Low-energy shock waves promote the cisplatin chemosensitivity of human osteosarcoma MNNG/HOS cells via the P2X7/Akt/mTOR pathway.

Background: The current dilemma of osteosarcoma treatment is the resistance of chemotherapeutic drugs after long-term usage, which also introduces life-threatening side effects. Methods and results: To minimize chemoresistance in osteosarcoma patients, the authors applied shock waves (SWs) to human osteosarcoma MNNG/HOS cells, then evaluated the cell viability and extracellular ATP levels, and further investigated the effect of SWs on cisplatin (DDP) cytotoxicity in MNNG/HOS cells. The authors' results showed that 400 SW pulses at 0.21 mJ/mm2 exhibited little influence on the MNNG/HOS cell viability. In addition, this SW condition significantly promoted the extracellular ATP release in MNNG/HOS cells. Importantly, low-energy SWs obviously increased Akt and mammalian target of rapamycin (mTOR) phosphorylation and activation in MNNG/HOS cells, which could be partially reversed in the presence of P2X7 siRNA. The authors also found that low-energy SWs strongly increased the DDP sensitivity of MNNG/HOS cells in the absence of P2X7. Conclusions: For the first time, the authors found that SW therapy reduced the DDP resistance of MNNG/HOS osteosarcoma cells when the ATP receptor P2X7 was downregulated. SW therapy may provide a novel treatment strategy for chemoresistant human osteosarcoma.

Shock wave assisted intracellular delivery of antibiotics against bone infection with Staphylococcus aureus via P2X7 receptors.

Background: Treatment of chronic osteomyelitis (bone infection) remains a clinical challenge; in particular, it requires enhanced delivery of antibiotic drugs for the treatment of intracellular Staphylococcus aureus (S. aureus), which prevents infection recurrence and resistance. Previous studies have found that noninvasive shock waves used to treat musculoskeletal diseases can alter cell permeability, however, it is unclear whether shock waves alter cell membrane permeability in chronic osteomyelitis. Furthermore, it remains unknown whether such changes in permeability promote the entry of antibiotics into osteoblasts to exert antibacterial effects. Methods: In our study, trypan blue staining was used to determine the shock wave parameters that had no obvious damage to the osteoblast model; the effect of shocks waves on the cell membrane permeability of osteoblast model was detected by BODIPY®FL vancomycin; high performance liquid chromatography-mass spectrometry (HLPC-MS) was used to detect the effect of shock wave on the entry of antibiotics into the osteoblast model; plate colony counting method was used to detect the clearance effect of shock wave assisted antibiotics on S. aureus in the osteoblast model. To explore the mechanism, the effect of different pulses of shock waves on S. aureus was examined by plate colony counting method, besides, P2X7 receptor in osteoblast was detected by immunofluorescence and the extracellular ATP levels was detected. Furthermore, the effect of P2X7 receptor antagonists KN-62 or A740003 on the intracellular antibacterial activity of shock-assisted antibiotics was observed. Then, we used S. aureus to establish a rat model of chronic tibial osteomyelitis and investigated the efficacy and safety of shock-wave assisted antibiotics in the treatment of chronic osteomyelitis in rats. Results: The viability of the osteoblast models of intracellular S. aureus infection was not significantly affected by the application of up to 400 shock wave pulses at 0.21 mJ/mm2. Surprisingly, the delivery of BODIPY®FL vancomycin to osteoblast model cells was markedly enhanced by this shock wave treatment. Furthermore, the shock wave therapy increased the delivery of hydrophilic antibiotics (vancomycin and cefuroxime sodium), but not lipophilic antibiotics (rifampicin and levofloxacin), which improved the intracellular antibacterial effect. Afterwards, we discovered that shock wave treatment increased the extracellular concentration of ATP (the P2X7 receptor activator)， while KN-62 or A740003, a P2X7 receptor inhibitor, decreased intracellular antibacterial activity. We then found that 0.1 mL of 1 × 1011 CFU/mL ATCC25923 S. aureus was suitable for modeling chronic osteomyelitis in rats. Besides, the shock wave-assisted vancomycin treatment with the strongest antibacterial and osteogenic effects among the tested treatments was confirmed in vivo by imaging examination, microbiological cultures, and histopathology, with favorable safety. Conclusions: Our results suggest that shock waves can promote the entry of antibiotics into osteoblasts for antibacteria by changing the cell membrane permeability in a P2X7 receptor-dependent manner. Besides, considering antibacterial and osteogenic efficiency and a high degree of safety in rat osteomyelitis model, shock wave-assisted vancomycin treatment may thus represent a possible adjuvant therapy for chronic osteomyelitis.

