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INTRODUCTION: Spinal cord injury (SCI) is a devastating injury and remains one of the largest medical and social burdens because of its intractable nature. According to the recent advances in stem cell biology, the possibility of spinal cord regeneration and functional restoration has been suggested by introducing appropriate stem cells. Multilineage-differentiating stress enduring (Muse) cells are a type of nontumorigenic endogenous reparative stem cell. The positive results of Muse cell transplantation for SCI was shown previously. As a first step for clinical application in human SCI, we conducted a clinical trial aiming to confirm the safety and feasibility of intravenously injected donor-Muse cells. METHODS: The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 106 cells, 2.1-2.7 × 105 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip. RESULTS: There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration. CONCLUSION: In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI. TRIAL REGISTRATION: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .
Subject(s)
Administration, Intravenous , Spinal Cord Injuries , Humans , Spinal Cord Injuries/therapy , Female , Male , Adult , Middle Aged , Feasibility Studies , Prospective Studies , Aged , Cervical VertebraeABSTRACT
STUDY DESIGN: A retrospective analysis. OBJECTIVE: This research sought to develop a predictive model for surgical outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using deep learning and machine learning (ML) techniques. SUMMARY OF BACKGROUND DATA: Determining surgical outcomes assists surgeons in communicating prognosis to patients and setting their expectations. Deep learning and ML are computational models that identify patterns from large datasets and make predictions. METHODS: Of the 482 patients, 288 patients were included in the analysis. A minimal clinically important difference (MCID) was defined as gain in Japanese Orthopaedic Association (JOA) score of 2.5 points or more. The predictive model for MCID achievement at 1 year post-surgery was constructed using patient background, clinical symptoms, and preoperative imaging features (x-ray, CT, MRI) analyzed via LightGBM and deep learning with RadImagenet. RESULTS: The median preoperative JOA score was 11.0 (IQR: 9.0-12.0), which significantly improved to 14.0 (IQR: 12.0-15.0) at 1 year after surgery (P < 0.001, Wilcoxon signed-rank test). The average improvement rate of the JOA score was 44.7%, and 60.1% of patients achieved the MCID. Our model exhibited an area under the receiver operating characteristic curve of 0.81 and the accuracy of 71.9% in predicting MCID at 1 year. Preoperative JOA score and certain preoperative imaging features were identified as the most significant factors in the predictive models. CONCLUSION: A predictive ML and deep learning model for surgical outcomes in OPLL patients is feasible, suggesting promising applications in spinal surgery. LEVEL OF EVIDENCE: 4.
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BACKGROUND: Suction drainages are commonly used after total knee arthroplasty (TKA) procedures; however, their use is somewhat controversial. Recently, some reports have claimed that the administration of tranexamic acid (TXA) may prevent postoperative bleeding following TKAs. Although numerous studies have reported regarding different dosages, timings of administration, or drain clamping times for intravenous and intra-articular TXA injections (IA-TXAs), few have examined whether suction drainage is necessary when TXA is administered. In this study, we compared using suction drainage without TXA administration and IA-TXA without suction drainage and aimed to examine the need for suction drainage during IA-TXA. METHODS: This retrospective study was conducted on 217 patients who had received TKA for osteoarthritis; 104 were placed on suction drainage after TKA without TXA (Group A), whereas the remaining 113 received IA-TXA immediately after surgery without suction drainage (Group B). Our clinical evaluation included assessments of the need for transfusion, presence of postoperative complications, incidence of deep vein thrombosis (DVT), and changes in hemoglobin (Hb), hematocrit (Hct), and D-dimer levels. RESULTS: No significant differences were observed in terms of postoperative complications and preoperative Hb, Hct, or D-dimer levels between the two groups. Although the prevalence of DVT was significantly higher in Group B (p < 0.05), all cases were asymptomatic. Hb and Hct levels were significantly lower in Group A than in Group B at 1, 3, 7, and 14 days postoperatively (p < 0.05), although none of the cases required blood transfusions. D-dimer levels were significantly higher in Group A than in Group B at 1 and 3 days postoperatively (p < 0.05). CONCLUSION: Suction drainage might not be necessary when IA-TXA is administered after TKA procedures.
