Factors associated with development of re-nonunion after primary revision in femoral shaft nonunion subsequent to failed intramedullary nailing.

BACKGROUND: Currently, there remains a lack of consensus regarding factors predictive of complication such as re-nonunion after primary revision in femoral shaft nonunion subsequent to failed intramedullary nailing (IMN). A better understanding of prognostic factors could potentially reduce the risk of re-nonunion happening and allow patients to maximize their recovery in the most expeditious manner. Our study aims to identify risk factors in the development of re-nonunion after primary revision inclusive of exchanging reamed nailing (ERN) and augmentative compression plating (ACP) with IMN in situ for femoral shaft nonunion subsequent to failed IMN. METHODS: A retrospective study was performed for 63 cases (61 patients) of femoral shaft nonunion subsequent to failed IMN, who were made primary revision with either ERN or ACP from June 2007 to June 2015. The following set of variables was selected based on the speculation that they would contribute to the outcome: sex (male or female), age, body mass index(BMI), smoking, alcohol abuse, cause of injury, fracture type, type of IMN (antegrade or retrograde), use of IMN locking screws(dynamic or static), site of nonunion, primary nonunion time, pathological type of nonunion, bone defect (mm), primary revision method (ERN or ACP), and adjuvant autogenous bone grafting (ABG) (yes or no). Univariate analysis and multiple regression were used to identify risk factors in the development of re-nonunion after primary revision with either ERN or ACP for femoral shaft nonunion subsequent to failed IMN. The minimum follow-up time was 1.5 years (standard deviation [SD] = 1.2, range 1.5-8 years). RESULTS: Of 63 cases (61 patients) of femoral shaft nonunion subsequent to failed IMN, primary revision with ERN was performed in 33 (52.4%) cases and primary revision with ACP was performed in 30 (47.6%) cases. Adjuvant ABG procedure was undertaken in 39 (61.9%) cases during primary revisions. Re-nonunion was diagnosed as in 18 (28.6%) cases after primary revision with either ERN or ACP. There was a significant difference in time to union between patients treated with primary ERN and those with primary ACP (log-rank, p = 0.006). Furthermore, the difference was also statistically significant between patients with adjuvant ABG procedure and those without it (log-rank, p = 0.009). The relative risk factors included smoking, BMI, site of nonunion, bone defect, primary revision method, and adjuvant ABG procedure. However, primary revision method and adjuvant ABG procedure were shown to be two independent risk factors in multiple logistic regression analysis. CONCLUSIONS: Patients with excessive tobacco use, BMI ≥ 30 kg/m2, bone defect ≥ 5 mm, primary revision with ERN, and no adjuvant ABG procedure had a higher likelihood of developing re-nonunion. Of these risk factors, primary revision with ERN and no adjuvant ABG procedure were two strongest risk factors.

Augmentative locking plate with autologous bone grafting for distal femoral nonunion subsequent to failed retrograde intramedullary nailing.

OBJECTIVE: To explore the indications and efficacy of augmentative locking compression plate (LCP) or less invasive stabilization system (LISS)with autogenous bone grafting (BG) in treating distal femoral nonunion subsequent to failed retrograde intramedullary nailing (RIN). METHODS: A retrospective study was performed for 21 patients with distal femoral nonunion subsequent to failed RIN, who received therapy with either augmentative LCP (n = 11) or LISS with autogenous BG (n = 13). Operation time, time to union, union rate, time to renonunion, complication rate and SF-36 scores a year after hardware removal were compared between the two groups. RESULTS: The bone union occurred in 13/13 (100%) cases in augmentative LISS group versus 9/11 (81.8%) cases in augmentative LCP group [odds ratio (OR) = 3.21, 95% confidence interval (CI) 0.7-13]. Time to union, time to renonunion, complication rate of the augmentative LCP group were significantly more than that of the augmentative LISS with autogenous BG group (p = 0.023, p = 0.021 and p = 0.033). No significant difference was found in the average operation time of two groups (p = 0.121). At the follow-up a year after hardware removal, statistically significant HRQOL improvement in the augmentive LISS group was measured at the level of pain (p = 0.003) and general health perception (p = 0.011), as compared to the augmentive LCP group. CONCLUSIONS: We suggest augmentative LCP, for distal femoral nonunios after RIN, may be optimal for that of typeAO33A fractures, whereas augmentative LISS for that of typeAO33C fractures more.

