Improvement of absorbability, osteoconductivity, and strength of a ß-tricalcium phosphate spacer for opening wedge high tibial osteotomy: clinical evaluations with 106 patients.

BACKGROUND: An ideal synthetic spacer for medial opening wedge high tibial osteotomy (MOWHTO) has not yet been developed. The authors have developed a new ß-tricalcium phosphate (ß-TCP) spacer with 60% porosity (N-CP60) by modifying the micro- and macro-pore structures of a conventional ß-TCP spacer (CP60) that is widely used in clinical practice. The purpose of this study was to compare the absorbability, osteoconductivity, and in vivo strength of the N-CP60 spacer with those of the CP60 spacer, when used in MOWHTO. METHODS: First, the porosity, diameter distribution of macro- and micropores, and compressive strength of each ß-TCP block were examined using methodology of biomaterial science. Secondly, a clinical study was performed using a total of 106 patients (106 knees) with MOWHTO, who were followed up for 18 months after surgery. In these knees, the N-CP60 and CP-60 spacers were implanted into 49 tibias and 57 tibias, respectively. The absorbability and osteoconductivity were radiologically evaluated by measuring the area of the implanted spacer remaining unabsorbed and assessing with the Hemert's score, respectively. The incidence of cracking in the implanted spacers was determined using computed radiography. Statistical comparisons were made with non-parametric tests. The significance level was set at p = 0.05. RESULTS: The N-CP60 and CP60 blocks had almost the same porosity (mean, 61.0% and 58.7%, respectively). The diameter of macropores was significantly larger (p < 0.0001) in the N-CP60 block than in the CP60 block, while the diameter of micropores was significantly smaller (p = 0.019) in the N-CP60 block. The ultimate strength of the N-CP60 block (median, 36.8 MPa) was significantly greater (p < 0.01) than that of the CP60 block (31.6 MPa). As for the clinical evaluations, the absorption rate of the N-CP60 spacer at 18 months after implantation (mean, 48.0%) was significantly greater (p < 0.001) than that of the CP60 spacer (29.0%). The osteoconductivity of the N-CP60 spacer was slightly but significantly higher (p = 0.0408) than that of the CP60 spacer only in zone 1. The incidence of in vivo cracking of the posteriorly located N-CP60 spacer at one month (mean, 75.5%) was significantly lower (p = 0.0035) than that of the CP60 spacer (91.2%). CONCLUSIONS: The absorbability, osteoconductivity, and compressive strength of the new N-CP60 spacer were significantly improved by modifying the macro- and micro-pore structures, compared with the conventional CP60 spacer. The N-CP60 spacer is more clinically useful than the CP60 spacer. TRIAL REGISTRATION NUMBER: H29-0002.

Extrusion of the medial meniscus is a potential predisposing factor for post-arthroscopy osteonecrosis of the knee.

BACKGROUND: Post-arthroscopic osteonecrosis of the knee (PAONK) is a rare condition. No studies have analyzed the relationship between the meniscus extrusion and PAONK. The purpose of this retrospective study is to test a hypothesis that the degree of the medial meniscus (MM) extrusion might be significantly greater in the knees with PAONK than in the matched control knees both before and after the meniscectomy. METHODS: Ten knees with PAONK were detected out of a total of 876 knees which had undergone arthroscopic partial meniscectomy of the MM. Ten matched control knees were randomly selected out of the remaining 866 knees without PAONK. The clinical data of these 20 patients were retrospectively collected from the medical records. To evaluate the location of the menisci on the joint line, Extrusion width and Inner width were defined on a coronal section of magnetic resonance imaging (MRI). The intra- and inter-rater reliability was evaluated by calculating the intra- and inter-class coefficients. Statistical comparisons between the 2 groups were made using the 3 non-parametric tests. RESULTS: Before the meniscectomy, the Extrusion width of the MM (mean 4.7 ± 1.4 mm) was significantly greater than that (3.0 ± 1.3 mm) in the Control group (P = 0.0195). In the MRI taken in a range from 3 to 50 weeks after the meniscectomy, the Extrusion width of the MM (5.9 ± 1.1 mm) in the PAONK group was significantly greater than that (3.4 ± 1.4 mm) in the Control group (P = 0.0009), and the Inner width of the MM (0.6 ± 1.7 mm) in the PAONK group was significantly less than that (3.9 ± 1.0 mm) in the Control group (P = 0.0001). CONCLUSION: A significant relationship was found between the degree of the MM extrusion and the onset of PAONK. This study suggested that the extrusion of the MM is a potential predisposing factor for PAONK.

