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Background The timely and accurate diagnosis of infected nonunion is challenging, and there is a need for more efficient biomarkers. Previous studies have shown that fibrinogen plays an important role in mediating inflammation in bacterial infections and, therefore, could be a valuable biomarker for infected nonunion. The purpose of this study was to evaluate and compare the performance of plasma fibrinogen and other traditional blood markers for the diagnosis of infected nonunion. Materials and Methods We retrospectively studied 146 patients who underwent surgery for primary nonunion between January 2018 and January 2020. The patients were divided into those with infected nonunion (n = 55) and those with aseptic nonunion (n = 91). The preoperatively analyzed parameters were plasma fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and white blood cell (WBC) count. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of the biomarkers, and Youden's index was calculated to determine their optimal cut-off values. Results The plasma fibrinogen values were significantly higher (p < 0.001) in the patients with infected nonunion than in those with aseptic nonunion. ROC curve analysis showed that plasma fibrinogen had a high value of area under the curve (0.816), which indicated that it had good diagnostic ability. Further, at the optimal threshold value of 2.75 g/L, plasma fibrinogen had the highest sensitivity (78.2%; 95% CI = 64.6-87.8) and good specificity (82.4%; 95% CI, 72.7-89.3). Conclusion In comparison to the traditional markers of infection, plasma fibrinogen showed good diagnostic ability for the detection of infected nonunion. It may have potential as a practical and cost-efficient biomarker for the diagnosis of infected nonunion.

Background: Previous studies have been conducted to evaluate the diagnostic values of platelet indices in some infectious diseases. However, the predictive values of platelet indices for infected nonunion have not yet been evaluated. The purpose of this study was to assess the diagnostic performance of platelet indices in infected nonunion.Methods: This study was performed retrospectively on patients who underwent primary fracture nonunion revision surgeries from January 2016 to December 2021. 297 patients with 96 infected nonunion (group A) and 201 aseptic nonunion (group B) who met our inclusion criteria were included. Receiver Operator Characteristic (ROC) curve, sensitivity, and specificity of preoperative clinical parameters were analyzed and compared. Results: The demographic characteristics were similar and had no significant difference between two groups. Compared with group B, the levels of WBC, CRP, ESR, plasma fibrinogen, plasma D-dimer, PC, PCT, and PC/MPV were significantly higher, but the levels of MPV and PDW were significantly lower in group A (p < 0.05). ROC curves showed that PC/MPV and plasma fibrinogen outperformed the other coagulation indicators, with areas under the curve of 0.801 and 0.807, respectively. The multiple tests of ESR, plasma fibrinogen and PC/MPV had good sensitivity and specificity for the diagnosis of infected nonunion, and the diagnostic values of PC/MP was better than ESR and plasma fibrinogen in the subgroup. Conclusions: Our study demonstrates that the diagnostic performance of coagulation indicators, plasma fibrinogen and PC/MPV, are high and they can increase the accuracy of infected nonunion diagnosis.

Background Volar locking plating remains a popular method for the surgical management of distal radius fractures. Dorsal metaphyseal comminution (DMC) is a common fracture pattern which weakens the stability during fracture fixation. In this study, we aimed to compare the radiographic and functional outcome of the intra- and extra-articular distal radius fractures with DMC following single volar locking plate fixation. Materials and methods Patients suffered from a distal radius fracture with DMC were reviewed in the clinical database of the authors’ institution between Jan 2016 and Jan 2020. The included patients were classified into the extra-articular (A3) group or the intra-articular (C2 and C3) group according to the AO/OTA system. The radiological parameters, wrist range of motion, and functional outcomes were evaluated following open reduction and volar locking plate fixation. Results A total of 130 patients were included in this study with a mean follow-up length of 17.2 months. Compared with the A3 fracture group, no significant fracture re-displacement or reduced wrist ROMs was observed in the C2 fractures after 12-month’s follow-up. However, significantly decreased volar tilt (P = 0.003) as well as the extension/flexion ROMs were observed in the C3 fractures comparing to the A3 fractures. Most of the patients achieved an excellent (n = 75) or good (n = 51) Gartland and Werley wrist score. Four patients with C3 fractures resulted in a fair functional outcome due to a significant loss of volar tilt during follow-up. Conclusions The single volar locking plate fixation provided sufficient stability for distal radius fractures with DMC, and resulted in similar radiological and functional outcomes in the intra-articular distal radius fractures with a simple articular component (C2 fractures) as those in the extra-articular fractures. Considering the intra-articular fractures with multifragmentary articular component (C3 fracture), despite of the subsequent loss of volar tilt, the majority of the patients achieved good to excellent wrist function following single volar locking plating. Trial registration This study has been registered on the ClinicalTrials.gov.

Background: Volar locking plating remains a popular method for the surgical management of distal radius fractures. Dorsal metaphyseal comminution (DMC) is a common fracture pattern which weakens the stability during fracture fixation. In this study, we aimed to compare the radiographic and functional outcome of the intra- and extra-articular distal radius fractures with DMC following volar locking plate fixation.Materials and methods: Patients suffered from a distal radius fracture with DMC were reviewed in the clinical database of the authors’ institution between Jan 2016 and Jan 2020. The included patients were classified into the extra-articular (A3) group or the intra-articular (C2 and C3) group according to the AO/OTA system. The radiological parameters, wrist range of motion, and functional outcomes were evaluated following open reduction and volar locking plate fixation.Results: A total of 130 patients were included in this study with a mean follow-up length of 17.2 months. Compared with the A3 fracture group, no significant fracture re-displacement or reduced wrist ROMs was observed in the C2 fractures after 12-month’s follow-up. However, significantly decreased volar tilt (P = 0.003) as well as the extension/flexion ROMs were observed in the C3 fractures comparing to the A3 fractures. Most of the patients achieved an excellent (n = 75) or good (n = 51) Gartland and Werley wrist score. Four patients with C3 fractures resulted in a fair functional outcome due to a significant loss of volar tilt during follow-up.Conclusions: The volar locking plate fixation provided sufficient stability for distal radius fractures with DMC, and resulted in similar radiological and functional outcomes in the intra-articular distal radius fractures with a simple articular component (C2 fractures) as those in the extra-articular fractures. Considering the intra-articular fractures with multifragmentary articular component (C3 fracture), despite of the subsequent loss of volar tilt, the majority of the patients achieved good to excellent wrist function following volar locking plating.Trial registration: Not applicable because the design of the study is retrospective.