Silicone rubber sealed channel induced self-healing of large bone defects: Where is the limit of self-healing of bone?

Background: Large defects of long tubular bones due to severe trauma, bone tumor resection, or osteomyelitis debridement are challenging in orthopedics. Bone non-union and other complications often lead to serious consequences. At present, autologous bone graft is still the gold standard for the treatment of large bone defects. However, autologous bone graft sources are limited. Silicon rubber (SR) materials are widely used in biomedical fields, due to their safety and biocompatibility, and even shown to induce nerve regeneration. Materials and methods: We extracted rat bone marrow mesenchymal stem cells (BMMSCs) in vitro and verified the biocompatibility of silicone rubber through cell experiments. Then we designed a rabbit radius critical sized bone defect model to verify the effect of silicone rubber sealed channel inducing bone repair in vivo. Results: SR sealed channel could prevent the fibrous tissue from entering the fracture end and forming bone nonunion, thereby inducing self-healing of long tubular bone through endochondral osteogenesis. The hematoma tissue formed in the early stage was rich in osteogenesis and angiogenesis related proteins, and gradually turned into vascularization and endochondral osteogenesis, and finally realized bone regeneration. Conclusions: In summary, our study proved that SR sealed channel could prevent the fibrous tissue from entering the fracture end and induce self-healing of long tubular bone through endochondral osteogenesis. In this process, the sealed environment provided by the SR channel was key, and this might indicate that the limit of self-healing of bone exceeded the previously thought. The translational potential of this article: This study investigated a new concept to induce the self-healing of large bone defects. It could avoid trauma caused by autologous bone extraction and possible rejection reactions caused by bone graft materials. Further research based on this study, including the innovation of induction materials, might invent a new type of bone inducing production, which could bring convenience to patients. We believed that this study had significant meaning for the treatment of large bone defects in clinical practice.

Gamma Nail Combined with One Cannulated Compression Screw Fixation for Treating Pauwels Type III Femoral Neck Fractures in Young and Middle-Aged Adults: Clinical Follow-Up and Biomechanical Studies.

OBJECTIVE: Recently, some clinical studies have reported the use of an intramedullary nailing system for treating unstable femoral neck fractures or femoral neck fractures combined with femoral shaft fractures in young adults, and the results have indicated certain advantages. However, no study has investigated the mechanical properties of this method. We aimed to evaluate the mechanical stability and clinical efficacy of the Gamma nail combined with one cannulated compression screw (CCS) fixation for treating Pauwels type III femoral neck fracture in young and middle-aged adults. METHODS: This study consists of two parts: a clinical retrospective study and randomized controlled biomechanical test. Twelve adult cadaver femora were used to test and compare the biomechanical properties among three fixation methods: three parallel CCS (group A), Gamma nail (group B), and Gamma nail combined with one cannulated compression screw (group C). The single continuous compression test, cyclic load test, and ultimate vertical load test were used to evaluate the biomechanical performance of the three fixation methods. We also conducted a retrospective study of 31 patients with Pauwels type III femoral neck fractures, including 16 patients with fractures fixed with three parallel CCS (CCS group) and 15 patients with fractures fixed with Gamma nail combined with one CCS (Gamma nail + CCS group). The patients were followed up for at least 3 years, and all were evaluated for surgical time (from skin incision to closure), surgical blood loss, hospital stay, and the Harris hip score. RESULTS: In mechanical experiments, we have found that the mechanical advantages of Gamma nail fixation are not as good as those of conventional CCS fixation. However, the mechanical properties of Gamma nail fixation combined with one cannulated screw perpendicular to the fracture line are much better than those of Gamma nail fixation and CCS fixation. No significant difference was found in the incidence of femoral head necrosis and nonunion between the CCS and Gamma nail + CCS groups. Moreover, there was no statistically significant difference in the Harris hip scores between the two groups. One patient in the CCS group showed significant withdrawal of cannulated screws at 5 months after surgery, whereas in the Gamma nail + CCS group, all patients, including those with femoral neck necrosis, showed no loss of stability of the fixation. CONCLUSION: Among the two fixation methods evaluated in this study, Gamma nail combined with one CCS fixation showed better biomechanical properties and may reduce complications associated with unstable fixation devices.

