FGF19 protects against obesity-induced bone loss by promoting osteogenic differentiation.

Human fibroblast growth factor 19 (FGF19) has become a potential therapeutic target for metabolic-related diseases. However, the effects of FGF19 on obesity-induced bone loss have not been completely elucidated. The aim of this study was to investigate the protective effects of FGF19 in high-fat diet (HFD)-fed obese mice and palmitic acid (PA)-treated osteoblasts and to further explore its underlying mechanisms. In vivo, we found that FGF19 alleviated the decreased bone mineral density (BMD) induced by HFD. Micro-CT analysis of femur samples and histological analysis indicated that FGF19 alleviated HFD-induced loss of bone trabeculae and damage to the bone trabecular structure. In vitro, the results suggested that FGF19 ameliorated the PA-induced decline in osteoblast proliferation, increased cell death and impaired cell morphology. Additionally, FGF19 protected against the decline in activation of alkaline phosphatase (ALP) and protein expression of Collagen-1, Runx-2, and osteopontin (OPN) induced by PA. Furthermore, FGF19 might enhance osteogenic differentiation via the Wnt/ß-catenin pathway and inhibit osteoclastogenesis by regulating the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis, thus attenuating the negative effect of PA in osteoblasts. In conclusion, our results suggested that FGF19 might promote osteogenic differentiation partially through activation of the Wnt/ß-catenin pathway and alleviate obesity-induced bone loss.

Implant complications after one-level or two-level cervical disc arthroplasty: A retrospective single-centre study of 105 patients.

The aim of study was to investigate the complications of cervical disc arthroplasty (CDA) and to discuss the factors affecting the mobility of the prosthesis and the measures to prevent these complications. Hundred and five patients who underwent CDA between 2009 and 2016 were enrolled. The clinical and radiographic outcomes were used to assess and the complications were recorded as well.All the patients were followed-up with an average of 41.30 ±â€Š16.90 months with an average age of 47.90 ±â€Š9.22 years. The visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopaedic Association (JOA) scores improved significantly at the final follow-up (FU) compared with the preoperative values. At the final FU, the overall incidence of heterotopic ossification (HO) was 51.42%. The distribution of different grades of HO was low-level HO (53.7%) and high-level HO (46.3%). No significant differences were found in the NDI, VAS, or JOA scores between patients with HO and those without HO (P > .05). In the high-level HO patients, the range of mobility (ROM) was significantly reduced compared with the low-level HO patients and those without HO (P < .05). The anterior displacement, subsidence, and instability were observed in 1 patient respectively and the segmental kyphosis, adjacent segment degeneration in 3 patients respectively. The patient of CDA instability also suffered severe neck pain and the revision surgery was performed.Postoperative complications in CDA such as HO, segmental kyphosis, and prosthesis displacement are prone to occur, affecting prosthesis mobility. Surgical indications should be strictly controlled, and intraoperative and postoperative treatments should be given great attention in order to reduce prosthesis-related complications.

Oblique lateral interbody fusion combined percutaneous pedicle screw fixation in the surgical treatment of single-segment lumbar tuberculosis: A single-center retrospective comparative study.