Purpose Infected nonunion after open reduction internal fixation (ORIF) is a serious complication. The aim of this study was to evaluate the usefulness of serum D-dimer for preoperative diagnosis of infected nonunion. Patients and methods Patients undergoing debridement and external fixation for infected nonunion (n=32) and replacement of internal fixation due to aseptic failure (n=34) were enrolled and compared in this retrospective study. The optimum cutoff value of D-dimer for identification of infected nonunion was determined by calculating the Youden J statistic. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of four preoperative laboratory parameters-serum D-dimer level, white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)-for diagnosis of infected nonunion were compared. Results Serum D-dimer level was significantly higher in patients with infected nonunion than in patients with aseptic nonunion: 2.62 mg/mL (range, 0.13-11.90 mg/mL) vs 0.35 mg/mL (range, 0.07-6.46 mg/mL; p 1.70 mg/mL) were 75.0% (95% CI: 56.25-87.87) and 91.2% (95% CI: 75.19-97.69). Conclusions Serum D-dimer level may be useful for preoperative prediction of infected nonunion in patients after ORIF.

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.

Brain-derived neurotrophic factor (BDNF) has been reported to participate in fracture healing, whereas the mechanism is still unclear. Since osteoblast migration is important for fracture healing, investigating effects of BDNF on osteoblasts migration may help to reveal its mechanism. Here, MC3T3-E1 cells were used in vitro while closed femur fracture mice were applied in vivo. Cells migration was assessed with Transwell assay. The protein expression was analysed by immunoblotting. X-ray and Micro-CT were performed at different time after fracture. Our results showed that BDNF promoted MC3T3-E1 cells migration, integrin β1 expression and ERK1/2 and AKT phosphorylation. K252a, a specific inhibitor for TrkB, suppressed BDNF-induced migration, integrin β1 expression and activation of ERK1/2 and AKT. PD98059 (an ERK1/2 inhibitor) and LY294002 (an AKT inhibitor) both inhibited BDNF-induced migration and integrin β1 expression while integrin β1 blocking antibody only suppressed cell migration. X-ray and Micro-CT analyses showed that the adenoviral carried integrin β1 shRNA group had slower fracture healing at 7 and 21 days, but not 35 days compared to the control group. Thus, we proposed that BDNF stimulated MC3T3-E1 cells migration by up-regulating integrin β1 via TrkB mediated ERK1/2 and AKT signalling, and this may help to enhance the fracture healing.

Brain‑derived neurotrophic factor (BDNF), a member of the neurotropic family, is expressed in osteoblast‑like cells of a fracture callus, however, its role in fracture healing remains to be fully elucidated. Osteoblasts isolated from Sprague Dawley rats were stimulated by BDNF in a dose‑ and time‑dependent manner. Immunoblotting and immunofluorescence was used to detect the expression and distribution of targeted proteins. The concentration of vascular endothelial growth factor (VEGF) released in medium was determined using an ELISA. PD98059 and K252a were used to investigate the signaling pathways that may be involved. The present study demonstrated that BDNF was involved in fracture repair by controlling the expression and secretion of VEGF from osteoblasts, which predominantly drives angiogenesis during fracture healing. Tropomyosin‑related kinase B (TrkB), the specific receptor of BDNF, was shown to be expressed at high levels in the osteoblasts. Following BDNF stimulation, TrkB and extracellular signal‑regulated kinase 1/2 (ERK1/2) were rapidly activated. The inhibition of TrkB by K252a decreased the expression and secretion of VEGF, and suppressed the phosphorylation level of ERK1/2. PD98059, an antagonist of ERK1/2, elicited the same effects on VEGF from the BDNF‑stimulated osteoblasts, however, it did not affect the phosphorylation of TrkB. In conclusion, during fracture healing, BDNF was found to stimulate the expression and secretion of VEGF from osteoblasts via the TrkB/ERK1/2 signaling pathway.

Background Management of segmental bone defects is a challenge for orthopedic surgeons. The most commonly used methods are the free vascularized bone transfer, bone transport, and induced membrane technique. However, none of these methods is fully suitable for some cases. Case Report A 41-year-old woman was presented with a Gustilo IIIA left distal femoral fracture (AO 32-C and 33-C) with bone loss. The length of femoral bone loss was 15 cm (12 cm medially and 18 cm laterally). After thorough debridement, the intercondylar fracture was fixed with K-wires, and an external fixator bridged the knee joint. The bone defect was filled with antibiotic cement spacer. After 2 months, the external fixator was removed; the femur was fixed by internal fixation. The induced membrane was opened and the antibiotic cement removed. A free vascularized fibular graft of 18 cm was transferred and the residual bony defect was filled with morcellized cancellous autologous bone graft. At 6 months postoperatively, the graft appeared completely integrated at X-ray and the patient could walk without brace at 11 months postoperatively. Conclusion The distal femur is a large-caliber bone and is under severe stress during weight bearing. When only the induced membrane technique is used, the autologous bone graft seems not enough for the present case. On the other hand, single free vascularized fibular graft also could not provide sufficient strength to allow weight bearing despite significant hypertrophy. Therefore, the induced membrane technique combined with free vascularized fibular graft used in the present case may be an alternative.

