Preoperative CT parameters to predict tibiofibular syndesmosis injury associated with ankle fracture: a propensity score-matched analysis.

BACKGROUND: Untreated ankle fractures with concomitant tibiofibular syndesmosis injury often lead to postoperative pain and early traumatic arthritis. CT has advantages in the preoperative diagnosis of combined ankle injuries. However, a few studies have investigated the best preoperative CT parameters to predict tibiofibular syndesmosis injuries associated with ankle fractures. This study aimed to identify and evaluate the optimal preoperative CT parameters for predicting tibiofibular syndesmosis injuries associated with ankle fractures. METHODS: We retrospectively analyzed 129 patients who underwent preoperative CT of an ankle fracture treated between January 2016 and April 2022 at a tertiary A hospital. All patients underwent open reduction and internal fixation and intraoperative stability testing. Based on the Cotton test, the patients were divided into the stable group (n = 83, 64.3%) and unstable group (n = 46, 35.7%). After 1:1 propensity score matching, the general conditions, anterior tibiofibular distance (TFD), posterior TFD, maximum TFD, tibiofibular syndesmosis area, sagittal fracture angle, Angle-A, and Angle-B were compared between the stable and unstable groups. RESULTS: The propensity score-matched cohort comprised 82 patients. There were no significant differences between the stable and unstable groups in sex, age, affected side, operation interval, injury mechanism, Lauge-Hansen classification, sagittal fracture angle, and Angle-A (all P > 0.05). Compared with the stable group, the unstable group had a significantly greater aTFD, pTFD, maxTFD, and area (all P < 0.05). PTFD, maxTFD, and area were positively correlated with joint instability. Angle-B was smaller in the unstable group (57.13°) than the stable group (65.56°). ROC analysis showed that Area (AUC 0.711) and maxTFD (AUC 0.707) had the highest diagnostic efficacy. CONCLUSION: MaxTFD and Area were the best predictive parameters; a larger Area was associated with a higher likelihood of instability of the tibiofibular syndesmosis after ankle fracture fixation.

Genetic Analysis and Functional Study of a Pedigree With Bruck Syndrome Caused by PLOD2 Variant.

Background: Bruck syndrome (BS) is a rare autosomal recessive inherited osteogenesis imperfecta disease characterized by increased bone fragility and joint contracture. The pathogenic gene of type I BS is FKBPl0, whereas that of type II BS is PLOD2. No significant difference has been found in the clinical phenotype between the two types of BS. In this study, we performed genetic analysis of a BS pedigree caused by PLOD2 variant and studied the corresponding cellular function. Methods: Serum biochemistry, parathyroid hormone (PTH), 25-hydroxyvitamin D [25-(OH) D], osteocalcin, and 24-h urinary calcium levels of a family member with BS was assessed. The genes of the proband were analyzed by second-generation sequencing and exon capture techniques. Sanger sequencing was also performed for the suspected responsible variant of the family member. Wild- and variant-type lentivirus plasmids were constructed by gene cloning and transfected into HEK293T cells. Cell function was verified by real-time quantitative polymerase chain reaction, western blotting, and immunofluorescence detection. Results: In this pedigree, the proband was found to have a homozygous variant c.1856G > A (p.Arg619His) in exon 17 of PLOD2 (NM_182943.3). His consanguineous parents and sisters were p.Arg619His heterozygous carriers. The mRNA expression of PLOD2 in the constructed p.Arg619His variant cells was significantly upregulated, while the expression of PLOD2 and collagen I protein in the cell lysate was significantly downregulated. Immunofluorescence revealed that the wild-type PLOD2 was mainly located in the cytoplasm, and the expression of the PLOD2 protein after c.1856G > A variant was significantly downregulated, with almost no expression, aligning with the western blot results. The serum sodium, potassium, calcium, phosphorus, magnesium, alkaline phosphatase, PTH, 25-(OH) D, osteocalcin, and 24 h urinary calcium levels of the proband, his parents, and sisters were normal. Conclusion: Through gene and cell function analyses, PLOD2 Arg619His missense variant was preliminarily confirmed to cause BS by reducing protein expression.