Subject(s)
Antifibrinolytic Agents , Arthroplasty, Replacement, Knee , Postoperative Hemorrhage , Tranexamic Acid , Humans , Tranexamic Acid/administration & dosage , Tranexamic Acid/adverse effects , Retrospective Studies , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Female , Male , Aged , Suction , Injections, Intra-Articular , Antifibrinolytic Agents/administration & dosage , Antifibrinolytic Agents/adverse effects , Middle Aged , Postoperative Hemorrhage/prevention & control , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/epidemiology , Aged, 80 and over , Osteoarthritis, Knee/surgery , Venous Thrombosis/prevention & control , Venous Thrombosis/etiology , Venous Thrombosis/epidemiology , Treatment OutcomeABSTRACT
(1) Introduction: Despite documented clinical and pain discrepancies between male and female osteoarthritis (OA) patients, the underlying mechanisms remain unclear. Synovial myofibroblasts, implicated in synovial fibrosis and OA-related pain, offer a potential explanation for these sex differences. Additionally, interleukin-24 (IL24), known for its role in autoimmune disorders and potential myofibroblast production, adds complexity to understanding sex-specific variations in OA. We investigate its role in OA and its contribution to observed sex differences. (2) Methods: To assess gender-specific variations, we analyzed myofibroblast marker expression and IL24 levels in synovial tissue samples from propensity-matched male and female OA patients (each n = 34). Gene expression was quantified using quantitative polymerase chain reaction (qPCR). The association between IL24 expression levels and pain severity, measured by a visual analog scale (VAS), was examined to understand the link between IL24 and OA pain. Synovial fibroblast subsets, including CD45-CD31-CD39- (fibroblast) and CD45-CD31-CD39+ (myofibroblast), were magnetically isolated from female patients (n = 5), and IL24 expression was compared between these subsets. (3) Results: Females exhibited significantly higher expression of myofibroblast markers (MYH11, ET1, ENTPD2) and IL24 compared to males. IL24 expression positively correlated with pain severity in females, while no correlation was observed in males. Further exploration revealed that the myofibroblast fraction highly expressed IL24 compared to the fibroblast fraction in both male and female samples. There was no difference in the myofibroblast fraction between males and females. (4) Conclusions: Our study highlights the gender-specific role of myofibroblasts and IL24 in OA pathogenesis. Elevated IL24 levels in females, correlating with pain severity, suggest its involvement in OA pain experiences. The potential therapeutic implications of IL24, demonstrated in autoimmune disorders, open avenues for targeted interventions. Notwithstanding the limitations of the study, our findings contribute to understanding OA's multifaceted nature and advocate for future research exploring mechanistic underpinnings and clinical applications of IL24 in synovial myofibroblasts. Additionally, future research directions should focus on elucidating the precise mechanisms by which IL24 contributes to OA pathology and exploring its potential as a therapeutic target for personalized medicine approaches.
Subject(s)
Interleukins , Myofibroblasts , Osteoarthritis , Aged , Female , Humans , Male , Middle Aged , Interleukins/genetics , Interleukins/immunology , Myofibroblasts/immunology , Osteoarthritis/genetics , Osteoarthritis/immunology , Pain/genetics , Pain/immunology , Propensity Score , Sex Factors , Synovial Membrane/innervationABSTRACT
Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage erosion, structural changes, and inflammation. Synovial fibroblasts play a crucial role in OA pathophysiology, with abnormal fibroblastic cells contributing significantly to joint pathology. Fibrocytes, expressing markers of both hematopoietic and stromal cells, are implicated in inflammation and fibrosis, yet their marker and role in OA remain unclear. ENTPD1, an ectonucleotidase involved in purinergic signaling and expressed in specific fibroblasts in fibrotic conditions, led us to speculate that ENTPD1 plays a role in OA pathology by being expressed in fibrocytes. This study aimed to investigate the phenotype of ENTPD1+CD55+ and ENTPD1-CD55+ synovial fibroblasts in OA patients. Proteomic analysis revealed a distinct molecular profile in ENTPD1+CD55+ cells, including the upregulation of fibrocyte markers and extracellular matrix-related proteins. Pathway analysis suggested shared mechanisms between OA and rheumatoid arthritis. Correlation analysis revealed an association between ENTPD1+CD55+ fibrocytes and resting pain in OA. These findings highlight the potential involvement of ENTPD1 in OA pain and suggest avenues for targeted therapeutic strategies. Further research is needed to elucidate the underlying molecular mechanisms and validate potential therapeutic targets.