OBJECTIVE: To evaluate the clinical efficacy of oblique lateral interbody fusion combined posterior percutaneous pedicle screw fixation in the treatment of single segment lumbar tuberculosis. METHODS: Patients who underwent surgical treatment for single segment lumbar tuberculosis from 2015 to 2018 in our department were retrospectively included in this study. The included patients were divided into two groups, namely oblique lateral interbody fusion combined percutaneous pedicle screw fixation (OLIF) group and traditional posterior transforaminal or transpedicular approach debridement and pedicle screws fixation (PTA) group, according to the surgical methods. Outcomes including operative time, operative blood loss, hospital stay, visual analogue scale (VAS) score, Oswestry disability index (ODI), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), Cobb angle correction and loss, bone fusion time, ASIA grade and complications were all recorded and compared. RESULTS: A total of 60 patients were included in this study, involving 23 patients in the OLIF group and 37 patients in the PTA group. The OLIF group had less operative time, blood loss and shorter hospital stay compared with the PTA group (P < 0.05). Both the two groups achieved significant improvements in ESR, CRP and ASIA grade at the last follow-up (P < 0.05), but no significant differences were found between them (P>0.05). There were no significant differences in Cobb angle correction and loss between the two groups (P > 0.05), but the bone graft fusion time of the OLIF group was significantly shorter than the PTA group (P < 0.05). The two groups achieved similar improvement in VAS score and ODI at 12 months postoperative and the last follow-up, however, OLIF group had a lower VAS score and ODI at 1 month, 3 months and 6 months postoperative (P < 0.05). No significant difference was found in complications between the two groups (P > 0.05) and all patients were cured after active treatment. CONCLUSIONS: Both OLIF and PTA can achieve satisfactory clinical efficacy in the surgical treatment of single segment lumbar TB, but OLIF has the advantages of less surgical trauma, faster postoperative recovery and shorter bone fusion time.

Comparison of three different bone graft methods for single segment lumbar tuberculosis: A retrospective single-center cohort study.

OBJECTIVE: To compare the clinical efficacy of one stage posterior debridement with iliac bone graft, titanium mesh bone graft or granular bone graft in the surgical treatment of single segment lumbar tuberculosis. METHODS: Ninety-eight patients who underwent one stage posterior debridement, bone graft and internal fixation for single segment lumbar tuberculosis from 2015 to 2018 were involved in this study, involving 32 case in iliac bone graft group, 32 case in titanium mesh bone graft group and 34 cases in granular bone graft group. The primary outcomes involved operative time, operative blood loss, postoperative hospital stay, visual analogue scale (VAS) score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), ASIA grade and postoperative complications. The secondary outcomes were Cobb angle correction and loss, and bone graft fusion time. All the outcomes were recorded and analyzed. RESULTS: Compared with iliac bone graft and titanium mesh bone graft group, granular bone graft had shorter operative time (P = 0.003), less operative blood loss (P = 0.010) and shorter bone graft fusion time (P < 0.001). With the follow-up of 14-36 months, the VAS score, ESR, CRP and neurological function in the three groups were all significantly improved (P < 0.05). The bone graft fusion time of the granular bone graft group was significantly shorter than iliac bone graft group and titanium mesh bone graft (P < 0.05), but no significant differences were found in the correction and loss of Cobb angle, and the incidence of complications among the three groups (n.s.). CONCLUSION: Granular bone graft has less surgical trauma and shorter bone graft fusion time compared with iliac bone graft and titanium mesh bone graft in the surgical treatment of single segment lumbar tuberculosis. The three methods may achieve comparable clinical efficacy in alleviating symptoms, correcting kyphosis and improving neurological function for appropriate cases.

Combined Application of Dexamethasone and Tranexamic Acid to Reduce the Postoperative Inflammatory Response and Improve Functional Outcomes in Total Hip Arthroplasty.

OBJECTIVE: To evaluate the efficacy and safety of combined use of tranexamic acid (TXA) and dexamethasone (DEX) for anti-inflammatory and clinical outcomes after total hip arthroplasty (THA). METHODS: A total of 100 patients were included in this randomized, controlled study. Patients in the TXA + DEX group were administered TXA at a dose of 15 mg/kg, which was repeated 3 h after THA, and received 20 mg DEX. In contrast, patients in the TXA group were administered TXA at a dose of 15 mg/kg, which was repeated at 3 h postoperatively. C-reactive protein (CRP), interleukin-6 (IL-6) and pain levels, incidence of postoperative nausea and vomiting (PONV), total blood loss and transfusion rates, postoperative fatigue, range of motion (ROM), length of hospital stay (LOS), analgesic rescue and antiemetic rescue consumption, and complications were compared in both groups. RESULTS: The CRP and IL-6 levels were lower in the TXA + DEX group than in the TXA group (all P < 0.001) at 24 h, 48 h, and 72 h postoperatively. Patients in the TXA + DEX group had lower pain scores at rest and walking at 24 h postoperatively (all P < 0.001). In the TXA + DEX group, the incidence of PONV was lower (P = 0.005), postoperative fatigue (P < 0.001) was reduced, and analgesia and antiemetic rescue consumption were also reduced. The total blood loss, transfusion rate, LOS and hip ROM were similar in the two groups. There was no thrombosis, infection, or gastrointestinal bleeding in either group. CONCLUSION: Compared to TXA alone, the combination of TXA + DEX can reduce postoperative inflammatory response, relieve pain, and reduce PONV and fatigue, without increasing the risk of complications. Therefore, the present study suggested that the combination of TXA + DEX is an effective and safe accelerated rehabilitation strategy for patients receiving primary unilateral THA.