Background Osteomyelitis is a challenge for orthopedic surgeons due to its protracted treatment process. Microwaves (MWs) can increase blood perfusion due to their thermal effect. Furthermore, MWs demonstrated significant bactericidal effects in vitro. In the present study, we assumed that the application of a 2450-MHz-frequency MW together with systemic antibiotic treatment would provide synergy for the treatment of acute osteomyelitis. Methods The medullary cavity of the right tibia was inoculated with 107 CFU of methicillin-sensitive Staphylococcus aureus (MSSA-ATCC 29213) in 40 rats, and the rats were randomly divided into four groups according to treatment: group I, saline (control); group II, saline + MW therapy; group III, systemic cefuroxime; and group IV, systemic cefuroxime + MW therapy. MWs were applied for 20 min per day to the infected limbs, and all rats were sacrificed on the 7th day. The severity of tibial osteomyelitis was assessed by quantitative culture analysis. Results Bacterial counts in groups III and IV were significantly reduced compared with those in the control (p = 0.001 and < 0.001, respectively). Furthermore, significant differences were detected between groups III and IV (p = 0.033). However, the difference between groups I and II was nonsignificant (p = 0.287). Conclusion Our experimental model suggests that MW therapy provides a significant synergy for systemic antibiotic treatment. However, further clinical trials are required to safely use this treatment modality in patients.

Zitao Zhang,1 Yuanhui Ji,2 Zhen Wang,1 Xusheng Qiu,1 Yixin Chen1 1Department of Orthopedics, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China; 2Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China Objectives: Deep surgical site infection (DSSI) is one of the most serious complications after open induction internal fixation (ORIF) for traumatic limb fractures. In this study, we aimed to investigate the diagnostic role of platelet indices (platelet count [PLT], mean platelet volume [MPV], and platelet distribution width [PDW]) in DSSI.Patients and methods: Data obtained between January 2011 and December 2017 in The Affiliated Drum Tower Hospital of Nanjing University Medical School from cases (n=29) with DSSI and fracture control subjects (n=29) matched for age, gender, and fracture type were analyzed. The white blood cell (WBC) count, neutrophil count, neutrophil percentage, and platelet indices from blood samples were compared between case and control groups. In addition, the cutoff value, sensitivity, and specificity were calculated by receiver-operating characteristic (ROC) curves.Results: No significant differences were detected in demographic features, the WBC count, neutrophil count, neutrophil percentage, and MPV values between two groups (P>0.05). The PLT values were significantly higher in the case group than in the control group (303.00±139.27 vs 196.10±59.61 [109/μL], P=0.001). The PDW values of the case and control groups were 11.77±2.71 and 13.19±2.39%, respectively, and were significantly lower in the case group (P=0.001). ROC curve analysis suggested a cutoff point for PLT as 215.50 (109/μL, larger values indicate pathology) for the diagnosis of DSSI with the sensitivity and specificity of 79.3 and 72.4%, respectively. For PDW, the cutoff point was 10.35% (smaller values indicate patients) for the diagnosis of DSSI with the sensitivity and specificity of 37.9 and 96.6%, respectively.Conclusion: Our results suggest that PDW combined with PLT can be used as an important additional test for the diagnosis of DSSI after ORIF for traumatic limb fractures, thus reducing the cost and loss of time. Keywords: surgical site infection, internal fracture fixation, fracture, platelet count, platelet function test&nbsp

Zhen Wang, Ji Xiao, Zitao Zhang, Xusheng Qiu, Yixin Chen Department of Orthopedics, Drum Tower Hospital Clinical College of Nanjing University, Nanjing, China Background: Preoperative deep vein thrombosis (DVT) is a common complication in patients with hip fractures. Chronic kidney disease (CKD) as a frequent comorbidity in middle-aged and elderly patients with hip fractures is known to promote a proinflammatory and prothrombotic state. We aimed to identify whether CKD can increase the risk of DVT in middle-aged and elderly patients with hip fractures, as well as identify other risk factors.Patients and methods: We retrospectively studied 248 middle-aged and elderly patients with hip fractures who were admitted to our hospital from January 2016 to June 2017, meeting all the inclusion criteria. Doppler ultrasonography was used to diagnose DVT. Patients with CKD were classified into five stages according to the Kidney Diseases Outcomes Quality Initiative. We identified whether CKD could increase the occurrence of preoperative DVT in middle-aged and elderly patients with hip fractures and further investigated other independent risk factors for preoperative DVT by using univariate and multivariate analyses.Results: The mean estimated glomerular filtration rate was 125.7±41.4 mL/min/1.73 m2. Briefly, 82.3% (n=204) had been diagnosed with normal kidney function, 11.7% (n=29) with mildly decreased kidney function, and 6.0% (n=15) with stage 3 and 4 CKD. In addition, of the 248 patients, 11.7% (n=29) developed DVT before surgery. Independent predictors of preoperative DVT identified by multivariate analyses were age, prolonged bedridden time, increased levels of fibrinogen, and lower estimated glomerular filtration rate.Conclusion: CKD can increase the risk rate of preoperative DVT in middle-aged and elderly patients with hip fractures. Additionally, age, prolonged bedridden time, and increased levels of fibrinogen were also independent risk factors for preoperative DVT in these patients. We should take preventive measures for these patients with risk factors in order to reduce the incidence of preoperative DVT. Keywords: CKD, preoperative DVT, hip fractures, middle-aged and elderly patients

Background Cement spacers (Masquelet technique) have traditionally been used for the treatment of segmental bone defects. However, no reports have used cement spacers for the treatment of small/partial segmental bone defects associated with osteomyelitis and compared the outcomes with cement beads. Methods We retrospectively analysed 40 patients with post-traumatic osteomyelitis of the tibia who underwent treatment, which was performed in two stages. In the first stage, thorough debridement was performed, and bone defects were filled with either antibiotic-impregnated cement beads (bead group, 18 patients) or spacers (spacer group, 22 patients). In the second stage, the cement beads or spacers were removed (for the spacer group, the induced membrane formed by the spacer was preserved) and the bone defects were filled with cancellous autografts. Results All patients in the bead group had small/partial segmental bone defects after debridement, while 3 patients in the spacer group had large/segmental bone defects. The mean volume of bone defects of the spacer group (40.4 cm 3 ) was significantly larger than that of the bead group (32.4 cm 3 ). The infection control rate (88.9%,16/18 vs 90.9%, 20/22), bone healing time (8.5 months vs 7.5 months) and complication rates (22.2%, 4/18 vs 27.2%, 6/22) were comparable between bead group and spacer group. Conclusion The results of this study suggest that cement spacers may have an infection control rate comparable to cement beads in the treatment of bone defects associated with post-traumatic osteomyelitis. Furthermore, cement spacers could be used for the reconstruction of small/partial segmental bone defects as well as for large/segmental bone defects, whereas cement beads were not suitable for the reconstruction of large/segmental bone defects.