Subject(s)
Fibroblasts , Proteomics , Humans , Synovial Membrane , CD55 Antigens , Extracellular Matrix Proteins , Inflammation , PainABSTRACT
This retrospective cohort study established malnutrition's impact on mortality and neurological recovery of older patients with cervical spinal cord injury (SCI). It included patients aged ≥ 65 years with traumatic cervical SCI treated conservatively or surgically. The Geriatric Nutritional Risk Index was calculated to assess nutritional-related risk. Overall, 789 patients (mean follow-up: 20.1 months) were examined and 47 had major nutritional-related risks on admission. One-year mortality rate, median survival time, neurological recovery, and activities of daily living (ADL) at 1 year post-injury were compared between patients with major nutrition-related risk and matched controls selected using 1:2 propensity score matching to adjust for age, pre-traumatic neurological impairment, and activity. In the Kaplan-Meier analysis, the median survival times were 44.9 and 76.5 months for patients with major nutrition-related risk and matched controls, respectively (p = 0.015). Matched controls had more individuals with a neurological improvement of American Spinal Injury Association Impairment Scale ≥ 1 grade (p = 0.039) and independence in ADL at 1 year post-injury than patients with major nutrition-related risk (p < 0.05). In conclusion, 6% of older patients with cervical SCI had major nutrition-related risks; they showed a significantly higher 1 year mortality rate, shorter survival time, poorer neurological improvement, and lower ADL at 1 year post-injury than matched controls.
Subject(s)
Malnutrition , Spinal Cord Injuries , Humans , Aged , Activities of Daily Living , Retrospective Studies , Spinal Cord Injuries/complications , Spinal Cord Injuries/therapy , Malnutrition/complications , Nutritional Status , Recovery of FunctionABSTRACT
STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To define the prognosis and predictive factors for neurological improvement in older patients with incomplete spinal cord injury (SCI) of American Spinal Injury Association Impairment Scale grade C (AIS-C). SETTINGS: Multi-institutions in Japan. METHODS: We included patients aged ≥65 years with traumatic SCI of AIS-C who were treated conservatively or surgically with >3 follow-up months. To identify factors related to neurological improvement, patients were divided into three groups according to their neurological status at the final follow-up, with univariate among-group comparisons of demographics, radiographic, and therapeutic factors. Significant variables were included in the multivariate logistic regression analysis. RESULTS: Overall, 296 older patients with SCI of AIS-C on admission were identified (average age: 75.2 years, average follow-up: 18.7 months). Among them, 190 (64.2%) patients improved to AIS-D and 21 (7.1%) patients improved to AIS-E at final follow-up. There were significant among-group differences in age (p = 0.026), body mass index (p = 0.007), status of pre-traumatic activities of daily living (ADL) (p = 0.037), and serum albumin concentrations (p = 0.011). Logistic regression analysis showed no significant differences in variables in the stratified group of patients who improved to AIS-D. Meanwhile, serum albumin was a significant variable in patients who improved to AIS-E (p = 0.026; OR: 6.20, pre-traumatic ADL was omitted due to data skewness). CONCLUSIONS: Most older patients with incomplete AIS-C SCI demonstrated at least 1 grade of neurological improvement. However, <10% of patients achieved complete recovery. Key predictors of complete recovery were high serum albumin levels on admission and independent pre-traumatic ADL. SPONSORSHIP: No funding was received for this study.
