The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (223Ra) combined with new-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapies remains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of 223Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bone mCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), five retrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the 223Ra+NHA combination group and the 223Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91-2.34, P = 0.66), but the incidences in both the 223Ra+NHA combination group (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01) and the 223Ra monotherapy group (OR: 2.24, 95% CI: 1.23-4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, in the meta-analysis involving only RCTs, there was no difference between the 223Ra monotherapy group and the NHA monotherapy group (OR: 1.14, 95% CI: 0.22-5.95, P = 0.88), while the difference between the 223Ra+NHA combination group and the NHA monotherapy group remained significant (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-free survival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significant difference. Our results indicate that the combination of 223Ra with NHAs was well tolerated in bone mCRPC patients compared to 223Ra monotherapy, even though the incidence of fracture was higher in patients who received 223Ra than that among those who received NHA monotherapy. More evidence is needed to explore the safety and efficiency of 223Ra combination therapies.

[Treatment of femoral periprosthetic fracture of Vancouver type B1 and C with bridge combined internal fixation system].

OBJECTIVE: To evaluate the clinical effect of bridge combined internal fixation system in the treatment of periprosthesis fracture of femur after hip replacement. METHODS: From October 2016 to June 2018, 5 patients of periprosthesis fractures of femur classified type B1 and type C in Vancouver were treated by open reduction and bridging combined with internal fixation, including 2 males and 3 females, with ages of 68, 70, 74, 75, 79 years;type B1 fractures in 4 and type C fractures in 1. Causes of injury:1 case of traffic injury, 4 cases of fall. After the operation, the patients were followed up for complications and fracture healing time by clinical and imaging examination, and Parker activity score was performed. RESULTS: The wounds of 5 patients healed without infection. One case of DVT was confirmed by venography. Five patients were followed up, and the durations were 2, 8, 9, 10, 15 months. One patient died of myocardial infarction 2 months after operation. The average healing time was 12.5 weeks. No loss of reduction or failure of internal fixation was found. Two patients could walk without protection and 1 patient needed to rely on single crutch. One case of periprosthetic fracture had to walk with a single crutch before operation and move indoors with two crutches after operation. The average Parker activity score was 51.8% before operation. CONCLUSION: The bridge combined internal fixation system can be used to fix the fracture after hip replacement with stable femoral prosthesis.

Efficacy and Safety of Tranexamic Acid in Intertrochanteric Fractures: A Single-Blind Randomized Controlled Trial.

OBJECTIVE: To investigate the efficacy and safety of tranexamic acid (TXA) in the reduction of bleeding and the need for transfusion in elderly intertrochanteric fracture patients. METHODS: A total of 100 patients with intertrochanteric fractures undergoing surgery were enrolled and randomly allocated to the TXA group in which patients (75.10 ± 8.27 years old) were treated with 1 g of TXA, or the control group (77.82 ± 6.42 years old) treated with a placebo. Surgery was performed by two senior orthopaedic surgeons from two institutions. The proximal femoral nail antirotation (PFNA) was conducted using the standard procedure. Three outcome measures, including blood loss, transfusion, and complications, were recorded. Blood loss and transfusion were investigated to assess TXA's effectiveness, while complications were investigated to assess TXA's safety. Statistical indicators for blood loss included total, intraoperative, postoperative, and hidden blood loss volumes, calculated by hemoglobin levels, hematocrit levels, and drainage volume. The number and amount of blood transfusions were recorded. Complications associated with surgery, including deep vein thrombosis, pulmonary embolism, wound hematoma, wound infection, cardiovascular and cerebrovascular accidents, and respiratory infections, were also recorded. RESULTS: All patients were followed up for 1 month after surgery. There were no significant differences in demographic and clinical characteristics between the two groups. The TXA group suffered significantly less total blood loss (563.37 ± 197.51 vs 819.25 ± 273.96 mL, 95% CI: -349.49 to -162.27, P < 0.01), intraoperative blood loss (140.3 ± 80.64 vs 230.5 ± 130.56 mL, 95% CI -132.74 to -47.66, P < 0.01), and hidden blood loss (410.42 ± 178.23 vs 571.19 ± 218.13 mL, 95% CI: -238.85 to -82.69, P < 0.01) than the control group. However, postoperative total blood loss was not significantly different (97.5 ± 20.93 vs 94.7 ± 35.78 mL; P = 0.63). A total of 5 patients from the TXA group and 27 from the control group received packed RBC for postoperative transfusion, but the mean number of transfusion units was not significantly different between groups. Complications including deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic cerebral infarction, hematoma, and infection were observed in both groups, but no significant differences were found. CONCLUSIONS: In intertrochanteric fracture surgery performed using PFNA, intravenous administration of TXA significantly reduced the risk of intraoperative, total and hidden blood loss, in addition to the need for allogeneic transfusion, without increasing the rate of complications.