Analysis of the efficacy of a modified posteromedial approach for Klammer III posterior Pilon fractures.

PURPOSE: To analyze the curative effect and technical points of a modified posteromedial approach in the treatment of Klammer III posterior Pilon fracture. METHODS: A retrospective analysis of patients with Klammer III posterior Pilon fractures were conducted in our department from January 2018 to December 2019. Before the surgery, the patients were fully relieved of swelling and pain, and a comprehensive examination was carried out. The posteromedial approach exposed the posterior and medial fracture block of the distal tibia. According to the fracture of external malleolus, it is determined whether to combine a lateral incision and protect tendons and vascular nerves by a retractor, and then perform a fracture reduction and internal fixation. Postoperatively, the patients were treated with analgesia, detumescence, anticoagulation and rehabilitation exercise. The American orthopaedic foot and ankle society (AOFAS) score and visual analogue score were recorded at regular follow-up after surgery. A t-test was used for the comparison of the preoperative and final AOFAS score. RESULTS: There were 7 male and 13 female (n = 20) included in the study, aged 22 to 88 years (average age 54.2 years). The injury mechanisms were falling from a height (n = 7), traffic accident (n = 6), walking injury (n = 2) and heavy injury (n = 5). The postoperative follow-up duration was 12-24 months (mean 16.95 months). The AOFAS score of the 20 patients before and after surgery were compared. The preoperative AOFAS score was 38.90 ± 3.91, and the final AOFAS score was 80.55 ± 4.20, (p < 0.001). The mean final visual analogue scores at rest, active and weight-bearing walking were 0.30, 0.85 and 1.70, respectively. One patient reported poor postoperative wound healing and required a return to hospital for debridement and anti-infection treatment. CONCLUSION: In the treatment of Klammer III posterior Pilon fractures, the modified posteromedial approach can fully expose the fracture block and the collapsed articular surface of the medial malleolus, achieve good reduction and internal fixation with limited injury of the tendon and vascular nerves, and have a better prognosis.

miR-199a-3p may be an early warning marker for acute rejection after liver transplantation in rats.

BACKGROUND: Prevention of acute rejection is the key of the success of liver transplantation. However, there are no specific indicators available for prediction of acute rejection after liver transplantation. MicroRNAs (miRNAs) are highly conserved and small noncoding RNA molecules that can be detected in peripheral blood. Here, we evaluated the potential of circulating miRNAs to serve as noninvasive biomarkers for acute rejection after liver transplantation in rats. METHODS: The liver grafts retrieved from Lewis rats were orthotopically transplanted into BN rats or Lewis rats in the acute rejection and immune tolerance group respectively, and the BN rats in the immune intervention group was intraperitoneally injected with transforming growth factor-ß1 overexpressed immature dendritic cells to suppress acute rejection before orthotopically transplanted with livers from Lewis rats. MiRNAs profiling studies were used to determine the regulation of circulating miRNAs in plasma samples of rats. Candidate miRNA was verified by quantitative reverse transcriptase polymerase chain reaction. Furthermore, the relationship between candidate miRNA and acute rejection was also evaluated. RESULTS: Microarray analysis revealed that miR-199a-3p was the mostly differentially regulated miRNAs in plasma samples among the three groups. The plasmid PCDH-CMV-EGFP-hTGF-ß1 was identified by PCR and DNA sequencing, and successfully expressed in imDCs. There were differences in the expression of miR-199a-3p in the liver tissues of the AR group on the 3rd, 7th and 10th day after liver transplantation (all p < 0.01). With time, the RAI score increased gradually, and the difference of miR-199a-3p expression gradually increased (rs = 0.92, p < 0.001), suggesting that it may be related to acute rejection. The expression of miR-199a-3p in the serum of the AR and TGF-ß1-imDCs groups gradually increased, reaching a peak at day 7 and then decreasing. There was positive relationship between the expression of miR-199a-3p and RAIs within 7 days post operation. (rs = 0.942, p < 0.05). CONCLUSION: miR-199a-3p might be an early warning marker for acute rejection after liver transplantation in rats.

