A randomized controlled clinical and radiological trial about outcomes of navigation-assisted TKA compared to conventional TKA: long-term follow-up.

PURPOSE: Well balanced knees with good alignment are essential for a well-functioning TKA with long survival of its implants. This prospective randomized study comparing navigation-assisted TKA and conventional TKA reported the clinical and radiological outcomes at a follow-up of 9 years. The purpose of this study was to compare the clinical and radiological outcomes for patients who underwent navigation-assisted TKA or conventional TKA after long-term follow-up. METHODS: A total of 80 patients (88 knees) were available for physical and radiological examination 9 years after TKA. Clinical outcomes were evaluated using HSS, WOMAC, and KS function and pain scores. And radiological outcomes of the component loosening and its survivorship during 9-year follow-up were also evaluated. RESULTS: There were no significant differences in the field of clinical outcomes between the two groups. In terms of radiological outcomes, the navigation group had fewer alignment outliers (7.3 vs 20 %, p = 0.006). Although the clinical outcomes showed no differences between the two groups, the survival rate was slightly better in the navigation group than in the conventional group without statistical significance (best-case scenario 100 vs 95.3 %, n.s., worst-case scenario 95.6 vs 88.4 %, n.s.). CONCLUSION: Navigation-assisted TKA produced better alignment outcomes and better survival rates than conventional instruments although some of the differences were not statistically significant. LEVEL OF EVIDENCE: I.

Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS).

BACKGROUND: Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382). RESULTS: Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3. CONCLUSIONS: SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.

Tumours with elevated levels of the Notch and Wnt pathways exhibit efficacy to PF-03084014, a γ-secretase inhibitor, in a preclinical colorectal explant model.

BACKGROUND: Dysregulation of the Notch pathway has been identified to play an important role in the development and progression of colorectal cancer (CRC). In this study, we used a patient-derived CRC explant model to investigate the efficacy of the clinical γ-secretase inhibitor (GSI) PF-03084014. METHODS: A total of 16 CRC explants were treated with PF-03084014. Knockdown of RBPjκ gene was used to determine the specificity of PF-03084014. Evaluation of the Notch and Wnt pathways in CRC explant tumours was performed by gene array and immunoblotting. RESULTS: We identified a subset of CRC tumours that exhibited elevations of the Notch and Wnt pathways sensitive to PF-03084014. Treatment with the GSI resulted in a significant reduction in cleaved Notch, Axin2 (Wnt-dependent gene) and active ß-catenin. In addition, knockdown of the RBPjκ gene showed that PF-03084014 has specificity for the Notch pathway in an HCT116 cell line xenograft model. Finally, an increase in apoptosis was observed in CRC001- and CRC021-sensitive tumours. CONCLUSION: This study provides evidence that inhibition of γ-secretase may be beneficial in a subset of patients with elevated levels of the Wnt and Notch pathways.

Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: MMP is a key enzyme in the degradation of extracellular matrices, and its expression plays important roles in inflammatory diseases. Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has been shown to exhibit many pharmacological activities, such as anti-cancer, anti-inflammatory and anti-infection activities. In this study, we aimed at the inhibitory effect of cordycepin on IL-1beta-induced MMP-1 and MMP-3 expression as well as the molecular basis using RA synovial fibroblasts (RASFs). METHODS: RASFs were isolated from synovial tissue obtained from 12 patients with RA and cultured in monolayer. Expression of MMP-1 and MMP-3 was evaluated using western blotting and real-time PCR. Chemokines were analysed by ELISA. The phosphorylation of mitogen-activated protein kinase was measured by western blotting. Electrophoretic mobility shift assay was performed to evaluate binding activities of DNA to nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). RESULTS: Cordycepin inhibited IL-1beta-induced MMP-1 and MMP-3 expressions in RASFs in a dose-dependent manner. Among various chemokines [such as monocyte chemoattractant protein-1 (MCP-1), GRO-alpha, regulated upon activation, normal T-cell expressed and presumably secreted (RANTES) and epithelial neutrophil activating peptide 78 (ENA-78)], cordycepin specifically blocked IL-1beta-induced ENA-78 production in RASF. Moreover, cordycepin significantly inhibited IL-1beta-induced p38/JNK and AP-1 activation, but not extracellular signal-regulated kinase (ERK) and NF-kappaB activation. CONCLUSIONS: Cordycepin is a potent inhibitor of IL-1beta-induced chemokine production and MMP expression and strongly blocks the p38/JNK/AP-1 signalling pathway in RASFs.