To explore whether the suppressor of cytokine signaling-3 (SOCS3) gene polymorphisms are associated with the susceptibility and abnormal growth pattern of adolescent idiopathic scoliosis (AIS).Three hundred and ninety eight AIS girls aged 10-18 years old were enrolled, and 367 age-matched healthy girls were recruited as controls. Only patients who had Cobb angles larger than 20º were included in this study. Anthropometric parameters including body weight, height, and body mass index (BMI) were measured for AIS girls. Rs4969198 was selected as tagSNP to cover all of the related polymorphisms on SOCS3. Genotyping was performed using PCR-based Invader assay with the probe sets designed and synthesized by third wave. The genotyping results were read with an ABI PRISM7900HT sequence detection system (Applied Biosystems, Foster City, CA). A subgroup of 322 skeletally mature AIS patients who did not received bracing or any other conservative treatment previously were analyzed to define the contribution of rs4969168 on curve severity, body height, body weight, and BMI.Rs4969198 was successfully genotyped. No significant difference of genotype frequencies from the Hardy-Weinberg equilibrium (HWE) test was noted for the AIS patients or the normal controls. Neither the genotype nor the allele frequencies of rs49691968 were significantly different between the AIS patients and the normal controls. Rs4969168 was not found to be associated with age, curve severity of scoliosis, and body height. AIS patients with AA genotype had significantly higher body weight and BMI than the patients with AG and GG genotype (P = 0.014).The SOCS3 gene polymorphisms are not associated with the occurrence of AIS, but the gene polymorphism (rs4969168) is associated with abnormal growth pattern of AIS, indicating that SOCS3 gene might be a disease-modifying gene of AIS.

To investigate the genotype of COL2A1 in a three-generation spondyloepiphyseal dysplasia congenita (SEDC) family. Five affected individuals from a Chinese SEDC family were enrolled in the study. All patients underwent thorough physical and radiographic examinations. DNA samples of the affected patients and the healthy controls were collected with the informed consent obtained from each participant. Two short tandem repeat polymorphic markers flanking COL2A1 gene region were detected to determine the haplotype of each patient. Subsequently, sequence analysis was performed in COL2A1 gene to identify potential genetic mutation. Haplotype analysis showed that the same disease-associated haplotype was segregated through the whole pedigree. A maximum LOD score of 1.5 was obtained with D12S85 and D12S368. DNA sequence analysis revealed a c.1636 G/A transition in exon 25 of the COL2A1 gene, which converted the codon GGT for glycine at position 546 to AGT, a codon for serine. The patients were all heterozygous for the mutation G546S, which was absent in either of the unaffected family members or of the normal individuals. This is the first familial report of G546S mutation in the COL2A1 gene that results in SEDC. Although great achievements have been made in the recognition of the mutation spectrum, more intensive studies are warranted to further identify correlations between genotype and phenotype.

The pelvis as the biomechanical foundation of spine, plays an important role in the balance of the stance and gait through the multi-link spinal-pelvic system. If the pelvic axial rotation (PAR) exists in adolescent idiopathic scoliosis (AIS) patients, it should theoretically have some effects on the body balance.To explore the probable effects of preoperative PAR on the spinal balance in coronal plane in AIS patients with main thoracolumbar/lumbar (TL/L) curve after posterior spinal instrumentation.Thirty-eight AIS patients (age: 15 ± 1.5 years) with main TL/L curve (51° ± 6.2°) were recruited retrospectively into this study. The mean follow-up period was 27 months (24-36 months). Standing full spine posteroanterior radiographs were taken preoperatively, 3 month and 1 year postoperatively, and at last follow-up. The convex/concave ratio (CV/CC ratio) of the anterior superior iliac spine laterally and the inferior ilium at the sacroiliac joint medially was measured on posteroanterior radiographs. According to the preoperative CV/CC ratios, the patients were divided into two groups: normal group (N-group: 0.95 ≤ CV/CC ≤ 1.05); and the asymmetrical group (A-group: CV/CC0.95, or1.05).In all the patients, the 3-month-postoperative CV/CC ratio (1.026 ± 0.087) was significantly different from the preoperative CV/CC ratio (0.969 ± 0.095, P0.001), indicating that the pelvis had rotated in the opposite direction of the corrective derotation load applied to the TL/L spine after surgery. No significant change was found in the CV/CC ratio from 3-month-postoperative to the last follow-up (1.013 ± 0.103, P0.05). There was no significant difference in the demographic, phenotypic, and treatment variables between the N- (n = 16) and A-groups (n = 22) (P0.05). However, more coronal decompensation occurred in the A-group after surgery (36.4 vs. 0.0 %, P = 0.013): two patients having trunk translation, three having lower instrumented vertebra (LIV) translation, and one having LIV tilt; meanwhile, one patient having both LIV translation and LIV tilt, and one having both trunk translation and LIV tilt.The present study confirmed the existence of PAR in AIS patients, and indicated that the pelvis would experience an active rebalancing in the transverse plane within 3 months after spinal correction, and since then, its position would remain stable. Moreover, TL/L-AIS patients with preoperative asymmetrical PAR probably had greater risk of coronal decompensation postoperatively.