Efficacy and safety of tranexamic acid in elderly patients with intertrochanteric fracture: An updated meta-analysis.

BACKGROUND: Intertrochanteric fracture (ITF) is a common type of injury, and nearly 30% of ITF patients die in the first 12 mo, especially the elderly with limited activity. Tranexamic acid (TXA) has been widely used in reducing traumatic and surgical bleeding, however, the paucity of studies regarding its use in orthopedic trauma surgery has limited its integration into this field, which may benefit most from TXA. The safety of TXA in this group has not achieved a consensus. AIM: This meta-analysis was designed to investigate the efficacy and safety of TXA in elderly ITF patients undergoing surgery. METHODS: Databases, including Medline and PubMed, were searched for randomized controlled trials (RCTs) that were published before October 2018 and that addressed the efficacy and safety of TXA in patients who underwent ITF surgery. The Consolidated Standards of Reporting Trials 2010 Statement Checklist was used to assess the methodological quality of each study. Trials without and with heterogeneity were compared by fixed-effects analysis and random-effects analysis, respectively. For each study, odds ratio (OR) and 95%CI and mean differences and 95%CI were calculated for dichotomous and continuous outcomes, respectively. The Power and Sample Size Program software was used to calculate power and sample size. Stability of the results was assessed via sensitivity analysis. RESULTS: A total of 836 patients from eight RCTs were subjected to meta-analysis. TXA treatment compared with the control group significantly reduced postoperative blood loss (95%CI, -20.83 to -7.93 mL, P < 0.0001), hidden blood loss (95%CI, -213.67 to -64.43 mL, P = 0.0003), and total blood loss (95%CI, -332.49 to -23.18 mL, P = 0.02) by weighted mean differences of -14.38, -139.05, and -177.83 mL, respectively. However, no significant difference was observed between groups for analysis of intraoperative blood loss. The meta-analysis also proved that the usage of TXA in ITFs may not significantly increase the incidence of deep venous thrombosis. Allogeneic blood transfusion data showed that significantly fewer patients in the TXA group (42%) required transfusion than the control group (95%CI, 0.36 to 0.69; P < 0.0001). CONCLUSION: In ITF surgery, intravenous administration of TXA reduces the risk of hidden blood loss and the need for allogeneic transfusion, without increasing thrombotic risk.

SLIT2/ROBO1 axis contributes to the Warburg effect in osteosarcoma through activation of SRC/ERK/c-MYC/PFKFB2 pathway.

Cellular metabolic reprogramming is the main characteristic of cancer cells and identification of targets using this metabolic pattern is extremely important to treat cancers, such as osteosarcoma (OS). In this study, SLIT2 and ROBO1 were upregulated in OS, and higher expression of ROBO1 was associated with worse overall survival rate. Furthermore, in vitro and in vivo experiments demonstrated that the SLIT2/ROBO1 axis promotes proliferation, inhibits apoptosis, and contributes to the Warburg effect in OS cells. Mechanistically, the SLIT2/ROBO1 axis exerted cancer-promoting effects on OS via activation of the SRC/ERK/c-MYC/PFKFB2 pathway. Taken together, the findings reveal a previously unappreciated function of SLIT2/ROBO1 signaling in OS, which is intertwined with metabolic alterations that promote cancer progression. Targeting the SLIT2/ROBO1 axis may be a potential therapeutic approach for patients with OS.

Polysaccharide from Angelica sinensis protects chondrocytes from H2O2-induced apoptosis through its antioxidant effects in vitro.