Danshensu inhibits the IL-1ß-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway.

PURPOSE: Osteoarthritis (OA) is the most common inflammatory disease associated with pain and cartilage destruction. Interleukin (IL)-1ß is widely used to induce inflammatory response in OA models. This study aimed to explore the role of Danshensu (DSS) in IL-1ß-induced inflammatory responses in OA. METHODS: IL-1ß was used to induce chondrocyte inflammation. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. IL-6, COX-2, TNF-α, and iNOS mRNA levels were detected by qRT-PCR. MMP3, MMP13, ADAMTS4, ADAMTS5, Aggrecan, Collagen, p-IκBα, and p-p65 protein levels were detected by Western blot. An OA mouse model was established by surgical destabilization of the medial meniscus (DMM), and the Osteoarthritis Research Society International (OARSI) score was evaluated by H&E staining. RESULTS: DSS did not affect the levels of inflammatory indicators including IL-6, COX-2, TNF-α, iNOS, PEG2, and NO but suppressed COX-2 and iNOS protein expression in IL-1ß treated chondrocytes. In addition, DSS downregulated IL-1ß-enhanced expression of MMP3, MMP13, ADAMTS4, and ADAMTS5 and upregulated aggrecan and collagen expression. Moreover, DSS significantly inhibited IL-1ß-induced phosphorylation of p-IκBα and p-p65 in a dose-dependent manner in chondrocytes, suggesting it plays a role in the NF-κB signaling pathway. Furthermore, DSS significantly reduced DMM-induced cartilage OARSI score in mice, further demonstrating its protective role in OA progression in vivo. CONCLUSIONS: Our study revealed the protective role of DSS in OA, suggesting that DSS might act as a potential treatment for OA.

High Mobility Group Box 1 Contributes to the Acute Rejection of Liver Allografts by Activating Dendritic Cells.

Acute rejection induced by the recognition of donor alloantigens by recipient T cells leads to graft failure in liver transplant recipients. The role of high mobility group box 1 (HMGB1), an inflammatory mediator, in the acute allograft rejection of liver transplants is unknown. Here, rat orthotopic liver transplantation was successfully established to analyze the expression pattern of HMGB1 in liver allografts and its potential role in promoting the maturation of dendritic cells (DCs) to promote T cell proliferation and differentiation. Five and 10 days after transplantation, allografts showed a marked upregulation of HMGB1 expression accompanied by elevated levels of serum transaminase and CD3+ and CD86+ inflammatory cell infiltration. Furthermore, in vitro experiments showed HMGB1 increased the expressions of co-stimulatory molecules (CD80, CD83, and MHC class II) on bone marrow-derived DCs. HMGB1-pulsed DCs induced naive CD4+ T cells to differentiate to Th1 and Th17 subsets secreting IFN-γ and IL-17, respectively. Further in vivo experiments confirmed the administration of glycyrrhizic acid, a natural HMGB1 inhibitor, during donor liver preservation had therapeutic effects by reducing inflammation and hepatocyte damage reflected by a decline in serum transaminase and prolonged allograft survival time. These results suggest the involvement of HMBG1 in acute liver allograft rejection and that it might be a candidate therapeutic target to avoid acute rejection after liver transplantation.

Agonism of GPR120 prevented IL-1ß-induced reduction of extracellular matrix through SOX-9.

Osteoarthritis (OA) is a whole-joint disease with extremely high prevalence. In all treatment approaches of OA, blocking the degradation of the cartilage extracellular matrix is an important treatment. In OA, overexpression of derivative enzymes leads to excessive catabolism and reduced synthesis of cartilage including type II collagen and aggrecan, which results in irreversible destruction of the joint. SOX9 is a transcription factor that regulates the synthesis of type II collagen and aggrecan and is significantly downregulated in OA. GPR120 has been reported to affect the pathophysiology of OA. In this study, we used the GPR120 agonist GW9508 and TUG891 in ATDC5 chondrocytes exposed to interleukin (IL)-1ß to investigate the involvement of GPR120 in SOX9-mediated expression of type II collagen and aggrecan. Our findings show that agonism of GPR120 can reduce inflammation by inhibiting the expression of IL-6 and IL-8 induced by IL-1ß. We also show that GW9508 and TUG891 rescue the expression of type II collagen and aggrecan by preventing the reduction of SOX9 expression. Additionally, we demonstrate that the effects of GW9508 on SOX9 expression are mediated through CREB and that GPR120 is indeed required for this effect. Thus, agonism of GPR120 by GW9508 might be a potential therapeutic strategy to halt or prevent cartilage degradation.

