Suramin ameliorates osteoarthritis by acting on the Nrf2/HO-1 and NF-κB signaling pathways in chondrocytes and promoting M2 polarization in macrophages.

Osteoarthritis (OA)-the most prevalent of arthritis diseases-is a complicated pathogenesis caused by cartilage degeneration and synovial inflammation. Suramin has been reported to enhance chondrogenic differentiation. However, the therapeutic effect of suramin on OA-induced cartilage destruction has remained unclear. Suramin is an anti-parasitic drug that has potent anti-purinergic properties. This study investigated the protective effects and underlying mechanisms of suramin on articular cartilage degradation using an in vitro study and mice model with post-traumatic OA. We found that suramin markedly suppressed the IL-1ß increased expression of matrix destruction proteases-such as ADAMT4, ADAMTS5, MMP3, MMP13, and inflammatory mediators-including the iNOS, COX2, TNFα, and IL-1ß; while greatly enhancing the synthesis of cartilage anabolic factors-such as COL2A1, Aggrecan and SOX9 in IL-1ß-induced porcine chondrocytes. In vivo experiments showed that intra-articular injection of suramin ameliorated cartilage degeneration and inhibited synovial inflammation in an anterior cruciate ligament transection (ACLT)-induced OA mouse model. In mechanistic studies, we found that exogenous supplementation of suramin can activate Nrf2, and accordingly inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) and mitogen-activated protein kinase (MAPK) pathways, thereby alleviating the inflammation and ECM degeneration of chondrocytes stimulated by IL-1ß. In addition, suramin also repolarized M1 macrophages to the M2 phenotype, further reducing the apoptosis of chondrocytes. Collectively, the results of the study suggests that suramin is a potential drugs which could serve as a facilitating drug for the application of OA therapy toward clinical treatment.

Suramin enhances chondrogenic properties by regulating the p67phox/PI3K/AKT/SOX9 signalling pathway.

AIMS: Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. METHODS: Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1ß; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67phox was involved in suramin-enhanced chondrocyte phenotype maintenance. RESULTS: Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67phox) activity and membrane translocation. Overexpression of p67phox but not p67phoxAD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67phox with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67phox-induced COL2A1 and ACAN expression was significantly inhibited. CONCLUSION: Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67phox activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway.Cite this article: Bone Joint Res 2022;11(10):693-708.

Joint hypermobility and preschool-age flexible flatfoot.

Flexible flatfoot is the most common condition seen in pediatric orthopedic practice and generalized joint hypermobility is widely regarded as one of the predisposing factors. However, in previous studies, the flatfoot was defined by observers' subjective evaluation of the eversion of the bare foot in the standing position; and the joint hypermobility was defined by the Beighton score. The objective of this study is to evaluate the correlation between preschool-age flexible flatfoot and joint hypermobility in preschool-age children objectively. Footprints were measured on a Harris and Beath footprint mat. Flatfoot flexibility was assessed by Staheli Plantar Arch Index (PAI). Other than the Beighton score, 2 new measurement methods, the thumb-to-forearm test and the thumb-thrust test were developed to evaluate joint hypermobility. Of the 291 preschool children from 4 different kindergarten schools included in this study, 156 were boys and 135 were girls. The mean age was 64.18 ± 9.33 months (range 35-88 months). Pearson correlation analysis demonstrated PAI was not associated with the Beighton score (R = 0.020, P = .735), thumb-to-forearm grade (R = 0.109, P = .066), and thumb-thrust grade (R = 0.027, P = .642). Two-sample t-test results showed that the normal and flatfoot groups did not differ significantly in the Beighton score (P = .404), thumb-to-forearm grade (P = .063), and thumb-thrust grade (P = .449). The results demonstrated no correlation between joint hypermobility and preschool-age flexible flatfoot when flatfoot was defined with Staheli PAI and joint hypermobility with the Beighton score. Even with 2 new methods, the thumb-to-forearm test and thumb-thrust test, to define joint hypermobility, we still found no correlation between preschool-age flexible flatfoot and joint hypermobility.

Zonal-Layered Chondrocyte Sheets for Repairment of Full-Thickness Articular Cartilage Defect: A Mini-Pig Model.