Assessment of valgus laxity after release of the medial structure in medial open-wedge high tibial osteotomy: an in vivo biomechanical study using quantitative valgus stress radiography.

BACKGROUND: To perform medial open-wedge high tibial osteotomy (OWHTO), surgeons expose the medial-proximal tibia by releasing or cutting the superficial layer of the medial collateral ligament (sMCL). Biomechanically, the sMCL provides primary restraint against valgus forces. Therefore, any release of the sMCL can cause valgus instability of the knee joint. The purpose of this study was to assess valgus laxity after release of the medial structure of the knee during OWHTO. METHODS: Between 2009 and 2015, 84 consecutive patients (93 knees) who underwent OWHTO using a locking plate were enrolled in this study. All patients underwent radiological examinations before surgery, during surgery, 1 year after surgery, and after plate removal to objectively assess valgus laxity. The medial joint space (MJS) and the joint line convergence angle (JLCA) of the knee were evaluated using quantitative valgus stress radiography. Clinical evaluation was performed 2 years after surgery. RESULTS: The mean functional knee score improved significantly, from 65.5 to 91.1 points (p < 0.0001). The mechanical axis percentage shifted to pass through a point 69.7% lateral from the medial edge of the tibial plateau. The MJS and JLCA increased significantly during OWHTO surgery (11.0 mm, 7.4 °, p < 0.0001). However, no significant differences were noted in the MJS and JLCA among preoperative, 1-year postoperative periods and after plate removal. CONCLUSION: Valgus laxity was significantly greater after release of the sMCL. However, no significant differences were noted in valgus laxity in preoperative, 1-year postoperative periods and after plate removal. Complete release of the sMCL did not cause postoperative valgus laxity after OWHTO surgery. TRIAL REGISTRATION: Trial registration number: No.012-0360.

Association of Oral Intake and Transient Mixed Venous Oxygen Desaturation in Patients Undergoing Fast-Track Postoperative Care After Open-Heart Surgery.

OBJECTIVE: The impact of early resumption of oral intake after cardiac surgery on hemodynamics has not been characterized. The authors examined the effects of early oral intake on the oxygen supply-demand relationship in patients undergoing on-pump cardiac surgery in an early recovery after surgery program. DESIGN: Prospective data were collected in postcardiac surgical patients in a multidisciplinary intensive care unit (ICU) during an 18-month period. SETTING: Single institution study. PARTICIPANTS: Forty-three patients who underwent either mitral or aortic valve repair and were successfully liberated from ventilatory support within 10 hours after surgery. INTERVENTIONS: Patients were either allowed to resume oral intake on the morning of the first postoperative day or not at the discretion of the surgical team after extubation. MEASUREMENTS AND MAIN RESULTS: The oxygen supply-demand relationship was assessed continuously with cardiac index and mixed venous oxygen saturation (SvO2). Among the subjects, 22 patients were allowed to eat, and transient SvO2 decrease was noted in 13 patients. All transient SvO2 decreases occurred in the patients with early oral intake. The hemodynamic status and oxygen supply-demand relationship did not differ between the patients with and without transient SvO2 decrease. All the subjects were discharged successfully from the ICU on the first postoperative day, and the length of hospital stay was similar irrespective of SvO2 decrease after early oral intake. CONCLUSIONS: Early oral intake shortly after extubation was associated with transient but significant SvO2 decrease in patients who underwent fast-track recovery after open-heart surgery. Because this phenomenon did not negatively affect the postoperative outcome, early oral intake may not be harmful.

Effects of initial graft tension on clinical outcome after anatomic double-bundle anterior cruciate ligament reconstruction: comparison of two graft tension protocols.

