomatic IVD degenerative disc diseases (DDDs), emphasizing the role of degeneration, inflammation, angiogenesis, and extracellular matrix (ECM) regulation during this process. In symptomatic DDD, pro-inflammatory mediators modulate catabolic reactions, resulting in changes in ECM homeostasis and, finally, neural/vascular ingrowth-related chronic intractable discogenic pain. In ECM homeostasis, anabolic protein-regulating genes show reduced expression and changes in ECM production, while matrix metalloproteinase gene expression increases and results in aggressive ECM degradation. The resultant loss of normal IVD viscoelasticity and a concomitant change in ECM composition are key mechanisms in DDDs. During inflammation, a macrophage-related cascade is represented by the secretion of high levels of pro-inflammatory cytokines, which induce inflammation. Aberrant angiogenesis is considered a key initiative pathologic step in symptomatic DDD. In reflection of angiogenesis, vascular endothelial growth factor expression is regulated by hypoxia-inducible factor-1 in the hypoxic conditions of IVDs. Furthermore, IVD cells undergoing degeneration potentially enhance neovascularization by secreting large amounts of angiogenic cytokines, which penetrate the IVD from the outer annulus fibrosus, extending deep into the outer part of the nucleus pulposus. Based on current knowledge, a multi-disciplinary approach is needed in all aspects of spinal research, starting from basic research to clinical applications, as this will provide information regarding treatments for DDDs and discogenic pain.

A Prospective, Multi-Center, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of the Synthetic Bone Graft Material DBM Gel with rhBMP-2 versus DBM Gel Used during the TLIF Procedure in Patients with Lumbar Disc Disease.

OBJECTIVE: This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). METHODS: This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. RESULTS: The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, 'Pyrexia' (5.00%) was the most common ADE, followed by 'Hypesthesia', 'Paresthesia', 'Transient peripheral paralysis', 'Spondylitis' and 'Insomnia' (2.50%, respectively). ADEs reported in control group included 'Pyrexia', 'Chest discomfort', 'Pain', 'Osteoarthritis', 'Nephropathy toxic', 'Neurogenic bladder', 'Liver function analyses' and 'Urticaria' (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ''Pyrexia' and 'Spondylitis' were 2.50%. SADE reported in the control group included 'Chest discomfort', 'Osteoarthritis' and 'Neurogenic bladder'. All SADEs described above were resolved after medical treatment. CONCLUSION: This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

Extra-domain B of fibronectin as an alternative target for drug delivery and a cancer diagnostic and prognostic biomarker for malignant glioma.

Extra-domain B of fibronectin (EDB-FN) is an alternatively spliced form of fibronectin with high expression in the extracellular matrix of neovascularized tissues and malignant cancer cells. In this study, we evaluated the practicality of using EDB-FN as a biomarker and therapeutic target for malignant gliomas (MGs), representative intractable diseases involving brain tumors. Methods: The microarray- and sequence-based patient transcriptomic database 'Oncopression' and tissue microarray of MG patient tissue samples were analyzed. EDB-FN data were extracted and evaluated from 23,344 patient samples of 17 types of cancer to assess its effectiveness and selectivity as a molecular target. To strengthen the results of the patient data analysis, the utility of EDB-FN as a molecular marker and target for MG was verified using active EDB-FN-targeting ultrasmall lipidic micellar nanoparticles (~12 nm), which had a high drug-loading capacity and were efficiently internalized by MG cells in vitro and in vivo. Results: Brain tumors had a 1.42-fold cancer-to-normal ratio (p < 0.0001), the second highest among 17 cancers after head and neck cancer. Patient tissue microarray analysis showed that the EDB-FN high-expression group had a 5.5-fold higher risk of progression than the EDB-FN low-expression group (p < 0.03). By labeling docetaxel-containing ultrasmall micelles with a bipodal aptide targeting EDB-FN (termed APTEDB-DSPE-DTX), we generated micelles that could specifically bind to MG cells, leading to superior antitumor efficacy of EDB-FN-targeting nanoparticles compared to nontargeting controls. Conclusions: Taken together, these results show that EDB-FN can be an effective drug delivery target and biomarker for MG.

A New Classification for Cervical Ossification of the Posterior Longitudinal Ligament Based on the Coexistence of Segmental Disc Degeneration.