The cell sheet technique is a promising approach for tissue engineering, and the present study is aimed to determine a better configuration of cell sheets for cartilage repair. For stratified chondrocyte sheets (S-CS), articular chondrocytes isolated from superficial, middle, and deep zones were stacked accordingly. Heterogeneous chondrocyte sheets (H-CS) were obtained by mixing zonal chondrocytes. The expressions of chondrocytes, cytokine markers, and glycosaminoglycan (GAG) production were assessed in an in vitro assay. The curative effect was investigated in an in vivo porcine osteochondral defect model. The S-CS showed a higher cell viability, proliferation rate, expression of chondrogenic markers, secretion of tissue inhibitor of metalloproteinase, and GAG production level than the H-CS group. The expressions of ECM destruction enzyme and proinflammatory cytokines were lower in the S-CS group. In the mini-pigs articular cartilage defect model, the S-CS group had a higher International Cartilage Repair Society (ICRS) macroscopic score and displayed a zonal structure that more closely resembled the native cartilage than those implanted with the H-CS. Our study demonstrated that the application of the S-CS increased the hyaline cartilage formation and improved the surgical outcome of chondrocyte implication, offering a better tissue engineering strategy for treating articular cartilage defects.

Hybrid versus total sublaminar wires in patients with spinal muscular atrophy undergoing scoliosis surgery.

BACKGROUND: Early versions of spinal muscular atrophy (SMA) scoliosis correction surgery often involved sublaminar devices. Recently, the utilization of pedicle screws has gained much popularity. Pedicle screws are generally believed to provide additional deformity correction, but pedicle size and rotational deformity limit their application in the thoracic spine, resulting in a hybrid construct involving pedicle screws and sublaminar wire. Studies of the efficacy of hybrid instrumentation in SMA scoliosis are often limited by the scarcity of the disease itself. In this study, we aimed to compare the surgical outcomes between hybrid constructs involving pedicle screws and sublaminar wire and sublaminar wire alone in patients with SMA scoliosis. METHODS: We retrospectively reviewed the clinical records and radiographic assessments of patients with SMA scoliosis who underwent corrective surgery between 1993 and 2017. The radiographic assessments included deformity correction and progressive changes in the major curve angle, pelvic tilt (PT) and coronal balance (CB). The correction of deformities was observed postoperatively and at the patient's 2-year follow-up to test the efficacy of each type of construct. RESULTS: Thirty-three patients were included in this study. There were 14 and 19 patients in the wiring and hybrid construct groups, respectively. The hybrid construct group demonstrated a higher major curve angle correction (50.5° ± 11.2° vs. 36.4° ± 8.4°, p < 0.001), a higher apical vertebral rotation correction (10.6° ± 3.9° vs. 4.8° ± 2.6°, p < 0.001), and a reduced progression of the major curve angle at the 2-year follow-up (5.1° ± 2.9° vs. 8.7° ± 4.8°, p < 0.001). A moderate correlation was observed between the magnitude of correction of the apical vertebral rotation angle and the major curve (r = 0.528, p = 0.002). CONCLUSION: This study demonstrated that hybrid instrumentation can provide a greater magnitude of correction in major curve and apical rotation as well as less major curve progression than sublaminar wire instrumentation alone in patients with SMA scoliosis. Level of evidence III.

A New Strategy for Rapid Diagnosis of the Source of Low Back Pain in Patients Scheduled to Undergo Treatment with Cooled Radiofrequency Ablation.

OBJECTIVE: The objective of this study was to develop a new strategy for rapid diagnosis of the source of low back pain (LBP) for treatment with cooled radiofrequency ablation (RFA). MATERIALS: Patients suffering from facet joint (FJ) or sacroiliac joint (SIJ) pain for more than 3 months were included. Two methods, Technetium Tc99m methylene diphosphonate single photon emission tomography/computed tomography (99mTc-MDP SPECT/CT) and a modified Fortin finger test were used to identify the source of LBP for treatment with cooled RFA. The visual analog scale (VAS) and Oswestry disability index (ODI) were used to assess the patients' pain levels and disabilities respectively. These two measures were recorded at baseline and 1-week, 1-month, 3-month, and 6-month follow-up visits. RESULTS: A total of 40 patients with LBP were included in this study. Our results demonstrated that the patients with LBP identified by our new strategy had significant improvements in VAS or ODI score at 1-week to 6-month follow-up visits (p < 0.001) after receiving cooled RFA. Similar results were also found in patients with FJ pain and those with FJ and SIJ pain respectively. Among all the patients, over 70% had greater than or equal to 50% reduction in VAS and ODI scores. No serious adverse events were observed after treatment. CONCLUSIONS: This new strategy could be successfully adopted for rapid diagnosis of the source of comprehensive LBP.

