Does a novel 3D printed individualized guiding template based on cutaneous fiducial markers contribute to accurate percutaneous insertion of pelvic screws? A preliminary phantom and cadaver study.

BACKGROUND: Most 3D-printed guiding templates require dissection of soft tissues to match the corresponding surfaces of the guiding templates. This study sought to explore the accuracy and acceptability of the novel 3D printed individualized guiding templates based on cutaneous fiducial markers in minimally invasive screw placement for pelvic fractures. METHODS: The printed template was tested on five high-fidelity biomimetic phantom models of the bony pelvis and its surrounding soft tissues as well as on two fresh frozen cadavers. Four cutaneous fiducial markers were transfixed on each phantom model prior to performing CT scans to reconstruct their 3D models. Personalized templates for guiding screw insertion were designed based on the positions of the fiducial markers and virtually planned target screw channels after scanning, followed by 3D printing of the guide. Phase 1 consisted of five expert surgeons inserting one anterograde supra-pubic screw and one sacroiliac screw percutaneously into each phantom model using the 3D-printed guide. The deviation of screw positions between the pre-operative planned and post-operative actual ones was measured after registering their 3D modelling. A Likert scale questionnaire was completed by the expert surgeons to assess their satisfaction and acceptability with the guiding template. Phase 2 consisted of repeating the same procedures on the fresh frozen cadavers in order to demonstrate face, content and concurrent validity. RESULTS: In Phase 1, all ten screws were successfully implanted with the assistance of the guiding template. Postoperative CT scans confirmed that all screws were safely positioned within the bony pelvic channels without breaching the far cortex. The mean longitudinal deviation at the bony entry point and screw tip between the pre-operative planned and post-operative actual screw paths were 2.83 ± 0.60 mm and 3.12 ± 0.81 mm respectively, with a mean angular deviation of 1.25 ± 0.41°. Results from the Likert questionnaire indicated a high level of satisfaction for using the guiding template among surgeons. In Phase 2, results were similar to those in Phase 1. CONCLUSIONS: The 3D-printed guiding template based on cutaneous fiducial markers shows potential for assisting in the accurate insertion of percutaneous screws in the pelvis.

Salvianolic acid C promotes osteogenic differentiation of bone marrow mesenchymal stem cells in osteoporotic rats through activation of AMPK/SIRT1 pathway.

PURPOSE: This study aimed to explore the molecular mechanism underlying the therapeutic effect of salvianolic acid C (SAC) on osteoporosis. METHODS: Osteoporotic (OVX) rats were used as the model, and the impacts of SAC treatment on their serum and urine biochemical indicators were assessed. The biomechanical parameters of these rats were also evaluated. The effects of SAC treatment on the bone of OVX rats was quantified using hematoxylin & eosin staining and alizarin red staining, which reflect calcium deposition. The potential signaling pathway involved in SAC treatment was identified and confirmed through Western blotting, AMP-activated protein kinase (AMPK) inhibitors, and sirtuin-1 (small interfering RNA-SIRT1). RESULTS: The results showed that SAC could ameliorate the serum and urine biochemical metabolism, and the pathological alterations of bone tissue in OVX rats. SAC promoted the osteogenic differentiation of bone marrow mesenchymal cells in OVX rats, one of the key mechanisms for modulation of Runx2, Osx, and OCN, involved in the AMPK/SIRT1 signaling pathway. CONCLUSION: The findings from this study suggest that SAC promotes the osteogenic differentiation of bone marrow mesenchymal stem cells in osteoporotic rats by activating the AMPK/SIRT1 pathway.

Positive medial cortical support versus anatomical reduction for trochanteric hip fractures: Finite element analysis and biomechanical testing.

