A modified intrafocal pinning technique with three-dimensional planning to facilitate volar plating in dorsally comminuted AO/OTA C2 and C3 distal radius fractures.

BACKGROUNDS: Theaim of this study was to assess the efficacy of a modified intrafocal pinningtechnique with three-dimensional (3D) planning to facilitate volar plating in dorsally comminuted intra-articular distal radius fractures. METHODS: Intotal 35 AO/OTA type C2 and C3 fractures were finally included.The 3D digital model of the fracture was reconstructed based on preoperative computedtomographic (CT) images, with the displacement of the comminuted dorsalfragment and the intra-articular fragment analyzed for preoperative planning. During operation, amodified intrafocal pinning technique was applied percutaneously from thedorsal aspect of the radius to reduce the collapsed intra-articular fragmentfollowing volar plating. Adequate reduction was confirmed in all of patientsconsidering radial height, radial inclination and volar tilt in postoperativeradiographs. RESULTS: No significant fracture re-displacement wasobserved in most of the cases during a mean follow-up period of 17.4 months, exceptfor two patients withthe C3 fracture. All of the patients achieved adequate clinicalROMs at 12 months postoperatively, with a mean DASH score of 12.0. Most of the patients achievedan excellent (n = 21) or good (n = 12) Gartland and Werley wrist score. CONCLUSIONS: Ourmodified intrafocal pinning technique with 3D planning contributes to a satisfactoryclinical and radiological outcome in dorsally comminuted intra-articular distalradius fractures fixed with a volar locking plate. TRIALREGISTRATION: Notapplicable because the design of the study is retrospective.

Comparison of the direct and indirect reduction techniques during the surgical management of posterior malleolar fractures.

BACKGROUND: The optimal method for the reduction and fixation of posterior malleolar fracture (PMF) remains inconclusive. Currently, both of the indirect and direct reduction techniques are widely used. We aimed to compare the reduction quality and clinical outcome of posterior malleolar fracture managed with the direct reduction technique through posterolateral approach or the indirect reduction technique using ligamentotaxis. METHODS: Patients with a PMF involving over 25% of the articular surface were recruited and assigned to the direct reduction (DR) group or the indirect reduction (IR) group. Following reduction and fixation of the fracture, the quality of fracture reduction was evaluated in post-operative CT images. Clinical and radiological follow-ups were performed at 6 weeks, 3 months, 6 months, 12 months, and then at 6 month-intervals postoperatively. Functional outcome (AOFAS score), ankle range of motion, and Visual Analog Scale (VAS) were evaluated at the last follow-up. Statistical differences were compared between the DR and IR groups considering the patient demographics, quality of fracture reduction, AOFAS score, and VAS. RESULTS: Totally 116 patients were included, wherein 64 cases were assigned to the DR group and 52 cases were assigned to the IR group. The quality of fracture reduction was significant higher in the DR group (P = 0.038). In the patients who completed a minimum of 12 months' follow-up, a median AOFAS score of 87 was recorded in the DR group, which was significantly higher than that recorded in the IR group (a median score of 80). The ankle range of motion was slightly better in the DR group, with the mean dorsiflexion restriction recorded to be 5.2° and 6.1° in the DR and IR group respectively (P = 0.331). Similar VAS score was observed in the two groups (P = 0.419). CONCLUSIONS: The direct reduction technique through a posterolateral approach provide better quality of fracture reduction and functional outcome in the management of PMF over 25% of articular surface, as compared with the indirect reduction technique using ligamentotaxis. TRIAL REGISTRATION: NCT02801474 (retrospectively registered, June 2016, ClinicalTrails.gov).

Radiographic analysis of the restoration of hip joint center following open reduction and internal fixation of acetabular fractures: a retrospective cohort study.

BACKGROUND: Unfavorable reduction is considered one of the key factors leading to joint degeneration and compromised clinical outcome in acetabular fracture patients. Besides the columns, walls, and superior dome, the postoperative position of hip joint center (HJC), which is reported to affect hip biomechanics, should be considered during the assessment of quality of reduction. We aimed to evaluate the radiographic restoration of HJC in acetabular fractures treated with open reduction and internal fixation. METHODS: Patients with a displaced acetabular fracture that received open reduction and internal fixation in the authors' institution during the past five years were identified from the trauma database. The horizontal and vertical shifts of HJC were measured in the standard anteroposterior view radiographs taken postoperatively. The radiographic quality of fracture reduction was graded according to Matta's criteria. The relationships between the shift of HJC and the other variables were evaluated. RESULTS: Totally 127 patients with 56 elementary and 71 associated-type acetabular fractures were included, wherein the majority showed a medial (89.0%) and proximal (93.7%) shift of HJC postoperatively. An average of 2.8 mm horizontal and 2.2 mm vertical shift of HJC were observed, which correlated significantly with the quality of fracture reduction (P < 0.001 for both). The horizontal shift of HJC correlated with the fracture type (P = 0.022). CONCLUSIONS: The restoration of HJC correlates with the quality of reduction in acetabular fractures following open reduction and internal fixation. Further studies are required to address the effects of HJC shift on the biomechanical changes and clinical outcomes of hip joint, especially in poorly reduced acetabular fractures.