This study aimed to explore the protective effects of Angelica sinensis polysaccharide (ASP) on rat chondrocyte injury induced by hydrogen peroxide (H2O2). Rat chondrocytes were cultured and treated with different concentrations of ASP alone or in combination with H2O2, and they were measured with cell viability, apoptosis, release of inflammatory cytokines, such as interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α), activity of superoxide dismutase (SOD), and catalase (CAT), and levels of malondialdehyde (MDA) production, respectively. In addition, quantitative real-time reverse transcription polymerase chain reaction was used to estimate the relative expression levels of osteoarthritis (OA)-associated genes, such as collagen type II (Col2a1), aggrecan, SOX9, matrix metalloproteinase (MMP)-1, -3, and -9, as well as tissue inhibitor of matrix metalloproteinase (TIMP)-1, respectively. Results indicated that ASP protected chondrocytes from H2O2-induced oxidative stress and subsequent cell injury through its antioxidant, antiapoptotic and anti-inflammatory effects in vitro. Our study suggests that ASP could become a therapeutic supplementation for the treatment of OA.

Outcomes of secondary laminoplasty for patients with unsatisfactory results after anterior multilevel cervical surgery.

OBJECTIVE: To investigate the causes for failed anterior cervical surgery and the outcomes of secondary laminoplasty. METHODS: Seventeen patients failed anterior multilevel cervical surgery and the following conservative treatments between Feb 2003 and May 2011 underwent secondary laminoplasty. Outcomes were evaluated by the Japanese Orthopaedic Association (JOA) Scale and visual analogue scale (VAS) before the secondary surgery, at 1 week, 2 months, 6 months, and the final visit. Cervical alignment, causes for revision and complications were also assessed. RESULTS: With a mean follow-up of 29.7±12.1 months, JOA score, recovery rate and excellent to good rate improved significantly at 2 months (p<0.05) and maintained thereafter (p>0.05). Mean VAS score decreased postoperatively (p<0.05). Lordotic angle maintained during the entire follow up (p>0.05). The causes for secondary surgery were inappropriate approach in 3 patients, insufficient decompression in 4 patients, adjacent degeneration in 2 patients, and disease progression in 8 patients. Complications included one case of C5 palsy, axial pain and cerebrospinal fluid leakage, respectively. CONCLUSION: Laminoplasty has satisfactory results in failed multilevel anterior surgery, with a low incidence of complications.

Application of lamina replantation with ARCH plate fixation in thoracic and lumbar intraspinal tumors.

The aim of the present study was to investigate the clinical effects of lamina replantation with ARCH plate fixation on patients with thoracic and lumbar intraspinal tumors, following laminectomy. Thirteen patients with thoracic and lumbar intraspinal tumors underwent total lamina replantation with ARCH plate fixation and repair of the supraspinous ligaments, following laminectomy and tumor enucleation. To investigate the clinical effect of lamina replantation with ARCH plate fixation, pre- and postoperative visual analog scale (VAS), and Oswestry Disability Index (ODI) scores were determined, and pre- and postoperative X-ray and magnetic resonance imaging (MRI) examinations were conducted. Computed tomography (CT) examinations were also included in the follow-up. No complications were observed pre- or postoperatively. The VAS and ODI results 2 weeks following surgery and at the final follow-up examination demonstrated a significant improvement compared with the corresponding preoperative results. The X-ray examination results indicated a satisfactory internal fixation location, without any characteristics of a fracture, lumbar scoliosis, kyphosis or instability. Following the surgery, the CT and MRI examination results demonstrated that healing of the lamina bone and repair of the supraspinous ligament had occurred without tumor recurrence or spinal epidural scar recompression. Two of the 13 cases were lost to follow-up. The results indicated that in patients with thoracic and lumbar intraspinal tumors, lamina replantation with ARCH plate fixation following total laminectomy is effective and provides thoracolumbar stability. Furthermore, this has been identified to be an effective technique for preventing intraspinal scar proliferation.

[Multi-ligaments reconstruction with single tendon with for the treatment of acute joint dislocation of the first carpometacarpal].