BACKGROUND AND OBJECTIVES: The anatomical reduction (AR) is usually considered the best option for fractures. Nevertheless, in unstable trochanteric hip fractures (UTHF), previous clinical reports found that the positive medial cortical support (PMCS, an over-reduction technique) attained higher mechanical stability, but this challenging clinical finding still needs experimental validation. METHODS: This study constructed in-silico and biomechanical PMCS and AR models, with the use of the most clinically-representative geometry design of fracture models, the multi-directional design in FE analysis, and the subject-specific (osteoporotic) bone material properties, to make the models better mimic the actual condition in clinical settings. Then multiple performance variables (von-Mises stress, strain, integral axial stiffness, displacement, structural changes, etc.) were assessed to uncover details of integral and regional stability. RESULTS: Among in-silico comparison, PMCS models showed significantly lower maximum displacement than AR models, and the maximum von Mises stress of implants (MVMS-I) was significantly lower in PMCS models than in AR models (highest MVMS-I in -30°-A3-AR of 1055.80 ± 93.37 MPa). Besides, PMCS models had significantly lower maximum von Mises stress along fracture surfaces (MVMS-F) (highest MVMS-F in 30°-A2-AR of 416.40 ± 38.01 MPa). Among biomechanical testing comparison, PMCS models showed significantly lower axial displacement. Significantly lower change of neck-shaft angle (CNSA) was observed in A2-PMCS models. A fair amount of AR models converted into the obvious negative medial cortical support (NMCS) condition, whereas all PMCS models kept the PMCS condition. The results were also validated through comparison to previous clinical data. CONCLUSIONS: The PMCS is superior to the AR in the UTHF surgery. The current study opens up the second thought of the role of over-reduction technique in bone surgery.

Classification and morphology of hyperextension tibial plateau fracture.

PURPOSE: This study was aimed at analyzing the incidence and characteristics of hyperextension tibial plateau fractures (HTPFs) by using a computed tomography (CT)-based "four-column and nine-segment" classification. METHODS: In the coronal plane, HTPFs are divided into four types: pure hyperextension, hyperextension-varus, hyperextension-valgus, and hyperextension-bicondylar. Fractures in the sagittal plane were divided into three types: type 1, pure depression; type 2, cleavage extending to the posterior cortex with no displacement; and type 3, cleavage extending to the posterior cortex with a significant displacement. A retrospective analysis of CT images of the tibial plateau fractures from December 2007 to December 2021 was conducted. Fracture mapping was analyzed and drawn using the new classification system. RESULTS: A total of 136 (10.9%, 136/1253) fractures fulfilled the radiographic criteria for HTPF pattern in 136 knees (53.5 ± 13.3 years). There were 11 knees with pure hyperextension fracture (8.1%), 23 with hyperextension-varus fracture (16.9%), 46 with hyperextension-valgus fracture (33.8%), and 56 with hyperextension-bicondylar fracture (41.2%) in the coronal plane. Furthermore, there were 64 (47.1%), 47 (34.6%), and 25 (18.4%) cases of type 1, type 2, and type 3 fractures, respectively, in the sagittal plane. In the three-dimensional heat map, the fracture lines were mainly located at the anterior rim of the tibial plateau, while the posterior articular surface was rarely involved. CONCLUSIONS: The main manifestations of HTPF are anterior compression and posterior avulsion injury. The CT-based four-column and nine-segment classification system could be used to categorize the injury characteristics of HTPF in the coronal and sagittal planes.

[Study on the Fixation Effect of Plate in the Middle Tibial Fracture Based on Finite Element Analysis].

In this study, tibial shaft fracture has been treated with implants as numerically to investigate the stress behavior and the effect of plate material, position and length under pressure load. Plates of stainless steel, titanium alloy(Ti6Al4V), or CF-PEEK(CF50) were used to fix the tibial shaft comminuted fracture in different location and different working length. The maximum stress, the maximum micromotion of fracture and the stress shielding of cortex bone were analyzed. CF50 is more ideal biomechanical fixation material than traditional metal material for the treatment of tibial shaft comminuted fractures. In the treatment of tibial shaft comminuted fracture, lateral position and with relatively long working length of the plate have the advantages in micromotion, stress and stress shielding rate of the fracture end.

Effect of Fracture Reduction with Different Medial Cortical Support on Stability After Cephalomedullary Nail Fixation of Unstable Pertrochanteric Fractures: A Biomechanical Analysis.