Background. A reemergence of interest in clavicle anatomy was prompted because of the advocacy for operative treatment of midshaft clavicle fractures. Several anatomical studies of the clavicle have been performed in western population. However, there was no anatomical study of clavicle in Chinese population.Patients and Methods. 52 patients were included in the present study. Three-dimensional reconstructions of the clavicles were generated. The length of the clavicle, the widths and thicknesses of the clavicle, curvatures of the clavicle, the areas of the intramedullary canal, and sectional areas of the clavicle were measured. All the measurements were compared between genders and two sides.Results. The mean length of the clavicles was144.2±12.0 mm. Clavicles in males were longer, wider, and thicker than in females; also males have different curvatures in both planes compared with females. The men’s intramedullary canals and sectional areas of the clavicle were larger than those of women. No significant difference between the sides was found for all the measurements.Conclusion. This study provided an anatomical data of the clavicle in a Chinese population. These clavicle dimensions can be applied to the modifications of the contemporary clavicle plate or a new development for the Chinese population.

To investigate whether rs11190870 near LBX1 correlates with the susceptibility or curve progression of adolescent idiopathic scoliosis (AIS) in a Han Chinese population.A total of 949 AIS patients and 976 age-matched healthy controls were recruited. All the subjects were genotyped using the PCR-based invader assay. Case-control study and case-only study were performed to define the contribution of rs11190870 to predisposition and curve severity of AIS. Additionally, we further conducted a meta-analysis of the study findings together with those of previously reported studies.A significant association of rs11190870 with AIS was observed in the Han Chinese population (P = 1.8 × 10(-9); odd ratio = 1.51; 95 % confidence interval = 1.33-1.71), and AIS patients with TT genotype had a larger Cobb angle than those with TC or CC genotype (P = 0.005). The meta-analysis confirmed that the positive association of this SNP with AIS in the East Asian population.The SNP rs11190870 near LBX1 is associated with both susceptibility and curve progression of AIS.

Standing posterior–anterior (PA) radiographs from our clinical practice show that the concave and convex ilia are not always symmetrical in patients with adolescent idiopathic scoliosis (AIS). Transverse pelvic rotation may explain this observation, or pelvic asymmetry may be responsible. The present study investigated pelvic symmetry by examining the volume and linear measurements of the two hipbones in patients with AIS. Forty-two female patients with AIS were recruited for the study. Standing PA radiographs (covering the thoracic and lumbar spinal regions and the entire pelvis), CT scans and 3D reconstructions of the pelvis were obtained for all subjects. The concave/convex ratio of the inferior ilium at the sacroiliac joint medially (SI) and the anterior superior iliac spine laterally (ASIS) were measured on PA radiographs. Hipbone volumes and several distortion and abduction parameters were measured by post-processing software. The concave/convex ratio of SI–ASIS on PA radiographs was 0.97, which was significantly 0.05). Furthermore, all distortion and abduction parameters were comparable between the convex and concave sides. Therefore, the present study showed that there was no pelvic asymmetry in patients with AIS, although the concave/convex ratio of SI–ASIS on PA radiographs was significantly

Objective: To investigate the efficiency and safety of articulating spacer for severe infection after total knee arthroplasty (TKA) in patients with medical comorbidities and local sinus tracts. Methods: Between January 2002 and March 2008, ten consecutive patients with late stage infected TKA complicated by local sinus tracts and medical comorbidities, were treated in our hospital by delayed two-stage reimplantation using articulating spacers. The modified Hospital for Special Surgery (HSS) knee scoring system was used to evaluate the results. Results: One patient underwent knee fusion as the infection could not be controlled after first-stage surgery. Infection was eradicated in the other nine patients. The mean follow-up was 50 months (range, 24–90 months), no recurrent infection developing in these nine patients. The average modified HSS score was 48 points (range, 32–63) before the first-stage surgery, 79 points (range, 62–91) at the end of the spacer period, and 89 points (range, 74–95) at the latest follow-up, and the good to excellent rate was 0%, 80% and 100%, respectively. The average range of motion had improved to 8° to 93° at the end of the spacer period, and 3° to 110° at the last follow-up, compared to 13° to 70° preoperatively. Conclusion: Delayed two-stage reimplantation using an articulating spacer is effective for treating infected TKA in patients with medical comorbidities or local sinuses.

Sufficient drainage is very important for preventing wound complications after open reduction and internal fixation (ORIF) of calcaneal fractures. However, the drainage amount varies among patients. The objective of this study was to identify factors associated with increased postoperative drainage after ORIF of calcaneal fractures.A retrospective study including 87 patients with 92 calcaneal fractures in our hospital was performed. Patients were divided into 2 groups based on whether they had increased drainage, which was defined as a total drainage of ≥340 mL (50th percentile). We gathered the following data on each patient: age; sex; smoking history; body mass index (BMI); American Society of Anesthesiologists (ASA) classification; fracture type; the time from injury to surgery; operative time; bone grafting; preoperative labs including prothrombin time (PT), activated partial thromboplastin time (APTT), hematocrit, and D-dimer level; and histories for hypertension, diabetes, and heart disease. Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors associated with increased drainage.Total drainage ranged from 105 to 1185 mL, and the average drainage for this cohort was 393.6 ± 232.4 mL (mean ± standard deviation). 57.6% (n = 53) of patients had increased drainage. Smoking history, Sanders type, operative time, and bone grafting were significantly associated with increased drainage on univariate analysis. Multivariate logistic regression analysis then demonstrated that active smoking and higher Sanders type were independent risk factors for increased drainage.Patients with calcaneal fractures who smoked or had a higher level of Sanders type had a higher risk of increased postoperative drainage. Therefore, we suggest that active precautions be taken for these patients to reduce the rate of postoperative wound complications.