DHRS12 inhibits the proliferation and metastasis of osteosarcoma via Wnt3a/ß-catenin pathway.

Aim: This experimental design was based on DHRS12 to explore its biological effects on osteosarcoma (OS). Materials & methods: The expression level of endogenous DHRS12 was analyzed by immunohistochemical analysis. DHRS12 was overexpressed in MG-63 and HOS cells by plasmid transfection. Cell proliferation, invasion, migration, apoptosis and western blot were used in the experiment. Results: The expression of DHRS12 was significantly reduced in OS. Overexpression of DHRS12 inhibited the proliferation, migration and invasion of MG-63 and HOS cells and induced apoptosis of OS cells. Overexpression of DHRS12 upregulated Bax, Caspase 9 and Caspase 3. Overexpression of DHRS12 resulted in inactivation of the Wnt3a/ß-catenin signaling pathway. Conclusion: Overexpression of DHRS12 inhibited the progression of OS via the Wnt3a/ß-catenin pathway.

Effects of IL-10- and FasL-overexpressing dendritic cells on liver transplantation tolerance in a heterotopic liver transplantation rat model.

Acute rejection is the major determinant for the long-term survival of donor liver after liver transplantation (LT). The aim of this study was to examine the therapeutic potential of interleukin (IL)-10-FasL-overexpressing immature dendritic cells (imDCs) to induce local immunosuppression in liver grafts. imDCs derived from donors were transduced by lentiviral vectors expressing human IL-10 and/or Fas ligand (FasL) gene(s), and the expression of surface molecules and the ability to induce T-cell proliferation were measured. imDCs were intraperitoneally injected into recipient rats as a model of LT to examine the rejection grade [Banff rejection activity index (RAI)], liver functions [Alanine aminotransferase, Aspartate aminotransferase (AST) and total bilirubin (TBIL)] and post-transplant survival. IL-10 and FasL co-transduction of imDCs induced a greater reduction in CD80, CD86 and major histocompatibility complex class II (MHC II) expression, as well as T-cell proliferation, but increased levels of IL-10 and FasL in culture supernatants compared with mono-transduced or untransduced imDCs (P < 0.05). The infusion of co-transduced imDCs in LT recipients reduced RAI scores, decreased plasma AST and TBIL, and prolonged survival compared with mono-transduced or untransduced imDC-treated liver allografts. These findings demonstrated that the transfusion of IL-10-FasL/imDCs enhanced immune tolerance and prolonged the survival of liver allografts after LT. The immunomodulatory activity of IL-10- and FasL-modified imDCs might be a new therapeutic approach to prevent organ rejection in clinical transplantation.