Efficacy of chemotherapy as a first-line treatment in ocular adnexal extranodal marginal zone B-cell lymphoma.

BACKGROUND: Radiotherapy is commonly used as a first-line treatment for localized ocular adnexal extranodal marginal zone B-cell lymphoma (EMZBL), despite its ophthalmologic complications. This study was undertaken to analyze the efficacy of first-line chemotherapy in treating EMZBL. Chemotherapy was followed by radiotherapy only in recurrent cases. PATIENTS AND METHODS: Twenty-one patients with histologically confirmed EMZBL were treated with combination of cyclophosphamide, vincristine, and prednisolone (CVP). Radiotherapy was given to CVP failure cases. RESULTS: CVP alone resulted in overall response rate of 100% [complete remission (CR), 76.2%]. After a median follow-up of 58 months, 14 (66.7%) of 21 cases were disease free with CVP alone, while seven cases showed disease progression, including two extra-orbital and five local failures. Radiotherapy was delivered to five local failure cases, who subsequently achieved CR with late ophthalmologic complications. There were tolerable adverse events associated with CVP. CONCLUSIONS: Front-line CVP, in conjunction with radiotherapy in recurrent cases, is effective and well tolerated in patients with localized ocular adnexal EMZBL.

Comparison of functional results with navigation-assisted minimally invasive and conventional techniques in bilateral total knee arthroplasty.

This study was undertaken to compare the clinical and radiological results achieved using navigation-assisted minimally invasive surgery (NA-MIS) and conventional (CON) techniques in 42 bilateral total knee arthroplasty (TKA) patients with a minimum follow-up of one year. Clinical evaluations were performed using range of motion (ROM), Hospital for Special Surgery (HSS) scores, and Western Ontario and McMaster University (WOMAC) scores (pain, functional, and total) at 3, 6 and 9 months and one year postoperatively. Patients' subjective preferences and radiological indices, including mechanical axis and coronal inclinations of the prostheses, were compared at one year postoperatively. NA-MIS TKA yielded better HSS and WOMAC total scores than CON TKA up to six months, and a better WOMAC pain score up to 9 months. However, these differences were not significant at one year postoperatively. ROM was comparable in both groups at all times, but more patients preferred the NA-MIS side to the CON side. Radiological results showed no differences in mean values between the two surgical groups, although the NA-MIS group contained fewer outliers than the CON group. In conclusion, NA-MIS TKA was associated with better clinical results up to 6 or 9 months after surgery, giving more accurate leg alignment than CON TKA.

Genetically engineered transgenic plants with the domain 1 sequence of tobacco mosaic virus 126 kDa protein gene are completely resistant to viral infection.

In many plant RNA viruses, Domains 1, 2 and 3 are conserved in replicase proteins. In order to examine the interference of viral replication by the Domain 1 sequence, we generated transgenic plants transformed with DNA corresponding to the Domain 1 sequence of the TMV 126 kDa protein. This DNA sequence includes the TMV RNA from nucleotides 1 to 2,149, which comprises both the 5'-untranslated and methyl transferase region. The transgenic plants obtained showed complete resistance to TMV infection. The presence of the Domain 1 sequence in the plants completely prevented local necrosis in Nicotiana tabacum cv. Xanthi nc, and any systemic development of symptoms in Nicotiana tabacum Xanthi upon TMV inoculation. Most transgenic plants sustained the conferred resistance even under TMV inoculum concentrations up to as high as 1,000 microg/ml. To detect any accumulation of TMV coat protein or viral RNA in infected transgenic plants, immunochemical tests and Northern blot analyses were carried out. Neither viral RNA or coat protein was detectable in the systemic leaves of the completely resistant transgenic plants, whereas they were accumulated in large quantities in all of the control plants. Because of the conservation of Domain 1 in many plant RNA viruses, the acquisition of resistance to virus infection using the Domain 1 sequence appears to be a very effective strategy for breeding of viral resistant plants.