Pain Control Affects the Radiographic Diagnosis of Segmental Instability in Patients with Degenerative Lumbar Spondylolisthesis.

BACKGROUND: Diagnosing intervertebral instability is crucial for the treatment of degenerative lumbar spondylolisthesis (DLS). Disabling back pain will reduce spinal mobility which leads to an underestimate of the incidence of intervertebral instability. We hypothesized that adequate analgesia could alter the flexion/extension exam performance, and thus increase the diagnostic accuracy of segmental instability. MATERIALS AND METHODS: One hundred patients with low-grade DLS were prospectively enrolled in the before-after cohort study. Standing lateral flexion/extension radiographs of lumbar spines were examined and analyzed before and after intramuscular injections of 30 mg ketorolac. RESULTS: Pain score decreased significantly after analgesic injections (p < 0.001). Dynamic slip (DS), dynamic segmental angle (DA), dynamic lumbar lordosis, and slip percentage (SP) were significantly increased after pain reduction (all p < 0.001). According to the diagnostic criteria for segmental instability (DS > 4.5 mm, DA > 15°, or SP > 15%), there were 4%, 4%, and 0.7% of total motion segments fulfilling the criteria which markedly increased to 42%, 32%, and 16.7% after analgesia was administered. The incidence of instability also increased from 6% to 38% after analgesia. CONCLUSIONS: The diagnosis rate of intervertebral instability is commonly underestimated in the presence of low back pain. This short-term pain relief facilitates reliable functional imaging adding to the diagnosis of intervertebral instability.

Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway.

AIMS: Interleukin (IL)-1ß is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. METHODS: Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1ß, 10 µM suramin, or 10 µM suramin plus IL-1ß. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. RESULTS: Suramin inhibited IL-1ß-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1ß-treated NP cells. IL-1ß-induced inflammation, assessed by IL-1ß, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1ß-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. CONCLUSION: Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498-513.

Shockwave Treatment Enhanced Extracellular Matrix Production in Articular Chondrocytes Through Activation of the ROS/MAPK/Nrf2 Signaling Pathway.

OBJECTIVE: Shockwave application is a potential treatment for osteoarthritis (OA), but the underlying mechanism remains unknown. Oxidative stress and a counterbalancing antioxidant system might be the key to understanding this mechanism. We hypothesized that reactive oxygen species (ROS) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2),which is an important regulator of cellular redox homeostasis, are plausible elements. DESIGN: Porcine chondrocytes were cultured in a 3-dimensional pellet model and subjected to shockwaves. The effects of shockwaves with various energy-flux densities on optimal extracellular matrix (ECM) synthesis were assessed. ROS, mitogen-activated protein kinase (MAPK) signaling, and the redox activity of Nrf2 were measured. To investigate the signaling mechanism involved in the shockwave treatment in chondrocytes, specific inhibitors of ROS, MAPK signaling, and Nrf2 activity were targeted. RESULTS: Shockwaves increased ECM synthesis without affecting cell viability or proliferation. Furthermore, they induced transient ROS production mainly through xanthine oxidase. The phosphorylation of ERK1/2 and p38 and the nuclear translocation of Nrf2 were activated by shockwaves. By contrast, suppression of ROS signaling mitigated shockwave-induced MAPK phosphorylation, Nrf2 nuclear translocation, and ECM synthesis. Pretreatment of chondrocytes with the specific inhibitors of MEK1/2 and p38, respectively, mitigated the shockwave-induced nuclear translocation of Nrf2 and ECM synthesis. Nrf2 inhibition by both small hairpin RNA knockdown and brusatol reduced the shockwave-enhanced ECM synthesis. CONCLUSIONS: Shockwaves activated Nrf2 activity through the induction of transient ROS signaling and subsequently enhanced ECM synthesis in chondrocytes. This study provided fundamental evidence confirming the potential of shockwaves for OA management.