OBJECTIVE: Classification systems for cervical ossification of the posterior longitudinal ligament (OPLL) have traditionally focused on the morphological characteristics of ossification. Although the classification describes many clinical features associated with the shape of the ossification, including the concept of spondylosis seems necessary because of the similarity in age distribution. METHODS: Patients diagnosed with OPLL who presented with increase signal intensity (ISI) on magnetic resonance imaging were surgically treated in our department. The patients were divided into two groups (pure versus degenerative) according to the presence of disc degeneration. RESULTS: Of 141 patients enrolled in this study, more than half (61%) were classified into the degenerative group. The pure group showed a profound male predominance, early presentation of myelopathy, and a different predilection for ISI compared to the degenerative group. The mean canal compromise ratio (CC) of the ISI was 47% in the degenerative group versus 61% in the pure group (p<0.0000). On the contrary, the global and segment motions were significantly larger in the degenerative group (p<0.0000 and p=0.003, respectively). The canal diameters and global angles did not differ between groups. CONCLUSION: Classifying cervical OPLL based on the presence of combined disc degeneration is beneficial for understanding the disorder's behavior. CC appears to be the main factor in the development of myelopathy in the pure group, whereas additional dynamic factors appear to affect its development in the degenerative group.

Coronavirus Disease (COVID-19) Outbreak and Its Impact on Spinal Daily Practice : Preliminary Report from a Single (Regional) University Hospital in Republic of Korea.

OBJECTIVE: Since the first discovery of the 2019 novel coronavirus (COVID-19), rapid and wide spread of the disease has been reported and the World Health Organization announced that a 'pandemic' has started. Up to date there is little known regarding the impact of this outbreak on spinal specialists' daily clinical practice. We intended to evaluate how COVID-19 has affected the number of spinal disease patients we meet and operate in daily practice. METHODS: The de-identified data regarding number of patients visiting the spine clinic at a tertiary referral hospital and a secondary level hospital from January, February and March of 2017 to 2020 were retrospectively reviewed. The number of out-patient department (OPD) visits, number of emergency room (ER) visits as well as number of surgeries performed during the reviewed period were collected and analyzed, comparing 2020 to the previous 3 years. RESULTS: The number of daily OPD visits showed a steady decrease starting from January, and presented a statistically significant decrease by early March 2020, compared to the previous 3 years. During the same period, decrease in number of daily ER visits was statistically significant as well. The number of elective surgeries or number of surgeries for patients admitted via ER during COVID-19 outbreak remained similar to that of 2017-2019 suggesting, despite the decrease of patients visiting the hospital for spinal diseases, those whom required surgery still visited the hospital. The results were consistant among other hospital level. CONCLUSION: The outbreak of COVID-19 affected our daily practice as OPD and ER visits reduced but did not affect the number of surgeries. We believe that this report will be informative to spinal specialists worldwide fighting the COVID-19 pandemic.

Comparison of Operating Conditions, Postoperative Pain and Recovery, and Overall Satisfaction of Surgeons with Deep vs. No Neuromuscular Blockade for Spinal Surgery under General Anesthesia: A Prospective Randomized Controlled Trial.

We aimed to investigate operating conditions, postoperative pain, and overall satisfaction of surgeons using deep neuromuscular blockade (NMB) vs. no NMB in patients undergoing lumbar spinal surgery under general anesthesia. Eighty-three patients undergoing lumbar fusion were randomly assigned to receive deep NMB (n = 43) or no NMB (n = 40). In the deep-NMB group, rocuronium was administered to maintain deep NMB (train-of-four count 0, post-tetanic count 1-2) until the end of surgery. In the no-NMB group, sugammadex 4 mg/kg at train-of-four (TOF) count 0-1 or sugammadex 2 mg/kg at TOF count ≥2 was administered to reverse the NMB 10 min after placing the patient prone. Peak inspiratory airway pressure, plateau airway pressure, lumbar retractor pressure significantly were lower in the deep-NMB group. Degree of surgical field bleeding (0-5), muscle tone (1-3), and satisfaction (1-10) rated by the surgeon were all superior in the deep-NMB group. Pain scores, rescue fentanyl consumption in post-anesthesia care unit (PACU), and postoperative patient-controlled analgesia consumption were significantly lower in the deep-NMB group, and this group had a shorter length of stay in PACU. Compared to no NMB, deep NMB provides better operating conditions, reduced postoperative pain and higher overall satisfaction in lumbar spinal surgery.

Inflammation by activated macrophage-like THP-1 cells increases human dura mater cell adhesion with alteration of integrin α2 ß1 and matrix metalloproteinase.