Cardiovascular risk factors mediating the protective effect of education on cervical spondylosis risk.

The causal association between education and cervical spondylosis may be mediated partly through risk factors of cardiovascular disease. The identification of the protective effect of education and the evaluation of risk factors will help to optimize disease prevention at both clinical and public health levels. In this study, we applied several different Mendelian randomization (MR) methods to identify which cardiovascular factors underlie the clustering of cervical spondylosis with cardiovascular disease, and the degree to which these mediate an effect of education. Univariable MR analyses provided evidence supporting a protective effect of genetically predicted education on cervical spondylosis risk, and MVMR further identified the direct effect of education level. Our results also provided evidence supporting the detrimental effects of BMI and smoking on cervical spondylosis risk, with evidence that the effect of education is mediated through BMI and smoking. The proportions of the effect of education mediated through BMI and smoking were 12% and 3%, respectively. These findings highlight education, obesity, and smoking as common mechanisms underlying the clustering of cervical spondylosis with risk factors of cardiovascular disease, which might represent clinical and public health targets for reducing multi-morbidity and the burden of these common conditions.

Effects of Bisphosphonates Treatments in Osteopenic Older Women: A Systematic Review and Meta-Analysis.

Aims: To review the effects of bisphosphonates on bone density, fractures, and bone markers in osteopenic older women. Methods: Relevant articles published before February 2022 were searched in PubMed, EMBASE, and the Cochrane Library. All randomized controlled trials that reported incident fractures, bone mineral density (BMD), bone markers, or adverse events with bisphosphonates in osteopenic older women were included. The quality of included studies was assessed using the Cochrane Risk of Bias tool. The risk ratios (RRs) for fractures, net percent change in bone mineral density and differences in bone markers were calculated using a meta-analysis. Results: A total of 11 studies were included in our meta-analysis. Bisphosphonates significantly increased the percent changes in the lumbar spine BMD (WMD, 5.60; 95% CI, 4.16-7.03; I 2 = 93.6%), hip BMD (WMD, 4.80; 95% CI, 2.93 to 6.66; I 2 = 97.1%), total body BMD (WMD, 3.24; 95% CI, 2.12-4.35; I 2 = 90.9%), femoral neck BMD (WMD, 4.02; 95% CI, 1.70-6.35; I 2 = 91.8%) and trochanter BMD (WMD, 5.22; 95% CI, 3.51-6.93; I 2 = 83.6%) when compared to placebo. Zoledronate was associated with a great treatment effect on fragility fracture (RR, 0.63; 95% CI, 0.50-0.79), clinical vertebral fracture (RR, 0.41; 95% CI, 0.22-0.76), and radiographic vertebral fracture (RR, 0.60; 95% CI, 0.27-1.35) compared to placebo. Meanwhile, alendronate was also associated with beneficial effects on fragility fracture (RR, 0.40; 95% CI, 0.15-1.07), clinical vertebral fracture (RR, 0.46; 95% CI, 0.17-1.24), and radiographic vertebral fracture (RR, 0.64; 95% CI, 0.38-1.09). In addition, the use of bisphosphonates reduced the concentration of procollagen type I N-terminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX) over placebo by 15.79 (95% CI, -18.92 to -12.66; I 2 = 28.4%), -0.23 (95% CI, -0.35 to -0.10; I 2 = 91.3%), respectively. Although there was insufficient evidence to determine their safety, these bisphosphonates may have an effect on cancer, cardiac events, and mortality in osteopenic older women. Conclusion: All bisphosphonates examined were associated with beneficial effects on fractures, BMD, and bone markers in women with osteopenia. Further randomized controlled trials are necessary to clarify the safety of bisphosphonates in women with osteopenia.