OBJECTIVE: To explore the clinical outcomes of multi-ligaments reconstruction with single tendon in treating acute joint dislocation of the first carpometacarpal. METHODS: From December 2008 to October 2012, 4 patients with acute dislocation of the first carpometacarpal were treated with single carpi radialis longus tendon to reconstruct periarticular four ligaments, which included dorsal ligament, palmar ligament, dorsal radiocarpal ligament, and intermetacarpal ligament between the first and second. There were 3 males and 1 female aged from 22 to 63 years old with an average of 38.7. X-ray, JAMAR grid strength testing, range of motion of carpometacarpal joint and VAS score were used to evaluate clinical outcomes. RESULTS: All patients were followed up from 6 to 40 months with an average of 19 months. The wound were healed well at stage I. No dislocation of the first carpometacarpal joint and signs of joints degeneration occurred on X-ray at 1, 3 and 6 months after operation. JAMAR grip strength recovered from 60 percent to 90 percent of health wide. The results of ROM showed 3 cases recovered flexion and extension of joints and 1 case limited adduction. VAS score was 0 to 1. CONCLUSION: For acute dislocation of the first carpometacarpal joint, reconstruction four ligaments with single carpi radialis longus tendon can be considered the selected treatment,which can restores joint stability and improve joint function.

[Pedicle screw fixation of thoracic spinal fracture assisted by CT-based navigation system].

OBJECTIVE: To evaluate the feasibility and accuracy of thoracic pedicle screw fixation when assisted by a CT-based navigation system. METHODS: A total of 102 thoracic pedicle screws inserted by a CT-based navigation system (n = 24) (Group A) and 98 thoracic pedicle screws inserted by X-ray fluoroscopy (n = 22) (Group B) were observed by postoperative CT scan. The accuracy of both series was compared. And the process of navigation was investigated. RESULTS: Among Group A, 99 were of grade I (97.1%), 3 grade II and 0 grade III; among Group B, 88 were of grade I (89.8%), 8 grade II and 2 grade III. One patient of grade III had the intractable pain of chest and back. Neural damage was not demonstrated. The difference was statistically significant (P < 0.05). CONCLUSION: A CT-based navigation system can increase accuracy of thoracic pedicle screw fixation.

Immunofluorescence laser confocal expression and localization study of rat nerve growth guidance cues Netrin-1 and Slit2 after spinal cord injury.

OBJECTIVE: To observe the expression and distribution of adult rat axon guidance cues Netrin-1 and Slit2 at different time points after spinal cord injury and to investigate the guidance mechanism of regenerated axons. METHODS: Twenty adult Sprague Dawley (SD) rats were divided randomly into five groups with 4 in each. Four groups of them were used to make Allen's spinal cord punch models and we took materials randomly from one of them on the 2nd, 4th, 7th and 14th day respectively after operation. The left one group was taken as the control group. Immunofluorescence laser confocal scan was used to examine the co-expression and localization of Netrin-1 and Slit2 proteins in the injured site of the spinal cord. RESULTS: Within two weeks after SCI, the expression of Netrin-1 and Slit2 proteins increased temporarily and there was co-expression of them on the neuron plasma membrane. CONCLUSIONS: Synchronous high expression and co-expression of axon attractant Netrin-1 and repellent Slit2 are found in the adult rat injured spinal cord in the damaged local and vicinity parts, and probably, they act as the key regulators of axon guidance regeneration.

Reconstruction of finger pulp defect with reversed fasciocutaneous island flap from same finger.

OBJECTIVE: To investigate the clinical curative effect of reconstruction of finger pulp defect by anastomosis of reversed fasciocutaneous island flap with dorsal branch of the digital nerve of the same finger. METHODS: The restoration of finger pulp defect with fasciocutaneous island flap from the same finger was conducted in 25 cases (30 fingers) from January 2002 to June 2003. Nine patients (11 fingers) whose flaps with dorsal branch of the digital nerve anastomosed with the digital inherent nerve around the surface of the wound were Group A and the others were Group B. The follow-up was carried out at 3 and 9 months after the operation to observe the shape of finger pulp and the sense restoration between two groups. RESULTS: All flaps of 25 cases (30 fingers) survived. Three months after operation, the patients had fully grown finger pulps and recovered the superficial sensation and tactile sense of finger pulps. The two point discrimination on average was 5.00 mm+/-0.23 mm in Group A and 6.00 mm+/-0.30 mm in Group B. The difference between two groups was highly significant. Nine months later, their senses of finger pulps between two groups were recovered basically. CONCLUSIONS: The reversed fasciocutaneous island flap from the same finger is the first choice to reconstruct the finger pulp defect, and the anastomosis of dorsal branch of the digital nerve shall be determined according to the specific condition.