BACKGROUND: In anatomic double-bundle anterior cruciate ligament (ACL) reconstruction, there are great controversies concerning the ideal graft tension protocols. The purpose of this study was to clarify differences in the effect of two graft tension protocols on the clinical outcome after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction by comparing the minimum 2-year clinical results. METHODS: Ninety-seven patients with unilateral anatomic double-bundle ACL reconstruction were divided into two groups. In the first 44 patients (Group I), a 40-N tension was applied to each of the two hamstring autografts at 30° of knee flexion, and simultaneously fixed onto the tibia. In the remaining 53 patients (Group II), a 30-N tension was applied to each graft at 10° of knee flexion, and simultaneously fixed onto the tibia. Each patient was examined 2 years after surgery. RESULTS: There wasn't a significant difference in the background of the two groups. There was no significant difference in the postoperative anterior laxity between the two groups. The average was 1.1 mm and 0.9 mm in Groups I and II, respectively. There wasn't any differences between the two groups in Lysholm knee score, International Knee Documentation Committee (IKDC) evaluation and muscle strength. Four patients had loss of knee extension in a range of 5° and 10° in Group I and none of the patients in Group II exhibited any loss in knee extension; which was statistically significant (p = 0.025). CONCLUSION: The two initial graft tension protocols did not result in any significant differences in the Lysholm knee score and IKDC grade. However, it was noted that the 40-N tension applied to each graft at 30° of knee flexion more significantly induced loss of knee extension in comparison to the 30-N tension applied to each graft at 10°. From a clinical viewpoint, the loss of knee extension is one of the pathological conditions that should be absolutely avoided after ACL reconstruction. Therefore, the 30-N tension applied to each graft at 10° is preferable to the other graft tension protocol.

Analysis of gene expression for microminipig liver transcriptomes using parallel long-read technology and short-read sequencing.

The microminipig is one of the smallest minipigs that has emerged as a possible experimental animal model, because it shares many anatomical and/or physiological similarities with humans, including the coronary artery distribution in the heart, the digestive physiology, the kidney size and its structure, and so on. However, information on gene expression profiles, including those on drug-metabolizing phase I and II enzymes, in the microminipig is limited. Therefore, the aim of the present study was to identify transcripts in microminipig livers and to determine gene expression profiles. De novo assembly and expression analyses of microminipig transcripts were conducted with liver samples from three male and three female microminipigs using parallel long-read and short-read sequencing technologies. After unique sequences had been automatically aligned by assembling software, the mean contig length of 50843 transcripts was 707 bp. The expression profiles of cytochrome P450 (P450) 1A2, 2C, 2E1 and 3A genes in livers in microminipigs were similar to those in humans. Liver carboxylesterase (CES) precursor, liver CES-like, UDP-glucuronosyltransferase (UGT) 2C1-like, amine sulfotransferase (SULT)-like, N-acetyltransferases (NAT8) and glutathione S-transferase (GST) A2 genes, which are relatively unknown genes in pigs and/or humans, were expressed strongly. Furthermore, no significant gender differences were observed in the gene expression profiles of phase I enzymes, whereas UGT2B17, SULT1E1, SULT2A1, amine SULT-like, NAT8 and GSTT4 genes were different between males and females among phase II enzyme genes under the present sample conditions. These results provide a foundation for mechanistic studies and the use of microminipigs as model animals for drug development in the future. Copyright © 2016 John Wiley & Sons, Ltd.

Beta-tricalcium phosphate shows superior absorption rate and osteoconductivity compared to hydroxyapatite in open-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to clinically and radiologically compare the utility, osteoconductivity, and absorbability of hydroxyapatite (HAp) and beta-tricalcium phosphate (TCP) spacers in medial open-wedge high tibial osteotomy (HTO). METHODS: Thirty-eight patients underwent medial open-wedge HTO with a locking plate. In the first 19 knees, a HAp spacer was implanted in the opening space (HAp group). In the remaining 19 knees, a TCP spacer was implanted in the same manner (TCP group). All patients underwent clinical and radiological examinations before surgery and at 18 months after surgery. RESULTS: Concerning the background factors, there were no statistical differences between the two groups. Post-operatively, the knee score significantly improved in each group. Concerning the post-operative knee alignment and clinical outcome, there was no statistical difference in each parameter between the two groups. Regarding the osteoconductivity, the modified van Hemert's score of the TCP group was significantly higher (p = 0.0009) than that of the HAp group in the most medial osteotomy zone. The absorption rate was significantly greater in the TCP group than in the HAp group (p = 0.00039). CONCLUSIONS: The present study demonstrated that a TCP spacer was significantly superior to a HAp spacer concerning osteoconductivity and absorbability at 18 months after medial open-wedge HTO. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Prospective clinical comparisons of semitendinosus versus semitendinosus and gracilis tendon autografts for anatomic double-bundle anterior cruciate ligament reconstruction.