BACKGROUND: This study evaluated the biomechanics of the proximal femoral nail antirotation-II (PFNA-II) in AO/OTA 31A2.2 intertrochanteric fractures based on the fracture reduction quality. METHODS: Unstable intertrochanteric fractures were created according to the AO classification and repaired by proximal femoral nail antirotation-II (PFNA-II) using one of three medial cortical support groups. The specimens were tested using cyclic axial loading. The following parameters were recorded: force and stiffness at failure, maximum vertical and horizontal displacement, neck-shaft angle, and location and patten of failure. RESULTS: In the cyclic loading test, the force at failure in the anatomical reduction (AR) group was greater than that of the positive medial cortical support (PMCS) group (984.22 ± 12.63 vs. 936.95 ± 16.78) N (P < 0.05) and negative medial cortical support (NMCS) group (918.04 ± 28.86) N (P < 0.05). The stiffness in the AR group was 4.77 and 31.9% higher than that in the PMCS group (P > 0.05) and NMCS group (P < 0.05). The maximum vertical displacement was the largest in the NMCS group. The maximum horizontal displacement in the NMCS group was 28.6 and 19.1% larger than that in the AR group (P > 0.05) and PMCS group (P < 0.05). The neck-shaft angle in the NMCS group was smaller than that in the anatomic reduction group (P < 0.05) and positive support group (P < 0.05). CONCLUSION: For the unstable AO/OTA 31A2.2 intertrochanteric fracture, there were significant differences in their mechanical stability among AR, PMCS and NMCS. The NMCS is not recommended during the intraoperative reduction.

Effects of Bone-Plate Material on the Predicted Stresses in the Tibial Shaft Comminuted Fractures: A Finite Element Analysis.

PURPOSE: In this research, low modulus carbon fiber (CF)-reinforced polyetheretherketone composite plates (CF-PEEK plates) were compared with traditional metal plates using finite element analysis to establish a reference for clinical application. MATERIAL AND METHODS: Plates of stainless steel, titanium alloy (Ti6Al4V), or CF-PEEK with different carbon fiber reinforcement ratios (CF30, CF50, and CF60) were used to fix the tibial shaft comminuted fracture. The maximum stress, the maximum displacement of fracture and the stress shielding of cortex bone were analyzed. RESULTS: Under 200 N axial compression, the maximum displacement was measured in the CF30 plate (4.62 mm) and the minimum in the stainless steel plate (0.23 mm). The stress shielding rates of stainless steel, titanium, CF30, CF50, and CF60 plates were 59.4%, 54.4%, 23.75%, 48.75% and 66.25%. Under 700 N axial compression, the internal fixation by the CF30 plate failed. Among the other 4 plates, the maximum displacement was measured in the CF50 plate (2.52 mm) and the minimum in the stainless steel plate (0.78 mm). The stress shielding rate of plates made of stainless steel, titanium, CF50, and CF60 were 57.1%, 52.0%, 48.1%, and 67.8%. CONCLUSIONS: CF50 plates can be safely used in the tibial shaft comminuted fracture. The micromotion in the CF50 and CF60 plate was more beneficial to callus formation and fracture healing. The stress shielding of the cortex bone under the CF50 plate was the lowest. The finite element analysis indicated that the CF-PEEK material is worthy of further study because of its biomechanical advantages.

A novel Patient-Specific Three-Dimensional Printing Template Based on External Fixation for Pelvic Screw Insertion.

PURPOSE: To investigate the clinical effect of novel patient-specific 3D printing templates based on external fixation for pelvic screw insertion compared with the fluoro-navigation technique. MATERIALS AND METHODS: We retrospectively studied 18 pelvic fracture patients from July 2017 to July 2018. For analysis, patients were divided into two groups: the template group (15 screws in 8 patients) and the fluoro-navigation group (22 screws in 10 patients). The screw insertion time, radiation exposure time, and accuracy of the screw insertion as evaluated by postoperative CT scans were analyzed. RESULTS: In the template group, the average screw insertion time (11.5 ± 2.3 min/screw) was significantly 50.6% less than that in the fluoro-navigation group (23.3 ± 3.1 min/screw; P < 0.05). The average time of X-ray exposure in the template group (11.5 ± 3.9 s/screw) was also significantly 39.8% less than in the fluoro-navigation group (19.1 ± 2.5 s/screw; P < 0.05). In the template group, the mean deviation distance and angle between the actual and planned screw position was 2.6 ± 0.2 mm and 2 ± 0.3°. CONCLUSIONS: The patient-specific template based on external fixation can guide the insertion of the pelvic screw accurately and safely while significantly reducing operation and radiation exposure time.