Minimally Invasive Percutaneous TightRope® System Fixation for an Unstable Posterior Pelvic Ring: Clinical Follow-up and Biomechanical Studies.

OBJECTIVE: To evaluate the mechanical stability and clinical efficacy of minimally invasive percutaneous TightRope® systems applied via gun-shaped reduction forceps for unstable posterior pelvic ring fractures. MATERIALS AND METHODS: This study consists of two parts: a clinical retrospective study and a randomized controlled biomechanical test. For the clinical study, a retrospective analysis of posterior pelvic ring fractures was performed between June 2015 and May 2020. Eighteen patients underwent surgery using two TightRope® systems to fix a broken posterior pelvic ring because of unstable AO type C1 and C2 pelvic ring fractures. The patients were followed up for at least 2 years, and all patients were evaluated using the Majeed scoring system and vertical displacement. In the biomechanical tests, six embalmed adult pelvic specimens were used. The fractures were subjected to TightRope®, IS screw, and TBP fixation in a randomized block design. The specimens were placed in a biomechanical testing machine in a standing neutral posture. A cyclic vertical load of up to 500 N was applied, and the displacement of the specimens was recorded by the testing machine. The ultimate load in each group of specimens was recorded. The displacement and ultimate load were compared and analyzed by statistical methods. RESULTS: At a mean follow-up of 38.89 ± 8.72 months, the functional Majeed score was excellent in 14 patients and good in four patients. The final radiological examinations showed that the outcome was excellent in 14 patients and good in four patients. In these patients, no serious clinical complications were found. Weight-bearing was delayed in four patients. In biomechanical tests, the displacement of the specimens fixed with TightRope® was significantly lower than that of the specimens fixed with TBP (P < 0.05) when the load ranged from 300 to 500 N. The displacement in the IS screw group was significantly lower than that in either the TBP or TightRope® group (P < 0.05) when the load ranged from 0 to 500 N. The ultimate load in the IS screw group (1798 ± 83.53 N) was significantly greater than that in the TBP group (1352 ± 74.41 N) (t = 9.78, P < 0.0001) and the TightRope® group (1347 ± 54.28 N) (t = 11.11, P < 0.0001). However, no significant difference was observed between the TightRope® and TBP groups (t = 0.13, P = 0.90). CONCLUSION: Percutaneous posterior TightRope® system shows strong stability in mechanical experiments and shows good results in clinical follow-up while this system has certain advantages in lower surgical requirements and lower risk of related nerve and vascular structural damage.

Changes of Migration, Immunoregulation and Osteogenic Differentiation of Mesenchymal Stem Cells in Different Stages of Inflammation.

Bone infection has always been the focus of orthopedic research. Mesenchymal stem cells (MSCs) are the natural progenitors of osteoblasts, and the process of osteogenesis is triggered in response to different signals from the extracellular matrix. MSCs exert important functions including secretion and immune regulation and also play a key role in bone regeneration. The biological behavior of MSCs in acute and chronic inflammation, especially the transformation between acute inflammation and chronic inflammation, has aroused great interest among researchers. This paper reviews the recent literature and summarizes the behavior and biological characteristics of MSCs in acute and chronic inflammation to stimulate further research on MSCs and treatment of bone diseases.

Macrophage-Osteoclast Associations: Origin, Polarization, and Subgroups.

Cellular associations in the bone microenvironment are involved in modulating the balance between bone remodeling and resorption, which is necessary for maintaining a normal bone morphology. Macrophages and osteoclasts are both vital components of the bone marrow. Macrophages can interact with osteoclasts and regulate bone metabolism by secreting a variety of cytokines, which make a significant contribution to the associations. Although, recent studies have fully explored either macrophages or osteoclasts, indicating the significance of these two types of cells. However, it is of high importance to report the latest discoveries on the relationships between these two myeloid-derived cells in the field of osteoimmunology. Therefore, this paper reviews this topic from three novel aspects of the origin, polarization, and subgroups based on the previous work, to provide a reference for future research and treatment of bone-related diseases.