Synergistic effects of recombinant Lentiviral-mediated BMP2 and TGF-beta3 on the osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) are considered good candidates for seed cells in bone engineering. The study aim to investigate the synergistic effects of human bone morphogenetic protein 2 (hBMP2) and transforming growth factor beta3 (hTGF-beta3) modified BMSCs on inducing osteogenic differentiation in vitro. METHODS: Lentivirus (LV) carrying hBMP2 and/or hTGF-beta3 genes were constructed and used to transduce rat BMSCs. The expression of osteogenic molecules was detected by qRT-PCR and western blotting. RESULTS: Targeted genes were PCR-amplified and confirmed by DNA sequencing and BLAST analysis. BMSCs infected by vectors effectively resulted in the overexpressions of hBMP2 and hTGF-beta3 and higher levels of hBMP2 and hTGF-beta3 in the culture supernatant. The co-transduction of hBMP2 and hTGF-beta3 induced BMSCs osteogenic differentiation more effectively than the transduction of hBMP2 or hTGF-beta3 individually. The expression levels of osteopontin (OPN), osteocalcin (OCN), and osteoprotegerin (OPG) in LV-hBMP2 + LV-hTGF-beta3 group (BMSCs transfected by vectors respectively carrying hBMP-2 gene and hTGF-beta3 gene) and LV-hBMP2-hTGF-beta3 group (BMSCs transfected by vector carrying hBMP2 and hTGF-beta3 fusion gene) were significantly higher than in LV-BMP2 (BMSCs transfected by vector carrying hBMP2 gene) and LV-TGF-beta3 (BMSCs transfected by vector carrying hTGF-beta3 gene) groups (P < 0.05). The hBMP2 and/or hTGF-beta3 overexpression upregulated alkaline phosphatase (ALP) activity. CONCLUSION: The present study showed that hBMP2 and/or hTGF-beta3 genes can be successfully overexpressed in BMSCs. Our study proved that the two cytokines (hBMP2 and hTGF-beta3) could induce bone differentiation synergistically, which foresees the use of the combination of these two cytokines as a therapeutic strategy in the future.

Chinese Trauma Surgeon Association for management guidelines of vacuum sealing drainage application in abdominal surgeries-Update and systematic review.

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.

Prolonged survival effects induced by immature dendritic cells and regulatory T cells in a rat liver transplantation model.

BACKGROUND: Dendritic cells (DCs) and regulatory T (Treg) cells are crucial for inducing immune tolerance. However, the suppressive function of infused Treg cells and immature DCs (imDCs) following solid organ transplantation remains unclear. METHODS: ImDCs derived from DA-donor rats and Treg cells isolated from spleens of Lewis rats were prepared. A heterotopic liver transplantation model was established to examine the immune tolerance effects of infusion of Treg-imDCs, imDCs and Treg cells individually. Th1/Th2 cytokines and TRAL were detected by ELISA. The overall rejection grade was assessed and the rejection activity index (RAI) was calculated. TUNEL-positive lymphocytes were detected in the portal area in liver sections. RESULTS: The infusion of Treg-imDCs was more effective than imDCs or Treg cells individually. Moreover, the expression of IL-10 and TGF-ß1 was significantly up-regulated, and IL-12 expression was significantly down-regulated, especially in the Treg-imDCs group. The percentage of TUNEL-positive cells was significantly higher in the Treg cells and imDCs groups. The RAI values in Treg-imDCs group on days 3 and 7 were lower than control, imDCs and Treg cells groups individually (p<0.05). Both TBIL and ALT levels in the Treg-imDCs and imDCs groups were significantly lower than those of the control and Treg cells groups, and serum TRAL levels increased significantly 10days after transplantation in the imDC and Treg-imDC groups compared with the control and Treg cells groups (P<0.001). CONCLUSION: These data demonstrated that infusion of Treg cells and/or imDCs induces alloantigen tolerance and prolongs liver allograft survival. The infusion of Treg-imDCs was more effective than imDCs or Treg cells individually. ImDCs synergize with Treg cells in inducing and maintaining the feedback loop between imDCs and Treg cells in vivo.

Increased expression of Notch 1 in a rat liver transplantation model.

Liver transplantation is the standard treatment for end­stage liver failure; however, rejection can result in allograft failure. In order to investigate the role of Notch 1 during rejection, the present study evaluated Notch 1 expression, as well as the levels of immune reactivity, in rat liver allografts. A heterotopic liver transplantation model was established using Dark Agouti (DA) rats as donors and Lewis rats as recipients (DA/Lewis), with DA recipient rats serving as controls (DA/DA). The concentration levels of immune reactivity markers and serum Notch 1 were measured on days 3, 5, and 7. The overall survival was significantly shorter (<10 days) in the DA/Lewis group, as compared with the DA/DA group (P<0.0001). The concentration levels of serum alanine aminotransferase and total bilirubin were significantly higher 5 and 7 days following transplantation in the DA/Lewis group, as compared with the DA/DA group (P<0.001). The concentration levels of serum Notch 1 were significantly higher in the DA/Lewis group, as compared with the DA/DA group on days 3, 5, and 7 following transplantation (P<0.0001). These results indicate that the expression levels of serum Notch 1 significantly increase during liver allograft rejection, suggesting that Notch 1 is involved in the mechanism underlying liver allograft rejection. Notch 1 may serve as a marker of acute rejection in a rat liver transplantation model.

