Single nucleotide polymorphisms of ABCB1 gene and response to etanercept treatment in patients with ankylosing spondylitis in a Chinese Han population.

BACKGROUND: Etanercept was highly recommended for patients with ankylosing spondylitis (AS), as its efficacy has been confirmed in AS, while genetic polymorphisms, by affecting drug metabolism or drug receptor, lead to interindividual variability in drug disposition and efficacy. Therefore, this study aims to investigate whether ABCB1 gene polymorphisms can predict therapeutic response to etanercept in patients with AS. METHODS: A total of 185 patients with AS in our hospital were recruited into our study from December 2012 to May 2015. The frequency distributions of genotype and allele of rs2032582, rs1128503, and rs1045642 were detected by polymerase chain reaction (PCR) and electrophoresis verification enzyme products method. AS patients received etanercept treatment for 12 weeks, followed by this would be evaluated by the bath AS disease activity index (BASDAI) score improvement and the assessment of spondyloArthritis international society 20/50/70 (ASAS20/50/70) score improvements to explore the relationship between genotype of ABCB1 gene polymorphisms and therapeutic response to etanercept in patients with AS. RESULTS: After 12 weeks, the BASDAI score mean improvement value of rs2032582 A/A genotype was 2.87 ±â€Š0.52. The ratios of patients with rs2032582 A/A genotype reaching the BASDAI50 and ASAS20 evaluation criteria were 64.29% and 92.86%, respectively. The results indicated that efficacy of etanercept was promoted in rs2032582 A/A genotype. The BASDAI score mean improvement value of rs1128503 C/C genotype was 2.79 ±â€Š0.54 after 12 weeks. The ratios of patients with rs1128503 C/C genotype reaching the BASDAI50 and ASAS20 evaluation criteria were 66.67% and 93.94%, respectively. The results indicated that efficacy of etanercept was promoted in rs1128503 C/C genotype. However, no significant associations were observed between rs1045642 and therapeutic response to etanercept in AS patients. CONCLUSION: ABCB1 gene rs2032582 and rs1128503 polymorphisms may be associated with the efficacy of etanercept in AS patients. ABCB1 gene polymorphisms can act as biological indicators of etanercept efficacy.

[Analysis on the long-term effects of modified double endobutton technique in the treatment of Tossy type III acromioclavicular joint dislocations].

OBJECTIVE: To investigate the long-term clinical effects of modified double Endobutton technique for the treatment of acromioclavicular joint dislocations of Tossy type III. METHODS: A retrospective study was done in 42 patients with acromioclavicular joint dislocations of Tossy type III treated with modified double Endobutton technique from December 2008 to December 2010. There were 24 males and 18 females, ranging in age from 21 to 56 years old (averaged, 32.5 years old). All the patients were treated with open reduction, coracoclavicular ligament reconstruction using double Endobutton technique, and repair of acromioclavicular ligament. The Karlsson system was used to evaluate therapeutic effects. The distance from coracoid to clavicle was measured to evaluate reduction loss. RESULTS: All the patients were followed up, and the duration ranged from 2.0 to 3.2 years (averaged,2.4 years). According to Karlsson system, 32 patients got an A degree and 10 patients got a B degree at three months post-operatively; 26 patients got an A degree and 16 patients got a B degree at the latest follow-up; 6 patients got an A degree at 3 months after operation lowered to B degree at the latest follow-up. The coracoid-clavicle distance increased from (26.91 +/- 0.91) mm at 3 months after operation to (27.41 +/- 1.10) mm at the latest follow-up. Te patients treated with over-reduction during operation or with heavy physical labour work after operation had obvious widened coracoid-clavicle distance. Bone absorption was found around the plate in most cases, mainly in the clavicular side. CONCLUSION: Treatment for acromioclavicular joint dislocations of Tossy type III with modified double Endobutton technique has satisfactory early clinical results. But with time passing, loss of reduction and bone absorption around the plate could be observed, and clinical outcomes of some cases downgrade during the long-term follow-up.