Shoulder balance is one of the key components to the body deformity in adolescent idiopathic scoliosis (AIS) patients with double thoracic curve and shoulder cosmesis plays an important role in patients' satisfaction of surgical outcomes. Up to now, only radiographic parameters were used to evaluate the shoulder balance in literatures; no corresponding cosmetic parameters have been developed to evaluate the cosmetic shoulder balance. Meanwhile, we often confronted that perfect radiographic shoulder balance was achieved, but the patients complained about the residual cosmetic deformity. This phenomenon implied that discrepancy may exist between radiographic shoulder balance and cosmetic shoulder balance. The present study was carried out to investigate the correlation between radiographic and clinical cosmetic shoulder balance in AIS patients with double thoracic curve. Thirty-four AIS patients were recruited for this study. All the patients had a double thoracic curve. Six cosmetic parameters--inner shoulder height (SHi), outer shoulder height (SHo), shoulder area index 1 (SAI1), shoulder area index 2 (SAI2), shoulder angle (alpha1) and axilla angle (alpha2) were developed and measured on the standing photographs. Also, seven radiographic parameters--T1 tilting (T1), first rib angle (FRA), clavicle angle (CA), coracoid process height (CPH), clavicle-rib cage intersection (CRCI), first rib-clavicle height (FRCH), trapezius length (TL) were measured on the standing posterior-anterior radiographs. Correlation analysis was made between cosmetic parameters and radiographic parameters. SHi was found to be significantly correlated with T1, FRA, CA, CPH, CRCI (P0.05), among which FRA had the highest correlation coefficient. SHo was found to be significantly correlated with T1, FRA, CA, CPH, CRCI, FRCH (P0.05), among which CRCI had the highest correlation coefficient. However, none of the correlation coefficient was greater than 0.8. The correlation coefficients between radiographic parameters and SAI1, SAI2, alpha1, alpha2 were also below 0.8 that were similar with SH. The results indicated that radiographic parameters could only partially reflect the shoulder cosmetic appearances. However, none of the existing parameters can accurately reflect the shoulder cosmetic appearance. As cosmesis is critical important to patients' satisfaction, spine surgeons should pay more attention to the cosmetic shoulder balance rather than radiographic shoulder balance.

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined=2.95 × 10−9), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined=7.59 × 10−13) and 18q21.33 near BCL-2 (rs4940576, Pcombined=2.22 × 10−12). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10−37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS., The authors perform a genome-wide association study of adolescent idiopathic scoliosis patients of Han Chinese descent, and identify 3 new loci for disease susceptibility.

Background Osteomyelitis is a challenge for orthopaedic surgeons. There is a lack of scientific evidence to guide treatment. The purpose of this study was to report the clinical outcome of unplanned retention of antibiotic-impregnated cement spacer (ACS) in the management of osteomyelitis. Methods Eight patients (7 with tibial infections and 1 with a calcaneal infection) with osteomyelitis received radical debridement and insertion of an ACS into the bone defect as the definitive management. The mean follow-up period was 2 years (6 months to 4 years). All of these patients had a cement spacer in place. Results No patient exhibited radiographic evidence of excessive bone loss. The patients reported no or occasional mild pain and exhibited complete weight-bearing abilities, with the exception of one patient who required a crutch because of a spinal cord injury. Signs of recurrence of the osteomyelitis were not noted in any of the patients, and no fractures occurred at last follow-up. Conclusion Our study suggests that a proportion of patients with unplanned retention of ACS appear to function well without necessarily requiring further surgical intervention.

Background A previous genome-wide association study (GWAS) suggested a strong association between the single nucleotide polymorphism (SNP) rs10510181 in the proximity of the gene encoding a cell adhesion molecule with homology to L1CAM (CHL1) and adolescent idiopathic scoliosis (AIS) in Caucasians. To clarify the role of CHL1 in the etiopathogenesis of AIS, we performed a case-control replication study in a Han Chinese population. Methods Five hundred female AIS patients between 10 and 18 years of age, as well as 500 age- and sex-matched controls were included. This study was conducted as a 2-stage case-control analysis: initial screening for the association between AIS and SNPs in and around the CHL1 gene (186 cases and 169 controls) followed by a confirmation test (314 cases and 331 controls). rs10510181 and 4 SNPs (rs2055314, rs331894, rs2272522, and rs2272524) in the CHL1 gene were selected for genotyping. Results Putative associations were shown between AIS and rs10510181, rs2055314, and rs2272522 in stage I. However, the associations were not confirmed in stage II. For rs10510181, the genotype frequencies were GG 28.8%, GA 46.2%, and AA 25.0% in AIS patients and GG 29.8%, GA 48.8%, and AA 21.4% in controls. No significant difference was found in genotype distribution between cases and controls (P = 0.39). Similarly, the genotype and allele distribution were comparable between case and control for rs2055314 and rs2272522. Conclusions There was no statistical association between polymorphisms of the CHL1 gene and idiopathic scoliosis in a Chinese population.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P=4.00 × 10(-8), odds ratio [OR]=2.05). Its association was replicated in a Chinese population (combined P=6.43 × 10(-12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

Background Although the pathogenesis of adolescent idiopathic scoliosis (AIS) remains controversial, genetic factors are thought to play key roles in the development of AIS. In a recent genome-wide association study, a polymorphism in the interleukin-17 receptor C (IL-17RC) gene was reported to be associated with the susceptibility to AIS, implicating IL-17RC as a novel predisposing gene for AIS. However, as this association has not been replicated in other populations, its global applicability remains unclear. Methods A total of 529 Chinese girls with AIS and 512 healthy age-matched controls were recruited in this case–control study from June 2007 to December 2009. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the genotype of the single-nucleotide polymorphism (SNP) rs708567 in the IL-17RC gene. Case–control and case-only studies were performed to determine the association between the IL-17RC gene polymorphism and the susceptibility to and curve severity of AIS. Results The GG genotype and G allele frequencies were significantly higher in the AIS patients than in the controls (χ 2 test: P = 0.023 and 0.028, respectively). The risk for the GG genotype is 1.550-fold (95% CI: 1.062 - 2.261) higher than the AG genotype, and the risk for the G allele is 1.507-fold (95% CI: 1.046 - 2.172) higher than the A allele. Additionally, a subgroup of skeletally mature AIS patients (n = 241) who carried the GG genotype showed a significantly higher mean maximum Cobb angle than those carrying the AG genotype (36.01 ± 13.12° vs. 28.92 ± 7.43°, P = 0.007). Conclusions This study confirms the significant association between the IL-17RC gene polymorphism and the susceptibility to and curve severity of AIS in a Chinese Han population, suggesting that the IL-17RC gene is an AIS-predisposing gene in Chinese Han population.