One-stage posterior debridement with transverse process strut as bone graft in the surgical treatment of single-segment thoracic tuberculosis: A retrospective single-center study.

This retrospective study investigated the effect of the novel bone graft transverse process strut (TPS) in single segmental thoracic spinal tuberculosis (TB) with the one-stage posterior approach of debridement, fusion, and internal instrumentation. Thirty patients treated in our department from March 2014 to October 2016 were retrospectively analyzed. Surgical time, blood loss, hospitalization time, drainage volume, and follow-up (FU) duration were recorded. The visual analog scale (VAS), Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American Spinal Injury Association (ASIA) grade, segmental angle, and bone fusion were compared between preoperative and final FU. All the patients were followed for a mean 50.10 ±â€Š25.10 months; the mean age, surgical time in minutes, blood loss, hospitalization time, and drainage volume were 46.23 ±â€Š17.20 years, 195.08 ±â€Š24.0 minutes, 280.77 ±â€Š189.90 mL, 17.31 ±â€Š4.23 days, 436.92 ±â€Š193.81 mL, respectively. VAS and ODI scores were significantly improved at the final FU. The ESR and CRP returned to normal. All patients achieved bony fusion with a mean time of 5.85 ±â€Š1.82 months and a mean segmental angle of 18.77 ±â€Š2.49° preoperatively, which significantly decreased to 9.31 ±â€Š1.54° at the final FU (P < .05). No complications, such as bone graft failure, pleural effusion, fistula, or wound infection were recorded except for cerebrospinal fluid leakage (one case), water electrolyte imbalance (5 cases), superficial infection (1 case), and mild intestinal obstruction (1 case). TPS as a bone graft is reliable, safe, and effective for segmental stability reconstruction for surgical management of single-segment thoracic spinal TB.

Adenovirus vector­mediated in vivo gene transfer of nuclear factor erythroid­2p45­related factor 2 promotes functional recovery following spinal cord contusion.

The aim of the present study was to investigate whether nuclear factor erythroid 2p45­related factor 2 (Nrf2) overexpression by gene transfer may protect neurons/glial cells and the association between neurons/glial cells and axons in spinal cord injury (SCI). In the present study, Nrf2 recombinant adenovirus (Ad) vectors were constructed. The protein levels of Nrf2 in the nucleus and of the Nrf2­regulated gene products heme oxygenase­1 (HO­1) and NAD (P)H­quinone oxidoreductase­1 (NQO1), were detected using western blot analysis in PC12 cells following 48 h of transfection. Furthermore, the expression of Nrf2 was localized using an immunofluorescence experiment, and the expression of Nrf2, HO­1 and NQO1 were detected using an immunohistochemical experiment in the grey matter of spinal cord in rats. Post­injury motor behavior was assessed via the Basso, Beattie and Bresnahan (BBB) locomotor scale method. In PC12 cells, subsequent to Ad­Nrf2 transfection, nuclear Nrf2, HO­1 and NQO1 levels were significantly increased compared with the control (P<0.01). There was statistically significant changes in the PC12­Ad­Nrf2 group [Nrf2 (1.146±0.095), HO­1 (1.816±0.095) and NQO1 (1.421±0.138)] compared with the PC12­control group [Nrf2 (0.717±0.055), HO­1 (1.264±0.081) and NQO1 (0.921±0.088)] and PC12­Ad­green fluorescent protein group [Nrf2 (0.714±0.111), HO­1 (1.238±0.053) and NQO1 (0.987±0.045); P<0.01]. The BBB scores of the rats indicated that they had improved functional recovery following the local injection of Ad­Nrf2. On the third day following the operation, BBB scores in the adenovirus groups (0.167±0.408) were significantly decreased compared with the SCI group (1±0.894; P<0.05). In the injured section of the spinal cord in the rats, the number of positive cells expressing Nrf2, HO­1 and NQO1 were raised compared with the control and SCI groups, indicating that the adenovirus vector­mediated gene transfer of Nrf2 promotes functional recovery following spinal cord contusion in rats.

