Deep vein thrombosis after major orthopedic surgery in Taiwan: A prospective cross-sectional study and literature review.

BACKGROUND/PURPOSE: Postoperative venous thromboembolism is an important complication in Taiwan. We prospectively investigated the occurrence of deep vein thrombosis (DVT) after major orthopedic surgery without pharmacologic thromboprophylaxis in a cohort of 120 patients (46 males, 74 females, median age 71 years) at our institute. METHODS: Color duplex compression ultrasonography (CUS) was used to detect DVT before and after the operation, while contrast venography was performed postoperatively for comparison and validation. RESULTS: Total knee arthroplasty (TKA, 57 cases) and total hip arthroplasty (23 cases) were the most commonly performed operations. The rate of postoperative DVT was 7.5% (9/120), including five with proximal DVT and four with distal DVT. All were detected in the limbs on the operated side. Four of them were symptomatic DVT cases. Venography was performed in 19 patients and confirmed most findings of CUS, indicating the effectiveness of CUS for detecting DVT. The type of surgery (TKA) was significantly correlated with postoperative DVT. No clinically symptomatic pulmonary embolism or sudden death events were noted. CONCLUSION: Nine out of 120 (7.5%) orthopedic patients without pharmacologic thromboprophylaxis developed postoperative sonographic DVT in our study. The DVT rate is consistent with other reports from various Asian countries and evidence from meta-analyses.

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis.

OBJECTIVES: Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. METHOD: The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with -1.0 > bone mineral density (BMD) T-score > -2.5 (low bone mass) and those with BMD T-score ≤ -2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. RESULTS: Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36-0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%-5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%-3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. CONCLUSION: The bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis.

Potential novel proteomic biomarkers for diagnosis of vertebral osteomyelitis identified using an immunomics protein array technique: Two cases reports.

RATIONALE: Although vertebral osteomyelitis (VO) is commonly associated with high morbidity and high recurrence rate, effective diagnostic and prognostic biomarkers of VO are still lacking. PATIENTS CONCERNS: Case 1: a 60-year-old male had had upper back pain for 3 days. Case 2: a 71-year-old female presented upper back pain for 2 days. DIAGNOSES: Based on physical examination and findings of magnetic resonance imaging and findings by matrix-assisted laser desorption ionization-time of flight mass spectrometry, they were diagnosed with Staphylococcus aureus VO. INTERVENTIONS: Using Sengenics Immunome Protein Array by analyzing autoantibodies in both VO patients, potential biomarkers of VO were explored. OUTCOMES: Four subjects with more than 1600 antigens screened while the results showed that 14-3-3 protein gamma, pterin-4-alpha-carbinolamine dehydratase, fructose-bisphosphate aldolase A, and keratin type II cytoskeletal 8 were highly differentially expressed among VO and controls. Relevant auto-antibody profiles were discovered after intra-group and inter-group comparison, and based on functional rationality, an adapter protein 14-3-3 protein gamma, and pterin-4-alpha-carbinolamine dehydratase that involved in tetrahydrobiopterin biosynthesis, might serve as valuable diagnostic biomarkers. LESSONS: This pilot study on 4 subjects with more than 1600 antigens screened on the Sengenics Immunome protein array provided a general outlook on autoantibody biomarker profiles of VO subjects. Future large-scale trials with longer follow-up times are warranted.

Betulin inhibits mTOR and induces autophagy to promote apoptosis in human osteosarcoma cell lines.

Betulin is a lupane type pentacyclic triterpenoid, and commonly found in the bark of birch trees. It displays various pharmacological properties, such as antibacterial, anti-inflammation, antitumor, and antiviral. In this report, we attempted to investigate the anti-proliferative and pro-apoptotic effects of betulin on osteosarcoma cell lines. Our results revealed that betulin significantly decreased cell viability and colony formation in osteosarcoma cell lines. Dose-dependent induction of Annexin V positive cells, activated caspase 8, activated caspase 9, activated caspase 3, and the cleavage of poly (ADP-ribose) polymerase were observed after the treatment with betulin, indicating betulin induces apoptosis in osteosarcoma cell lines. mTOR has been identified as a key modulator of autophagy in response to different stresses. In this study, we found that the treatment with betulin suppressed the activation of mTOR, and increased the level of LC 3-II, the autophagy marker, in osteosarcoma cell lines. Co-administration of the autophagy inhibitor chloroquine significantly rescued the cell viability and the clonogenic activity in betulin-treated osteosarcoma cell lines. Our data showed that betulin induced autophagy, and the up-regulated autophagy positively contributed to the apoptosis. Taken together, our findings suggested that betulin may serve as a promising anti-proliferative agent for treating osteosarcoma.