Subject(s)
Spinal Cord Injuries , Humans , Middle Aged , Aged , Spinal Cord Injuries/diagnosis , Spinal Cord Injuries/epidemiology , Spinal Cord Injuries/therapy , Retrospective Studies , Activities of Daily Living , Recovery of Function , Serum AlbuminABSTRACT
STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: The effectiveness of early surgery for cervical spinal injury (CSI) has been demonstrated. However, whether early surgery improves outcomes in the elderly remains unclear. This study investigated whether early surgery for CSI in elderly affects complication rates and neurological outcomes. METHODS: This retrospective multicenter study included 462 patients. We included patients with traumatic acute cervical spinal cord injury aged ≥65 years who were treated surgically, whereas patients with American Spinal Injury Association (ASIA) Impairment Scale E, those with unknown operative procedures, and those waiting for surgery for >1 month were excluded. The minimum follow-up period was 6 months. Sixty-five patients (early group, 14.1%) underwent surgical treatment within 24 hours, whereas the remaining 397 patients (85.9%) underwent surgery on a standby basis (delayed group). The propensity score-matched cohorts of 63 cases were compared. RESULTS: Patients in the early group were significantly younger, had significantly more subaxial dislocations (and fractures), tetraplegia, significantly lower ASIA motor scores, and ambulatory abilities 6 months after injury. However, no significant differences in the rate of complications, ambulatory abilities, or ASIA Impairment Scale scores 6 months after injury were observed between the matched cohorts. At 6 months after injury, 61% of the patients in the early group (25% unsupported and 36% supported) and 53% of the patients in the delayed group (34% unsupported and 19% supported) were ambulatory. CONCLUSIONS: Early surgery is possible for CSI in elderly patients as the matched cohort reveals no significant difference in complication rates and neurological or ambulatory recovery between the early and delayed surgery groups.
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Diabetes mellitus (DM) has been suggested as a potential risk factor for knee osteoarthritis (KOA), and its underlying mechanisms remain unclear. The infrapatellar fat pad (IPFP) contributes to OA through inflammatory mediator secretion. Mast cells' (MCs) role in diabetic IPFP pathology is unclear. In 156 KOA patients, hemoglobin A1c (HbA1c) was stratified (HbA1c ≥ 6.5, n = 28; HbA1c < 6.5, n = 128). MC markers (TPSB2, CPA3) in IPFP were studied. Propensity-matched cohorts (n = 27 each) addressed demographic differences. MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF) were isolated, comparing MC markers and genes elevated in diabetic skin-derived MC (PAXIP1, ARG1, HAS1, IL3RA). TPSB2 and CPA3 expression were significantly higher in HbA1c ≥ 6.5 vs. <6.5, both before and after matching. MC-RF showed higher TPSB2 and CPA3 expression than MC-PF in both groups. In the HbA1c ≥ 6.5 group, PAXIP1 and ARG1 expression were significantly higher in the MC-RF than MC-PF. However, no statistical difference in the evaluated genes was detected between the High and Normal groups in the MC-RF. Elevated TPSB2 and CPA3 levels in the IPFP of high HbA1c patients likely reflect higher numbers of MCs in the IPFP, though no difference was found in MC-specific markers on a cell-to-cell basis, as shown in the MC-RF comparison. These findings deepen our understanding of the intricate interplay between diabetes and KOA, guiding targeted therapeutic interventions.