Exchanging reamed nailing versus augmentative compression plating with autogenous bone grafting for aseptic femoral shaft nonunion: a retrospective cohort study.

OBJECTIVE: The purpose of this study was to compare the outcomes of exchanging reamed nailing (ERN) and augmentative compression plating (ACP) with autogenous bone grafting (BG) for the treatment of aseptic femoral shaft nonunion secondary to the treatment of intramedullary nailing (IMN). METHODS: A multicenter retrospective study was performed for 178 patients (180 cases) of aseptic femoral shaft nonunion secondary to first treatment of IMN. All cases were fixed with either ERN (n=87) or ACP (n=93). In the ERN group, 42 cases (48.3%) were nonisthmal nonunions and 45 (51.7%) were isthmal nonunions. In the ACP group, 46 cases (49.5%) were nonisthmal nonunions, and 47 (50.5%) were isthmal nonunions. Operation time, blood loss, time to union, union rate, volume of drainage, time to renonunion, and complication rate were compared between the 2 groups. RESULTS: All patients were followed up, with a mean period of 4.1 years (range: 1-7.1 years). Bone union occurred in 93/93 cases (100%) in the ACP group versus 75/87 cases (86.2%) in the ERN group (odds ratio [OR]=3.28, 95% confidence interval [CI] 0.8-14). Of the 12 cases involved with renonunion in the ERN group, 10 were nonisthmal nonunions, and 2 were isthmal nonunions with cortical bone defect >3 cm. The union time, blood loss, and complication rate of the ERN group were significantly higher than those of the ACP group (p=0.028, p=0.035, and p=0.021, respectively). No significant difference was found in the average operation time of the 2 groups (p=0.151). However, for the nonisthmal nonunions, a significant difference was found between the ERN and ACP groups (p=0.018). CONCLUSION: ACP with autogenous BG can obtain a higher bone union rate and shorter time to union than ERN in the treatment of aseptic femoral shaft nonunion after failed IMN. Especially for nonisthmal femoral shaft nonunions or isthmal nonunions with larger bone defects, ACP with autogenous BG can be more advantageous than ERN for patients. A future prospective observational study should be conducted.

[Posterior partial trochanteric osteotomy for the treatment of the roof involved acetabular fractures].

OBJECTIVE: To introduce a new trochanteric osteotomy,and evaluate the outcome of the procedure combined a posterior lateral approach in treating acetabular fractures which involving the roof. METHODS: Between March 2007 and Novmber 2010,30 patients with displaced acetabular fractures involving the dome need trochanteric osteotomy were retrospectively reviewed. There were 21 males and 9 females,ranging in age from 18 to 70 years with an average of 35.2 years at the time of injury. According to Letournel-Judet classification, there were 10 posterior wall fractures,7 posterior column fractures,5 transverse fractures, 2 T-shape fractures, 1 transverse associated with posterior wall fracture, 3 posterior column and wall fractures and 2 bicolumn fractures. The standards of Matta,the modified Merle d'Aubigne-Postel, Medical Research Council were respectively used to evaluate the reduction result, function of hip joint and the strength of hip abduction. RESULTS: All patients were followed up with an average time of 25 months (18 to 40) and all osteotomy sites obtained bone union with an average time of 8.4 weeks (6 to 12). No bone non-union, bone block displaceing, internal fixation looseing and breaking,infection of deep part were found. Seventeen patients got anatomic reduction, 12 got satisfied reduction, and 1 got unsatisfied result according to the criteria of Matta. At final follow-up, function of hip joint obtained excellent results in 11 cases, good in 15, fair in 3 and poor in 1. The strength of the abductors of 3 patients were grade 4 and 27 patients were grade 5. CONCLUSION: Posterior partial great trochanteric osteotomy can enhance the exposure and provide a more accurate reduction and degrade the difficulty of acetabular fracture fixation without increasing the risk of complications. The method provide a new way for the treatment of the roof involved acetabular fractures.

Comparison of the pedicle screws placement between electronic conductivity device and normal pedicle finder in posterior surgery of scoliosis.

