Middle-term outcome and complications after primary total hip arthroplasty using a contemporary titanium tapered wedge cementless femoral stem.

The purpose of this study is to evaluate the results and intraoperative or postoperative complications of primary total hip arthroplasty (THA) using a contemporary tapered wedge titanium femoral component. A total of 213 THAs in 187 patients were followed up more than 5 years (mean, 102 months ; range, 60-150). The mean age at surgery was 64.2 years (range, 20?89 years). These patients were clinically evaluated using the JOA scoring system and radiographically host bone reactions around the implants, as well as femoral loosening. The mean JOA score improved from 49 (range, 21?75) to 92 (range, 59?100). All 12 patients with poor results (JOA < 75) coexisted with cerebral, spinal, joint, and musculoskeletal disorders. At the final follow-up, implant survival was 100%. Complications occurred in 23 hips. They consisted of 12 hips with intra-operative fractures, 2 hips with sciatic nerve palsy, one hip with infections, 3 hips with recurrent dislocations, and 8 hips with aseptic cup loosening. In conclusion, we have shown excellent survival rate of the contemporary tapered wedge stem in primary THA ; however, patients with coexisting diseases could not acquire sufficient improvement in hip function and ambulatory ability. J. Med. Invest. 70 : 471-475, August, 2023.

Effectiveness of Primary Total Hip Arthroplasty Combined with Intra-articular and Intravenous Tranexamic Acid: A Retrospective Analysis of Number of Doses and Dose Strength.

Introduction: Total hip arthroplasty is a very effective reconstructive surgery but is often associated with massive perioperative bleeding, which leads to anemia. Tranexamic acid (TXA) minimizes bleeding and the need for blood transfusion. However, no universal standard TXA dosing regimen has been established. The objectives of this study were (1) whether there was a difference in the amount of decrease in perioperative mean hemoglobin (Hb) level between a single topical administration of TXA and intravenous and topical combination administration, and we also investigated whether there was a difference in the amount of decrease in the perioperative mean Hb level due to the difference in the local dose of TXA. Methods: We retrospectively reviewed 292 hips between June 2013 and October 2020. The decrease in Hb level (difference between the preoperative value and the 7-day postoperative value) was used to estimate total perioperative blood loss. The mean perioperative reduction in Hb was compared between hips that received intravenous TXA preoperatively and intra-articular TXA at wound closure (combination administration group) and those that received only intra-articular TXA (single dose group). It was also compared by different local doses of tranexamic acid. Results: The mean reduction in Hb was significantly smaller in the combination administration group than in the single dose group. However, no significant difference was observed due to the difference in the local dose of TXA administered at the time of wound closure. Conclusion: Reducing perioperative bleeding decreases the invasiveness of surgery, which is important from the perspective of medical safety.

OLA-1, an Obg-like ATPase, integrates hunger with temperature information in sensory neurons in C. elegans.

Animals detect changes in both their environment and their internal state and modify their behavior accordingly. Yet, it remains largely to be clarified how information of environment and internal state is integrated and how such integrated information modifies behavior. Well-fed C. elegans migrates to past cultivation temperature on a thermal gradient, which is disrupted when animals are starved. We recently reported that the neuronal activities synchronize between a thermosensory neuron AFD and an interneuron AIY, which is directly downstream of AFD, in well-fed animals, while this synchrony is disrupted in starved animals. However, it remained to be determined whether the disruption of the synchrony is derived from modulation of the transmitter release from AFD or from the modification of reception or signal transduction in AIY. By performing forward genetics on a transition of thermotaxis behavior along starvation, we revealed that OLA-1, an Obg-like ATPase, functions in AFD to promote disruption of AFD-AIY synchrony and behavioral transition. Our results suggest that the information of hunger is delivered to the AFD thermosensory neuron and gates transmitter release from AFD to disrupt thermotaxis, thereby shedding light onto a mechanism for the integration of environmental and internal state to modulate behavior.

Efficacy of preoperative autologous blood storage in one-stage bilateral total knee arthroplasty.

BACKGROUND: One-stage bilateral total knee arthroplasty (TKA) has the advantages of a single hospital stay, shorter rehabilitation, and reduced financial burden on patients. However, perioperative bleeding is greater with one-stage bilateral TKA than with unilateral TKA and is more likely to require allogeneic blood transfusion. At our hospital, we normally store autologous blood about 1 month before surgery to reduce the need for allogeneic blood transfusion and avoid its adverse reactions as much as possible. The purpose of this study was to determine the efficacy of preoperative autologous blood storage for patients undergoing one-stage bilateral TKA. METHODS: We retrospectively examined the allogeneic blood transfusion avoidance rate and the perioperative decrease in hemoglobin (Hb) level in 166 patients according to whether or not they had preoperative autologous blood stored. The patients for whom blood was stored were then subdivided according to whether the amount of blood stored was 400 mL or 200 mL. RESULTS: Excluding allogeneic transfusion cases, the mean perioperative decrease in Hb was significantly lower in the patients with stored blood than in those without stored blood (3.5 g/dL vs 4.4 g/dL, p < 0.001). The allogeneic blood transfusion avoidance rate was significantly higher in the group with stored blood (98.5% vs 86.7%, p < 0.01). In the group with stored blood, the transfusion avoidance rate was higher, but not significantly, in the subgroup with 400 mL of blood stored than in those with 200 mL of blood stored (100% vs 97.5%) and the mean perioperative decrease in Hb was 3.5 g/dL in both blood storage volume groups. CONCLUSIONS: Preoperative autologous blood storage can help increase the likelihood of avoiding allogeneic blood transfusion in patients undergoing one-stage bilateral TKA.