Cotransfection with IL-10 and TGF-ß1 into immature dendritic cells enhances immune tolerance in a rat liver transplantation model.

Dendritic cells transfected with interleukin (IL)-10 and transforming growth factor-ß1 (TGF-ß1) enhance T cell immunity and tolerance. However, no quantitative studies have investigated the suppressive functions of immature dendritic cells (imDC) cotransfected with IL-10 and TGF-ß1. The effects of imDC cotransfected with IL-10 and TGF-ß1 (IL-10-TGF-ß1-imDC) on immune tolerance induction in a rat transplantation model were investigated. In addition, effects of IL-10-TGF-ß1-imDC relative to IL-10-transfected imDC (IL-10-imDC) and TGF-ß1-transfected imDC (TGF-ß1-imDC) were compared. The infusion of IL-10-TGF-ß1-imDC into recipients prolonged liver graft survival, which was sustained for >90 days. IL-12 serum levels decreased, whereas alanine transaminase and total bilirubin slightly increased in rats infused with IL-10-TGF-ß1-imDC compared with the IL-10-imDC and TGF-ß1-imDC groups. Furthermore, a higher percentage of terminal transferase-mediated UTP nick end-labeling-positive cells was observed, and histological analysis of the allografts indicated a rejection activity index of mild acute rejection. Our results suggest infusion of IL-10 and TGF-ß1 cotransfected imDC induces alloantigen-specific T cell hyporesponsiveness, inhibits antigen-specific immunological responses to liver allografts, prolongs liver allograft survival, and enhances the immune tolerance. This approach may provide a promising alternative for enhancing donor-specific tolerance during liver transplantation.

Functional study of immature dendritic cells co-transfected with IL-10 and TGF-beta 1 genes in vitro.

Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previous studies suggest that immature dendritic cells (imDCs) might be involved in the induction of peripheral T cell tolerance. While interleukin-10 (IL-10) functions at different levels of the immune response, transforming growth factor-beta 1 (TGF-beta 1) is considered to be a key factor in immune tolerance. In this study, we investigated the effects of immature DC (imDC) co-transfected with IL-10 and TGF-beta 1 genes (IL-10-TGF-beta 1-imDC) on inducing immune tolerance. Moreover, we compared the effects of IL-10-TGF-beta 1-imDC with IL-10 transfected imDC (IL-10-imDC) and TGF-beta 1-transfected imDC (TGF-beta 1-imDC), respectively. IL-10-TGF-beta 1-imDC resulted in the down-regulation of MHC class II, CD80 and CD86. IL-10-TGF-beta 1-imDC could induce T cell hyporesponsiveness, and was reluctant to proliferate. IL-10-TGF-beta 1-imDC was more effective than IL-10-imDC and TGF-beta 1-imDC, respectively. In summary, co-expression of IL-10 and TGF-beta 1 affected the immunity of imDCs and enhanced their tolerogenicity. It might be a promising therapy for donor-specific tolerance after organ transplantation.

Effect of lumbar angular motion on central canal diameter: positional MRI study in 491 cases.