Inhibitory effects of butanol fraction of the aqueous extract of Forsythia koreana on the nitric oxide production by murine macrophage-like RAW 264.7 cells.

The aim of this study was to investigate the effect of butanol fraction of the aqueous extract of Forsythia koreana fruits on the nitric oxide (NO) production and inducible nitric oxide synthesis (iNOS) gene expression in murine macrophage-like RAW 264.7 cells. Butanol fraction alone affected neither NO production nor iNOS gene expression in macrophage-like RAW 264.7 cells. However, the butanol fraction inhibited NO production and iNOS gene expression in RAW 264. 7 cells stimulated with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). These findings suggest that inhibition of NO production by this butanol fraction in RAW 264.7 cells stimulated with IFN-gamma plus LPS was due to the suppression of iNOS gene expression.

Aseptic synovitis after meniscal repair using the biodegradable meniscus arrow.

We report a case of aseptic synovitis in a 19-year-old man. The synovitis of the left knee developed 13 months after meniscal repair using the biodegradable Meniscus Arrow (Bionx Inc, Malvern, PA). Histologic examination revealed chronic nonspecific synovitis and birefringent materials. Immunohistochemical tests were positive in lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. After arthroscopic synovectomy, pain and swelling of the knee joint were relieved and the patient's range of motion fully recovered. We have found no previous report of aseptic synovitis accompanying meniscal repair using the biodegradable Meniscus Arrow.

Bent plate fixation in combined intertrochanteric and subtrochanteric fractures of the femur.

Twenty-five combined intertrochanteric and subtrochanteric fractures of the femur (Type IV of Kyle's or Type V of Seinsheimer's classification) were treated with a bent plate and followed up through union (average: 2 years). All of the patients received immediate supplementary bone grafting and additional external supports. All but one of the fractures united between 3 and 6 months. Complications were: delayed union (1 case), which was treated by bone graft, trochanteric bursitis (3), and mild coxa vara (2). Anatomical reduction of scattered fragments and its maintenance through bony union were achieved in all cases. The bent plate provided excellent fixation in combined intertrochanteric and subtrochanteric fracture of the femur, and could be a successful alternative for these combined fractures.

Delayed-type hypersensitivity reaction to piperacillin/tazobactam in a patient with an infected total knee replacement.

We describe a patient who developed a delayed-type hypersensitivity reaction to piperacillin/tazobactam in the cement beads and a spacer inserted at revision of total replacement of the left knee. We believe that this is the first report of such a problem. Our experience suggests that a delayed-type hypersensitivity reaction should be considered when a mixture of antibiotics such as piperacillin/tazobactam has been used in the bone cement, beads or spacer and the patient develops delayed symptoms of pain or painful paraesthesiae, fever, rash and abnormal laboratory findings in the absence of infection. The diagnosis was made when identical symptoms were induced by a provocation challenge test.

The complications of high tibial osteotomy: closing- versus opening-wedge methods.

