Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts.

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.

Muscle strength rather than appendicular skeletal muscle mass might affect spinal sagittal alignment, low back pain, and health-related quality of life.

Sarcopenia is defined as decreasing in muscle strength and mass, and dynapenia is defined as decreasing in muscle strength and maintained muscle mass. This study elucidated the prevalence and characteristics of sarcopenia and dynapenia and evaluate in elderly spinal disorders patients. 1039 spinal disorders patients aged ≥ 65 years were included. We measured age, grip strength, muscle mass, spinal sagittal alignment parameters, low back pain (LBP) scores and health-related quality of life (HR-QoL) scores. Based on the previous reports, patients were categorised into normal group: NG, pre-sarcopenia group: PG, dynapenia group: DG, and sarcopenia group: SG. Pre-sarcopenia, dynapenia, and sarcopenia were found in 101 (9.7%), 249 (19.2%), and 91 (8.8%) patients, respectively. The spinal sagittal alignment parameters, trunk muscle mass, LBP, and HR-QoL scores were significantly worse in DG and SG compared with those in PG and NG. Spinal alignment, trunk muscle mass, and clinical outcomes, including LBP and HR-QoL scores, were maintained in the PG and poor in the DG and SG. Thus, intervention for muscle strength may be a treatment option for changes of spinal sagittal alignment and low back pain.

Posterior Spinal Fusion Surgery for Neuromuscular Disease Patients with Severe Scoliosis Whose Cobb Angle Was over 100 Degrees.

Background and objectives: Patients with neuromuscular diseases usually have progressive neuromuscular scoliosis (NMS), requiring invasive surgery. Some patients present with severe scoliosis at the time of consultation and are difficult to treat. Posterior spinal fusion (PSF) surgery combined with anterior release and pre- or intraoperative traction would be effective for severe spinal deformities but would be invasive. This study aimed to evaluate the outcomes of PSF-only surgery for patients with severe NMS with a Cobb angle > 100°. Materials and Methods: Thirty NMS patients (13 boys and 17 girls; mean age 13.8 years) who underwent PSF-only surgery for scoliosis with a Cobb angle > 100° were included. We reviewed the lower instrumented vertebra (LIV), duration of surgery, blood loss, perioperative complications, preoperative clinical findings, and radiographic findings, including Cobb angle and pelvic obliquity (PO) in the sitting position pre- and postoperatively. The correction rate and correction loss of the Cobb angle and PO were also calculated. Results: The mean duration of surgery was 338 min, intraoperative blood loss was 1440 mL, preoperative %VC was 34.1%, FEV1.0 (%) was 91.5%, and EF was 66.1%. There were eight cases of perioperative complications. The Cobb angle and PO correction rates were 48.5% and 42.0%, respectively. We divided the patients into two groups: the L5 group, in which the LIV was L5, and the pelvis group, in which the LIV was the pelvis. The duration of surgery and PO correction rate in the pelvis group were significantly higher than those in the L5 group. Conclusions: Patients with severe NMS demonstrated severe preoperative restrictive ventilatory impairments. PSF surgery without anterior release or any intra-/preoperative traction showed satisfactory outcomes, including acceptable scoliosis correction and improved clinical findings, even in patients with extremely severe NMS. Instrumentation and fusion to the pelvis for severe scoliosis in patients with NMS showed good PO correction and low correction loss of Cobb angle and PO, but a longer duration of surgery.

A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs.

Animal studies suggest that pain-related-molecule upregulation in degenerated intervertebral discs (IVDs) potentially leads to low back pain (LBP). We hypothesized that IVD mechanical stress and axial loading contribute to discogenic LBP's pathomechanism. This study aimed to elucidate the relationships among the clinical findings, radiographical findings, and pain-related-molecule expression in human degenerated IVDs. We harvested degenerated-IVD samples from 35 patients during spinal interbody fusion surgery. Pain-related molecules including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, calcitonin gene-related peptide (CGRP), microsomal prostaglandin E synthase-1 (mPGES1), and nerve growth factor (NGF) were determined. We also recorded preoperative clinical findings including body mass index (BMI), Oswestry Disability Index (ODI), and radiographical findings including the vacuum phenomenon (VP) and spinal instability. Furthermore, we compared pain-related-molecule expression between the VP (-) and (+) groups. BMI was significantly correlated with the ODI, CGRP, and mPGES-1 levels. In the VP (+) group, mPGES-1 levels were significantly higher than in the VP (-) group. Additionally, CGRP and mPGES-1 were significantly correlated. Axial loading and mechanical stress correlated with CGRP and mPGES-1 expression and not with inflammatory cytokine or NGF expression. Therefore, axial loading and mechanical stress upregulate CGRP and mPGES-1 in human degenerated IVDs, potentially leading to chronic discogenic LBP.