[One-stage compound grafting of antibiotic-impregnated calcium sulfate and autogenous cancellous bone for the treatment of chronic calcaneal osteomyelitis].

OBJECTIVE: To explore the treatment of chronic calcaneal osteomyelitis with bone defect after debridement and evaluate its clinical outcomes. METHODS: From June 2009 to June 2011, 52 patients with chronic calcaneal osteomyelitis were treated with stage-one compound grafting of antibiotic-impregnated calcium sulfate and autogenous cancellous bone,including 12 females and 40 males with an average age of 43 years old ranging from 18 to 67. According to Cierny-Mader classification, there were 34 cases with stage III and 18 with stage IV. There were 32 cases on right side and 20 on left,with a course of 6 months to 3 years. The area of soft tissue wound ranged from 3.0 cm x l.5 cm to 23.0 cm x l2.0 cm. The clinical effects were evaluated according to infection controlling, calcium sulfate absorption,bone defect repair and heel functional recovery. RESULTS: All patients were followed up for 2 to 3.8 years (averaged 2.8 years). Primary healing was achieved in 52 patients. Two cases of recurrence were found post-operatively, 1 case in 3 months and another in 5 months,which were cured after a second operation. Bone repair healing was gained in 1.5 to 3.5 months (averaged 2.5 months). Complete radiological absorption of calcium sulfate was found in 1.2 to 3 months(averaged 2.2 months). Local exudation after removal of drainage tube had been persisting in 10 patients for 2 to 3 months, which was consistent with the time when cacium sulfate were totally absorbed. Flap had partial necrosis in 4 cases,and the wounds were closed after appropriate treatment finally. The mean Maryland score was 88.15±7.70. There were excellent results in 32 cases, good in 14, fair in 6. CONCLUSION: A satisfactory short-term clinical results can be gained by one-stage compound grafting of antibiotic-impregnated calcium sulfate and autogenous cancellous bone in chronic calcaneal osteomyelitis, but the long-term results need further follow-up. And much more study is also demanded to reduce the exudation of calcium sulfate.

[Treatment of acute ankle fractures with arthroscopy-assisted open reduction and internal fixation].

OBJECTIVE: To explore the clinical results of arthroscopy-assisted open reduction and internal fixation for the treatment of acute Lauge-Hansen stage IV ankle fractures. METHODS: A prospective cohort of study was done in 42 patients of acute ankle fractures treated with arthroscopy-assisted open reduction and internal fixation from January 2008 to December 2009. According to Lauge-Hansen classification, there were 26 supination-eversion stage IV fractures, including 11 females and 15 males; with an average age of (36.8 +/- 11.7) years; and there were 16 pronation-eversion stage IV fractures, including 6 females and 10 males, with an average age of (37.6 +/- 11.2) years. All the patients were treated with arthroscopy-assisted open reduction and internal fixation,and intra-articular disorders were observed. Syndesmotic diastasis was treated with three-cortices syndesmotic screw, and osteochondral injuries were disposed by Cheng-Ferkel staging system. The clinical effects were evaluated according to AOFAS scores. RESULTS: All the patients were followed up for 1 year. At the final review,the mean AOFAS score was (92.00 +/- 9.32). Twenty-eight patients got an excellent result, 11 good, 3 fair. Lesions of the cartilage were found in 31 cases. The AOFAS scores of patients with osteochondral lesions were higher than those of patients without osteochondral lesions. The AOFAS scores of patients with osteochondral lesions below C grade were higher than those of patients with osteochondral lesions above C grade. The AOFAS scores of patients with osteochondral lesions were higher than those of patients with osteochondral lesions above C grade. The AOFAS scores of patients with syndesmosis fixation were lower than those of patients without syndesmosis fixation. CONCLUSION: Intra-articular disorders are common in Lauge-Hansen stage IV ankle fractures, and osteochondral lesion and sydesmosis diastasis are the most important prognostic factor that leads to unsatisfactory ankle functions. Arthroscopy-assisted open reduction and internal fixation for the treatment of acute ankle fractures is not only helpful to anatomical reduction of the articular surface, but also can improve the clinical results with effective diagnosis and treatment of combined intra-articular disorders.