Brachial muscle injury resulting in acute compartment syndrome of the upper arm: a case report and literature review.

BACKGROUND: Acute compartment syndrome (ACS) is a potentially devastating condition. ACS is rare in the upper arm. CASE PRESENTATION: We report a case of acute compartment syndrome of the anterior compartment of the upper arm due to brachial muscle injury. The patient experienced abnormal progressive swelling and pain in his right upper arm, and passive pulling pain of the right wrist and right hand. It was highly suspected to be right upper arm compartment syndrome, and was confirmed by surgery. The patient transferred to the emergency operating room for fasciotomy that was performed under general anesthesia using the anterolateral approach. The brachial muscle was found to be heavily swollen and had the greatest tension. The brachial muscle fibers were split lengthwise, and a large amount of hematoma was cleared. The brachial muscles were injured and partly ruptured. After full decompression, a negative pressure drainage device was used to cover the wound in the first stage. Ten days after injury, the swelling of the affected limb subsided and the wound was sutured. The patient's limbs completely recovered to normal. The shoulder and elbow joints could move freely and the patient resumed normal farming work ability. CONCLUSION: Clinicians should fully recognize the fact that acute compartment syndrome can occur in the upper arm, rather than only the forearm and leg, and therefore avoid serious consequences caused by missed diagnosis and misdiagnosis.

Comparison of single versus double TightRope system in the treatment of acute acromioclavicular joint dislocation.

BACKGROUND: Reconstruction of the coracoclavicular (CC) ligament using a single TightRope (ST) system has some complications. We attempted to use a double TightRope (DT) system to reduce complications and obtain the ideal therapeutic effect. PURPOSE: This investigation aimed to compare the ST and DT systems in terms of efficacy and safety in treating acromioclavicular (AC) joint dislocation. METHODS: Sixty-six cases of acute AC joint dislocation between January 2013 and January 2018 were retrospectively reviewed. All patients were divided into 2 groups based on treatment with the ST or DT system. Patients were evaluated radiologically and clinically using the Disability of Arm, Shoulder, and Hand, Constant, and visual analog scale scores as clinical outcome measures at 1 day, 3 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery. The CC distance and displacement ratio were assessed radiologically. RESULTS: The mean follow-up period was 49 months. Satisfactory clinical outcomes were obtained after CC fixation in both groups. No intergroup difference was found regarding the visual analog scale (P = .80), Disability of Arm, Shoulder, and Hand (P = .42), or Constant score (P = .28) at 2 years. However, there was a significant difference in the displacement ratio at 6 weeks (P < .0001), 3 months (P < .0001), 6 months (P < .0001), 1 year (P < .0001), and 2 years (P < .0001) postoperatively between the 2 groups. There were 3 complications in the ST group, including 1 case of secondary coracoid fracture, 1 case of AC joint arthrosis combined with ossification of the CC ligaments, and 1 case of clavicular erosion. All complications occurred in the ST group. CONCLUSIONS: Both surgical methods are effective in treating AC joint dislocation, but the DT system is more reliable for reduction maintenance.

Popliteal artery transection associated with a minimally displaced tibial plateau fracture: a case report and review of the literature.

BACKGROUND: Poplital artery transection injury is potentially catastrophic, or even life-threatening. Severe traumas, including open fracture, gunshot, stabs, and knee dislocation and complex fracture of proximal tibia or distal femur, are the common causes of high rate of amputation due to popliteal artery trauma. No report mentions vascular injury associated with minimally displaced tibial plateau fracture in adult. CASE PRESENTATION: A 30-year-old male presented with popliteal artery transection injury associated with minimally displaced tibial plateau fracture. He presented to emergency department, 6 h after fall from ground into a 1-m height hole. Physical examination suggested acute ischemia, with signs of paleness, coldness, anesthesia, hemorrhagic bullae below the right knee level. There was severe swelling and ecchymosis in popliteal fossa and around the leg with significant calf tenderness and pedal edema. Tibialis posterior, dorsalis pedis, and popliteal arterial pulses were not palpable. Radiograph suggested minimally displaced tibial plateau fracture with no evidence of knee dislocation. The patient was taken up for emergency surgery after consultation with vascular surgeon. During the closed reduction external fixation and compartment decompression, popliteal artery trunk was found transected and end-to-end repair was performed. During the post-operational period, no complication was developed and the patient was followed-up for 1 year. At the one-year follow-up, he acquired good stability of his right knee with full range of motion. CONCLUSION: Significant swelling and ecchymosis should alert the surgeons to the possibility of vascular injury in knee joint injury, even if there is no fracture or dislocation, or fracture is minimally displaced.