Prevalence and location of endplate fracture and subsidence after oblique lumbar interbody fusion for adult spinal deformity.

BACKGROUND: Recently, Oblique lumbar interbody fusion (OLIF) is commonly indicated to correct the sagittal and coronal alignment in adult spinal deformity (ASD). Endplate fracture during surgery is a major complication of OLIF, but the detailed location of fracture in vertebral endplate in ASD has not yet been determined. We sought to determine the incidence and location of endplate fracture and subsidence of the OLIF cage in ASD surgery, and its association with fusion status and alignment. METHODS: We analyzed 75 levels in 27 patients were analyzed using multiplanar CT to detect the endplate fracture immediately after surgery and subsidence at 1 year postoperatively. The prevalence was compared between anterior and posterior, approach and non-approach sides, and concave and convex side. Their association with fusion status, local and global alignment, and complication was also investigated. RESULTS: Endplate fracture was observed in 64 levels (85.3%) in all 27 patients, and the incidence was significantly higher in the posterior area compared with the anterior area (85.3 vs. 68.0%, p=0.02) of affected vertebra in the sagittal plane. In the coronal plane, there was no significant difference in incidence between left (approach) and right (non-approach) sides (77.3 and 81.3%, respectively), or concave and convex sides (69.4 and 79.6%) of wedged vertebra. By contrast, cage subsidence at 1 year postoperatively was noted in 14/75 levels (18.7%), but was not associated with endplate fracture. Fusion status, local and global alignment, and complications were not associated with endplate fracture or subsidence. CONCLUSION: Endplate fracture during OLIF procedure in ASD cases is barely avoidable, possibly induced by the corrective maneuver with ideal rod counter and cantilever force, but is less associated with subsequent cage subsidence, fusion status, and sustainment of corrected alignment in long fusion surgery performed even for elderly patients.

Aqueous Synthesis of Manganese Phosphate Hydrate Crystals for Creating Inorganic Pigment Materials.

Manganese phosphate hydrate crystals were prepared from aqueous solutions containing MnCl2, (NH4)2HPO4, and citric acid. Switzerite [Mn3(PO4)2·7H2O] and niahite (NH4MnPO4·H2O) phases were produced at room temperature, and then, hureaulite [Mn5(PO3OH)2(PO4)2·4H2O] particles were obtained by aging at 80 °C or by hydrothermal treatment at 100-180 °C. The lower aging temperature (80 °C) and the chelation of Mn2+ ions by citric acid provided a slower crystal growth, resulting in large hexagonal prism blocks of ca. 500 µm in size. These were found to be single crystals of hureaulite by powder and single-crystal X-ray diffraction analysis. Diffuse reflectance spectroscopy and evaluation using L*a*b* color parameters indicated that the large single crystals present a vivid pink color and high transparency.

Acceleration of bone formation using in situ-formed hyaluronan-hydrogel containing bone morphogenetic protein-2 in a mouse critical size bone defect model.