High expression of ID1 facilitates metastasis in human osteosarcoma by regulating the sensitivity of anoikis via PI3K/AKT depended suppression of the intrinsic apoptotic signaling pathway.

A lack of understanding of the molecular basis underlying the regulation of metastatic disease and its effective therapy are the primary causes of high mortality in osteosarcoma. Thus, new insights into metastases and novel effective targets for metastatic osteosarcoma are urgently required. Anoikis resistance is considered a hallmark of cancer cells with metastatic ability. However, the molecular mechanism of anoikis is poorly understood in osteosarcoma. We applied immunohistochemistry to investigate the correlation between inhibitor of differentiation or DNA binding 1 (ID1) and clinicopathological features, and investigated the correlation between ID1 and the metastatic behavior of osteosarcoma cells, in vitro and in vivo. The results revealed that ID1 is overexpressed in human osteosarcoma tissues, is positively associated with lung metastases, and is a potential biomarker of poor prognosis. Overexpression of ID1 could increase anoikis insensitivity of osteosarcoma cells to facilitate metastasis through the PI3K/AKT-dependent mitochondrial apoptosis pathway. Knockdown of ID1 partly reversed the high potential of metastasis in anoikis-resistant osteosarcoma cells. Our findings revealed, that ID1 is a candidate molecular target for metastatic potential osteosarcoma by highlighting the role of anoikis resistance. In addition ID1 might be a potential predictor of poor prognosis in patients with osteosarcoma.

TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis.

BACKGROUND: Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear. METHODS: We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing. RESULTS: We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models. CONCLUSIONS: Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.

Preparation of a biphase composite scaffold and its application in tissue engineering for femoral osteochondral defects in rabbits.

PURPOSE: Three-dimensional bioactive scaffolds are useful tools for stem cell implant in tissue-engineering. For chondral and subchondral repair, the chondroinductive and osteoinductive property of a scaffold is a major challenge. The scaffolds that aim to osteogenic differentiation have been well studied. However, cartilage cells can hardly be induced for osteogenesis, and monophase scaffolds cannot ideally repair both cartilage and subchondral defects at the same time. METHODS: We developed a novel biphase composite scaffold and observe its application osteochondral defects. We combined the advantages of silk-fibroin/chitosan (SF/CS) scaffold in chondrogenic differentiation and the silk-fibroin/chitosan/nano-hydroxyapatite (SF/CS/nHA) scaffold in osteogenic differentiation and bone regeneration, and synthesized a SF/CS-SF/CS/nHA scaffold, which contained both the chondrocytic phase (SF/CS) and the osteoblastic phase (SF/CS/nHA). RESULTS: The biphase scaffold exhibited a porosity ratio around 90% and a water absorption ratio about 822%. A similar degradation property to traditional monophase scaffolds was observed. Bone mesenchymal stem cells (BMSCs) showed a good proliferation on this scaffold. Expression of two types of collagen was inducable for BMSCs on the scaffold. Neoformative extracellular matrix integrated with the scaffold was observed by the scanning electron microscope. When implanted in the lesion site in the rabbit femur with cartilage injury, mixing and filling function were exerted by the cell-scaffold constructs (CSCs). Micro-CT scanning revealed both chondral and subchondral layers were repaired. Moreover, type I and II collagens were both expressed in the implanted CSCs. CONCLUSIONS: Chondral and subchondral repair can be achieved using the biphase scaffold implant that permits both chondrogenesis and osteogenesis from BMSCs. This approach has the potential to be clinically used for tissue engineering implantation.