A New Coracoclavicular Guider for Minimally Invasive Anatomic Coracoclavicular Reconstruction with Two TightRope Systems in Acute Acromioclavicular Joint Dislocation.

High-grade injuries of complete acromioclavicular (AC) joint disruption (types IV - VI) are typically treated surgically. Since the coracoclavicular (CC) ligament is most often used for stabilizing the AC joint, most reconstruction techniques to treat dislocation of this joint rely upon CC interval fixation. A TightRope system is usually used to augment the CC ligament to treat acute AC dislocations with arthroscopic assistance. The conventional arthroscopic technique employing one TightRope system is associated with some complications, including anterior subluxation of the clavicle and clavicular bony avulsion as a consequence of rotational movements. As an alternative, two TightRope systems can be used to anatomically reconstruct the CC ligament to avoid these complications. We present a new CC guider with which the surgeon can replicate the native CC ligament complex orientation using two TightRope systems via two minimally invasive incisions without arthroscopic assistance. This procedure relies upon the accommodation and stable placement of the clavicle and coracoid bone tunnels for the two TightRope systems in place of the trapezoid and conoid of the CC ligament. We retrospectively reviewed the outcomes for 16 patients with acute dislocation of the AC joint that had been treated by a single surgeon using a double-button fixation system. An independent reviewer conducted functional testing of these patients, including the use of Disability of Arm, Shoulder and Hand (DASH), Constant and visual analog scale (VAS) scores. Standard radiographs were used for assessing the CC distance for the impacted shoulder relative to that of the unaffected contralateral shoulderThe new CC guider leads to an excellent cosmetic result. Our clinical results show that this technique can be easily performed and is similarly invasive to other current arthroscopic techniques.

Shockwaves Inhibit Chondrogenic Differentiation of Human Mesenchymal Stem Cells in Association with Adenosine and A2B Receptors.

Extracorporeal shockwave therapy (ESWT) has emerged as the important choice for the treatment of many orthopedic disorders. Our previous mechanistic studies suggest that ESWT promoted osteogenesis of human mesenchymal stem cells (hMSCs) through mechanisms that involve adenosine 5'-triphosphate (ATP) release. In this study, we investigated the effect of ESWT on chondrogenesis of hMSCs. We demonstrate that ESWT treatment caused a significant release of adenosine from hMSCs; ESWT treatment increased the levels of A2B receptor (A2BR) in hMSCs under 3-D culture conditions. ESWT, exogenous adenosine and specialized A2BR agonist suppressed hMSC chondrogenic differentiation through downregulating the expressions of aggrecan (ACAN), Collagen Type I alpha 2(COL1A2), Collagen Type II alpha 1(COL2A1), Sex-Determining Region YBox 9 (SOX9) and Sex-Determining Region YBox 6 (SOX6). Selective A2BR antagonists induced chondrogenic differentiation of hMSCs. This study indicated that shockwave therapy inhibits hMSC chondrogenic differentiation through or partially through regulation of adenosine release and activation of A2B receptor under 3-D culture conditions.

Shock wave-induced ATP release from osteosarcoma U2OS cells promotes cellular uptake and cytotoxicity of methotrexate.

