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Analgesic effectiveness of continuous versus single-injection adductor canal block in addition to continuous popliteal sciatic nerve block for bimalleolar and trimalleolar ankle fracture surgery: Prospective randomized controlled trial
No full textBackground: The adductor canal block is a well-known procedure for controlling postoperative pain after medial malleolus fracture surgery. Continuous nerve block is a viable option for blocking pain for a longer period although the literature on this subject is scarce. Therefore, this study aimed to compare continuous adductor canal block (cACB) group to single-injection adductor canal block (sACB) group in those with bimalleolar or trimalleolar ankle fractures. The procedure was performed in addition to a continuous sciatic nerve block for postoperative pain relief and patient satisfaction. Methods: The study included 57 patients who had bimalleolar or trimalleolar ankle fractures and underwent open reduction and internal fixation between August 2016 and June 2018. Each patient received a continuous sciatic nerve block and was divided into two groups: those who received cACB and those who received sACB. Each postoperative pain was scored at 4, 8, 12, 24, 48, and 72 h after surgery. Additionally, the consumption of rescue medications and patient satisfaction were evaluated. Results: The two groups displayed no disparity in medial side ankle pain at 4 h and 8 h after surgery, but significantly higher pain in the sACB group at 12, 24, 48, and 72 h after surgery. However, there was no difference in the pain at the lateral side of ankle and consumption of rescue medication. In addition, the cACB group showed more satisfaction than the sACB group did. Conclusion: CACB is better than sACB in terms of postoperative pain control and patient satisfaction. cACB can be used for postoperative pain control in ankle fractures involving the medial malleolus. Level of evidence: Prospective Randomized Controlled Trial, Level 2
An intra articular injectable Mitocelle recovers dysfunctional mitochondria in cellular organelle disorders
No full textMitochondrial dysfunction increases ROS production and is closely related to many degenerative cellular organelle diseases. The NOX4-p22phox axis is a major contributor to ROS production and its dysregulation is expected to disrupt mitochondrial function. However, the field lacks a competitive inhibitor of the NOX4-p22phox interaction. Here, we created a povidone micelle-based Prussian blue nanozyme that we named “Mitocelle” to target the NOX4-p22phox axis, and characterized its impact on the major degenerative cellular organelle disease, osteoarthritis (OA). Mitocelle is composed of FDA-approved and biocompatible materials, has a regular spherical shape, and is approximately 88 nm in diameter. Mitocelle competitively inhibits the NOX4-p22phox interaction, and its uptake by chondrocytes can protect against mitochondrial malfunction. Upon intra-articular injection to an OA mouse model, Mitocelle shows long-term stability, effective uptake into the cartilage matrix, and the ability to attenuate joint degradation. Collectively, our findings suggest that Mitocelle, which functions as a competitive inhibitor of NOX4-p22phox, may be suitable for translational research as a therapeutic for OA and cellular organelle diseases related to dysfunctional mitochondria
Gut-brain axis and environmental factors in Parkinson's disease: bidirectional link between disease onset and progression
No full textParkinson's disease has long been considered a disorder that primarily affects the brain, as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing alpha-synuclein protein. In recent decades, however, accumulating research has revealed that Parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut, called the "gut-brain axis." Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson's disease patients, with findings including impaired intestinal permeability, heightened inflammation, and distinct gut microbiome profiles and metabolites. Furthermore, alpha-synuclein deposition has been consistently observed in the gut of Parkinson's disease patients, suggesting a potential role in disease initiation. Importantly, individuals with vagotomy have a reduced Parkinson's disease risk. From these observations, researchers have hypothesized that alpha-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut-brain axis, leading to Parkinson's disease. This review comprehensively examines the gut's involvement in Parkinson's disease, focusing on the concept of a gut-origin for the disease. We also examine the interplay between altered gut-related factors and the accumulation of pathological alpha-synuclein in the gut of Parkinson's disease patients. Given the accessibility of the gut to both dietary and pharmacological interventions, targeting gut-localized alpha-synuclein represents a promising avenue for developing effective Parkinson's disease therapies
Toll-Like Receptor Blockage by TIP-1 and MIP-2 Treatment Mitigates Inflammation in a Mouse Model of Adult-Onset Still's Disease or Still's Disease