STUDY DESIGN: Prospective randomized clinical trial. OBJECTIVE: To compare the accuracy and time using of pedicle screw placement between electronic conductivity device (ECD) and normal pedicle finder (NPF) in posterior surgery of scoliosis, through a randomized clinical trial. SUMMARY OF BACKGROUND DATA: Pedicle screw insertion for scoliosis correction can be associated with increased pedicle perforations. The malposition rates using various techniques in different region of the spine have been reported to occur with a frequency of 3.3%-43%. An ECD has been reported in spine surgeries, but its accuracy and surgical time comparing with NPF in the presence of scoliosis has not been reported. METHODS: The 42 patients of adolescent idiopathic scoliosis with average major Cobb angle of 55.3±7 degrees (range, 45-78 degrees), who received posterior correction surgeries using pedicle screws system only were divided into 2 groups by random: group NPF (22 patients); and group ECD (20 patients). NPF group had 332 screws and ECD group had 362 screws. The 2 groups were compared for accuracy of screw placement, time for screw insertion, and the number of times the C-arm had to be brought into the field. RESULTS: There were 47 (14.2%) pedicle perforation in the NPF group as compared with only 15 (4.1%) in the ECD group (P<0.001). Although in different region of the spine, screw accuracy showed discrepant statistical result, with upper (T1-T3), middle (T4-T7), and lower thoracic (T8-T10) comparison showing significant statistical difference (P=0.010, 0.001, and 0.041, respectively) and thoracolumbar (T11-L2) and lower lumbar (L3-L5) comparison showing no significant statistical difference (P=0.278 and 0.292, respectively). Average screw insertion time in the NPF group was 241±61 seconds compared with 204±33 seconds in the ECD group (P=0.009). The C-arm had to be moved into the operation field on an average of 1.59±0.67 times in the NPF group compared with 1.20±0.52 in the ECD group (P=0.040). CONCLUSIONS: ECD increases pedicle screw accuracy, especially in T1-T10, and reduces insertion time and radiation in posterior adolescent idiopathic scoliosis.

[Case-control study on two methods for the treatment of calcaneal fractures].

OBJECTIVE: To investigate clinical results of percutaneous reduction and hollow screw internal fixation for the treatment of calcaneal fractures, and to compare therapeutic effects between close reduction hollow screw internal fixation and open reduction plate internal fixation. METHODS: From August 2007 to May 2010, 53 patients with calcaneal fractures were retrospectively analyzed. All the patients were divided into two groups, 25 patients in group A (PR group) treated with percutaneous reduction and hollow screw internal fixation, including 17 males and 8 females, with an average age of (39.4 +/- 9.9) years. While 28 patients in group B (OR group) treated with open reduction and plate internal fixation, including 18 males and 10 females, with an average age of (38.6 +/- 10.2) years. According to Sanders classification, there were 18 patients with type II fractures, 29 patients with type III and 6 type IV. In both groups, operative time, blood loss, postoperative complications and radiology were recorded. Functional recovery was evaluated by Maryland score. RESULTS: All the patients were followed up, and the duration ranged from nine months to thirty-five months (averaged 20.4 months). There were no significant differences in sex, age, fracture type, fracture classification, initial Böhler angle, or late complications between the two groups. But significant difference can be seen between operative time, blood loss, and skin complications (in group A no nonunion and skin complications occurred, but subtalar posttraumatic arthritis occurred in 1 case; in group B, 3 patients had complications of skin necrosis, 1 patient suffered from a delayed union due to large defect filled with artificial bone, and 1 patient got subtalar posttraumatic arthritis). No difference were found in the latest X-ray film. According to Maryland score, in group A, 8 got an excellent result and 12 good. In group B, 10 got an excellent and 14 good. There were no significant differences between the two groups in Margland score. CONCLUSION: The results of this study suggest that in comparison with open reduction, percutaneous reduction and hollow screw internal fixation minimizes complications and achieves good results. Further study of this technique is needed.

Advanced glycation end-products induce heparanase expression in endothelial cells by the receptor for advanced glycation end products and through activation of the FOXO4 transcription factor.