BACKGROUND: Lumbar spinal stenosis is a common problem that is receiving attention with the advent of novel treatment procedures. Prior positional MRI studies demonstrated lumbar canal diameter changes with flexion and extension. There have not been any studies to examine the amount of spinal canal diameter change relative to the amount of angular motion. The purpose of this study was to evaluate the correlation between the lumbar canal diameter change and the angular motion quantitatively. METHODS: Positional MRI (pMRI) images for 491 patients, including 310 males and 181 females (16 years-85 years of age), were obtained with the subjects in sitting flexion 40 degree, upright, and with extension of 10 degrees within a 0.6 T Positional MRI scanner. Quantitative measurements of the canal diameter and segmental angle of each level in the sagittal midline plane were obtained for each position. Then the diameter change and angular motion were examined for correlation during flexion and extension with linear regression analysis. RESULTS: The lumbar segmental angles were lordotic in all positions except L1-2 in flexion. The changes of canal diameters were statistically correlated with the segmental angular motions during flexion and extension (P < 0.001). The amount of canal diameter change correlated with the amount of angular change and was expressed as a ratio. CONCLUSIONS: Positional MRI demonstrated the amount of spinal canal diameter change that was statistically correlated with the segmental angular motion of the spine during flexion and extension. These results may be used to predict the extent of canal diameter change when interspinous devices or positional changes are used to treat spinal stenosis and the amount of increased canal space may be predicted with the amount of angular or positional change of the spine. This may correlate with symptomatic relief and allow for improved success in the treatment of spinal stenosis.

Bone morphogenetic protein binding peptide mechanism and enhancement of osteogenic protein-1 induced bone healing.

STUDY DESIGN: In vitro and in vivo evaluation of BBP interactions with BMP. OBJECTIVE: To explore bone morphogenetic protein-binding peptide (BBP)'s mechanism of action, investigate an extended repertoire for BBP applications, and evaluate the usefulness of BBP as a surgical adjuvant when used with recombinant human osteogenic protein-1 (rhOP-1). SUMMARY OF BACKGROUND DATA: Bone morphogenetic proteins (BMPs) are osteoinductive proteins that provide a potential alternative to autograft. Their utility is limited by cost, and potential dose-dependent risks, such as local inflammatory reactions and ectopic bone formation. BBP, a cyclized synthetic peptide, avidly binds recombinant human BMP-2(rhBMP-2) and has been shown to accelerate and enhance its osteogenic qualities. METHODS: BBP binding with 4 growth factors from the transforming growth factor -beta family were assessed using surface plasmon resonance. The in vivo retention of rhBMP-2 was quantified by comparing the percentage of retained [¹²5I]-labeled rhBMP-2 in absorbable collagen sponge implants with or without BBP at 1, 3, and 7 days postimplantation. The adjunctive effect of BBP with rhOP-1-induced bone growth was evaluated by comparing time to fusion and fusion rates in a rodent posterolateral fusion model with 2 different doses of rhOP-1 with or without BBP. RESULTS: BBP bound all 4 growth factors with an intermediate affinity. The in vivo retention of rhBMP-2 alone ranged from about 40% on day 1 to about 30% on day 7, whereas, the retention of rhBMP-2 in the presence of BBP was about 85% on day 1 and about 55% on day 7. The addition of BBP to rhOP-1 resulted in significantly earlier and greater fusion rates than achieved with rhOP-1 alone. CONCLUSION: The mechanism of the BBP enhanced osteoinductive properties of BMPs involves the binding and retention of the growth factor, resulting in a prolonged exposure of BMP to the desired fusion site. The use of BBP in conjunction with BMPs may prove to provide satisfactory fusion outcomes, while reducing the costs and side effects associated with BMP use.

Enhanced effects of BMP-binding peptide combined with recombinant human BMP-2 on the healing of a rodent segmental femoral defect.

BMP-binding peptide (BBP) enhances the osteogenic activity of recombinant human bone morphogenetic protein-2 (rhBMP-2), but the mechanism underlying the enhancement remains unclear. We aimed to elucidate the potential enhanced efficacy of BBP using critical-sized segmental femoral bone defects in rats. Seventy defects in seven groups of rats were filled with various amounts (0, 2, 5, and 10 microg) of rhBMP-2 with or without 1000 microg BBP. Radiographs were obtained after 4 and 8 weeks. The animals were euthanized at 8 weeks, and femoral specimens were assessed manually, evaluated for bone volume using microcomputed tomography, and subjected to histological or biomechanical analysis. Although 10 microg rhBMP-2 yielded consistent results in terms of bone healing and quality of bone repair across the segmental defect, lower doses of rhBMP-2 failed to induce satisfactory bone healing. However, the combined administration of lower doses of rhBMP-2 and BBP induced the formation of significantly large amounts of bone. Our results suggest that the combined administration of rhBMP-2 and BBP facilitates bone healing and has potential clinical applications.