Carnosol-Induced ROS Inhibits Cell Viability of Human Osteosarcoma by Apoptosis and Autophagy.

Carnosol is an anti-oxidant and anti-inflammatory compound from rosemary. In this paper, we investigated antitumor activity of carnosol against human osteosarcoma cells. We found the viability of human osteosarcoma MG-63 cells was significantly decreased in the presence of carnosol (cell viabilities: 17.2% for 20[Formula: see text]µg/ml of CS vs. 100% for control, [Formula: see text]). Carnosol induced apoptosis and cell cycle arrest in a dose-dependent manner in MG-63 cells. Furthermore, carnosol exposure increased the levels of reactive oxygen species (ROS). The pre-treatment of NAC, the ROS scavenger, blocked the inhibition of cell viability in the carnosol treatment, indicating that ROS is important in the antiproliferation effect. Moreover, we demonstrated that carnosol significantly induced autophagy and co-administration of autophagy inhibitor reduced the antiproliferating effect of carnosol. This result exhibited the cytotoxic effect of autophagy induced by carnosol in MG-63 cells. Interestingly, the treatment of NAC decreased carnosol-induced autophagy. Collectively, these data indicate that carnosol suppresses the viability of human osteosarcoma MG-63 cells by upregulation of apoptosis and autophagy, which are both mediated by ROS. Thus, carnosol might serve as a potential therapeutic agent against osteosarcoma.

Methyl Protodioscin Induces Apoptosis in Human Osteosarcoma Cells by Caspase-Dependent and MAPK Signaling Pathways.

Methyl protodioscin (MPD), a furostanol saponin derived from the rhizomes of Dioscorea collettii var. hypoglauca (Dioscoreaceae), has been shown to exhibit broad bioactivities such as anti-inflammation and antitumor activities. Here, we explored the molecular mechanisms by which MPD induced apoptosis in MG-63 cells. The data showed that MPD significantly suppressed cell growth (cell viabilities: 22.5 ± 1.9% for 8 µM MPD versus 100 ± 1.4% for control, P < 0.01) and enhanced cell apoptosis. The exposure to MPD resulted in a significant induction of reactive oxygen species, loss of mitochondrial membrane potential, and activation of caspase-9 and caspase-3 (P < 0.01, all cases). Furthermore, treatment with MPD increased the levels of phosphorylated JNK and p38 MAPK and markedly decreased the levels of phosphorylated ERK in MG-63 cells. Co-administration of the JNK-specific antagonist, the p38-specific antagonist, or the caspase antagonist (P < 0.05, all cases) has reversed the apoptotic effects in MPD treatment. We also found that exposure to MPD resulted in a significant reduction in the protein level of anti-apoptotic proteins Bcl-2, survivin, and XIAP (P < 0.05, all cases). In conclusion, our results indicate that MPD induces apoptosis of human osteosarcoma MG-63 cells, at least in part, by caspase-dependent and MAPK signaling pathways.

Ursolic Acid Triggers Apoptosis in Human Osteosarcoma Cells via Caspase Activation and the ERK1/2 MAPK Pathway.

Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, has been shown to trigger apoptosis in several lines of tumor cells in vitro. We found that treatment with UA suppressed the viability of human osteosarcoma MG-63 cells and induced cell cycle arrest at sub-G1 and G2/M phases. Furthermore, exposure to UA induced intracellular oxidative stress and collapse of mitochondrial membrane permeability, resulting in the subsequent activation of apoptotic caspases 8, 9, and 3 as well as PARP cleavage, and ultimately apoptosis in MG-63 cells. Moreover, protein analysis of mitogen-activated protein kinase (MAPK)-related protein expression showed an increase in activated ERK1/2, JNK, and p38 MAPK in UA-treated MG-63 cells. In addition, UA-induced apoptosis was significantly abolished in MG-63 cells that had been pretreated with inhibitors of caspase 3, 8, and 9 and ERK1/2. Furthermore, UA-treated MG-63 cells also exhibited an enhancement in Bax/Bcl-2 ratio, whereas anti-apoptotic XIAP and survivin were down-regulated. Taken together, we provide evidence demonstrating that UA mediates caspase-dependent and ERK1/2 MAPK-associated apoptosis in osteosarcoma MG-63 cells.

Dodecyl gallate induces apoptosis by upregulating the caspase-dependent apoptotic pathway and inhibiting the expression of anti-apoptotic Bcl-2 family proteins in human osteosarcoma cells.

Dodecyl gallate (DG) is a gallic acid ester that has been shown to inhibit tumor growth. The aim of this study was to investigate the mechanism by which DG induces antiproliferative and apoptotic effects in MG-63 human osteosarcoma cells. Dose- and time-dependent cytotoxic effects of DG were determined using an MTT assay. The results showed that the half-maximal inhibitory concentration (IC50) of DG in MG-63 cells was 31.15 µM at 24 h, 10.66 µM at 48 h, and 9.06 µM at 72 h. Flow cytometric analysis demonstrated that exposure to 20 and 40 µM DG resulted in an increase in the sub-G1 phase population and in S-phase cell cycle arrest. Furthermore, western blot analysis of apoptosis-related protein expression revealed an increase in the activation of caspases 8 and 3, cleavage of poly (ADPribose) polymerase (PARP), and disruption of mitochondrial membrane permeability was measured by flow cytometry. An increase in the Bax/Bcl-2 ratio and a decrease in the expression of inhibitor of apoptosis protein (IAP) family members, namely X-linked inhibitor of apoptosis protein and survivin, were also observed following DG treatment. These data provide insight into the molecular mechanisms governing the ability of DG to induce apoptosis in human osteosarcoma cells in vitro.

Surgical treatment of intramuscular, infiltrating lipoma.

Lipoma may occasionally be found within the muscle, which is the intramuscular, infiltrating lipoma. Intramuscular, infiltrating lipoma is an uncommon lesion, and local recurrence can be expected if the surgical margin is not clear. We report 8 patients in a 2-year period diagnosed with intramuscular, infiltrating lipoma who were treated by marginal excision combined with wide excision in the Department of Orthopaedic Surgery, Changhua Christian Hospital. The surgical results were satisfactory, and no local recurrence was noted in an average followup period of 40 months. Surgical excision is the best way to treat the symptomatic intramuscular, infiltrating lipoma. Careful preoperative evaluation and complete tumor excision with clear margins are most important to ensure successful surgical results.

Surgical treatment of symptomatic sacral cysts: report of 5 cases.

Sacral cysts are collections of cerebrospinal fluid (CSF) between the endoneurium and the perineurium of the sacral nerve root sheath. Surgery is recommended for large cysts with symptoms attributable to them. We report 5 patients with symptomatic sacral cysts treated at our institution, including 1 male and 4 females with an average age of 51.8 years (range, 36-66 years). Surgical intervention included posterior laminectomy, direct excision of the cysts and repair, and replication or cover of the dura defect by sutures or biomaterials. Pathologic examination disclosed cystic lesions with a fibrous wall without an inner arachnoid lining. All patients recovered and remained symptom-free for 39.6 months (range, 30-51 months). Treatment methods for symptomatic sacral cysts vary. Direct decompression and cyst excision are effective methods with highly successful rates and expectations.

Septic hip dislocation in a child.