As an endo-ß (1-4)-D: -glucuronidase, heparanase can specifically cleave carbohydrate chains of heparan sulfate (HS) and has been implicated in development of endothelial cells dsyfunction. The advanced glycation end products (AGEs) play a pivotal role in the pathology of diabetic complications. In the present study, we investigated the effect of AGE-bovine serum albumin (AGE-BSA) on heparanase expression in human microvascular endothelial cells (HMVECs) and the underlying molecular mechanisms. The results indicated that in vitro direct exposure of HMVECs to AGE-BSA (300, 1000, and 3000 µg/ml) could increase heparanase mRNA and protein expression in a dose and time-dependent manner. The effect of 1000 µg/ml AGE-BSA could be abolished by neutralization with antibody of the receptor for advanced glycation end products (RAGE). Moreover, pretreatment with inhibitors of nuclear factor-κB (NF-κB) or PI3-kinase did not affect heparanase expression induced by AGE-BSA. Nevertheless, small interference RNA (siRNA) for transcriptional factor FOXO4 could reduce the increase of heparanase expression in HMVECs induced by 1000 µg/ml AGE-BSA. These results suggest that AGEs could induce heparanase expression in HMVECs by RAGE and predominantly through activation of the FOXO4 transcription factor.

[Design of ABC damage variable and positioning system for acetabular fractures and 1122 cases multi-center statistic analysis].

OBJECTIVE: To design ABC damage variable and positioning system for acetabular fracture and explore the feasibility and clinical practical value of the system through the multi-center analysis of 1122 acetabular fractures. METHODS: According to acetabular three-column conception, and pelvic ring lesions damage direction caused by acetabular fracture domino effect and injury degree of proximal femur joint, it defined class A as any column acetabular fracture; class B as any two-column acetabular fracture; class C as front, dome and posterior mixture acetabular fracture. Lower case English letters a, m, p represented front, dome, posterior fracture, respectively. Acetabular damage variables: 1 was simple displaced fractures; 2 was comminuted fractures; 3 was compression fractures. Pelvic ring lesions damage variables: alpha was sacroiliac joints or sacroiliac fracture horizontal separation deflection; beta was sacroiliac joints or sacroiliac fracture vertical separation deflection; gamma was pubic symphysis separation/superior and inferior ramus of pubis fracture deflection; alpha beta gamma delta was compound floating damage. Proximal humerus joint damage variables: I was femoral head fracture; II was femoral neck fracture; II was intertrochanteric fractures of femur; IV was I to III compound fracture. The ABC damage variable positioning system for acetabular fracture was made up by the above-mentioned variables. The statistics from March 1997 to February 2010 showed 1122 cases acetabular fractures with 18 cases of double side acetabular fracture and 1140 cases of acetabular fractures. The pelvics anterior-posterior view, ilium and obturator oblique view, and 2/3D-CT materials were analyzed and researched. RESULTS: Each damage variables distribution situation in 1140 cases of acetabular fracture involved A in 237 cases (20.8%), B in 605 cases (53.1%), C in 298 cases (26.1%);front column fracture in 808 cases(70.9%), dome fracture in 507 cases (44.5%), posterior fracture in 1026 cases (90%). Acetabular variables: variabe 1 in 203 cases of simple displaced fracture (17.8%); variabe 2 in 516 cases of comminuted fracture(45.3%); variabe 3 in 421 cases of compression fracture (36.9%); 249 cases of pelvic ring lesions damage (21.8%), 75 cases femoral head fracture (6.6%); 18 cases of double side acetabular fracture and relative pelvic ring and proximal humerus joint variables (1.58%). Key part and curative effect elements of 1140 cases acetabular fracture: 507 cases of dome or posterior acetabular fracture (44.5%); 421 cases of compression fracture (36.9%); 249 cases of pelvic ring variables (21.8%); 75 cases of proximal humerus joint variables (6.6%); 486 cases of simple Aa/pl/2,Bapl/2 acetabular fracture (42.6% ). CONCLUSION: Compression fracture, especially defected compression fracture, takes important part in acetabular damage variables, and also presents that acetabular fracture with pelvic ring and proximal femoral damage variables are not rare at all. The relationship of the acetabular fracture damage variables, and its percentage shows the key points and elements in clinical treatment: weight-bearing to dome accounts for 44.5%; compression to defects account for 36.9%, pelvic ring to float accounts for 21.8%; dome fracture to double side fracture account for 6.6%. The system has significant guiding effects on clinic in terms of evaluation of injury severity, anatomic localization, difficulty index, alternative strategy, operative approach, effect of treatment,and prognosis. And the most important thing is that the system creates the comparison of damage variables in same type of fracture and the communication of homo-language and explores a new method.

Central administration of kisspeptin-10 inhibits water and sodium excretion of anesthetized male rats and the involvement of arginine vasopressin.