Atrial fibrillation and concomitant left subclavian, axillary and brachial artery embolism after fiberoptic bronchoscopy: A case report.

BACKGROUND: Fiberoptic bronchoscopy has been widely used in the diagnosis and treatment of respiratory diseases. Numerous major and minor complications have been reported following this procedure. The incidence of major postoperative complications is approximately 0.5% and includes respiratory depression, pneumothorax, pulmonary edema, pneumonia, airway obstruction and cardiorespiratory arrest. Minor complications include vasovagal reactions, cardiac arrhythmias, hemorrhage, pneumothorax, aphonia, nausea, vomiting and fever. However, to our knowledge, a case of atrial fibrillation (AF) concomitant with fatal arterial embolism in the upper extremities following diagnostic bronchoscopy has never been reported. CASE SUMMARY: A 70-year-old female patient presented with a history of rheumatic heart disease beginning at 10 years of age and an approximately 10-year history of hypertension. The patient was transferred from the cardiology department to the respiratory department due to recurrent coughing, pneumonia, and fever. She underwent fiberoptic bronchoscopy in the respiratory department. Approximately 2 h after completion of bronchoscopy, she complained of left arm numbness and weakness. Physical examination detected cyanosis of the left upper extremity, grade III weakened limb muscle strength, and undetectable left brachial artery pulsation. Auscultation indicated AF. B-mode ultrasound examination of the blood vessels showed hyperechoic material in the left subclavian, axillary and brachial arteries, and parallel veins. As our hospital has no vascular surgery capability, the patient was transferred to a specialized hospital for emergency thrombectomy that day. A tracking investigation found that the patient's conditions improved after successful thrombectomy. CONCLUSION: Thromboembolism following bronchoscopy is rare, and only a few cases of cerebral air embolism after bronchoscopy have been reported.

Classification and Treatment Strategies of Concomitant Fibular Column Injuries in Tibial Plateau Fractures.

BACKGROUND: About 1/3 of tibial plateau fractures are associated with proximal fibula fractures, but most proximal fibula fractures are often ignored. The aim of this study was to precisely explain the classification and treatment strategies of six injury types of the fibular column associated with tibial plateau fractures. METHODS: Patients with ipsilateral proximal fibula and tibial plateau fractures treated in our hospital were retrospectively reviewed from Aug 2007 to Mar 2020. Two experienced surgeons and two radiologists divided fibular column injury into 6 injury types according to the AO classification and four-column nine-segment classification. The treatment scheme (surgically treated or conservatively treated) was also recorded. RESULTS: In total, 355 proximal fibula fractures were included. Type 2 fibular head fracture was the most common type of injury in 122, and the segregate of superior tibiofibular syndesmosis was the rarest type in 3. In avulsion injury proximal of fibular pattern, the proportion of patients who need surgical intervention is the highest. CONCLUSIONS: Six injury types in the four-column nine-segment classification covered all types of bony and soft tissue injuries of the fibular column and concisely explained the injury mechanism. The classification is helpful for the precise judgement and decision-making of the concomitant fibular column injuries in tibial plateau fractures.