Comparison of Efficacy among Three Radiofrequency Ablation Techniques for Treating Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

Radiofrequency ablation (RFA) was first introduced for treating knee osteoarthritis (OA) in 2010 and has emerged as a minimally invasive treatment option. Three RFA techniques have been adopted for treating knee OA, including conventional, pulsed, and cooled RFA. However, the efficacy among different RFA techniques in the treatment of knee OA is still unclear. Three electronic databases were systematically searched for relevant articles, including PubMed, Embase, and Cochrane Library. A meta-analysis of articles that investigated the use of RFA techniques in the treatment of knee OA was conducted to pool the effect size in pain before and after treatment. A total of 20 eligible articles (including 605 patients) were included for our meta-analysis. After treatment, the patients had significant improvements in pain for all three RFA techniques when compared with the baseline level for the 1, 3-, and 6-month follow-ups (p < 0.00001). However, there were no significant differences in the efficacy among the three RFA techniques for all follow-up visits (p > 0.05). The three RFA techniques demonstrated a significant improvement in pain for up to 6 months after treatment. Comparing the efficacy of the three RFA techniques in the treatment of knee OA, our results showed that no significant differences in pain relief among the three RFA techniques were observed at the 1-, 3-, 6, and 12-month follow-up visits.

High Risk of Early Cataracts in Young Type 1 Diabetes Group: A Nationwide Cohort Study.

BACKGROUND: Chronic hyperglycemia in type 1 diabetes (T1D) patients results in ocular problems over time, but only a few studies emphasized on cataracts. AIM: To evaluate the epidemiology of cataracts in the T1D population. METHOD: A two-part study was conducted using data from the National Health Insurance Research Database in Taiwan. Information from the Longitudinal Health Insurance Database (LHID) was served as a template of the general population. In the first part, a total of 3,622 T1D cases registered between 1998 and 2007 were enrolled and compared with a matched group from the LHID. For identifying risk factors of cataracts in the T1D population in the second part, a total of 9032 T1D cases registered between 1998 and 2013 were included. RESULT: Compared to the LHID, the hazard ratio (HR) of cataracts in the T1D group was 5.81 (95% CI 4.60-7.33), and the HR was higher in females (6.29, 95% CI 4.63-8.55). The peak incidence of cataracts occurred between age 20 and 29 in the T1D group, while in the LHID, it was after 60. The overall incidence of cataracts in the T1D group was 9.1%. In T1D patients with cataracts, they were found with higher rates of associated diabetic complications. CONCLUSION: Compared to the nondiabetic population, cataracts seemed more rampant and premature in T1D patients, especially those of female gender. Early ophthalmologic examination should be considered in T1D patients.

Extracorporeal shock wave promotes activation of anterior cruciate ligament remnant cells and their paracrine regulation of bone marrow stromal cells' proliferation, migration, collagen synthesis, and differentiation.

AIMS: Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells' activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells. METHODS: Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-ß), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm2, 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)' viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system. RESULTS: ESW-treated ACL remnant cells presented higher cell viability, proliferation, migration, and increased expression of COL-I A1, TGF-ß, and VEGF. BMSC proliferation and migration rate significantly increased after coculture with ACL remnant cells with and without ESW stimulation compared to the BMSCs alone group. Furthermore, ESW significantly enhanced ACL remnant cells' capability to upregulate the collagen gene expression and tenogenic differentiation of BMSCs, without affecting cell viability, TGF-ß, and VEGF expression. CONCLUSION: ACL remnant cells modulated activity and differentiation of surrounding cells. The results indicated that ESW enhanced ACL remnant cells viability, proliferation, migration, and expression of collagen, TGF-ß, VEGF, and paracrine regulation of BMSC proliferation, migration, collagen expression, and tenogenesis.Cite this article: Bone Joint Res 2020;9(8):458-468.

Steady Augmentation of Anti-Osteoarthritic Actions of Rapamycin by Liposome-Encapsulation in Collaboration with Low-Intensity Pulsed Ultrasound.