BACKGROUND: The data available from the previously reported clinical studies remains insufficient concerning the hamstring graft preparation in double-bundle anterior cruciate ligament (ACL) reconstruction. OBJECTIVE: To test the hypothesis that there are no significant differences between the semitendinosus tendon alone and the semitendinosus and gracilis tendon graft fashioning techniques concerning knee stability and clinical outcome after anatomic double-bundle ACL reconstruction. METHODS: A prospective study was performed on 120 patients who underwent anatomic double-bundle ACL reconstruction according to the graft fashioning technique. The authors developed the protocol to use hamstring tendon autografts. When the harvested doubled semitendinosus tendon is thicker than 6 mm, each half of the semitendinosus tendon is doubled and used for the anteromedial (AM) and posterolateral (PL) bundle grafts (Group I). On the other hand, when the harvested semitendinosus tendon is under 6 mm in thickness, the gracilis tendon is harvested additionally. The distal half of the semitendinosus and gracilis tendons are doubled and used for the AM bundle graft, and the remaining proximal half of the semitendinosus tendon is doubled and used for the PL bundle grafts (Group II). Sixty-one patients were included in Group I, and 59 patients in Group II. The two groups were compared concerning knee stability and clinical outcome 2 years after surgery. RESULTS: The postoperative side-to-side anterior laxity averaged 1.3 mm in both groups, showing no statistical difference. There were also no significant differences between the two groups concerning the peak isokinetic torque of the quadriceps and the hamstrings, the Lysholm knee score, and the International Knee Documentation Committee evaluation. CONCLUSION: There were no significant differences between the two graft fashioning techniques after anatomic double-bundle ACL reconstruction concerning knee stability and postoperative outcome. The present study provided orthopedic surgeons with important information on double-bundle ACL reconstruction with hamstring tendons. LEVEL OF EVIDENCE: Level II; prospective comparative study.

Effect of Patient Age on Clinical and Radiological Outcomes After Medial Open-Wedge High Tibial Osteotomy: A Comparative Study With 344 Knees.

Background: There exists some controversy regarding whether patient age is a predictive factor for outcomes after high tibial osteotomy (HTO). Purpose/Hypothesis: The purpose of this study was to evaluate whether patient age affects clinical and radiological outcomes after medial open-wedge HTO (OWHTO) in a large population with a wider age range than previous studies. It was hypothesized that there would be no differences in outcomes when compared across age-groups. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective comparative study was conducted using 344 patients (303 knees) who underwent OWHTO from 2009 to 2018. These patients were divided into 3 groups based on age at the time of surgery: ≥55 years (group Y: 76 knees in 57 patients), 56 to 64 years (group M: 129 knees in 120 patients), and ≤65 years (group O: 139 knees in 126 patients). Clinical and radiological evaluations were performed immediately before surgery and at the final follow-up period, at a mean of 5.1 years (range, 3-11 years). Comparisons among the 3 groups were conducted with 1-way analysis of variance for continuous variables. When a significant result was obtained, a post hoc test with Bonferroni correction was conducted for multiple comparisons. Results: In clinical evaluations, there were no significant differences among the 3 groups either preoperatively or postoperatively concerning the Japanese Orthopaedic Association score, the Lysholm score, or the Knee injury and Osteoarthritis Outcome Score (KOOS), with the exception of the preoperative KOOS Symptoms subscale, which was significantly higher in group Y versus group O (48.9 ± 18.7 vs 58.7 ± 15.4, respectively; P = .011). The Tegner activity score was significantly different among the groups, both preoperatively and postoperatively (P < .001 for both). There was no significant difference in the occurrence of complications or the survival rate at final follow-up among the 3 groups. Conclusion: The study findings suggest that patient age does not affect clinical and radiological outcomes after OWHTO.

Implantation of autogenous meniscal fragments wrapped with a fascia sheath induces fibrocartilage regeneration in a large meniscal defect in sheep: A histological and biomechanical study.