Objective: To investigate the efficiency and safety of articulating spacer for severe infection after total knee arthroplasty (TKA) in patients with medical comorbidities and local sinus tracts. Methods: Between January 2002 and March 2008, ten consecutive patients with late stage infected TKA complicated by local sinus tracts and medical comorbidities, were treated in our hospital by delayed two‐stage reimplantation using articulating spacers. The modified Hospital for Special Surgery (HSS) knee scoring system was used to evaluate the results. Results: One patient underwent knee fusion as the infection could not be controlled after first‐stage surgery. Infection was eradicated in the other nine patients. The mean follow‐up was 50 months (range, 24–90 months), no recurrent infection developing in these nine patients. The average modified HSS score was 48 points (range, 32–63) before the first‐stage surgery, 79 points (range, 62–91) at the end of the spacer period, and 89 points (range, 74–95) at the latest follow‐up, and the good to excellent rate was 0%, 80% and 100%, respectively. The average range of motion had improved to 8° to 93° at the end of the spacer period, and 3° to 110° at the last follow‐up, compared to 13° to 70° preoperatively. Conclusion: Delayed two‐stage reimplantation using an articulating spacer is effective for treating infected TKA in patients with medical comorbidities or local sinuses.

To investigate whether the predisposition genes previously reported to be associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS) play a role in the effectiveness of brace treatment.A total of 312 AIS patients treated with bracing were enrolled in this study. The Cobb angle of the main curve was recorded at the beginning of brace treatment as well as at each follow-up. The patients were divided into two groups according to the outcome of brace treatment (success/failure). The failure of brace treatment was defined as a curve progression of more than 5° compared to the initial Cobb angle or surgical intervention because of curve progression. Single nucleotide polymorphism (SNP) sites in the genes for estrogen receptor α (ERα), estrogen receptor β (ERβ), tryptophan hydroxylase 1 (TPH-1), melatonin receptor 1B (MTNR1B) and matrillin-1 (MATN1), which were previously identified to be predisposition genes for AIS, were selected for genotyping by the PCR-RFLP method. Differences of genotype and allele distribution between the two groups were compared by the χ(2) test. A logistic regression analysis was used to figure out the independent predictors of the outcome of brace treatment.There were 90 cases (28.8%) in the failure group and 222 cases (71.2%) in the success group. Patients in the failure group were associated with the genotype GA (50.9 vs. 17.9% p0.001) and the G allele (27.1 vs. 12.0%, p0.001) at SNP rs9340799 of the ERα gene. Similarly, they were also associated with the genotype AT (33.3 vs. 13.0%, p = 0.002) and the A allele (16.7 vs. 9.6%, p = 0.033) at SNP rs10488682 of the TPH-1 gene. For MTNR1B, the difference of genotype distribution between the two groups was found to be statistically significant, while the difference of allele distribution between the two groups was found to be marginally statistically significant; for the MATN1 and ERβ genes, we found no significant differences of the genotype or allele distribution between the two groups. In the logistic regression analysis, ERα and TPH-1 were demonstrated to be independent factors predictive of bracing effectiveness.ERα and TPH-1 might be potential genetic markers that could predict the outcome of brace treatment. Patients with the G allele at the rs9340799 site of the ERα gene and the A allele at the rs10488682 site of the TPH-1 gene are prone to be resistant to brace treatment.

To investigate the association of FBN3 gene polymorphism with abnormal growth pattern in adolescent idiopathic scoliosis (AIS) patients.Blood samples were obtained from 273 AIS patients, aged (14.6 +/- 2.1) (10 - 18), and 287 healthy age-matched females adolescents. The anthropometric parameters of the AIS group, including age, body height, weight, arm span, Cobb angle, time of menarche, and Risser's sign were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the FBN3 gene distribution.The genotype and allele frequency distribution were comparable between the AIS and normal control groups. There was no association with curve severity, arm span, BMI in patients with AIS. In the rs7257948, There were not significant differences in the FBN3 gene polymorphism sites rs35579498, rs12608849, and rs7257948, and allele distribution between these 2 groups. In the AIS group, the patients with GG genotype the number of those whose body height wasor = 160 cm was higher than those whose body height was160 cm (P = 0.01). In rs35579498, the frequency of allele T was relatively higher in the AIS patients than in the controls (P = 0.051). In the AIS patients, the expression rate of CT genotype in those whose menarche age wasor = 12 years was significantly higher than those whose menarche was12 years (P = 0.042).The polymorphisms of the 4 SNPs in the exons of FBN3 gene are neither associated with the occurrence nor the curve severity of AIS. However, in rs35579498, T allele appears to be overrepresented in the patients compared with the controls. Mutation in this site my plays a role in the occurrence and progression of AIS, and in rs7257948, polymorphism of FBN3 gene may be associated with body height of the AIS patients.