Bone marrow stem cells therapy alleviates vascular injury in a chronic obstructive pulmonary disease­obstructive sleep apnea overlap syndrome rat model.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are highly prevalent potential risk factors for systemic disease. Previous studies have reported that COPD and OSA are major independent risk factors for cardio­ or cerebrovascular diseases. The present study aimed to investigate the role of bone marrow mesenchymal stem cells (BMSCs) on vascular injury in a COPD­OSA overlap syndrome (OS) rat model. Rats were randomly divided into three groups: Sham, OS model and BMSC. BMSC localization in major organs was detected via confocal laser fluorescence microscopy, and the aortic tissue pathological changes and related genes were measured using hematoxylin & eosin and Masson staining. Genes associated with vascular endothelial cell injury, including endothelin 1, vascular cell adhesion molecule 1 and endothelial nitric oxide synthase, were detected via reverse transcription­quantitative PCR and western blotting. Apoptosis of vascular endothelial cells was detected using TUNEL and immunofluorescence assays. The endothelial cell marker CD31 in injured vessels was analyzed via immunohistochemistry. BMSCs migrated into the heart, liver, spleen, lung, kidney, brain and aorta in the OS model. The green fluorescence expression of BMSCs demonstrated the highest level in the lung, followed by the aorta. Aortic tissue had a more severe vascular injury and increased apoptosis in the model group compared with the BMSC group. Vascular endothelial cell apoptosis was decreased in the BMSC group compared with the model group. The findings suggested that BMSCs could repair vascular injury by inhibiting endothelial cell damage and apoptosis. These data provide a theoretical basis for the treatment of cardiovascular diseases caused by OS with BMSCs.

Protective effect of Corynoline on the CFA induced Rheumatoid arthritis via attenuation of oxidative and inflammatory mediators.

Rheumatoid arthritis (RA) is a long-standing and growing autoimmune disease. Therefore, the present study was intended to investigate the effect of Corynoline (COR) on CFA induced rheumatoid arthritis in a rat model. Results suggested that COR causes significant reduction in paw swelling, edema, arthritis score, thymus and spleen indexes and neutrophil infiltration (p < 0.01). Moreover, the levels of inflammatory cytokines (interleukin- 1ß, -6, and -17, and TNF-α) and anti-collagen II-specific immunoglobulins (IgG1 and IgG2a) were decreased significantly (p < 0.01) together with increase in antioxidant enzymes (SOD, CAT, and GSH) (p < 0.01) in COR-treated group in dose-dependent manner. In western blot analysis, COR-treated group showed concentration-dependent reduction of expression of COX-2, 5-LOX and NF-p65 as compared to CFA rats. Moreover, COR-treated group showed mild inflammation of cartilage with fewer cartilage erosion and synovititis with most significant reversal of arthritic features in the rats treated with 30 mg/kg. It has been concluded that, COR alleviates oxidative stress and inflammation in arthritic rats, thus verifying its anti-rheumatoid arthritis property.

A biomechanical matched-pair comparison of two different locking plates for tibial diaphyseal comminuted fracture: carbon fiber-reinforced poly-ether-ether-ketone (CF-PEEK) versus titanium plates.

BACKGROUND: Several methods have been proposed to reduce plate construct stiffness and promote secondary bone healing. In this study, we explored the stiffness and strength of the new carbon fiber-reinforced poly-ether-ether-ketone (CF 50) plate compared with the titanium alloy plate (Ti6Al4V). METHODS: Titanium and CF-PEEK locking plates were tested in a tibial non-osteoporotic diaphyseal comminuted fracture model to determine construct stiffness in axial compression, torsion, and bending. Subsequently, constructs were loaded until construct failure to determine construct strength. RESULTS: Relative to the titanium locking plate, the stiffness of the CF-PEEK locking plate was 6.8% and 30.8% lower in 200 N and 700 N axial compression, respectively (P < 0.05), 64.9% lower in torsion (P < 0.05), and 48.9% lower in bending (P < 0.05). The strength of the CF-PEEK locking plate was only 2.6% lower under axial compression, 7.8% lower in torsion, and 4.8% lower in bending than the titanium locking plate (P > 0.05). CONCLUSIONS: The CF-PEEK locking plate significantly reduced axial, torsion, and bending stiffness compared with the titanium locking plate. Nonetheless, axial, torsional, and bending strength showed only a modest reduction. Considering its other advantages, which include radiolucency and artifact-free imaging, the CF-PEEK locking plate therefore deserves further clinical investigation.

3D mapping and classification of tibial plateau fractures.