INTRODUCTION: Currently, various studies have been reported to regenerate the meniscus tissue in a large defect after partial meniscectomy using biological or synthetic scaffolds with or without fibrochondrocytes. However, the clinical utility of those treatments has not been established as of yet. HYPOTHESIS: Purposes of this study were to develop a sheep model to evaluate feasibility of this new surgical strategy to treat the irreparable meniscus injury, and to test the hypothesis that implantation of autogenous meniscal fragments wrapped with a fascia sheath may significantly induce fibrocartilage regeneration in a large meniscal defect in the sheep model. METHODS AND METHODS: Twenty Suffolk sheep were used. In each animal, an anterior 10-mm width of the right medial meniscus was resected. Then, the animals were divided into the following 2 groups. In Group I, the defect was enveloped with a fascia from the left thigh. In Group II, the resected meniscus fragmented into small pieces was grafted into the defect. Then the defect was enveloped with a fascia. In each group, 5 of 10 sheep were used for histological and biomechanical evaluations, respectively, at 12 weeks after surgery. RESULTS: In Group I, the defect was incompletely filled with thin fibrous tissues, while fibrocartilage tissues rarely regenerated in the tissue. In Group II, all defects were completely filled with thick fibrocartilage tissues, which were richly stained with the safranin O staining. Both the gross and histological observation score of Group II was significantly (p=0.0005, p=0.0005) greater than that of Group I. Concerning the cross-sectional area of the regenerated tissue, Group II was significantly (p=0.0002) greater than Group I. In the biomechanical evaluation, the maximal load and the linear stiffness of the meniscus-tibia complex were significantly (p=0.0015, p=0.0283) greater in Group II than in Group I. DISCUSSION: Implantation of autogenous meniscal fragments wrapped with a fascia sheath significantly induces fibrocartilage regeneration into a large meniscal defect in the sheep model. LEVEL OF EVIDENCE: Not applicable; Controlled Laboratory Study, Experimental in vivo study.

High Rate of Radiographic Union at the Fibular Osteotomy Site With No Complications After an Acute Oblique Osteotomy and Ligation Procedure to Shorten the Fibula in High Tibial Osteotomy.

Background: A fibular shortening osteotomy is needed to perform lateral closing-wedge high tibial osteotomy (LCW-HTO). To achieve this shortening, we have recently developed an acute oblique osteotomy and ligation (AO/L) procedure for the center of the fibular shaft, based on the AO procedure. Purpose: To compare the 2-year follow-up outcomes between the AO/L procedure and the AO procedure. Study Design: Cohort study; Level of evidence, 2. Methods: A prospective comparative cohort study was conducted involving 83 patients (83 knees) who underwent shortening osteotomy of the fibula in LCW-HTO between April 2017 and March 2019. The first consecutive 41 knees (AO group) underwent fibular osteotomy with the AO procedure. The remaining 42 knees (AO/L group) underwent fibular osteotomy with the AO/L procedure. All of the patients were evaluated for at least 2 years postoperatively via clinical and radiological assessments. To determine the time needed for complete union at the osteotomy site, we evaluated the radiographs using a radiographic union score for tibial fractures, which was modified for fibular osteotomy. Comparison of outcomes between the 2 groups was performed using the Student t test for continuous variables and the Mann-Whitney U test or Fisher exact test for discrete variables. Results: Around the fibular osteotomy site, no perioperative complications were found in either group. The radiographic union score was significantly higher in the AO/L group than in the AO group (P < .0001 at 2, 3, and 6 months; P = .0290 at 12 and 24 months). The union rate at the fibular osteotomy site was significantly higher in the AO/L group (97.6%) than in the AO group (82.9%) at 12 months (P = .0290). Conclusion: The AO/L procedure significantly accelerated the formation of bridging callus at the fibular osteotomy site and provided a significantly higher union rate compared with the AO procedure. Both AO/L and AO procedures were free from perioperative complications. These results suggest that the AO/L procedure is clinically useful as an osteotomy procedure to shorten the fibula in LCW-HTO.

Validation of inflationary non-invasive blood pressure monitoring in adult surgical patients.

Oscillometric determination of blood pressure may be advantageous, as cuff inflation requires lower cuff pressure and shorter duration than deflation. In this observational study, we compared the blood pressure value, cuff pressure, and duration of cuff inflation between a prototype of inflationary non-invasive blood pressure (NIBP) and conventional deflationary NIBP in adult patients during anesthesia. Three hundred and twenty-three pairs of measurements were obtained from 64 subjects. The bias and precision of systolic pressure and diastolic pressure were 2.9 ± 8.3 and 5.6 ± 6.1 mmHg, respectively. Inflationary NIBP could better determine NIBP with lower cuff pressure than deflationary NIBP (124 ± 22 vs. 160 ± 33 mmHg, p < 0.05). Inflationary NIBP could also determine NIBP more quickly (13.0 ± 2.3 vs. 32.7 ± 13.6 s, p < 0.05). These data suggest that inflationary NIBP may reduce cuff-related discomfort and complications, and has reasonable accuracy compared to deflationary NIBP in adult surgical patients.