Inhibitory effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at early stage of steroid-induced femoral head necrosis.

Apoptosis and DNA oxidative damage serve significant roles in the pathogenesis of steroid­induced femoral head necrosis. Vitamin E demonstrates anti­apoptotic and anti­oxidant properties. Therefore, the present study investigated the effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at an early stage of steroid­induced femoral head osteonecrosis. Japanese white rabbits were randomly divided into three groups (steroid, vitamin E­treated, and control groups), each comprising 12 rabbits. Those in the steroid group (group S) were initially injected twice with an intravenous dose of 100 µg/kg Escherichia coli endotoxin, with a 24 h interval between the two injections, and then with an intramuscular dose of 20 mg/kg methylprednisolone, three times at intervals of 24 h in order to establish a rabbit model of osteonecrosis. The vitamin E treated group (group E) received the same treatment as group S, and were administered 0.6 g/kg/d vitamin E daily from the beginning of modeling. The control group (group C) was injected with normal saline at the equivalent dosage and times as the aforementioned two groups. Two time points, weeks 4 and 6 following the completion of modeling, were selected. Osteonecrosis was verified by histopathology with hematoxylin-eosin staining. The apoptosis rate of osteonecrosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The apoptosis expression levels of caspase­3 and B­cell lymphoma 2 (Bcl­2), and DNA oxidative damage of bone marrow hematopoietic cells were analyzed by immunohistochemistry. At weeks 4 and 6 following the completion of modeling, the vacant bone lacunae rates of group E were 15.87±1.97 and 25.09±2.67%, respectively, lower than the results of 20.02±2.21 and 27.79±1.39% for group S; and the osteocyte apoptosis indexes of group E were 20.99±2.95 and 33.93±1.62%, respectively, lower than the results of 26.46±3.37 and 39.90±3.74% from group S. In addition, the Bcl-2 expression at week 4 in the femoral head tissues of group E was higher compared with group S; and the proportion of Bcl­2­positive cells of group E was 9.81±1.01%, higher compared with group S at 8.26±1.13%. The caspase­3 staining data at week 4 in femoral head tissues demonstrated that in the 12 femoral heads of group S, four were negative (32%) and eight were positive (68%); in group E, five were negative (45%) and seven were positive (55%); and in group C, 11 were negative (95%) and one was positive (5%). In addition, the DNA oxidative damage rate at week 4 in the bone marrow hemopoietic cells of group E was (7.24±1.44%), lower compared with group S (11.80±1.26%), and higher compared with group C (5.75±1.47%). Vitamin E is effective in intervening in apoptosis through decreasing caspase­3 expression and upregulating Bcl­2 expression, and by alleviating DNA oxidative damage in bone marrow hemopoietic cells at the early stage of steroid­induced femoral head necrosis in rabbit models.

Altered Chondrocyte Apoptosis Status in Developmental Hip Dysplasia in Rabbits.

BACKGROUND: Developmental dysplasia of the hip (DDH) is an important factor leading to early adult osteoarthritis. Chondrocyte apoptosis has been proven to be an important factor causing osteoarthritis. AIMS: The current study aims to explore whether a rabbit model of developmental dysplasia of the hip through cast immobilization in the legs results in chondrocyte apoptosis. STUDY DESIGN: Animal experimentation. METHODS: Thirty-two New Zealand white rabbits were divided in three groups with cast plaster-induced dislocation at 2, 4 and 6 weeks. The contralateral hip joint was utilized as a control group. Ten rabbits in each group were sacrificed, and hip specimens were obtained. Bcl-2/Bax, cleaved caspase-3 and cleaved caspase-8 expression were examined by western blot analysis. Chondrocyte apoptosis was analyzed through transmission electron microscopy (TEM) and TUNEL analysis. All experiments were repeated at least three times. RESULTS: In the experimental group, Bcl-2/Bax, cleaved caspase-3 and cleaved caspase-8 expression were significantly altered. The Bcl-2/Bax ratio decreased with time (all p<0.01), whereas levels of cleaved caspase-3 (p<0.01 and p<0.05) and cleaved caspase-8 (all p<0.05) gradually increased. Chondrocyte apoptosis was observed through transmission electron microscopy (TEM) and TUNEL analysis (p<0.05 at 4 weeks and p<0.01 at 6 weeks). CONCLUSION: Prolonged immobilization of rabbit hip caused chondrocyte apoptosis. Reduction of the hip joint may protect chondrocytes from apoptosis, thus preventing secondary osteoarthritis.