Subject(s)
Diabetes Mellitus , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/genetics , Glycated Hemoglobin , Mast Cells , Phenotype , Serine Proteases , Diabetes Mellitus/geneticsABSTRACT
BACKGROUND: Although previous studies have demonstrated the advantages of early surgery for traumatic spinal cord injury (SCI), the appropriate surgical timing for cervical SCIs (CSCIs) without bone injury remains controversial. Here, we investigated the influence of relatively early surgery within 48 h of injury on the neurological recovery of elderly patients with CSCI and no bone injury. METHODS: In this retrospective multicenter study, we reviewed data from 159 consecutive patients aged ≥65 years with CSCI without bone injury who underwent surgery in participating centers between 2010 and 2020. Patients were followed up for at least 6 months following CSCI. We divided patients into relatively early (≤48 h after CSCI, n = 24) and late surgery (>48 h after CSCI, n = 135) groups, and baseline characteristics and neurological outcomes were compared between them. Multivariate analysis was performed to identify factors associated with neurological recovery. RESULTS: The relatively early surgery group demonstrated a lower prevalence of cardiac disease, poorer baseline American Spinal Injury Association (ASIA) impairment scale grade, and lower baseline ASIA motor score (AMS) than those of the late surgery group (P < 0.030, P < 0.001, and P < 0.001, respectively). Although the AMS was lower in the relatively early surgery group at 6 months following injury (P = 0.001), greater improvement in this score from baseline to 6-months post injury was observed (P = 0.010). Multiple linear regression analysis revealed that relatively early surgery did not affect postoperative improvement in AMS, rather, lower baseline AMS was associated with better AMS improvement (P < 0.001). Delirium (P = 0.006), pneumonia (P = 0.030), and diabetes mellitus (P = 0.039) negatively influenced postoperative improvement. CONCLUSIONS: Although further validation by future studies is required, relatively early surgery did not show a positive influence on neurological recovery after CSCI without bone injury in the elderly.
Subject(s)
Cervical Cord , Soft Tissue Injuries , Spinal Cord Injuries , Aged , Humans , Treatment Outcome , Cervical Cord/injuries , Spinal Cord Injuries/complications , Spinal Cord Injuries/surgery , Retrospective Studies , Cervical Vertebrae/surgery , Cervical Vertebrae/injuries , Multicenter Studies as TopicABSTRACT
BACKGROUND: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms. METHODS: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness. RESULTS: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL. CONCLUSIONS: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly. LEVEL OF EVIDENCE: II, prospective cohort study.
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Recent studies utilizing single-cell analysis have unveiled the presence of various fibroblast (Fb) subsets within the synovium under inflammatory conditions in osteoarthritis (OA), distinguishing them from those in rheumatoid arthritis (RA). Moreover, it has been reported that pain in knee OA patients is linked to specific fibroblast subsets. Single-cell expression profiling methods offer an incredibly detailed view of the molecular states of individual cells. However, one limitation of these methods is that they require the destruction of cells during the analysis process, rendering it impossible to directly assess cell function. In our study, we employ flow cytometric analysis, utilizing cell surface markers CD39 and CD55, in an attempt to isolate fibroblast subsets and investigate their relationship with OA pathology. Synovial tissues were obtained from 25 knee OA (KOA) patients. Of these, six samples were analyzed by RNA-seq (n = 3) and LC/MS analysis (n = 3). All 25 samples were analyzed to estimate the proportion of Fb (CD45-CD31-CD90+) subset by flow cytometry. The proportion of Fb subsets (CD39+CD55- and CD39-CD55+) and their association with osteoarthritis pathology were evaluated. CD39+CD55- Fb highly expressed myogenic markers such as CNN1, IGFBP7, MYH11, and TPM1 compared to CD39-CD55+ Fb. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of upregulated differentially expressed genes (DEGs) in CD39+CD55- Fb identified the Apelin pathway and cGMP-PKC-signaling pathway as possibly contributing to pain. LC/MS analysis indicated that proteins encoded by myogenic marker genes, including CNN1, IGFBP7, and MYH11, were also significantly higher than in CD39-CD55+ Fb. CD39-CD55+ Fb highly expressed PRG4 genes and proteins. Upregulated DEGs were enriched for pathways associated with proinflammatory states ('RA', 'TNF signaling pathway', 'IL-17 signaling pathway'). The proportion of CD39+CD55- Fb in synovium significantly correlated with both resting and active pain levels in knee OA (KOA) patients (resting pain, ρ = 0.513, p = 0.009; active pain, ρ = 0.483, p = 0.015). There was no correlation between joint space width (JSW) and the proportion of CD39+CD55- Fb. In contrast, there was no correlation between the proportion of CD39-CD55+ Fb and resting pain, active pain, or JSW. In conclusion, CD39+CD55- cells exhibit a myofibroblast phenotype, and its proportion is associated with KOA pain. Our study sheds light on the potential significance of CD39+CD55- synovial fibroblasts in osteoarthritis, their myofibroblast-like phenotype, and their association with joint pain. These findings provide a foundation for further research into the mechanisms underlying fibrosis, the impact of altered gene expression on osteoarthritic joints, and potential therapeutic strategies.