[Case-control studies on therapeutic effects for the treatments of tibial plateau fractures between arthroscopic technique in minimally invasion surgery and minimally invasive internal fixation with plates and screws].

OBJECTIVE: To investigate therapeutic effects of minimally invasive arthroscopic internal fixation with plates and screws in treating tibial plateau fractures. METHODS: A retrospective study from December 2006 to June 2010 was done on 69 patients with tibial plateau fractures. According to Schatzker classification, 5 patients were type I, 5 patients were type II, 25 patients were type III, 20 patients were type IV, 9 patients were type V and 5 patients were type VI. Thirty-six patients were treated with arthroscopy-assisted reduction and internal fixation, including 21 males and 15 females, ranging in age from 17 to 59 years (averaged, 34.2 years); another 33 patients were treated with small incision and fixed with plates and screws,including 19 males and 14 females, ranging in age from 18 to 62 years (averaged, 35.4 years). The operation time, blood loss during operation,drainage volume of blood, healing time, weight-bearing time and function of effected knee were compared between the two groups. RESULTS: All the patients were followed up,and the duration ranged from 6 to 12 months (averaged, 10.3 months). All the patients had no complications such as infection, articular collapse, re-fracture and joint stiffness. There were no significant differences in weight-bearing time, complications and Rasmussen scores between two groups (P>0.05); but there were significant differences in the operative time, blood loss, drainage volume of blood, hospital stay time, the healing time between two groups (P<0.05). The results showed that arthroscopy-assisted technique was better than minimally invasive internal fixation in operation duration, blood loss during operation and the healing time. CONCLUSION: Different types of fracture of tibial plateau should be treated with different surgical treatments. Arthroscopic technique for reduction of fractures, which has less influence on bony union and minimally invasive, and can provide a good clinical outcome.

Intermittent watt-level ultrasonication facilitates vancomycin release from therapeutic acrylic bone cement.

Ultrasound holds promise for enhancing the vancomycin release from cement though the length of time when local drug level exceeded the minimum inhibitory concentration (T(>MIC)) was not prolonged by the previous protocol of milliwatt-level ultrasonication. Here vancomycin-loaded cements were subjected to continuous watt-level ultrasonication (CUG), intermittent watt-level ultrasonication (IUG) or no ultrasonication (NUG) for 14 d during immersion in 40-ml phosphate buffered saline (PBS) for 28 d. The T(>MIC) for IUG was more than three times that for NUG. In contrast, T(>MIC) for CUG was slightly shortened. The subtherapeutic release of vancomycin between 15 d and 28 d for IUG was one-ninth that for NUG. The fitting equations indicated a significant enhancement on the burst release and the slow release for IUG; however, the continuous ultrasonication hampered the slow release. SEM images exhibited denser craters and pores with larger diameters and less residual drug in specimens from IUG relative to those from both CUG and NUG. Intermittent watt-level ultrasonication improved the ultrasound-enhanced vancomycin release from cement in view of the prolonged T(>MIC) and the inhibited subtherapeutic release compared with continuous ultrasonication. The mechanisms may be associated with the distinctive effects of detaching forces and pushing forces by acoustic microstreams.

[Treatment of syndesmosis diastasis with screw fixation in ankle fractures].