No full textThe inflammatory response triggered by Toll-like receptors (TLRs) may implicated in the development of the pathogenesis of adult-onset Still's disease (AOSD). This study evaluated the efficacy of TLR inhibitor peptides, specifically TLR inhibitor peptide 1 (TIP-1) and MAL/MyD88 inhibitory peptide 2 (MIP-2) in animal models of AOSD. THP-1 cells were stimulated with TLR agonists and treated with TIP-1 or MIP-2. Interferon (IFN)-gamma knock-out mice were induced with AOSD-like symptoms using Mycobacterium mixed with Freund's complete adjuvant (CFA), then treated with the peptides. THP-1 cells treated with TIP-1 and MIP-2 showed significantly decreased expression of TLRs agonist-induced MyD88 and phosphorylated NF-kappaB, except TLR9 agonists. Furthermore, the peptides resulted in a significant decrease in the concentrations of interleukin (IL)-1beta and IL-6 in the culture supernatants, except TLR9 agonists. In animal models of AOSD, treatment with inhibitor peptides significantly improved their clinical symptoms. The administration of these peptides resulted in a significant decrease in serum levels of IL-1beta and IL-18. The expression of inflammatory cytokines were downregulated in the spleen and lymph node of TIP-1 and MIP-2 treated mice. These findings suggest that TIP-1 and MIP-2 may be effective candidates for AOSD treatment, as they have broad specificity for TLRs
Cloning of nf-profilin and intercellular interaction with nf-actin in Naegleria fowleri cysts
No full textNaegleria fowleri is a free-living amoeba found in lakes, soil, hot springs, and poorly chlorinated swimming pools. It is pathogenic to humans, causing a rare and fatal brain infection known as primary amoebic meningoencephalitis (PAM). A previous study utilized RNA-seq analysis to examine genes expressed in N. fowleri cysts and trophozoites, focusing on the nf-profilin gene, which showed high expression in cysts. Profilin is a small actin-binding protein that regulates nf-actin polymerization and cell movement. Sequence analysis revealed 83% similarity with non-pathogenic N. gruberi and 38% similarity with Acanthamoeba castellanii. Nf-profilin was found to be associated with N. fowleri lysates but not with lysates from other amoebae, as shown by Western blot analysis. Immunofluorescence assays demonstrated that nf-profilin primarily localized to the cell membrane in N. fowleri cysts, while nf-actin localized to the cytoplasm, pseudopodia, and food-cup structures. Real-time RT-PCR indicated higher expression of the nf-profilin gene in cysts compared to trophozoites. In co-culture experiments with target cells, Nf-profilin was initially expressed in the cytoplasm of N. fowleri cysts and the morphology of cyst gradually transitioned to the trophozoite form. Concurrently, the expression of Nf-profilin protein decreased, while Nf-actin protein began to appear in the pseudopodia and food-cups of trophozoites. In conclusion, the nf-profilin and nf-actin genes exhibited complementary expression patterns based on the life stage of N. fowleri, indicating their critical roles in the survival and proliferation. This study emphasizes the significance of actin-binding proteins in understanding the infection and pathogenic mechanisms of N. fowleri
Cardiovascular risk prediction in hemodialysis patients using the triglyceride-glucose index: a multicenter prospective cohort study
No full textBACKGROUND: Triglyceride-glucose (TyG) index has recently been established as an indicator of insulin resistance and has predictive value for cardiovascular (CV) disease. However, the clinical significance of the TyG index in patients undergoing hemodialysis remains unknown. METHODS: We prospectively enrolled 759 patients undergoing maintenance hemodialysis. The participants were divided into tertiles based on their baseline TyG index. Echocardiographic parameters, vascular calcification scores, and several plasma biomarkers were obtained and compared using the TyG index. RESULTS: The TyG index was positively correlated with levels of circulating vascular pathologic markers, endostatin (rho = 0.134, P = .025) and vascular adhesion protein-1 (rho = 0.130, P = .012), but not with vascular calcification score. The TyG index was not correlated with any echocardiographic parameters. Patients in tertile 3 showed the highest cumulative event rates of CV and cardiac events (P < .001 and P = .001, respectively). In the multivariable Cox regression analysis, patients in the TyG index tertile 3 had a significantly increased risk of CV and cardiac events compared to those in the TyG index tertile 1 [adjusted hazard ratio (HR): 1.89, 95% confidence interval (CI): 1.08-3.30, and adjusted HR: 2.01, 95% CI: 1.05-3.82, respectively]. A 1 standard deviation increase in the TyG index was also associated with significantly higher risks of CV and cardiac events. CONCLUSIONS: The TyG index was associated with vascular pathology markers and an increased risk of adverse CV outcomes in patients undergoing hemodialysis. Our study suggests that the TyG index has the potential to assist clinicians in identifying a high CV risk in hemodialysis patients
F-18 FDG PET-derived imaging biomarkers of airway inflammation and their clinical associations in patients with non-small cell lung cancer