BACKGROUND: Osteosarcoma is the most prevalent primary malignant bone tumor, but treatment is difficult and prognosis remains poor. Recently, large-dose chemotherapy has been shown to improve outcome but this approach can cause many side effects. Minimizing the dose of chemotherapeutic drugs and optimizing their curative effects is a current goal in the management of osteosarcoma patients. METHODS: In our study, trypan blue dye exclusion assay was performed to investigate the optimal conditions for the sensitization of osteosarcoma U2OS cells. Cellular uptake of the fluorophores Lucifer Yellow CH dilithium salt and Calcein was measured by qualitative and quantitative methods. Human MTX ELISA Kit and MTT assay were used to assess the outcome for osteosarcoma U2OS cells in the present of shock wave and methotrexate. To explore the mechanism, P2X7 receptor in U2OS cells was detected by immunofluorescence and the extracellular ATP levels was detected by ATP assay kit. All data were analyzed using SPSS17.0 statistical software. Comparisons were made with t test between two groups. RESULTS: Treatment of human osteosarcoma U2OS cells with up to 450 shock wave pulses at 7 kV or up to 200 shock wave pulses at 14 kV had little effect on cell viability. However, this shock wave treatment significantly promoted the uptake of Calcein and Lucifer Yellow CH by osteosarcoma U2OS cells. Importantly, shock wave treatment also significantly enhanced the uptake of the chemotherapy drug methotrexate and increased the rate of methotrexate-induced apoptosis. We found that shock wave treatment increased the extracellular concentration of ATP and that KN62, an inhibitor of P2X7 receptor reduced the capacity methotrexate-induced apoptosis. CONCLUSIONS: Our results suggest that shock wave treatment promotes methotrexate-induced apoptosis by altering cell membrane permeability in a P2X7 receptor-dependent manner. Shock wave treatment may thus represent a possible adjuvant therapy for osteosarcoma.

Study and Therapeutic Progress on Intracranial Serpentine Aneurysms.

An intracranial serpentine aneurysm (SA) is a clinically rare entity, and very few multi-case studies on SA have been published. The present study reviewed the relevant literature available on PubMed. The studied information included the formation mechanism and natural history of SA as well as its clinical manifestation, imaging characteristics, and current treatments. After reviewing the literature, we conclude that intracranial SA can be managed surgically and by endovascular embolization, but the degree of blood flow in normal brain tissue distal to the SA must be evaluated. A balloon occlusion test (BOT) or cross compression test is recommended for this evaluation. If the collateral circulation is sufficiently compensatory, direct excision or embolization can be performed. However, if the compensatory collateral circulation is poor, a bypass surgery is necessary. Satisfactory results can be achieved in the majority of SA patients after treatment. However, the size of the aneurysm may increase in some patients after endovascular treatment. Special attention should be paid to cases exhibiting a significant mass effect to avoid subsequent SA excision due to an intolerable mass effect. Satisfactory results can be achieved with careful treatment of SA.

Death Due to Intra-aortic Migration of Kirschner Wire From the Clavicle: A Case Report and Review of the Literature.

Migration of orthopedic fixation wires into the ascending aorta though a rare occurrence can have devastating consequences. Therefore, prompt recognition, with immediate and cautious retrieval of the implant is paramount in averting these complications.We present a case of a 5-year-old boy with the intra-aortic migration of a K-wire used for the treatment of a right clavicle fracture. He was transferred to us with a history of syncope, chest pain, and shortness of breath 7 days after K-wire placement, which was performed at another hospital. On CT scan, the wire was found to be partially inside the ascending aorta, which was associated with massive hemopericardium and cardiac tamponade. The patient was taken up for emergency surgery for the removal K-wire and for the management of cardiac temponade. However, the patient developed cardiac arrest during the induction of intravenous anesthesia and endotracheal intubation. The K-wire was retrieved from the thorax via thoracotomy. However, the patient died 10 days after the surgery.As the migration of wires and pins during orthopedic surgery can cause potentially fatal complications, these should be used very cautiously, especially for percutaneous treatment of shoulder girdle fractures. The patients with such implants should be followed frequently, both clinically and radiographically. If migration occurs, the patient should be closely monitored for emergent complications and the K-wire should be extracted immediately.

Incidence and risk factors for venous thromboembolism following surgical treatment of fractures below the hip: a meta-analysis.