Changes in the Contact Stress Distribution Pattern of the Patellofemoral Joint After Medial Open-Wedge High Tibial Osteotomy: An Evaluation Using Computed Tomography Osteoabsorptiometry.

BACKGROUND: Medial open-wedge high tibial osteotomy (OWHTO) theoretically causes distalization and lateralization of the tibial tuberosity and the patella. PURPOSE/HYPOTHESIS: The purpose of the study was to identify any changes in the stress distribution of subchondral bone density across the patellofemoral (PF) joint before and after OWHTO through the use of computed tomography (CT) osteoabsorptiometry. We hypothesized that OWHTO would alter the distribution of contact stress in the PF joint. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 17 patients (17 knees) who underwent OWHTO were enrolled in this study between September 2013 and September 2015. All patients underwent radiologic examination preoperatively and at 1 year postoperatively, and the distribution patterns of subchondral bone density through the articular surface of the femoral trochlea and patella were assessed preoperatively and >1 year postoperatively using CT osteoabsorptiometry. The quantitative analysis of the obtained mapping data focused on location of the high-density area (HDA) through the articular surface of the PF joint. The percentage of HDA at each divided region of the articular surface of the femoral trochlea and the patella was calculated. RESULTS: In the radiologic evaluation, the Blackburne-Peel ratio was significantly reduced (P < .001) after surgery, and the tilting angle of the patella was significantly decreased (P < .001). On CT evaluation, the percentage of HDA in the lateral notch and lateral trochlea of the femur and in the medial portion of the lateral facet of the patella increased significantly after OWHTO surgery (P ≤ .038). CONCLUSION: OWHTO significantly increased the stress distribution pattern of the lateral trochlea of the femur and the medial portion of the lateral facet of the patella. The procedure significantly lowered the patellar height and significantly decreased the patellar tilting angle after surgery.

Anti-tumor effect of small interfering RNA targeting the androgen receptor in human androgen-independent prostate cancer cells.

Early phase prostate cancer is usually androgen-dependent, with the androgen/androgen receptor (AR) signaling pathway playing a central role. At this stage, the cancer responds well to androgen ablation therapy, but prostate cancers eventually acquire androgen independence and more aggressive phenotypes. Several studies, however, have shown that the majority of tumors still express functional AR, which is often amplified and mutated. To determine if the AR is a plausible therapeutic target, we investigated the anti-tumor effect of small interfering RNAs targeting the AR (siAR) in the human prostate cancer cells, LNCaP and 22Rv1, which express mutated AR. In both types of cells, transfection of siAR suppressed mutated AR expression and significantly reduced cell growth. Furthermore, atelocollagen-mediated systemic siAR administration markedly inhibited the growth of 22Rv1 cells subcutaneously xenografted in castrated nude mice. These results suggest that the AR is still a key therapeutic target even in androgen-independent prostate cancer (AIPC). Silencing of AR expression in AIPC opens promising therapeutic perspectives.

Knockdown of Akt isoforms by RNA silencing suppresses the growth of human prostate cancer cells in vitro and in vivo.

The serine/threonine kinase Akt has three highly homologous isoforms in mammals: Akt1, Akt2, and Akt3. Recent studies indicate that Akt is often constitutively active in many types of human malignancy. Here we investigated the expression and function of Akt isoforms in human prostatic carcinoma cells. Initially, we used Western blotting to examine Akt expression in four human prostate cancer cell lines. Next, small-interfering RNAs (siRNAs) specific for Akt isoforms were used to elucidate their role on the in vitro and in vivo growth of prostate cancer cells. Expression of Akt1 and Akt2 was detected in all cells tested, but Akt3 was expressed only in cancer cells that did not express androgen receptors. All synthetic siRNAs against Akt isoforms suppressed their expression and inhibited the growth of cancer cells in vitro. Furthermore, atelocollagen-mediated systemic administration of siRNAs significantly reduced the growth of tumors that had been subcutaneously xenografted. These results suggest that targeting Akt isoforms could be an effective treatment for prostate cancers.