We compared the incidence and severity of complications during and after closing- and opening-wedge high tibial osteotomy used for the treatment of varus arthritis of the knee, and identified the risk factors associated with the development of complications. In total, 104 patients underwent laterally based closing-wedge and 90 medial opening-wedge high tibial osteotomy between January 1993 and December 2006. The characteristics of each group were similar. All the patients were followed up for more than 12 months. We assessed the outcome using the Hospital for Special Surgery knee score, and recorded the complications. Age, gender, obesity (body mass index > 27.5 kg/m(2)), the type of osteotomy (closing versus opening) and the pre-operative mechanical axis were subjected to risk-factor analysis. The mean Hospital for Special Surgery score in the closing and opening groups improved from 73.4 (54 to 86) to 91.8 (81 to 100) and from 73.8 (56 to 88) to 93 (84 to 100), respectively. The incidence of complications overall and of major complications in both groups was not significantly different (p = 0.20 overall complication, p = 0.29 major complication). Logistic regression analysis adjusting for obesity and the pre-operative mechanical axis showed that obesity remained a significant independent risk factor (odds ratio = 3.23) of a major complication after high tibial osteotomy. Our results suggest that the opening-wedge high tibial osteotomy can be an alternative treatment option for young patients with medial compartment osteoarthritis and varus deformity.

The effect of anteroposterior laxity on the range of movement and knee function following a cruciate-retaining total knee replacement.

The amount of anteroposterior laxity required for a good range of movement and knee function in a cruciate-retaining total knee replacement (TKR) continues to be debated. We undertook a retrospective study to evaluate the effects of anteroposterior laxity on the range of movement and knee function in 55 patients following the e-motion cruciate-retaining TKR with a minimum follow-up of two years. The knees were divided into stable (anteroposterior translation, < or = 10 mm, 38 patients) and unstable (anteroposterior translation, > 10 mm, 17) groups based on the anteroposterior laxity, measured using stress radiographs. We compared the Hospital for Special Surgery (HSS) scores, the Western Ontario MacMasters University Osteoarthritis (WOMAC) index, weight-bearing flexion, non-weight-bearing flexion and the reduction of flexion under weight-bearing versus non-weight-bearing conditions, which we referred to as delta flexion, between the two groups at the final follow-up. There were no differences between the stable and unstable groups with regard to the mean HHS and WOMAC total scores, as well as weight-bearing and non-weight-bearing flexion (p = 0.277, p = 0.082, p = 0.095 and p = 0.646, respectively). However, the stable group had a better WOMAC function score and less delta flexion than the unstable group (p = 0.011 and p = 0.005, respectively). Our results suggest that stable knees with laxity < or = 10 mm have a good functional outcome and less reduction of flexion under weight-bearing conditions than unstable knees with laxity > 10 mm following an e-motion cruciate-retaining TKR.

Arthroscopic release for painful subtalar stiffness after intra-articular fractures of the calcaneum.

We describe the surgical technique and results of arthroscopic subtalar release in 17 patients (17 feet) with painful subtalar stiffness following an intra-articular calcaneal fracture of Sanders' type II or III. The mean duration from injury to arthroscopic release was 11.3 months (6.4 to 36) and the mean follow-up after release was 16.8 months (12 to 25). The patient was positioned laterally and three arthroscopic portals were placed anterolaterally, centrally and posterolaterally. The sinus tarsi and lateral gutter were debrided of fibrous tissue and the posterior talocalcaneal facet was released. In all, six patients were very satisfied, eight were satisfied and three were dissatisfied with their results. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score improved from a mean of 49.4 points (35 to 66) pre-operatively to a mean of 79.6 points (51 to 95). All patients reported improvement in movement of the subtalar joint. No complications occurred following operation, but two patients subsequently required subtalar arthrodesis for continuing pain. In the majority of patients a functional improvement in hindfoot function was obtained following arthroscopic release of the subtalar joint for stiffness and pain secondary to Sanders type II and III fractures of the calcaneum.

Effectiveness of raloxifene on bone mineral density and serum lipid levels in post-menopausal women with low BMD after discontinuation of hormone replacement therapy.