AIMS: Tibial plateau fractures (TPFs) are complex injuries around the knee caused by high- or low-energy trauma. In the present study, we aimed to define the distribution and frequency of TPF lines using a 3D mapping technique and analyze the rationalization of divisions employed by frequently used classifications. METHODS: In total, 759 adult patients with 766 affected knees were retrospectively reviewed. The TPF fragments on CT were multiplanar reconstructed, and virtually reduced to match a 3D model of the proximal tibia. 3D heat mapping was subsequently created by graphically superimposing all fracture lines onto a tibia template. RESULTS: The cohort included 405 (53.4%) cases with left knee injuries, 347 (45.7%) cases with right knee injuries, and seven (0.9%) cases with bilateral injuries. On mapping, the hot zones of the fracture lines were mainly concentrated around the anterior cruciate ligament insertion, posterior cruciate ligament insertion, and the inner part of the lateral condyle that extended to the junctional zone between Gerdy's tubercle and the tibial tubercle. Moreover, the cold zones were scattered in the posteromedial fragment, superior tibiofibular syndesmosis, Gerdy's tubercle, and tibial tubercle. TPFs with different Orthopaedic Trauma Association/AO Foundation (OTA/AO) subtypes showed peculiar characteristics. CONCLUSION: TPFs occurred more frequently in the lateral and intermedial column than in the medial column. Fracture lines of tibial plateau occur frequently in the transition zone with marked changes in cortical thickness. According to 3D mapping, the four-column and nine-segment classification had a high degree of matching as compared to the frequently used classifications.Cite this article: Bone Joint Res 2020;9(6):258-267.

Effects of bone marrow­derived mesenchymal stem cell transplantation on chronic obstructive pulmonary disease/obstructive sleep apnea overlap syndrome in rats.

Bone marrow­derived mesenchymal stem cells (BMSCs) possess potential therapeutic properties for treating patients with chronic obstructive pulmonary disease (COPD), which is characterized by emphysema and obstructive sleep apnea (OSA). However, their effects on overlap syndrome (OS) remain unclear. We investigated the potential therapeutic effects and possible mechanisms of BMSC transplantation in OS rats. To generate the OS model in rats, the animals underwent daily exposure to cigarette smoke and intermittent hypoxia. BMSCs were intravenously injected into rats. At 4 weeks post­transplantation, the severity of emphysema was assessed by lung hematoxylin and eosin (H&E) staining. The levels of oxidative stress and the malondialdehyde (MDA) and superoxide dismutase (SOD) contents in serum and lung were detected. The apoptosis of alveolar septal cells was also detected by TUNEL assay. Finally, we determined the expression of CD31 and VWF in lung tissues by an immunohistochemical (IHC) assay. It was found that BMSCs were able to migrate to the injured lung and aorta tissues. In lung tissues, transplanted BMSCs, some of which had differentiated into endotheliocytes, were found in the alveolar walls. The mean linear intercept (MLI) and pathological scores were higher and the mean alveolar number (MAN) was lower in the OS group than these parameters in the control group. These values were significantly reduced in the OS+BMSC group compared to those in the OS group. The MDA content was decreased and SOD activity was increased in the OS+BMSC group compared to those in the OS group. The apoptotic index of alveolar wall cells in the OS group was higher than that in the OS+BMSC group. The expression levels of CD31 and VWF in alveolar wall cells in the OS group were lower than those in the OS+BMSC group. These results indicate that BMSCs may inhibit the progression of emphysema in the OS model by differentiating into endotheliocytes and suppressing the apoptosis of endotheliocytes and oxidative stress. There is a possibility that the release of growth factors and structural support may be a determinant for the regenerative effects observed following treatment with BMSCs.

The pilot-scale preparation of the SA-hGM-CSF bi-functional fusion protein.

The granulocyte-macrophage colony-stimulating factor (GM-CSF) can be used to induce a powerful immune response. Based on the specific binding of biotin and streptavidin, SA-hGM-CSF was anchored on the surface of biotinylated tumor cells, which could enhance the anti-tumor effect of tumor cell vaccines in our previous reports, suggesting it would have potential clinical value. Preparation of the biologically active proteins in large-scale production is the basis of clinical application, however, only a small amount of biologically active protein was obtained according to previous studies. In this study, we researched the effects of various factors on the purification and simultaneous renaturation of SA-hGM-CSF fusion protein by single factor experiment and orthogonal experiment. Here, we developed a viable pilot-scale trial in the fermentation, purification, refolding and freeze-drying of SA-hGM-CSF proteins in order to efficiently obtain more biologically active proteins with high purity, which will lay the foundation for industrial production.