Venous thromboembolism (VTE) is a common complication after surgical treatment of fractures, which is associated with significant morbidity and mortality. Identifying the risk factors for VTE is important for preventive strategies to reduce the incidence of VTE. Therefore, we conducted a meta-analysis to evaluate the incidence of VTE and the risk factors influencing the development of VTE in patients who underwent surgery for fractures below the hip. PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China) and CNKI (National Knowledge Infrastructure, China) databases were systematically searched to identify cohort or case-control studies that investigated the incidence and risk factors for VTE following surgical treatment of fractures below the hip. VTE risk ratios (RRs) were pooled by use of a fixed-effect model or a random-effect model, depending on the heterogeneity among the included studies. Heterogeneity between the studies was assessed by I2 statistics. Twenty-three studies with a total of 191 294 patients who met the inclusion criteria were included in this meta-analysis. Our results demonstrated that age (≥60 years) (RR = 1·85, 95% confidence interval (CI): 1·34, 2·55; P = 0·000), previous VTE(RR = 5·25, 95% CI: 2·77, 9·96; P = 0·000), heart failure (RR = 1·74, 95% CI: 1·34, 2·27; P = 0·000), current smoking status (RR = 1·23, 95% CI: 1·07, 1·41; P = 0·004), hypertension (RR = 1·62, 95% CI: 1·27, 2·06; P = 0·000), hyperlipidaemia (RR = 2·16, 95% CI: 1·79, 2·62; P = 0·000), diabetes mellitus (RR = 1·46, 95% CI: 1·27, 1·68; P = 0·000), obesity (RR = 1·58, 95% CI: 1·35,·1·85; P = 0·000), multiple fractures (RR = 2·14, 95% CI: 1·00, 4·60; P = 0·050), varicose veins (RR = 3·07, 95% CI: 1·12, 8·47; P = 0·030), prolonged operation time (weighted mean differences (WMD) = 1·22, 95% CI: 0·63, 1·81; P = 0·000) and prolonged bed rest time (WMD = 3·12, 95% CI: 2·96, 3·29; P = 0·000) were associated with an increased risk of developing VTE. The other variables, including age (<60 years), previous smoking, immobility, pregnancy, cancer, open fractures and combination with trauma were not identified as significant risk factors for VTE. Almost all the risk factors mentioned above are in line with the known risk factors for VTE following surgery for fractures below the hip. Thus, surgeons should pay close attention to patients with these medical conditions in order to reduce the incidence of VTE following surgical treatment of fractures below the hip.

Current Status of the Application of Intracranial Venous Sinus Stenting.

The intracranial venous sinus is an important component of vascular disease. Many diseases involve the venous sinus and are accompanied by venous sinus stenosis (VSS), which leads to increased venous pressure and high intracranial pressure. Recent research has focused on stenting as a treatment for VSS related to these diseases. However, a systematic understanding of venous sinus stenting (VS-Stenting) is lacking. Herein, the literature on idiopathic intracranial hypertension (IIH), venous pulsatile tinnitus, sinus thrombosis, high draining venous pressure in dural arteriovenous fistula (AVF) and arteriovenous malformation (AVM), and tumor-caused VSS was reviewed and analyzed to summarize experiences with VS-Stenting as a treatment. The literature review showed that satisfactory therapeutic effects can be achieved through stent angioplasty. Thus, the present study suggests that selective stent release in the venous sinus can effectively treat these diseases and provide new possibilities for treating intracranial vascular disease.

A novel technique to prevent guide wire related complications while inserting the 4.0 mm cannulated screws.

BACKGROUND: Cannulated screws (4.0 mm) provide inter-fragmentary compression and stability to fractures. A guide wire is used to define the screw trajectory and hold the fracture fragment while the screw is being inserted. The cannulated shaft typically accommodates a 1.25 mm guide pin. Since the guide pin is very slender and undergoes elastic deformation during insertion, there is a high probability of pin breakage. METHODS: The authors have devised a new way to place the 4.0 mm cannulated screws in a manner that prevents the intraoperative complication of guide wire breakage. For this technique, predrilling was achieved using a 2.0 mm K-wire which was subsequently replaced with a 1.25 mm guide pin under the protection of sleeve. 4.0 mm cannulated screws were then inserted into a defined trajectory over the guide pin. RESULTS: Using the technique, over 20 patients were managed in our department over a period of two years without any complications. CONCLUSION: We have observed that patients treated with this method experience short operation time, combined with good clinical outcome and we recommend its use in cases where cannulated screw use is warranted.