Relationship of facet tropism with degeneration and stability of functional spinal unit.

PURPOSE: The authors investigated the effect of lumbar facet tropism (FT) on intervertebral disc degeneration (DD), facet joint degeneration (FJD), and segmental translational motion. MATERIALS AND METHODS: Using kinetic MRI (KMRI), lumbar FT, which was defined as a difference in symmetry of more than 7 degrees between the orientations of the facet joints, was investigated in 900 functional spinal units (300 subjects) in flexion, neutral, and extension postures. Each segment at L3-L4, L4-L5, and L5-S1 was assessed based on the extent of DD (grade I-V) and FJD (grade 1-4). According to the presence of FT, they were classified into two groups; one with FT and one with facet symmetry. For each group, demographics, DD, FJD and translational segmental motion were compared. RESULTS: The incidence of FT was 34.5% at L3-L4, 35.1% at L4-L5, and 35.2% at L5-S1. Age and gender did not show any significant relationship with FT. Additionally, no correlation was observed between DD and FT. FT, however, was found to be associated with a higher incidence of highly degenerated facet joints at L4-L5 when compared to patients without FT (p < 0.01). Finally, FT was not observed to have any effects upon translational segmental motion. CONCLUSION: No significant correlation was observed between lumbar FT and DD or translational segmental motion. However, FT was shown to be associated significantly with the presence of high grades of FJD at L4-L5. This suggests that at active sites of segmental motion, FT may predispose to the development of facet joint degeneration.

Lumbar segmental mobility according to the grade of the disc, the facet joint, the muscle, and the ligament pathology by using kinetic magnetic resonance imaging.

STUDY DESIGN: The kinematic study of human lumbar spinal movements. OBJECTIVE: To investigate how disc degeneration and the degeneration of facet joint, ligaments, and paraspinal muscles are associated with lumbar segmental mobility. SUMMARY OF BACKGROUND DATA: Previous studies revealed relationship between spinal motion and osteoarthritic changes of facet joint as well as disc degeneration; however, little is known about the association of disc, facet joint, ligament, and muscle degeneration with lumbar segmental motion characteristics. METHODS: The 1580 lumbar motion segments from 316 patients (200 male, 116 female) underwent Kinetic magnetic resonance imaging, which were used to assess disc degeneration (grade I-V) and facet joint degeneration (grade 1-4), interspinous ligament (ISL) degeneration (grade 1-4), ligamentum flavum hypertrophy (LFH), and fatty degeneration of muscles. Segmental translational and angular motion in the flexion, extension, and neutral postures were digitally automatically measured by MR analyzer. RESULTS: Grade II (46.77%) disc, grade 1 (48.35%) facet joint degeneration, and grade 1 (64.1%) ISL were most common. LFH was most common in L4-L5 (49/330, 14.8%). In younger age (<35), grade I disc and grade 1 facet joint were predominant compared with the older age (35< or = and <45) in which grade III, IV, and V disc and grade 2 facet joint were predominant (P < 0.05). Translational motion increased significantly in high grade of disc and facet joint (except grade V disc and grade 4 facet joint) and with LFH in L1-L5 (P < 0.05). Angular motion significantly decreased in grade V disc, grade 4 ISL, and without LFH in L1-L5 (P < 0.05). According to muscle fatty degeneration, translational and angular motions were not significantly changed. CONCLUSION: Our results support that facet joint degeneration is followed by disc degeneration according to age. Increased translational movements of the lumbar segments occurred in severe disc degeneration accompanied by facet joint degeneration or the presence of LFH even if the movements were stabilized in the advanced status. Therefore, the current status of the intervertebral discs, facet joints, and ligamentum flavum should be taken into consideration when evaluating stability within the lumbar spine.