Bone marrow mesenchymal stem cells tune the differentiation of myeloid-derived suppressor cells in bleomycin-induced lung injury.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSC) transfer has been attempted as a therapeutic strategy in experimental lung injury and fibrosis. Reduction of neutrophilic infiltration is one of the mechanisms involved in this effect. However, the mechanisms by which BMSC modulate neutrophil remains unknown. METHODS AND RESULTS: Exposure of mice to bleomycin (BLM) resulted in significant accumulation of cells that express neutrophilic markers Gr-1HighCD11b+Ly-6GHighF4/80-CD115-CD49d-. These cells lacked immunosuppressive activity and could not be defined as myeloid-derived suppressor cells (MDSC). When BMSC were administrated to BLM-treated mice, they tuned the differentiation of Gr-1HighCD11b+ toward Gr-1LowCD11b+ cells. Gr-1LowCD11b+ cells exhibited unsegmented nuclei and expressed F4/80, Ly-6C, CD49d, and CD115 markers. These cells had potent immunosuppressive activity and thus could be defined as monocytic MDSC. As a result of such immunoregulation, BMSC mediated a decrease of pro-inflammatory products and amelioration of lung injury in BLM-treated mice. Further study using antibody array showed increased expression of macrophage colony-stimulating factor (M-CSF) in BMSC-treated mice. Accumulation of Gr-1LowCD11b+ cells in BMSC-treated mice was abrogated in M-CSF neutralizing mice. The beneficial effect of BMSC was independent of the ability of the cells to engraft in lung and in vitro coculture study of BMSC with Gr-1+CD11b+ cells showed that the induction of Gr-1LowCD11b+ cells by BMSC was independent of cell-cell contact. CONCLUSIONS: These results document the generation of Gr-1HighCD11b+ cells in BLM-treated mice, and suggest that BMSC tune the differentiation of Gr-1HighCD11b+ toward Gr-1LowCD11b+ cells and therefore inhibit the progression of BLM-induced lung injury.

Clinical and radiological outcome of Gustilo type III open distal tibial and tibial shaft fractures after staged treatment with posterolateral minimally invasive plate osteosynthesis (MIPO) technique.

OBJECTIVES: To evaluate the methods and the outcomes of Gustilo type III open distal tibial and tibial shaft fractures with severe anterior and medial soft-tissue injuries, treated with posterolateral minimally invasive plate osteosynthesis (MIPO) technique. METHODS: From May 2015 to May 2016, 10 patients with Gustilo type III open distal tibial and tibial shaft fractures with severe anterior and medial soft-tissue injuries (Gustilo-Anderson classification IIIA, 6; IIIB, 4) were treated with staged protocol using posterolateral minimally invasive plate osteosynthesis (MIPO) technique. The initial wound lavage, debridement, and application of a spanning external fixator were performed within 24 h and the mean interval from injury to definitive surgical treatment was 12.8 (range 4-21) days. An additional bone graft was performed in two patients when definitive internal fixation was performed. All patients were followed to union. Postoperative radiographs, postoperative complications, bone union, ankle joint motion, and limb functional outcome information of AOFAS ankle-hindfoot score were recorded. RESULTS: The mean follow-up period was 17.8 (range 12-26) months. The mean interval to bony union was 25.8 (range 20-40) weeks. Bone union was achieved in all cases. There were no complications, such as incision breakdown, deep infection, or impingement of the flexor hallucis longus tendon. The average AOFAS score was 90 (range 83-96). In ten patients, two patients had a superficial wound infection and another one patient showed a 6° varus deformity. CONCLUSIONS: Staged treatment using MIPO technique through a posterolateral approach is a reasonable and safe treatment option for open distal tibial and tibial shaft fractures, especially Gustilo type III with severe anterior and medial soft-tissue injuries. However, it should have a higher level of research evidence in more patients to confirm the safety of the clinical application of this technique.