Clinical Outcomes and Complications During and After Medial Open-Wedge High Tibial Osteotomy Using a Locking Plate: A 3- to 7-Year Follow-up Study.

BACKGROUND: Outcomes and complications at mid- or long-term follow-up after medial open-wedge high tibial osteotomy (MOWHTO) with the TomoFix locking plate have not been fully evaluated. PURPOSE: To evaluate the complications and midterm clinical outcomes after MOWHTO using a TomoFix. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Enrolled in this study were 80 patients (85 knees) who underwent MOWHTO with the TomoFix locking plate between 2009 and 2013. There were 66 women and 14 men, with a mean age of 61.5 years at the time of surgery. The diagnosis was medial osteoarthritis in 76 knees and spontaneous osteonecrosis of the knee in 9 knees. Metal removal and second-look arthroscopy were performed in all cases. Clinical and radiological examinations were performed at final follow-up after surgery (mean, 4.5 years). RESULTS: The mean Japanese Orthopaedic Association score and Knee injury and Osteoarthritis Outcome Score improved significantly from pre- to postoperatively (P < .0001). The weightbearing line percentage shifted to pass through a point 67.7% lateral from the medial edge of the tibial plateau. The Caton-Deschamps index changed significantly from 0.88 to 0.66 at final follow-up (P < .0001). The mean posterior tibial slope changed significantly from 8.9° to 11.9° at final follow-up (P < .0001). Limb length was significantly increased after MOWHTO (10.3 mm; P < .0001). During plate removal, 14 locking screws were found to be broken in 9 knees (10.6%). The articular cartilage grade of the patellofemoral joint was significantly higher in the second arthroscopy than in the first arthroscopy (P < .0001). The cumulative rate of all complications was 41.2%, with major complications (ie, those requiring additional or extended treatment) in 24.7%. CONCLUSION: Postoperative outcome scores indicated significant improvement after MOWHTO, although the cumulative rate of all complications was 41.2% and the rate of major complications was 24.7%. These results indicate that MOWHTO with the TomoFix is a technically demanding procedure. Careful preoperative planning and meticulous surgical technique are needed to decrease the incidence of complications associated with MOWHTO.

An Acute Oblique Osteotomy and Suture Ligation Procedure to Shorten the Fibula in Lateral Closing-Wedge High Tibial Osteotomy.

The purpose of this description is to report an "acute oblique osteotomy and ligation" (AOOL) procedure to shorten the fibula in high tibial osteotomy (HTO). A 4-cm longitudinal skin incision is made at the lateral aspect of the leg. After the central portion of the fibula is circumferentially isolated from all the periosteal tissues, a simple osteotomy is performed at the mid-portion of the fibular diaphysis in the quasi-frontal plane, which is inclined by 25 to 30° to the long axis of the fibula. Two thin holes are created beside the osteotomy line on the lateral surface of the fibula. A polyester thread is passed through the 2 holes. After the HTO is completed, the surgeon easily reduces the displaced fibular ends using this thread. This thread is securely tied to keep the contact between the 2 osteotomized surfaces. The AOOL procedure is technically easy and safely performed. We believe that the AOOL procedure is clinically useful to shorten the fibular shaft in HTO.

A soluble factor (EMMPRIN) in exudate influences knee motion after total arthroplasty.

Few studies have been conducted to investigate biological factors that affect postoperative knee motion after total knee arthroplasty (TKA). The purpose of this study is to test the hypothesis that range of knee motion (ROM) at 4 weeks after TKA is correlated with the concentration of extracellular matrix metalloproteinase inducer (EMMPRIN) and transforming growth factor (TGF)-beta1 in the exudative fluid harvested from the joint after surgery. A prospective measurement study was conducted with 20 osteoarthritis patients who underwent TKA. At 48 h after surgery, the exudate was harvested from a closed drainage system. Enzyme-linked immunosorbent assay was performed to measure the concentration of TGF-beta1, EMMPRIN, MMP-1, 2, 9, tissue inhibitor of metalloproteinase-1, and Hyalunonan. Knee flexion angle was measured before and at 4 weeks after surgery. There was a significant correlation between the EMMPRIN levels and knee flexion angle (r = 0.557, p = 0.0148). Western blot analysis of the exudate showed a prominent band for EMMPRIN at 27 kDa. On the other hand, there was no correlation between the TGF-beta1 levels and the knee flexion angle. This study showed that EMMPRIN levels after TKA affect the postoperative ROM. As to clinical relevance, EMMPRIN in the exudate after TKA is a promising biological indicator to predict difficulty in restoring postoperative ROM.