Management of Acute Hematogenous Infection Following Total Knee Arthroplasty: A Case Series of 11 Patients.

OBJECTIVE: Acute hematogenous infection is a devastating complication that can occur after total knee arthroplasty (TKA). The best strategies for management of this infection remain controversial. Two-stage revision has been well described as the gold standard for the management of chronic late infections. However, there is a paucity of information presently available on the management and outcomes of patients treated for acute hematogenous infections. The purpose of the present study was to report the outcome of acute hematogenous infections following TKA with the treatment of irrigation, debridement, and retention of the prosthetic components. METHODS: Eleven patients who had been diagnosed with acute hematogenous infection of the knee following TKA underwent irrigation and debridement between 2002 and 2012. To improve the efficiency of irrigation, a vacuum constriction device was used and the most sensitive antibiotics were injected into the irrigation saline. The mean age of the 11 patients was 56.3 ± 11.8 years (range, 35-73 years), with 2 male patients (18.2%) and 9 female patients (81.8%). The diagnosis at primary operation was osteoarthritis in three cases, rheumatoid arthritis in seven and osteoarthritis (OA) secondary to fracture in 1. They had pain and swell with the acute onset of pain after a previously well-functioning TKA, and met the Musculoskeletal Infection Society (MSIS) criteria for prosthetic joint infection. Before the onset of symptoms in the operated knees, patients had a history of bacteriaemia, and blood culture was consistent with the culture result of local infection. Failure was defined as: (i) death before the end of antibiotic treatment; (ii) a further surgical intervention for treatment of infection was needed; and (iii) life-long antibiotic treatment, or chronic infection. The prosthesis survivorship, Knee Society Score (KSS) and the factors that may lead to the infection recurrence, such as type of bacteria, age, sex, rheumatoid arthritis, history of diabetes, and interval surgery time, were analyzed. RESULTS: Among the 11 patients, the most common infecting organisms were staphylococcal and streptococcus species. The 2 staphylococcal species cases included: Staphylococcus epidermidis (1) and Staphylococcus aureus (1); The 7 Streptococcus species cases included: Streptococcus agalactiae (1), ß-Hemolytic Streptococcus (1), Streptococcus pneumonia (3), Streptococcus dysgalactiae (1), Viridans streptococci (1) and Enterobacter cloacae (1). The survivorship at the endpoint was 9 in 2 years. The survival rate for patients with a staphylococcal infection was 0%, and 100% for patients infected with non-staphylococcus species, with a mean KSS of 72.6 points. The duration of symptoms prior to operation and the type of pathogen affected the outcome (P = 0.00). CONCLUSIONS: Patients who developed an acute hematogenous infection with non-staphylococcus species following operative debridement and continuous irrigation with prosthetic retention had satisfactory outcomes, but patients infected with staphylococcal had poor results. To improve the success rate of treatment, patients should be treated as soon as possible and individually according to the bacterial culture results.

Clinical outcomes of two types of cages used in transforaminal lumbar interbody fusion for the treatment of degenerative lumbar diseases: n-HA/PA66 cages versus PEEK cages.