To investigate the association of vitamin D receptor (VDR) gene polymorphisms with abnormal growth pattern and low bone mass in adolescent idiopathic scoliosis (AIS) patients.Peripheral blood samples were obtained from 164 female patients with AIS, aged 14.4 +/- 2 (9 - 20), and 122 age-matched healthy girls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the VDR gene distributions.The frequency of Bb genotype was significantly higher in the AIS patients than in the controls (P0.01). The frequency of B alleles of the AIS patients was significantly higher than that of the controls (P0.01). In AIS patients, the expression rate of Aa genotype of the AIS patients with the body mass index (BMI)or = 18 kg/m(2) was significantly higher than those with the BMI18 kg/m(2) (P0.05), and the expression rate of Bb genotype of the AIS patients with the BMI18 kg/m(2) and arm span160 cm was significantly higher than that of the AIS patients with the BMIor = 18 kg/m(2) and arm spanor = 160 cm (P0.05).The BsmI site polymorphism of vitamin D receptor gene may be associated with abnormal growth pattern and low bone mass in girls with AIS.

To investigate the correlation between the circulating leptin level and the anthropometric parameters and parameters related to pubertal growth, and to explore the role of leptin in the abnormal growth pattern in girls with adolescent idiopathic scoliosis (AIS).One hundred and twenty AIS girls selected randomly from the out-patient and in-patient departments, divided into 2 groups: Group A1 (n = 73, aged 10 - 13) and Group A2 (n = 47, aged 14 - 17), and 80 14 - 17 year-old healthy girl students receiving physical examination underwent measurement of body height and weight. Body mass index (BMI) was calculated. Peripheral fasting blood samples were collected to detect the level of leptin. The anthropometric data, pubertal status, and circulating leptin level were compared between the AIS girls and the controls. The relationships between leptin and age, menstrual status, body weight, height, BMI and Risser sign were analyzed in the AIS girls.Eighty-eight AIS girls (73%) and 14 healthy girls (18%) had a BMI score less than 18.0. The mean leptin level of Group A1 was 6.2 microg/L, significantly lower than of Group A2 (8.6 microg/L, P = 0.024). Compared with the healthy controls, the AIS girls had significantly greater corrected height (162.7 cm vs. 160.2 cm, P = 0.026), lower weight (44.3 kg vs. 53.6 kg, P = 0.01), lower BMI (17.5 kg/m(2) vs. 20.9 kg/m(2), P = 0.01), and lower circulating leptin (8.6 microg/L vs. 14.9 microg/L), even after the adjustment for age and menstrual status. An inverse correlation was observed between the leptin level and the age at menarche (AIS, r = -0.428, P0.001; controls, r = -0.280, P = 0.013). Whereas, positive correlations were found between leptin and age, menstrual status, body weight, height, BMI, and Risser sign (r = 0.234 - 0.506, P = 0.01 -0.001).AIS girls have markedly decreased circulating leptin level. Circulating leptin level is associated with body weight, BMI, and other growth parameters, suggesting that leptin may play an important role in the lower body mass in AIS girls.

Background The ulnar styloid is an important supportive structure for the triangular fibrocartilage complex. However, it remains inconclusive whether or not a fractured ulnar styloid should be fixed in an unstable distal radius fracture (DRF) with a stable distal radioulnar joint (DRUJ). The purpose of this study is to evaluate the effect of an untreated ulnar styloid fracture on the outcome of unstable DRF treated with transarticular external fixation when the DRUJ is stable. Methods 106 patients with an unstable DRF and a stable DRUJ were included in this study following external fixation. The patients were divided into the non-fracture, the tip-fracture and the base-fracture groups according to the location of the ulnar styloid fracture at the time of injury. Postoperative evaluation included the range of wrist motion, the radiological index, the grip strength, the PRWE-HK scores, the wrist pain scores, and the instability of DRUJ at the external fixator removal time, three months postoperatively and the final follow-up visit. Results The patients were followed for 12 to 24 months (15 months in average). Sixty-two of 106 patients (58%) had ulnar styloid fracture and 16 patients (26%) showed radiographic evidence of union of ulnar styloid fractures at the final follow-up visit. No significant difference in the radiological findings, the range of wrist motion, the grip strength, the PRWE-HK scores, and the wrist pain scores among three patient groups was detected at the external fixator removal time, three months postoperatively, or the final follow-up visit. Six of the 106 patients (5.7%) complained of persistent ulnar-side wrist pain during daily activities. One patient (0.9%) showed a positive sign in a stress-test, three patients (2.8%) showed a positive sign in a provocative-test, and five patients (4.7%) showed a positive sign in a press-test. There was no significant difference in the percentages of patients who complained of persistent ulnar-side wrist pain or showed a positive sign in the physical examination of the distal radioulnar joint among the three groups at the final follow-up time points. Conclusion When the DRUJ is stable, an untreated ulnar styloid fracture does not affect the wrist outcome of the patient with an unstable DRF treated with external fixation.

Introduction: Developmental dysplasia of the hip (DDH) is a common skeletal disease, which is characterized by abnormal seating of the femoral head in the acetabulum. Genetic factors play a considerable role in the etiology of DDH. Asporin (ASPN) is an ECM protein which can bind to TGF-b1 and sequentially inhibit TGF-b/Smad signaling. A functional aspartic acid (D) repeat polymorphism of ASPN was first described as an osteoarthritisassociated polymorphism. As TGF-b is well known as an important regulator in the development of skeletal components, ASPN may also be involved in the etiology of DDH. Our objective is to evaluate whether the D repeat polymorphism of ASPN is associated with DDH in Han Chinese. Methods: The D repeat polymorphism was genotyped in 370 DDH patients and 445 control subjects, and the allelic association of the D repeat was examined. Results: From D11 to D18, eight alleles were identified. D13 allele is the most common allele both in control and DDH groups, the frequencies are 67.3% and 58.1% respectively. In the DDH group, a significantly higher frequency of the D14 allele and significantly lower frequency of D13 was observed. The association of D14 and D13 was found in both females and males after stratification by gender. There was no significant difference in any other alleles we examined. Conclusions: Our results show an obvious association between the D repeat polymorphism of ASPN and DDH. It indicates that ASPN is an important regulator in the etiology of DDH.