Haploinsufficiency of endogenous parathyroid hormone-related peptide impairs bone fracture healing.

Previous studies have demonstrated that endogenous parathyroid hormone-related peptide (PTHrP) plays a central role in the physiological regulation of bone formation. However, it is unclear whether endogenous PTHrP plays an important function in enhancing bone fracture healing. To determine whether endogenous PTHrP haploinsufficiency impaired bone fracture healing, closed mid-diaphyseal femur fractures were created in 8-week-old wild-type and Pthrp(+/-) mice. Callus tissue properties were analysed 1, 2 and 4 weeks after fracture by radiography, histology, histochemistry, immunohistochemistry and molecular biology. The size of the calluses was reduced 2 weeks after fracture, and the fracture repairs were poor 4 weeks after fractures, in Pthrp(+/-) compared with wild-type mice. Cartilaginous callus areas were reduced 1 week after fracture, but were increased 2 weeks after fracture in Pthrp(+/-) mice. There was a reduction in the number of ostoblasts, alkaline phosphatase (ALP)-positive areas, Type I collagen immunopositive areas, mRNA levels of ALP, Runt-related transcription factor 2 (Runx2) and Type I collagen, Runx2 and insulin-like growth factor-1 protein levels, the number of osteoclasts and the surface in callus tissues in Pthrp(+/-) compared with wild-type mice. These results demonstrate that endogenous PTHrP haploinsufficiency impairs the fracture repair process by reducing cartilaginous and bony callus formation, with downregulation of osteoblastic gene and protein expression and a reduction in endochondral bone formation, osteoblastic bone formation and osteoclastic bone resorption. Together, the results indicate that endogenous PTHrP plays an important role in fracture healing.

Early application of pulsed electromagnetic field in the treatment of postoperative delayed union of long-bone fractures: a prospective randomized controlled study.

BACKGROUND: Pulsed electromagnetic field (PEMF) is reported to be an effective adjunct for the management of nonunion long-bone fractures. Most studies implement PEMF treatment after 6 months or longer of delayed union or nonunion following fracture treatment. Despite these variations in treatment, the early application of PEMF following a diagnosis of a postoperative delayed union has not been specifically analyzed. In this study, the outcomes of postoperative delayed union of long-bone fractures treated with an early application of PEMF were evaluated as compared with a sham-treated control group. METHODS: In this prospective, randomized controlled study, a total of 58 long-bone fracture patients, who presented with delayed union of between 16 weeks and 6 months, were randomly split into two groups and subjected to an early application of PEMF or sham treatment. Clinical and radiological assessments were performed to evaluate the healing status. Treatment efficacy was assessed at three month intervals. RESULTS: Patients in the PEMF group showed a higher rate of union than those in the control group after the first three months of treatment, but this difference failed to achieve statistical significance. At the end of the study, PEMF treatment conducted for an average of 4.8 months led to a success rate of 77.4%. This was significantly higher than the control, which had an average duration of 4.4 months and a success rate of 48.1%. The total time from operation to the end of the study was a mean of 9.6 months for patients in the PEMF group. CONCLUSIONS: Fracture patients treated with an early application of PEMF achieved a significantly increased rate of union and an overall reduced suffering time compared with patients that receive PEMF after the 6 months or more of delayed union, as described by others.

Increased expression of insulin-like growth factor-1 receptor is correlated with tumor metastasis and prognosis in patients with osteosarcoma.