INTRODUCTION: Rapamycin has been considered as a potential treatment for osteoarthritis (OA). Drug carriers fabricated from liposomes can prolong the effects of drugs and reduce side effects of drugs. Low-intensity pulsed ultrasound (LIPUS) has been found to possess anti-OA effects. MATERIALS AND METHODS: The anti-osteoarthritic effects of liposome-encapsulated rapamycin (L-rapa) combined with LIPUS were examined by culture of normal and OA chondrocytes in alginate beads and further validated in OA prone Dunkin-Hartley guinea pigs. RESULTS: L-rapa with LIPUS largely up-regulated aggrecan and type II collagen mRNA in human OA chondrocytes (HOACs). L-rapa with LIPUS caused significant enhancement in proteoglycan and type II collagen production in HOACs. Large decreases in both MMP-13 and IL-6 proteins were found in the HOACs exposed to L-rapa with LIPUS. Intra-articular injection of 40 µL L-rapa at both 5 µM and 50 µM twice a week combined with LIPUS thrice a week for 8 weeks significantly increased GAGs and type II collagen in the cartilage of knee. Results on OARSI score showed that intra-articular injection of 5 µM L-rapa with LIPUS displayed the greatest anti-OA effects. Immunohistochemistry revealed that L-rapa with or without LIPUS predominantly reduced MMP-13 in vivo. The values of complete blood count and serum biochemical examinations remained in the normal ranges after the injections with or without LIPUS. These data indicated that intra-articular injection of L-rapa collaborated with LIPUS is not only effective against OA but a safe OA therapy. CONCLUSION: Taken together, L-rapa combined with LIPUS possessed the most consistently and effectively anabolic and anti-catabolic effects in HOACs and the spontaneous OA guinea pigs. This study evidently revealed that liposome-encapsulation collaborated with LIPUS is able to reduce the effective dose and administration frequency of rapamycin and further stably reinforce its therapeutic actions against OA.

Comparative effectiveness of various treatment strategies for trigger finger by pairwise meta-analysis.

OBJECTIVE: To compare the efficacy of various strategies in the treatment of trigger finger. DATA SOURCES: A systematic literature search for randomized controlled trials to compare treatments for trigger finger was conducted through three online databases, Pubmed, Embase and Cochrane Library, from their inception dates to 22 May 2020. METHODS: Relative risk (RR) with 95% confidence interval (CI) was used to evaluate the effect sizes in success rate for included articles. RESULTS: Sixteen articles (n = 1185) were included in our meta-analysis. The results showed that the efficacy of steroid injection was significantly better than the placebo group at short-term follow-ups (RR = 19.00, 95% CI = 1.17-309.77 for one-week; RR = 3.70, 95% CI = 3.70, 95% CI = 1.61-8.53 for one-month), and then became non-significant at four months (RR = 3.21, 95% CI = 0.88-11.79). There was no significant difference in success rate between steroid injection and nonsteroidal anti-inflammatory drug injection, and between open surgery and percutaneous release at all the follow-ups. Only surgical treatment had significantly better efficacy in success rate than steroid injection at all follow-ups (RR = 0.48, 95% CI = 0.34-0.66 for one-month; RR = 0.87, 95% CI = 0.80-0.96 for three-month; RR = 0.58, 95% CI = 0.48-0.68 for six-month; RR = 0.38, 95% CI = 0.20-0.72 for 12-month). CONCLUSION: There were no differences in efficacy between steroid injection and shockwave or nonsteroidal anti-inflammatory drug injection. The surgical treatments had the best efficacy among these treatments.

A comparison of efficacy among different radiofrequency ablation techniques for the treatment of lumbar facet joint and sacroiliac joint pain: A systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of different radiofrequency techniques (thermal, pulsed, and cooled radiofrequency) for treating lumbar facet joint (LFJ) or sacroiliac joint (SIJ) pain. PATIENTS AND METHODS: The inclusion criteria were as follows: (1) age > 18 years; (2) patients suffering from LFJ or SIJ pain; and (3) patients receiving radiofrequency treatments. Four electronic databases, including Pubmed, Embase, Cochrane Library, and ISI Web of Knowledge were systematically searched from inception until December 2019 for relevant articles. The search was conducted on 2 January 2020. When the outcomes among articles showed heterogeneity, then a random-effects model was adopted to calculate the effect size; otherwise, a fixed-effects model was adopted. RESULTS: All the three techniques showed significant improvements in LFJ or SIJ pain for up to 12 months compared with the baseline level. However, no significant differences among the three techniques were observed at any follow-up visits except for possibly a trend for variance in efficacy. For treating LFJ pain, cooled radiofrequency was the most effective, followed by thermal radiofrequency and then pulsed radiofrequency as the least respectively for the follow-up visit at 6 months. No serious complications were reported after receiving treatment using the three techniques. CONCLUSION: Sequentially, cooled radiofrequency followed by thermal radiofrequency and then pulsed radiofrequency for treating LFJ pain were identified as most to least effective at the 6-month follow-up.