This study reports the clinical effects of nano-hydroxyapatite/polyamide66 cages (n-HA/PA66 cages) and compares the clinical outcomes between n-HA/PA66 and polyetheretherketone cages (PEEK cages) for application in transforaminal lumbar interbody fusion (TLIF). A retrospective and case-control study involving 124 patients using n-HA/PA66 cages and 142 patients using PEEK cages was conducted. All patients underwent TLIF and had an average of 2-years of follow-up. The Oswestry Disability Index and Visual Analog Scale were selected to assess the pain of low back and leg, as well as neurological status. The intervertebral space height and segmental angle were also measured to estimate the radiological changes. At the 1-year and final follow-ups, the fusion and subsidence rates were evaluated. There was no significant difference between the two groups regarding clinical and radiological results. At the final follow-up, the bony fusion rate was 92.45 and 91.57 % for the n-HA/PA66 and PEEK groups, respectively, and the subsidence rate was 7.55 and 8.99 %, respectively. The study indicated that both n-HA/PA66 and PEEK cages could promote effective clinical and radiographic outcomes when used to treat degenerative lumbar diseases. The high fusion and low subsidence rates revealed that n-HA/PA66 cages could be an alternative ideal choice as the same to PEEK cages for lumbar reconstruction after TLIF.

Biosafety of the Novel Vancomycin-loaded Bone-like Hydroxyapatite/Poly-amino Acid Bony Scaffold.

BACKGROUND: Recently, local sustained-release antibiotics systems have been developed because they can increase local foci of concentrated antibiotics without increasing the plasma concentration, and thereby effectively decrease any systemic toxicity and side effects. A vancomycin-loaded bone-like hydroxyapatite/poly-amino acid (V-BHA/PAA) bony scaffold was successfully fabricated with vancomycin-loaded poly lactic-co-glycolic acid microspheres and BHA/PAA, which was demonstrated to exhibit both porosity and perfect biodegradability. The aim of this study was to systematically evaluate the biosafety of this novel scaffold by conducting toxicity tests in vitro and in vivo. METHODS: According to the ISO rules for medical implant biosafety, for in vitro tests, the scaffold was incubated with L929 fibroblasts or rabbit noncoagulant blood, with simultaneous creation of positive control and negative control groups. The growth condition of L929 cells and hemolytic ratio were respectively evaluated after various incubation periods. For in vivo tests, a chronic osteomyelitis model involving the right proximal tibia of New Zealand white rabbits was established. After bacterial identification, the drug-loaded scaffold, drug-unloaded BHA/PAA, and poly (methyl methacrylate) were implanted, and a blank control group was also set up. Subsequently, the in vivo blood drug concentrations were measured, and the kidney and liver functions were evaluated. RESULTS: In the in vitro tests, the cytotoxicity grades of V-BHA/PAA and BHA/PAA-based on the relative growth rate were all below 1. The hemolysis ratios of V-BHA/PAA and BHA/PAA were 2.27% and 1.42%, respectively, both below 5%. In the in vivo tests, the blood concentration of vancomycin after implantation of V-BHA/PAA was measured at far below its toxic concentration (60 mg/L), and the function and histomorphology of the liver and kidney were all normal. CONCLUSION: According to ISO standards, the V-BHA/PAA scaffold is considered to have sufficient safety for clinical utilization.

Novel application of vacuum sealing drainage with continuous irrigation of potassium permanganate for managing infective wounds of gas gangrene.