A 4-year-old girl presented with pain and disability of right side hip of about 1-week duration. High-grade fever and upper respiratory tract infection were also noted. A pelvic computed tomography scan showed a dislocated hip accompanied by a huge intrapelvic abscess. Culture of pus from the hip showed Streptococcus pneumonia. Emergency arthrotomy, drainage of abscess and reduction of hip, and immobilization with a hip spica cast were undertaken. Thereafter, intravenous antibiotics were given for 6 weeks. The infection was resolved. At a 2-year follow-up, the clinical result was fair and the radiography showed persisting hip damage.

Painful scoliosis secondary to osteoid osteoma of the lumbar spine in adolescents.

Painful scoliosis is a well-recognized presentation of spinal osteoid osteoma, especially in adolescents, and is thought to be caused by pain-provoked muscle spasm on the side of the lesion. The diagnosis, however, is often initially missed, and prolonged duration of symptoms and rigid spinal curve may result. In this report, we present two cases of adolescent patients with painful scoliosis, subsequently diagnosed with spinal osteoid osteomas. Complete surgical excision resulted in dramatic symptomatic resolution after surgery and improved spinal curve at 1-year follow-up in both cases.

Femoral head avascular necrosis after interlocking nail of a femoral shaft fracture in a male adult: a case report.

Reamed interlocking nail through the piriformis fossa remains the golden standard for treatment of femoral shaft fracture. Fracture healing rates are 95-99%, and infection rates less than 1% (Clawson et al. in J Bone Joint Surg (Am) 53:681-692, 1971; Winquist et al. in J Bone Joint Surg (Am) 66:529-539, 1984; Brumback et al. in J Bone Joint Surg (Am) 70:1453-1462, 1988). Previous reports recognize avascular necrosis of the femoral head as a complication of antegrade interlocking nail in the adolescent (Beaty et al. in J Pediatr Orthop 14:178-183, 1994; Mileski et al. in J Bone Joint Surg (Am) 76:1706-1708, 1994; O'Malley et al. in J Pediatr Orthop 15:21-23, 1995; Buckaloo et al. in J Southern Orthop Assoc 6(2):97-100, 1997). This report describes a male adult who developed avascular necrosis of the femoral head after an open antegrade interlocking nail of a proximal third femoral shaft fracture. To our knowledge, there is no similar report in the English medical literature.

Iliac vessel injury by a cement spacer: report of a case.

The use of antibiotic-impregnated acrylic cement as a bone spacer between the intervals of revision hip arthroplasty for infection has been widely practiced. Vascular injuries caused by the migration of a cement spacer with subsequent erosion of the vessel wall have never been reported. A 67-year-old woman presented with tense swelling over her left lower extremity and hemarthroses of the left hip after implantation of a cement spacer for infected hip arthroplasty. Complete external compression of the external iliac vein and laceration of the iliac artery by the spacer were found. The symptoms were resolved after surgical debridement, removal of the spacer and femoral stem, and repair of the vessel. Cautious placement of a cement spacer in the acetabular fossa accompanied with poor bone stock must be emphasized.

Simultaneous bilateral anterior fracture dislocation of the shoulder with neurovascular injury: report of a case.

This paper reports an unusual case of orthopedic trauma in a 29-year-old man who experienced concomitant bilateral anterior shoulder fracture dislocation with associated brachial plexus and axillary artery injury. We also highlight the mechanism underlying this rare workplace injury related to use of a forklift.

Tumoral calcinosis of the shoulder.

Tumoral calcinosis is a rare clinical and histopathologic syndrome that causes the formation of calcium salt crystal deposits in periarticular soft tissue. This soft tissue calcification typically behaves as a large-sized tumor. However, the mechanism is unknown for the massive periarticular calcification caused by tumoral calcinosis. In addition, tumor calcinosis occurs infrequently in patients who have been on long-term hemodialysis and have end-stage renal disease (ESRD). This report describes a 40-year-old male uremia patient on long-term hemodialysis. This patient developed a huge tumor mass and pain over the left shoulder and was diagnosed with tumoral calcinosis. Although common treatments include management of metabolic levels such as calcium and phosphate, in some cases, surgical intervention may be needed. In this patient case, complete surgical excision was done successfully with an excellent outcome at the 2-year follow-up.