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STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate the treatments of the geriatric population with hangman's fractures using a multicenter database under the Japan Association of Spine Surgeons with Ambition (JASA). METHODS: The multicenter database included data from 1512 patients. We employed the Levine and Edwards classification for categorizing hangman's fractures. The study incorporated epidemiological data, including the prevalence of hangman's fractures, patient age, and follow-up duration. Bony fusion rates and length of hospitalization were recorded for Type I and Type II fractures, and the degree of neurological impairment was assessed. RESULTS: Hangman's fractures represented 62 cases, accounting for 7.4% of all cervical spine injuries. The patients had an average age of 76.6 ± 6.5 years, and the mean duration of follow-up was 21.5 ± 23.6 months. The study found that the bony fusion rate for hangman's fractures in the geriatric population was 88.9%. Surgical treatment was associated with a shorter hospitalization period for Type II fractures compared to conservative treatment. Thirteen cases of hangman's fractures in the geriatric population, accounting for 21%, were complicated by spinal cord injury. CONCLUSIONS: This is the largest study to date on hangman's fractures in geriatric population ≥65 years. Type I and Type II fractures, according to the Levine and Edwards classification, had a bony fusion rate of up to 90%. In patients with Type II fractures, surgical treatment led to a shorter initial hospital stay. Geriatric patients are at risk of spinal cord injury due to hangman's fractures.
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Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease.
Subject(s)
Osteoarthritis , Tumor Necrosis Factor-alpha , Humans , Anti-Bacterial Agents , Cytokines , Fibroblasts , Inflammation/drug therapy , Interleukin-6/genetics , Interleukin-8/genetics , Osteoarthritis/drug therapy , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
In critically ill patients requiring intensive care, increased oxidative stress plays an important role in pathogenesis. Sedatives are widely used for sedation in many of these patients. Some sedatives are known antioxidants. However, no studies have evaluated the direct scavenging activity of various sedative agents on different free radicals. This study aimed to determine whether common sedatives (propofol, thiopental, and dexmedetomidine (DEX)) have direct free radical scavenging activity against various free radicals using in vitro electron spin resonance. Superoxide, hydroxyl radical, singlet oxygen, and nitric oxide (NO) direct scavenging activities were measured. All sedatives scavenged different types of free radicals. DEX, a new sedative, also scavenged hydroxyl radicals. Thiopental scavenged all types of free radicals, including NO, whereas propofol did not scavenge superoxide radicals. In this retrospective analysis, we observed changes in oxidative antioxidant markers following the administration of thiopental in patients with severe head trauma. We identified the direct radical-scavenging activity of various sedatives used in clinical settings. Furthermore, we reported a representative case of traumatic brain injury wherein thiopental administration dramatically affected oxidative-stress-related biomarkers. This study suggests that, in the future, sedatives containing thiopental may be redeveloped as an antioxidant therapy through further clinical research.
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While research suggests that increasing body mass index (BMI) is a risk factor for hip osteoarthritis (HOA), the mechanisms of this effect are not fully understood. Tryptases are among the main proteases found in mast cells (MCs) and contribute to OA pathology. TPSB2, which encodes ß-tryptase, is increased in the synovium of overweight and obese knee OA patients. However, it remains unclear whether tryptase in the synovium of HOA is increased with increasing BMI. Here, we investigated tryptase genes (TPSB2 and TPSD1) in the synovium of overweight HOA patients. Forty-six patients radiographically diagnosed with HOA were allocated to two groups based on BMI, namely normal (<25 kg/m2) and overweight (25-29.99 kg/m2). TPSB2 and TPSD1 expression in the synovium of the two groups was compared using real-time polymerase chain reaction. To compare TPSB2 and TPSD1 expression in MCs between the groups, we isolated the MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF), extracted using magnetic isolation. TPSB2 and TPSD1 expression was increased in the overweight group compared with the normal group. Expression of both genes in the MC-RF was significantly higher than that in MC-PF in both groups. However, TPSB2 and TPSD1 expression levels in the MC-RF did not differ between the groups. Tryptase genes were highly expressed in the synovium of overweight HOA patients. Further investigation to reveal the role of tryptase in the relationship between increasing BMI and HOA pathology is required.