BACKGROUND: An enzymatic crosslinking strategy using hydrogen peroxide and horseradish peroxidase is receiving increasing attention for application with in situ-formed hydrogels (IFHGs). IFHGs may also be ideal carrier materials for bone repair, although their ability to carry bone morphogenetic protein-2 (BMP2) has yet to be examined. OBJECTIVE: We examined the effectiveness of an IFHG made of hyaluronan (IFHG-HA) containing BMP2 for promoting bone formation in a mouse critical size bone defect model. METHODS: C57/BL6J mice received a 2-mm femoral critical-sized bone defect before being randomly assigned to one of the following treatment groups (n = 6): control (no treatment), IFHG-HA only, PBS with BMP2, and IFHG-HA with BMP2. X-ray radiographs were utilized to track new bone formation, and micro-computed tomography and histological examination were performed on new bone formed at the bone defect site two weeks after surgery. RESULTS: Mice treated with PBS with BMP2 and IFHG-HA with BMP2 had greater bone volume (BV) and bone mineral content (BMC) than those receiving control, and successfully achieved consolidation. Mice treated with IFHG-HA with BMP2 had significantly higher BV and BMC than those treated with PBS with BMP2. CONCLUSIONS: IFHG-HA may be an effective carrier for BMP2 to enable delivery for bone defect repair.

Poly(POG)n loaded with recombinant human bone morphogenetic protein-2 accelerates new bone formation in a critical-sized bone defect mouse model.

BACKGROUND: Delivery of bone morphogenetic protein-2 (BMP-2) via animal-derived absorbable collagen materials is used for the treatment of large bone defects. However, the administration of bovine proteins to humans is associated with the risk of zoonotic complications. We therefore examined the effect of combining BMP-2 with collagen-like peptides, poly(POG)n, in a critical-sized bone defect mouse model. METHODS: A 2-mm critical-sized bone defect was created in the femur of 9-week-old male C57/BL6J mice. Mice were randomly allocated into one of four treatment groups (n = 6 each): control (no treatment), poly(POG)n only, 0.2 µg, or 2.0 µg BMP-2 with poly(POG)n. New bone formation was monitored using soft X-ray radiographs, and bone formation at the bone defect site was examined using micro-computed tomography and histological examination at 4 weeks after surgery. RESULTS: Administration of 2.0 µg of BMP-2 with poly(POG)n promoted new bone formation and resulted in greater bone volume and bone mineral content than that observed in the control group and successfully achieved consolidation. In contrast, bone formation in all other groups was scarce. CONCLUSIONS: Our findings suggest the potential of BMP-2 with poly(POG)n as a material, free from animal-derived collagen, for the treatment of large bone defects.

Digital zoom is a useful, simple, and cost-effective method of reducing radiation exposure in percutaneous coronary intervention.

Reducing radiation exposure is a very important issue in interventional cardiology techniques such as percutaneous coronary intervention. Although novel techniques to reduce radiation exposure are valuable, we should also reconsider older techniques. Digital zoom has been available in Japan from 2005. Digital zoom enlarges an 8-inch field of view (FOV) by 1.2 times, allowing visualization of a 6.7-inch FOV without FOV switching. We identified 2101 suitable cases of percutaneous intervention (PCI) and divided them into two groups according to the use of digital zoom; 1195 patients were included in the digital zoom group and 906 patients in the conventional group. We collected data regarding the reference air kerma (RAK) and dose-area product (DAP). We calculated RAK and DAP per minute fluoroscope time (RAK/min, DAP/min, respectively). There were intergroup differences in RAK, DAP, RAK/min, and DAP/min (digital zoom group vs conventional group; RAK, 1590 mGy [990-2410] vs 1850 [1220-2720], p < 0.01, RAK/min; 54.7 mGy/min [38.5-73.2] vs 71.2 [51.5-93.0], p < 0.01; DAP, 16,000 cGy × cm2 [10,300-24,400] vs 20,700 [13,400-29,500], p < 0.001; DAP/min, 557 cGy × cm2/min [392-737] vs 782 [571-1010], p < 0.01, respectively). Because of baseline differences between the two groups, we performed propensity score matching. Even after score matching, there were intergroup differences in DAP, DAP/min, RAK, and RAK/min. Furthermore, the least squares method showed that digital zoom is a significant predictor of RAK (ß = 0.14, p < 0.01) and DAP (ß = 0.20, p < 0.01). Digital zoom is an older cost-effective technique that can significantly reduce radiation exposure in PCI.

Correction to: The lactate clearance calculated using serum lactate level 6 h after is an important prognostic predictor after extracorporeal cardiopulmonary resuscitation: a single-center retrospective observational study.

[This corrects the article DOI: 10.1186/s40560-018-0302-z.].