Impact of Surgical Timing on Clinical Outcomes in Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using Hamstring Tendon Autografts.

BACKGROUND: To date, no studies have analyzed the influence on clinical outcomes of the interval between an anterior cruciate ligament (ACL) injury and double-bundle (DB) reconstruction with hamstring tendon autografts. HYPOTHESES: (1) Performing ACL reconstruction sooner after an injury will reduce postoperative anterior and rotatory knee instability, (2) postoperative range of knee motion or functional results will not be affected by different intervals between injury and surgery, and (3) preoperative isokinetic peak torque of the quadriceps and hamstring muscles will be lower in patients undergoing surgery earlier, while postoperative muscle strength will not be affected by surgery timing. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study was conducted on a total of 171 patients who had undergone anatomic DB ACL reconstruction with hamstring tendon autografts. The patients were divided into 3 groups based on the time to surgery: (1) ≤1 month after the injury (group E; n = 25), (2) between 1 and 3 months after the injury (group M; n = 72), and (3) >3 months after the injury (group D; n = 74). Patients were assessed for a minimum of 2 years after surgery. RESULTS: Concerning postoperative anterior laxity, 1-way analysis of variance demonstrated a significant difference (P = .0274) among the 3 groups. Anterior laxity was significantly less in group E than in group D (P = .0206). Spearman rank correlation analysis showed a significant correlation (ρ = 0.200; P = .0327) between anterior knee laxity and time to surgery. Also, a significant correlation (P = .0461) was found between the degree of the pivot-shift phenomenon and time to surgery. There were no significant differences in loss of knee extension or flexion among the 3 groups, nor were there any differences in the Lysholm knee score or International Knee Documentation Committee grade. Postoperatively, there were no significant differences in peak torque of the quadriceps or hamstring muscles among the 3 groups. CONCLUSION: Early DB reconstruction led to significantly less anterior laxity compared with delayed reconstruction. There were no significant differences in postoperative range of knee motion or functional results among the 3 time intervals between injury and surgery in this study.

Effects of Remnant Tissue Preservation on Tunnel Enlargement After Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using the Hamstring Tendon.

BACKGROUND: The effects of remnant tissue preservation on tunnel enlargement after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction have not yet been established. HYPOTHESIS: The preservation of ACL remnant tissue may significantly reduce the degree and incidence of tunnel enlargement after anatomic double-bundle ACL reconstruction, while the remnant-preserving procedure may not significantly increase the incidence of tunnel coalition after surgery. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 79 patients underwent anatomic double-bundle ACL reconstruction. Based on the Crain classification of ACL remnant tissue, 40 patients underwent the remnant-preserving procedure (group P), and the remaining 39 patients underwent the remnant-resecting procedure (group R). There were no differences between the 2 groups concerning all background factors, including preoperative knee instability and intraoperative tunnel positions. All patients were examined using computed tomography and a standard physical examination at 2 weeks and 1 year after surgery. RESULTS: During surgery, the femoral and tibial anteromedial (AM) tunnel sizes in both groups averaged 6.6 and 6.5 mm, respectively. The femoral and tibial posterolateral (PL) tunnel sizes in both groups averaged 6 and 6 mm, respectively. There were no differences in the intraoperative tunnel positions and tunnel sizes between groups. Concerning the femoral AM tunnel, the degree of tunnel enlargement in the oblique coronal and oblique axial views in group P was significantly less than that in group R (P = .0068 and .0323, respectively). Regarding the femoral AM tunnel cross-sectional area, the degree and incidence of tunnel enlargement in group P were significantly less than those in group R (P = .0086 and .0278, respectively). There were no significant differences in tunnel coalition between groups. In each group, there were no significant relationships between tunnel enlargement and each clinical outcome. CONCLUSION: Remnant preservation in anatomic double-bundle ACL reconstruction reduced enlargement of the femoral AM tunnel and did not increase the incidence of tunnel coalition. This is one of the advantages of remnant-preserving ACL reconstruction.