BACKGROUND: The aim of this study was to investigate the association of insulin-like growth factor-1 receptor (IGF-1R) with metastasis and prognosis of osteosarcoma patients. METHODS: RT-PCR and Western blot assays were performed to detect IGF-1R mRNA and protein expression in 26 osteosarcoma and noncancerous bone tissues. Immunohistochemistry was performed to analyze the correlation of IGF-1R expression in 84 osteosarcoma tissues with clinicopathological factors or survival of patients. Lentivirus-mediated RNA interference system was employed to downregulate IGF-1R expression and analyze the effects of IGF-1R downregulation on invasion and metastasis of osteosarcoma cells. RESULTS: The relative levels of IGF-1R mRNA and protein expression were significantly higher in osteosarcoma tissues than in corresponding noncancerous bone tissues. The expression of IGF-1R protein was closely associated with surgical stage and distant metastasis of osteosarcoma patients. Osteosarcoma patients with high IGF-1R expression had poorer survival, and multivariate Cox analyses showed that high IGF-1R expression was an independent prognostic maker. Lentivirus-mediated targeting IGF-1R could significantly inhibit adhesion, migration, invasion, and metastasis of osteosarcoma cells, which might be correlated with of inactivation of Akt signaling pathway. CONCLUSIONS: IGF-1R is an independent prognostic marker for osteosarcoma patients and increased expression of this molecular is correlated with metastasis of osteosarcoma.

Lentivirus-mediated shRNA targeting insulin-like growth factor-1 receptor (IGF-1R) enhances chemosensitivity of osteosarcoma cells in vitro and in vivo.

The overexpression of the type 1 insulin-like growth factor receptor (IGF-1R) has been reported to be associated with malignant transformation, tumor development and chemo- or radioresistance of tumor cells. Previously, we have reported that inhibition of IGF-1R could reverse the radioresistance of human osteosarcoma cells. However, whether inhibition of IGF-1R could enhance chemosensitivity of ostesosarcoma cells is unclear. In this study, lentivirus-mediated shRNA was employed to downregulate endogenous IGF-1R expression to study the function of IGF-1R in chemoresistance of osteosarcoma cells. Results showed that lentivirus-mediated shRNA targeting IGF-1R combined with chemotherapy (CDDP or DTX) could lead to growth suppression of osteosarcoma cells not only in vitro but also in vivo. Moreover, inhibition of IGF-1R gene combined with chemotherapy also synergistically enhanced Caspase-3-mediated apoptosis of osteosarcoma cells. The synergistical enhancement of apoptosis might be associated with downregulation of Bcl-2 and upregulation of Bax in osteosarcoma cells induced by IGF-1R inhibition. Therefore, the overexpression of IGF-1R gene might play important roles in chemoresistance of osteosarcoma cells, and lentivirus-mediated RNAi targeting IGF-1R would be an attractive anti-cancer strategy to chemosensitization of osteosarcoma cell.

Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits growth, reduces invasion, and enhances radiosensitivity in human osteosarcoma cells.

The type 1 insulin-like growth factor receptor (IGF-1R) is essential for tumorigenicity, tumor proliferation, and protection from apoptosis. IGF-1R overexpression has been found in many human cancers including osteosarcoma. To explore its possibility as a therapeutic target for the treatment of osteosarcoma, lentivirus-mediated siRNA was employed to downregulate endogenous IGF-1R expression to study the function of IGF-1R in tumorigenesis and radioresistance of osteosarcoma cells. The IGF-1R expression was persistently and markedly reduced by lentivirus-mediated RNAi. Downregulation of IGF-1R expression in osteosarcoma cells significantly suppressed their growth rates in vitro and reduced the potential of tumorigenicity in vivo. Moreover, the specific downregulation arrested cells in G(0)/G(1) phase of cell cycle and also induced apoptosis which correlated with the activation of Caspase-3. Furthermore, we also observed that suppression of IGF-1R could reduce the invasiveness of osteosarcoma cells and enhance their radiosensitivity. Our study suggested that lentivirus-mediated RNAi silencing targeting IGF-1R could induce potent antitumor activity and radiosensitizing activity in human osteosarcomas.

Expression and localization of mesothelin in developing rat pancreas.

To define a genetic network that regulates development of the pancreas, we used high-density microarray (Affymetrix) to generate transcriptional profiles of rat pancreas from five biologically significant stages of development: embryonic day 12.5 (E12.5), E15.5, E18.5, postnatal day 0 (P0) and adult. Many genes were notably highly expressed in the later gestation when islet architecture and function are gradually forming. The expression and localization of mesothelin, one of these genes, was further examined. Reverse transcription-polymerase chain reaction and Western blot analysis revealed that mRNA and protein levels of mesothelin were high from later gestation to 2-3 weeks after birth, and with relatively low but detectable expression levels in adult rat pancreas. Immunolocalization indicated that mesothelin localized not only in islet beta-cells but also in the mesenchyme of developing rat pancreas. Transient mesothelin expression was concomitant with the development of islets architecture formation, remodeling and maturation. These findings indicate that mesothelin is dynamically expressed in the developing rat pancreas and that mesothelin might be involved in some developmental events during development of rat pancreas.