Traumatic gas gangrene is a fatal infection mainly caused by Clostridium perfringens. It is a challenge to manage gas gangrene in open wounds and control infection after debridement or amputation. The aim of the present study was to use vacuum sealing drainage (VSD) with continuous irrigation of potassium permanganate to manage infective wounds of gas gangrene and observe its clinical efficacy. A total of 48 patients with open traumatic gas gangrene infection were included in this study. Amputations were done for 27 patients, and limb salvage procedures were performed for the others. After amputation or aggressive debridement, the VSD system, including polyvinyl alcohol (PVA) foam dressing and polyurethane (PU) film, with continuous irrigation of 1:5000 potassium permanganate solutions, was applied to the wounds. During the follow-up, all the patients healed without recurrence within 8-18 months. There were four complications. Cardiac arrest during amputation surgery occurred in one patient who suffered from severe septic shock. Emergent resuscitation was performed and the patient returned to stable condition. One patient suffered from mixed infection of Staphylococcal aureus, and a second-stage debridement was performed. One patient suffered from severe pain of the limb after the debridement. Exploratory operation was done and the possible reason was trauma of a local peripheral nerve. Three cases of crush syndrome had dialysis treatment for concomitant renal failure. In conclusion, VSD can convert open wound to closed wound, and evacuate necrotic tissues. Furthermore, potassium permanganate solutions help eliminate anaerobic microenvironment and achieve good therapeutic effect on gas gangrene and mixed infection. VSD with continuous irrigation of potassium permanganate is a novel, simple and feasible alternative for severe traumatic open wounds with gas gangrene infection.

Treatment of Staphylococcus aureus-induced chronic osteomyelitis with bone-like hydroxyapatite/poly amino acid loaded with rifapentine microspheres.

PURPOSE: The purpose of this study was to investigate the curative effect of bone-like hydroxyapatite/poly amino acid (BHA/PAA) as a carrier for poly(lactic-co-glycolic acid)-coated rifapentine microsphere (RPM) in the treatment of rabbit chronic osteomyelitis induced by Staphylococcus aureus. METHODS: RPM was prepared through an oil-in-water emulsion solvent evaporation method, and RPM was combined with BHA/PAA to obtain drug-loaded, slow-releasing materials. Twenty-six New Zealand white rabbits were induced to establish the animal model of chronic osteomyelitis. After debridement, the animals were randomly divided into three groups (n=8): the experimental group (with RPM-loaded BHA/PAA), the control group (with BHA/PAA), and the blank group. The RPM-loaded BHA/PAA was evaluated for antibacterial activity, dynamics of drug release, and osteogenic ability through in vitro and in vivo experiments. RESULTS: In vitro, RPM-loaded BHA/PAA released the antibiotics slowly, inhibiting the bacterial growth of S. aureus for up to 5 weeks. In vivo, at week 4, the bacterial colony count was significantly lower in the experimental group than in the control and blank groups (P<0.01). At week 12, the chronic osteomyelitis was cured and the bone defect was repaired in the experimental group, whereas the infection and bone defect persisted in the control and blank groups. CONCLUSION: In vitro and in vivo experiments demonstrated that RPM-loaded BHA/PAA effectively cured S. aureus-induced chronic osteomyelitis. Therefore, BHA/PAA has potential value as a slow-releasing material in clinical setting. Further investigation is needed to determine the optimal dosage for loading rifapentine.

Decreased local and systematic matrix Gla protein (MGP) expression and its link to radiographic progression in ankylosing spondylitis patients.

BACKGROUND: Decreased serum levels of uncarboxylated matrix Gla-protein (ucMGP) have been detected in Ankylosing Spondylitis (AS) patients. The current study was to investigate the expression of MGP in AS tissues as well as the relationship between serum ucMGP (an inactive form of MGP) levels and radiographic severity in AS patients. METHODS: Local MGP expression were assessed by Western blot and RT-PCR in hip synovial tissues from patients with AS and control subjects. In addition, the serum level of ucMGP was assessed by enzyme-linked immunosorbent assay in 68 healthy subjects and 62 patients with AS. The radiographic progression of AS was classified according to the radiographic events of modified New York Criteria for sacroiliac joint evaluation and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) system for spine assessment. RESULTS: MGP expression was downregulated in AS patients compared to controls in hip tissues. Decreased levels of ucMGP in serum were found in AS patients compared with healthy controls. ucMGP levels in serum of AS patients were significantly negatively correlated with the disease radiographic severity evaluated by modified New York grading criteria (r = -0.293, p = 0.045) and mSASSS system (r = -0.361, p = 0.03). CONCLUSIONS: MGP expression is impaired in patients with AS. A low serum level of ucMGP in the setting of AS is linked to increased structural damage, emphasizing the role of MGP in the suppression of new bone formation.