OBJECTIVE: To explore the operative method for the treatment of syndesmosis injury in ankle fractures. METHODS: A retrospective study was done on 21 ankles of 20 patients included male 11 and female 9;the range of age were from 27 to 52 years with an average of 36 years) with syndesmosis injury in closed ankle fractures from September 2005 to December 2007. All patients with ankle fractures and syndesmosis injury were diagnosed by the history, physical examination and radiology, then treated with open reduction, internal fixation, and syndesmotic stabilization with a three-cortices syndesmotic screw according to the Lauge-Hansen classification system. Radiological evaluation comprised tibiofibular overlap, total clear space and medial clear space. The clinical effects were evaluated according to modified Baird-Jackson standard. RESULTS: All patients were followed up from 1.0 to 2.2 years with an average of 1.3 years. Radiographic measurements were detailed as follows: tibiofibular overlap averaged (0.46 +/- 3.56) mm in preoperative and (7.14 +/- 0.62) mm in postoperative; mean total clear space (5.69 +/-0.88) mm in preoperative and (3.28 +/- 0.39) mm in postoperative; medial clear space averaged (5.67 +/- 1.23) mm in preoperative and (3.12 +/- 0.33) mm in postoperative; tibiofibular overlap in mortise view averaged (-0.87 +/- 0.96) mm in preoperative and (2.91 +/- 0.30) mm in postoperative. There was significant difference above data between preoperative and postoperative (P < 0.01). Four cases were confirmed minor tibiofibular diastasis through CT scans during postoperative. The modified Baird-Jackson scoring was from 62 to 98 scores with an average of (86.24 +/- 13.26) score at the final review. Of them, 13 ankles had not pain; 16 ankles reported no instability complaints; 11 ankles gained normal walking ability; 8 ankles could run normally; 11 ankles could return work without any restrictions. Activity of ankle in dorsiflexion, plantar flexion, inversion and eversion were respectively (21.05 +/- 5.00) degrees, (33.57 +/- 5.76) degrees, (19.48 +/- 4.57) degrees and (24.05 +/- 4.86) degrees. Three cases had radiological and clinical manifestations of osteoarthritis, but no breakage of syndesmotic screw in all cases. There were excellent results in 12 cases, good in 2, fair in 4, poor in 3. CONCLUSION: The treatment for the syndesmosis diastasis with a three-cortices screw fixation in ankle fractures is effective. Good functional outcome can be obtained with anatomical restoration of the tibiofibular syndesmosis. The repair of deltoid ligament is important for stability of the lower tibiofibular syndesmosis. Removal of the screw before weight loading should be performed to avoid possible screw breakage.

Effect of delayed pulsed-wave ultrasound on local pharmacokinetics and pharmacodynamics of vancomycin-loaded acrylic bone cement in vivo.

This study sought to investigate the effect of delayed pulsed-wave ultrasound with low frequency on drug release from and the antimicrobial efficacy of vancomycin-loaded acrylic bone cement in vivo and the possible mechanism of this effect. After the implantation of cement and the inoculation of Staphylococcus aureus into the bilateral hips of rabbits, ultrasound (average intensity, 300 mW/cm(2); frequency, 46.5 kHz; on/off ratio, 20 min/10 min) was applied to animals in the normal ultrasound group (UG(0-12)) from 0 through 12 h after surgery and to those in the delayed-ultrasound group (UG(12-24)) from 12 through 24 h after surgery. The control group (CG) was not exposed to ultrasound. Based on vancomycin concentrations in left hip cavities at projected time intervals, the amount of time during which the local drug concentration exceeded the MIC (T(>MIC)) in UG(12-24) was significantly prolonged compared with that in either CG or UG(0-12), and the ratios between the areas under the concentration-time curves over 24 h and the MIC for UG(0-12) and UG(12-24) were both increased compared with that for CG. The greatest reductions in bacterial densities in both right hip aspirates and right femoral tissues at 48 h were achieved with UG(12-24). Local hemorrhage in rabbits of UG(0-12) during the 12-h insonation was more severe than that in rabbits of UG(12-24). Of four variables, the T(>MIC) and the bioacoustic effect were both identified as parameters predictive of the enhancement of the antimicrobial efficacy of cement by ultrasound. Sustained concentrations above the MIC replaced early high maximum concentrations and long-term subtherapeutic release of the drug, provided that ultrasound was not applied until local hemorrhage was relieved. The enhancement of the antimicrobial efficacy of cement by ultrasound may be attributed to the prolonged T(>MIC) and the bioacoustic effect caused by ultrasound.