Management of nonunion of humeral medial condyle fracture: A case series and review of the literature.

Pediatric humeral medial condyle fracture (HMCF) is a rare condition and is difficult to detect, especially in young children. The management of late presentation of HMCF is challenging and lacks consensus. Herein, we reported four cases of HMCF nonunion received open reduction and internal fixation (ORIF) or supracondyle osteotomy from our institution. In addition, 12 cases of ORIF and 4 cases of osteotomy reported in the previous studies were also reviewed. The HMCF nonunion can heal after ORIF, but the indication and the optimal techniques need to be clarified. Supracondylar osteotomy alone is an effective and safe treatment option to improve the functional and cosmetic outcomes of HMCF nonunion.

Predictors for Deformity Progression in a Spinal Muscular Atrophy Cohort After Scoliosis Correction Surgery.

STUDY DESIGN: This was a single-center, retrospective study. OBJECTIVE: The objective of this study was to assess the risk factors for deformity progression after scoliosis correction surgery in spinal muscular atrophy (SMA) patients. SUMMARY OF BACKGROUND DATA: Moderate residual postoperative scoliosis curve is common in SMA populations; however, the acceptable postoperative scoliosis curve for preventing deformity progression remains uncertain. MATERIALS AND METHODS: Twenty-nine SMA patients undergoing scoliosis correction surgery were included. Scoliosis progression was defined as an increase of 10 degrees in the major curve of Cobb angle (MCCA); pelvic obliquity (PO) or concave-side hip progression was arbitrarily defined as an increase of ≥1 grade after surgery. Risk factors for deformity progression were examined using Cox proportional hazard models. The cumulative incidence rate of deformity progression was performed by the Kaplan-Meier survival analysis RESULTS:: The mean age at surgery was 13.3 years (range: 8-25 y) and the mean follow-up time was 7 years (range: 2-22.9 y). The mean MCCA was corrected from 69 to 34.6 degrees at initial follow-up and 42.2 degrees at the final follow-up. Postoperative MCCA (P=0.002) and PO (P=0.004) at initial follow-up were the risk factors for scoliosis progression. Postoperative MCCA at initial follow-up (P=0.007) and age at the time of surgery (P=0.017) were the risk factors for PO progression. Different cutoff points of postoperative MCCA at initial follow-up were compared for predicting deformity progression. We found the patient with postoperative MCCA of <30 degrees at initial follow-up had a significantly less cumulative incidence rate of progression than their counterparts for scoliosis (P=0.005), PO (P=0.023), and concave-side hip progressions (P=0.008). CONCLUSIONS: We recommended that MCCA should be corrected to <30 degrees to prevent postoperative scoliosis, PO, and concave-side femoral head coverage percentage progressions. Patients receiving surgery earlier had less postoperative MCCA at initial follow-up but with no increase in the risk of postoperative scoliosis progression.

(-)-Epigallocatechin-3-Gallate Decreases Osteoclastogenesis via Modulation of RANKL and Osteoprotegrin.

Osteoporosis is the second most common epidemiologic disease in the aging population worldwide. Previous studies have found that frequent tea drinkers have higher bone mineral density and less hip fracture. We previously found that (-)-epigallocatechin gallate (EGCG) (20⁻100 µmol/L) significantly suppressed receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis and pit formation via inhibiting NF-κB transcriptional activity and nuclear transport of NF-κB in RAW 264.7 cells and murine primary bone marrow macrophage cells. The most important regulation in osteoclastogenesis is the receptor activator of nuclear factor-kB/RANKL/osteoprotegrin (RANK/RANKL/OPG) pathway. In this study, we used the coculture of RAW 264.7 cells and the feeder cells, ST2, to evaluate how EGCG regulated the RANK/RANKL/OPG pathway in RAW 264.7 cells and ST2 cells. We found EGCG decreased the RANKL/OPG ratio in both mRNA expression and secretory protein levels and eventually decreased osteoclastogenesis by TRAP (+) stain osteoclasts and TRAP activity at low concentrations-1 and 10 µmol/L-via the RANK/RANKL/OPG pathway. The effective concentration can be easily achieved in daily tea consumption. Taken together, our results implicate that EGCG could be an important nutrient in modulating bone resorption.