This study was designed to investigate (i) extracellular matrix to specify adhesive substrates to human dura mater cell (hDMC); (ii) the alteration on adhesion-related molecules in hDMC; and (iii) secreted matrix metalloproteinases (MMPs) linked with extracellular matrix remodeling after exposure to inflammation. The hDMC was cultured from human dura mater tissue, and the studies were performed with hDMC after co-culturing with macrophage like THP-1 cells (Mϕ). The adhesion of co-cultured hDMC through collagen I increased 6.4-fold and through collagen IV increased 5.0-fold compared with the adhesion of naïve cells (p < 0.001). Integrin subtype α2 ß1 expression was increased 6.3-fold (p < 0.001) and α1 expression was decreased 2.0-fold (p < 0.001) in the co-cultured cells compared with the naïve cells. Co-culturing induced significant increases in MMP-1 (13.9-fold, p < 0.01), MMP-3 (7.6-fold, p < 0.01), and VEGF (VEGF: 3.8-fold, p < 0.05) expression and decreases in MMP-9 (0.1-fold, p < 0.01) compared with the sum of naïve hDMC and Mϕ values. Increased hDMC adhesion under inflammatory conditions is caused by an increased cellular affinity for collagen I and IV mediated by increased hDMC levels of integrin subtype α2 ß1 and environmental MMP-1, -3 and decreased MMP-9. Selective integrin subtype α2 ß1 inhibition assay showed 37.8% and 35.7% reduction in adhesion of co-cultured hDMC to collagen I (p < 0.001) and IV (p = 0.057), respectively. The present study provides insight into the pathological conditions related to dura mater adhesion in inflammation. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-11, 2019.

Pharmacological target therapy of neuropathic pain and patient-reported outcomes in patients with chronic low back pain in Korea: Results from the NLBP Outcomes Research.

A number of studies have demonstrated an association of neuropathic pain and chronic low back pain (CLBP), but the outcome difference in each medical management is poorly understood. This study is aimed to investigate treatment patterns of neuropathic pain in CLBP patients and to explore patient-reported outcomes (PROs) including quality of life (QoL) and functional disability by treatment patterns.Data were extracted from the neuropathic low back pain (NLBP) outcomes research. It was a multicenter and cross-sectional study in which 1200 patients were enrolled at 27 general hospitals, from 2014 to 2015. Of total, 478 patients classified as neuropathic pain were used for this subgroup analysis. The patients were divided into 2 groups according to treatment patterns (with vs. without the targeted therapy [TT] of neuropathic pain). Demographic and clinical features were collected by chart reviews and PROs were measured by patient's survey. QoL was assessed by EuroQoL 5-dimension (EQ-5D) questionnaire. Functional disability was measured by the Quebec Back Pain Disability Scale (QBPDS). Multiple linear regression analyses were conducted to compare the PROs between TT group and non-targeted therapy (nTT) group.Among the NLBP patients (mean age 63years, female 62%), EQ-5D index, EuroQoL-Visual Analog Scale (EQ-VAS), and QBPDS Scores (mean ±â€Šstandard deviation) were 0.40 ±â€Š0.28, 54.98 ±â€Š19.98, and 46.03 ±â€Š21.24, respectively. Only 142 (29.7%) patients had pharmacological TT of neuropathic pain. Univariate analyses revealed no significant mean differences between TT group and nTT group in the EQ-5D index (0.41 ±â€Š0.27 and 0.39 ±â€Š0.28), EQ-VAS (56.43 ±â€Š18.17 and 54.37 ±â€Š20.69), and QBPDS (45.31 ±â€Š21.32 and 46.31 ±â€Š21.24). After adjustment with covariates, TT group had higher scores of EQ-5D index (ß = 0.07; P < 0.01) and EQ-VAS (ß = 4.59; P < 0.05) than the nTT group. The TT group's QBPDS score was lower than the nTT group, although its statistical significance still has not been reached (ß = -4.13; P = 0.07).We found that considerable proportion of the NLBP patients remains untreated or undertreated. Although TT group had significantly better QoL than nTT group, only 29.7% of NLBP patients had pharmacological TT. Therefore, clinicians should consider using TT for better QoL of neuropathic pain patients.

Photobiomodulation of extracellular matrix enzymes in human nucleus pulposus cells as a potential treatment for intervertebral disk degeneration.

Intervertebral disc (IVD) degeneration is associated with imbalances between catabolic and anabolic responses, regulated by extracellular matrix (ECM)-modifying enzymes such as matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs). Potential contributing factors, such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, derived from infiltrated, activated macrophages within IVD tissues, can trigger abnormal production of ECM-modifying enzymes and progression of IVD degeneration. Novel therapies for regulating ECM-modifying enzymes can prevent or ameliorate IVD degeneration. Photobiomodulation (PBM), known to regulate wound repair, exhibits regenerative potential by modulating biological molecules. This study examined the effects of PBM, administered at various wavelengths (630, 525, and 465 nm) and energy densities (16, 32, and 64 J/cm2), on the production of ECM-modifying enzymes in replicated degenerative IVD. Our results showed that PBM selectively inhibited the production of ECM-modifying enzymes in a dose- and wavelength-dependent manner, suggesting that it could be a novel tool for treating symptomatic IVD degeneration.