Subject(s)
Osteoarthritis, Hip , Overweight , Synovial Membrane , Humans , Mast Cells/metabolism , Osteoarthritis, Hip/genetics , Osteoarthritis, Hip/pathology , Overweight/complications , Overweight/genetics , Overweight/pathology , Synovial Membrane/metabolism , Tryptases/biosynthesis , Tryptases/metabolismABSTRACT
STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: The purpose of this study was to compare the prognosis of elderly patients with injuries related to cervical diffuse idiopathic skeletal hyperostosis (cDISH) to matched control for each group, with and without fractures. METHODS: The current multicenter study was a retrospective analysis of 140 patients aged 65 years or older with cDISH-related cervical spine injuries; 106 fractures and 34 spinal cord injuries without fracture were identified. Propensity score-matched cohorts from 1363 patients without cDISH were generated and compared. Logistic regression analysis was performed to determine the risk of early mortality for patients with cDISH-related injury. RESULTS: Patients with cDISH-related injuries with fracture did not differ significantly in the incidence of each complication and ambulation or severity of paralysis compared to matched controls. In patients with cDISH-related injury without fracture, those who were nonambulatory at discharge comprised 55% vs 34% of controls, indicating significantly poorer ambulation in those with cDISH-related injuries (P = .023). There was no significant difference in the incidence of complications and ambulation or paralysis severity at 6 months as compared with controls. Fourteen patients died within 3 months. Logistic regression analysis identified complete paralysis (odds ratio [OR] 36.99) and age (OR 1.24) as significant risk factors for mortality. CONCLUSIONS: The current study showed no significant differences in the incidence of complications, ambulation outcomes between patients with cDISH-related injury with fracture and matched controls, and that the ambulation at discharge for patients with cDISH-related injury without fractures were significantly inferior to those of matched controls.
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Introduction: Lateral lumbar interbody fusion (LLIF) has been introduced in Japan in 2013. Despite the effectiveness of this procedure, several considerable complications have been reported. This study reported the results of a nationwide survey performed by the Japanese Society for Spine Surgery and Related Research (JSSR) on the complications associated with LLIF performed in Japan. Methods: JSSR members conducted a web-based survey following LLIF between 2015 and 2020. Any complications meeting the following criteria were included: (1) major vessel, (2) urinary tract, (3) renal, (4) visceral organ, (5) lung, (6) vertebral, (7) nerve, and (8) anterior longitudinal ligament injury; (9) weakness of psoas; (10) motor and (11) sensory deficit; (12) surgical site infection; and (13) other complications. The complications were analyzed in all LLIF patients, and the differences in incidence and type of complications between the transpsoas (TP) and prepsoas (PP) approaches were compared. Results: Among the 13,245 LLIF patients (TP 6,198 patients [47%] and PP 7,047 patients [53%]), 389 complications occurred in 366 (2.76%) patients. The most common complication was sensory deficit (0.5%), followed by motor deficit (0.43%) and weakness of psoas muscle (0.22%). Among the patient cohort, 100 patients (0.74%) required revision surgery during the survey period. Almost half of the complications developed in patients with spinal deformity (183 patients [47.0%]). Four patients (0.03%) died from complications. Statistically more frequent complications occurred in the TP approach than in the PP approach (TP vs. PP, 220 patients [3.55%] vs. 169 patients [2.40%]; p<0.001). Conclusions: The overall complication rate was 2.76%, and 0.74% of the patients required revision surgery because of complications. Four patients died from complications. LLIF may be beneficial for degenerative lumbar conditions with acceptable complications; however, the indication for spinal deformity should be carefully determined by the experience of the surgeon and the extent of the deformity.