The lactate clearance calculated using serum lactate level 6 h after is an important prognostic predictor after extracorporeal cardiopulmonary resuscitation: a single-center retrospective observational study.

BACKGROUND: Serum lactate level can predict clinical outcomes in some critical cases. In the clinical setting, we noted that patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) and with poor serum lactate improvement often do not recover from cardiopulmonary arrest. Therefore, we investigated the association between lactate clearance and in-hospital mortality in cardiac arrest patients undergoing ECPR. METHODS: Serum lactate levels were measured on admission and every hour after starting ECPR. Lactate clearance [(lactate at first measurement - lactate 6 h after)/lactate at first measurement × 100] was calculated 6 h after first serum lactate measurement. All patients who underwent ECPR were registered retrospectively using opt-out in our outpatient's segment. RESULT: In this retrospective study, 64 cases were evaluated, and they were classified into two groups according to lactate clearance: high-clearance group, > 65%; low-clearance group, ≤ 65%. Surviving discharge rate of high-clearance group (12 cases, 63%) is significantly higher than that of low-clearance group (11 cases, 24%) (p < 0.01). Considering other confounders, lactate clearance was an independent predictor for in-hospital mortality (odds ratio, 7.10; 95% confidence interval, 1.71-29.5; p < 0.01). Both net reclassification improvement (0.64, p < 0.01) and integrated reclassification improvement (0.12, p < 0.01) show that adding lactate clearance on established risk factors improved the predictability of in-hospital mortality. CONCLUSION: In our study, lactate clearance calculated through arterial blood gas analysis 6 h after ECPR was one of the most important predictors of in-hospital mortality in patients treated with ECPR after cardiac arrest.

Low-dose ramosetron accelerates gastric emptying in the early phase: A crossover study in healthy volunteers using a continuous real-time 13C breath test (BreathID System).

BACKGROUND/AIMS: The aim of this study was to determine the correlation between low-dose ramosetron pre-treatment and gastric emptying using a novel, non-invasive technique for measuring gastric emptying, namely, the continuous real-time 13C breath test (BreathID system: Exalenz Bioscience Ltd., Israel). MATERIALS AND METHODS: Twelve healthy male volunteers participated in this randomized two-way crossover study. The subjects fasted overnight and were randomly assigned to receive the test meal (200 kcal per 200 mL) after an hour pre-treatment with 5 µg ramosetron or the test meal alone. Gastric emptying was monitored for 4 hours after administration of the test meal with the 13C-acetic acid breath test performed continuously using the BreathID system. Using Oridion Research Software (ß version), T 1/2, T lag, GEC and the regression-estimated constants (ß and κ) were calculated. The differences in the parameters measured at two time-points were analyzed using Wilcoxon's signed-rank test. RESULTS: There was a significant difference in the calculated parameter ß. No significant differences in the calculated parameters T 1/2, T lag, GEC or κ were observed between the test meal with ramosetron group and the test meal alone group. CONCLUSION: This study showed that ramosetron pre-treatment enhances the early gastric emptying of liquid nutrients.

Comparative study of the QUEST questionnaire and GerdQ questionnaire for Japanese students.

BACKGROUND/AIMS: The aim of this study was to comparatively examine the convenience of use of the QUEST and GerdQ questionnaires as self-administered diagnostic instruments. METHODOLOGY: This was a two-way crossover study conducted from December 2011 to April 2012. The subjects were 70 third-year nursing students of Yokohama Soei University in Yokohama, Japan. They were randomly assigned to fill in either of the study questionnaires first, and then the other on a later. RESULTS: A significant difference was observed in the questionnaire completion time between the QUEST and GerdQ questionnaires (125.5 vs. 44 seconds, P < 0.0001) and also in the number of subjects asking questions while completing the questionnaires (26 vs. 1 subject, respectively: P < 0.0001). To detect GERD based on a QUEST score of ≥4, ROC analysis revealed an area under the curve for the GerdQ score of 0.616. The optimal cutoff value of the GerdQ score was 6, and the sensitivity and specificity calculated using this cutoff value were 0.842 and 0.312, respectively. CONCLUSIONS: This study revealed that Japanese subjects may find it easier to complete the GerdQ than the QUEST questionnaire.