AIM: To investigate the effect of hypothalamus kisspeptin on water and sodium excretion and the possible mechanism. METHOD: The intracerebroventricular (icv) administration and radioimmunoassay were used to observe the effect of kisspeptin-10 on urine flow, sodium and potassium excretion, plasma arginine vasopressin (AVP), and atrial natriuretic peptide (ANP) concentrations in anesthetized male rats. The mediation of renal sympathetic nerve was also investigated by studies conducted on rats with bilateral renal sympathetic denervation. RESULTS: The urine flow, sodium excretion, and free water clearance decreased significantly by icv injection of 5 nmol kisspeptin-10 (p < 0.05) from 30 to 60 min post-injection. Meanwhile, plasma AVP concentrations increased significantly 30 min after the icv injection of 5 nmol kisspeptin-10 (p < 0.05), whereas the equal dose of kisspeptin-10 did not significantly change plasma ANP concentrations. The mean arterial blood pressure, heart rate, and potassium excretion did not significantly change during the experiment. Furthermore, pretreatment with 5 nmol kisspeptin-10 could still significantly decrease urine flow and sodium excretion in renal sympathetic denervated rats. CONCLUSION: Central administration of kisspeptin-10 could inhibit sodium excretion and urine flow in anesthetized male rats, which is probably mediated by increasing the plasma AVP concentration and is independent of plasma ANP concentration and renal sympathetic nerve activity.

Orphanin FQ and glutamate connection in the regulation of gonadotropin-releasing hormone secretion in the preoptic area of conscious male rats.

Utilizing the method of push-pull perfusion and radioimmunoassay (RIA), the secretory profile of gonadotropin-releasing hormone (GnRH) in the preoptic area (POA) and serum-luteinizing hormone (LH) levels were examined in conscious male rats after administration of [Nphe(1)]NC(1-13)NH(2), a competitive antagonists of the opioid receptor-like 1 receptor (ORL1 receptor) which is endogenous receptor for Orphanin FQ (OFQ). Glutamate release in the POA was also measured by high-performance liquid chromatography (HPLC) after perfusion of [Nphe(1)]NC(1-13)NH(2), i.e. NC13. The results showed that GnRH secretion from the POA and serum LH levels was increased significantly 40 min and 60 min, respectively after perfusion of 2 and 20 mmol/L NC13 in freely moving male rats (p<0.05). Pretreatment with a glutamate, N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801, s.c., 0.2 mg/kg) abolished the increase of GnRH release in the POA induced by 2 mmol/L NC13. Additionally, 20 mmol/L NC13 significantly enhanced glutamate release in the POA at 40 min post-perfusion in a dose-dependent manner. These findings suggest that hypothalamic OFQ/ORL1 receptor system plays a role in the physiological inhibitory control of GnRH secretion in the POA of male rats, and provide evidence for involvement of an OFQ and glutamate pathway in the control of GnRH secretion.

[Development of a fusion toxin IL15M-PEdelta293 based on a receptor-specific IL-15 antagonist].

IL-15 and IL-15 receptors (IL-15R) play a crucial role in the pathogenesis of adult T-cell leukemia (ATL), multiple myeloma and inflammatory autoimmune diseases. To develop a novel therapeutic agent capable of eliminating IL-15R-over-expressing abnormal cells, the gene coding for human IL-15 antagonist (IL-15M) was fused with a DNA fragment coding for the mutated form of Pseudomonas exotoxin, PEdelta293. The resulting gene fusion was cloned into pET16b under the control of T7 promoter, giving rise to the expression plasmid pET-IL15M-PEdelta293. Using Ni2+ -NTA affinity chromatography, IL15M-PEdelta293 was purified from E. coli BL21 (DE3) pLysS transformed with pET-IL15M-PEdelta293. The fusion toxin showed cytotoxicity to IL-15R-bearing myelogenous leukemia cell line K562 and K562-derived multidrug resistant cell line K562/AO2. However, IL-15R negative cell line Jurkat was insensitive to IL15M-PEdelta293. In addition, the toxic effect of IL15M-PEdelta293 on K562 was completely blocked by excessive amount of recombinant human IL-15. These results demonstrated that the selective cytotoxicity of IL15M-PEdelta293 correlated with the appropriate IL-15R expression on target cells. The present data suggest that the chimeric toxin constructed in this report may have therapeutic potential in the treatment of diseases associated with abnormal expression of IL-15/IL-15R, even in the treatment of chemotherapy refractory tumors.