No full textBACKGROUND: Airway inflammation is believed to play a crucial role in the development and progression of non-small cell lung cancer (NSCLC). However, no study has yet employed quantified imaging biomarkers to assess airway inflammation in patients with NSCLC. This study aimed to validate the hypothesis that airway inflammation is more pronounced in a large cohort of patients with NSCLC compared to controls, using airway imaging biomarkers derived from fluorine-18-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET), as well as to explore their associations with clinical parameters. METHODS: We retrospectively enrolled 618 patients with NSCLC and 441 controls who underwent F-18 FDG PET/computed tomography (CT). The F-18 FDG PET/CT images were subjected to airway segmentation to determine the airway maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG). We compared the airway PET parameters between patients with NSCLC and controls. Additionally, we investigated the associations between airway PET parameters and tumor SUVmax, stages, smoking pack-years, histological subtypes, systemic inflammation, and lung function in patients with NSCLC. RESULTS: The median airway SUVmax (P < 0.0001) and TLG (P < 0.0001) were significantly higher in patients with NSCLC than in controls. The median airway SUVmax (P = 0.0098) and TLG (P < 0.0001) were significantly higher in patients with squamous cell carcinoma than in those with adenocarcinoma. Airway SUVmax and TLG showed weak positive correlations with tumor SUVmax, stages, white blood cell count, and neutrophil-to-lymphocyte ratio, but weak to moderate negative correlations with lung function parameters. Airway TLG showed a moderate positive correlation with smoking pack-years. CONCLUSIONS: F-18 FDG PET-derived airway imaging biomarkers were higher in patients with NSCLC than in controls. Additionally, these biomarkers were associated with tumor SUVmax, stages, histological subtypes, serologic inflammatory markers, lung function, and smoking, suggesting their potential to provide insights into the development and severity of NSCLC
McMurray’s test is influenced by perimeniscal synovitis in degenerative meniscus tears
No full textBACKGROUND: McMurray's test is a useful physical examination in determining meniscus tears, yet its sensitivity is only 38-62%. Furthermore, the relationship between degenerative meniscus tears (DMT) and mechanical symptoms during McMurray's test is not well defined. Perimeniscal synovitis occurs in osteoarthritic (OA) knees, inducing localized symptoms such as posterior knee pain in medial meniscus posterior horn DMTs. This study aimed to determine the relationship between McMurray's test with medial meniscus DMT and perimeniscal synovitis in patients with knee OA. METHODS: We retrospectively analyzed 60 patients who underwent medial unicompartmental knee arthroplasty (UKA) with positive (n = 20) and negative (n = 40) preoperative McMurray's tests. Preoperative magnetic resonance imaging (MRI), intraoperative gross morphology, and histological analysis of meniscus and synovium were evaluated to determine meniscal tears and perimeniscal synovitis. Univariate and multivariate regression analyses were done to determine the effects of meniscus tears and synovitis on McMurray's test results. RESULTS: Gross morphology of the medial meniscus (MM) showed 14 out of 20 torn menisci in the McMurray's (+) group compared with 22 out of 40 in the (-) group, with no difference in meniscus tear severity among groups. The (+) group showed higher values of synovial thickness (p < 0.001) and area (p < 0.001) compared with the (-) group on magnetic resonance imaging (MRI). Histological analysis showed higher synovitis (p < 0.001) scores and expression of inflammatory markers [interleukin (IL)-1beta (p < 0.001), IL-6 (p = 0.007), nerve growth factor (NGF) (p = 0.003), inducible nitric oxide synthase (iNOS) (p < 0.001)] in the perimeniscal synovium of (+) group compared with the (-) group. Multivariable logistic analysis revealed that larger synovial area [odds ratio (OR) = 1.106, p = 0.008] and a higher histologic synovitis score (OR = 2.595, p = 0.011) were independently significant predictive factors for a positive McMurray's test. CONCLUSIONS: McMurray's test may be influenced by perimeniscal synovitis in DMT patients. The clinical implications of our results may influence not only the interpretation of McMurray's test but also the target tissue in treating mechanical symptoms related to meniscus tears. LEVEL OF EVIDENCE: Level II
Response to letter to the Editor regarding “What are the risk factors for a second osteoporotic vertebral compression fracture?”
No full textSurvival of Children with Acute Lymphoblastic Leukemia with Risk Group–Based Protocol Changes: A Single-Center Experience with 460 Patients over a 20-Year Period
No full textPURPOSE: Recent treatments for pediatric acute lymphoblastic leukemia (ALL) are founded on risk stratification. We examined the survival rates and prognostic factors of patients over a 20-year period at a single institution. MATERIALS AND METHODS: This study analyzed patients diagnosed with ALL and treated at the Pediatric Department of Samsung Medical Center (SMC). Patients were categorized into standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. The SMC protocol for the HR group underwent two changes during the study period: a modified Children's Cancer Group (CCG)-1882 protocol was used from 2000 to 2005, the Korean multicenter HR ALL-0601 protocol from 2006 to 2014, and the Korean multicenter HR ALL-1501 protocol from 2015 to 2019. RESULTS: Of the 460 patients, complete remission was achieved in 436 patients (94.8%). The 10-year overall survival rate (OS) was 83.8+/-1.9% for all patients. OS according to the SMC risk group was as follows: 95.9%+/-1.4% in the SR group, 83.8%+/-3.6% in the HR group, and 66.2%+/-6.9% in the VHR group. The 5-year OS within the HR group varied according to the treatment protocol: 73.9%+/-7.5%, in the modified CCG-1882 protocol, 83.0%+/-3.9%, in the 0601 protocol, and 96.2%+/-2.6%, in the 1501 protocol. For those aged 15 years and older, the OS was only 56.5%+/-13.1%. Relapse occurred in 71 patients (15.4%), and the OS after relapse was 37.7%+/-6.0%. CONCLUSION: The treatment outcomes of patients with ALL improved markedly. However, there is a need to further characterize adolescents and young adult patients, as well as those who have experienced relapses