OBJECTIVE: To evaluate the effect of raloxifene on bone mineral density (BMD) and serum lipid levels in post-menopausal women who had discontinued hormone replacement therapy (HRT). METHODS: Thirty-four post-menopausal women with low BMD who had taken 60 mg of raloxifene daily for 12 months after discontinuing HRT were evaluated retrospectively. Information about their demographics, fracture history, BMD, lipid profiles and adverse events were collected from medical records and intranet database. The outcome measures were changes in the spine (L2-L4) and femur BMD, serum lipid concentrations, fracture rate and tolerability. RESULTS: The post-menopausal women had a significant increase in their spine (L2-L4) and femur BMD from their baseline BMD [spine, 2.9 +/- 4.6% (P < 0.001); femur, 3.0 +/- 6.6% (P = 0.01)]. Serum low-density lipoprotein (LDL) cholesterol was significantly reduced by 22.6% below baseline after 12 months (P = 0.007). No fractures were observed during therapy. Raloxifene was well tolerated. The most common adverse event was hot flash, which was generally mild. CONCLUSIONS: Raloxifene increases BMD at important skeletal sites, and lowers LDL cholesterol with tolerable adverse events.

Biomechanical test comparing the load to failure of the biodegradable meniscus arrow versus meniscal suture.

The biodegradable Meniscus Arrow (Bionx, Blue Bell, PA) is a newly introduced method for repair of meniscal injury. However, because of a lack of studies, there is still little understanding of its biomechanical behavior. Biomechanical test was carried out to evaluate the load to failure and failure modes of the Meniscus Arrow and to compare the results with those of three traditionally used methods. Thirty-five lateral menisci obtained from Yorkshire pigs were incised longitudinally, simulating a peripheral longitudinal tear, and were repaired by means of Meniscus Arrows (one-point and two-point fixation), as well as with the techniques of knot-end, horizontal, and vertical suture using No. I PDS II monofilament suture. Tensile strength testing was performed according to each repair method with the Instron tensometer (Model No. 5569; Instron, Canton, MA) and its results were analyzed using a computerized statistical program. The average maximal tensile strengths were 113.9 +/- 14.6 N in vertical suture, 75.1 +/- 18.4 N in horizontal suture, 53.9 +/- 6.4 N in knot-end suture, 38.3 +/- 4.3 N in one-point fixation Meniscus Arrow repair, and 56.5 +/- 3.5 N in two-point fixation Meniscus Arrow repair. The initial failure strength for two-point fixation Meniscus Arrow repair is comparable to that of a knot-end suture. Following the results of this study, meticulous caution should be taken when meniscal tears are repaired with Meniscus Arrows.

The intraoperative evaluation of the neurosensory function of the anterior cruciate ligament in humans using somatosensory evoked potentials.

Most of the investigation of the properties of the anterior cruciate ligament (ACL) has focused on its biomechanical functions. There has been increasing interest in the study of the possible neuroreceptor function of the ACL and its role in providing important proprioceptive feedback. Anatomic and histologic studies in humans have shown the presence of neuroreceptors within the anterior cruciate ligament. Indirect evidence exists that proprioception is diminished in the ACL-deficient knee. However, direct evidence in humans of the actual origin of the afferent impulses from within the ACL itself is lacking. Measurement of direct electrical afferent activity, occurring on stimulation of the ACL, should provide this evidence. Somatosensory evoked potentials (SEP) measure the electric potentials evoked in the cerebral cortex upon stimulation of a peripheral neuroreceptor. Carried by the posterior columns of the spinal cord, they reflect activity of the proprioceptive fibers. During arthroscopic procedures performed on nine patients, the normal ACL was stimulated by the use of electrodes applied to the femoral end, midsubstance, and tibial end, and cortical potentials thus evoked were recorded. In all cases, SEPs were recorded at the cerebral cortex upon stimulation of the ACL. The greatest potentials were reported upon stimulation of the midsubstance of the ligament. These findings provide direct evidence for, and strongly support the presence of, active proprioceptive receptors within the intact anterior cruciate ligament of the human knee.