A Rare Case of Extremely Severe Heterotopic Ossification after Primary Total Hip Arthroplasty due to Persistent Mild Periprosthetic Joint Infection.

Periprosthetic joint infection (PJI) caused by coagulase-negative staphylococci (CNS) can be a mild, persisting infection. Although heterotopic ossification (HO) is common following total hip arthroplasty (THA), the etiology of severe HO remains unclear. Herein, we describe a rare case of extremely severe HO after a PJI associated with a Staphylococcus caprae infection in a 78-year-old male patient. The patient had poorly controlled diabetes mellitus with no diabetic complications. The patient had no previous history of hip surgery, hip injury, or systemic bacterial infection. Immediately after the initial THA, he developed intermittent low-grade fever (37°C), which persisted for 3 months; consequently, he also reported mild hip pain during walking. He experienced a gradual decrease in hip range of motion within 5 years after the surgery, with progressive gait impairment. Two revision surgeries were required for the successful treatment of this difficult case. The patient's hip function improved, and the PJI was controlled following the second revision surgery. Based on the clinical course, CNS-caused PJI may lead to severe HO. This possibility warrants verification from an accumulated number of cases.

Changes in muscle strength of the hip after rotational acetabular osteotomy: a retrospective study.

AIMS: Rotational acetabular osteotomy (RAO) is an effective joint-preserving surgical treatment for acetabular dysplasia. The purpose of this study was to investigate changes in muscle strength, gait speed, and clinical outcome in the operated hip after RAO over a one-year period using a standard protocol for rehabilitation. PATIENTS AND METHODS: A total of 57 patients underwent RAO for acetabular dysplasia. Changes in muscle strength of the operated hip, 10 m gait speed, Japanese Orthopaedic Association (JOA) hip score, and factors correlated with hip muscle strength after RAO were retrospectively analyzed. RESULTS: Three months postoperatively, the strength of the operated hip in flexion and abduction and gait speed had decreased from their preoperative levels. After six months, the strength of flexion and abduction had recovered to their preoperative level, as had gait speed. At one-year follow-up, significant improvements were seen in the strength of hip abduction and gait speed, but muscle strength in hip flexion remained at the preoperative level. The mean JOA score for hip function was 91.4 (51 to 100)) at one-year follow-up. Body mass index (BMI) showed a negative correlation with both strength of hip flexion (r = -0.4203) and abduction (r = -0.4589) one year after RAO. Although weak negative correlations were detected between strength of hip flexion one year after surgery and age (r = -0.2755) and centre-edge (CE) angle (r = -0.2989), no correlation was found between the strength of abduction and age and radiological evaluations of CE angle and acetabular roof obliquity (ARO). CONCLUSION: Hip muscle strength and gait speed had recovered to their preoperative levels six months after RAO. The clinical outcome at one year was excellent, although the strength of hip flexion did not improve to the same degree as that of hip abduction and gait speed. A higher BMI may result in poorer recovery of hip muscle strength after RAO. Radiologically, acetabular coverage did not affect the recovery of hip muscle strength at one year's follow-up. A more intensive rehabilitation programme may improve this. Cite this article: Bone Joint J 2019;101-B:1459-1463.

KIN-4/MAST kinase promotes PTEN-mediated longevity of Caenorhabditis elegans via binding through a PDZ domain.

PDZ domain-containing proteins (PDZ proteins) act as scaffolds for protein-protein interactions and are crucial for a variety of signal transduction processes. However, the role of PDZ proteins in organismal lifespan and aging remains poorly understood. Here, we demonstrate that KIN-4, a PDZ domain-containing microtubule-associated serine-threonine (MAST) protein kinase, is a key longevity factor acting through binding PTEN phosphatase in Caenorhabditis elegans. Through a targeted genetic screen for PDZ proteins, we find that kin-4 is required for the long lifespan of daf-2/insulin/IGF-1 receptor mutants. We then show that neurons are crucial tissues for the longevity-promoting role of kin-4. We find that the PDZ domain of KIN-4 binds PTEN, a key factor for the longevity of daf-2 mutants. Moreover, the interaction between KIN-4 and PTEN is essential for the extended lifespan of daf-2 mutants. As many aspects of lifespan regulation in C. elegans are evolutionarily conserved, MAST family kinases may regulate aging and/or age-related diseases in mammals through their interaction with PTEN.

Screening for nasal carriage of Staphylococcus aureus among patients scheduled to undergo orthopedic surgery: Incidence of surgical site infection by nasal carriage.

BACKGROUND: Staphylococcus aureus (S. aureus), including MRSA, is considered to be the leading cause of surgical site infection (SSI) after orthopedic surgery. We screened for nasal carriers of S. aureus among patients who were scheduled to undergo orthopedic surgery at our hospital to reveal the effect of nasal S. aureus carriage on SSI. Our study design clearly has the intent of finding S. aureus nasal carriage and eradicating MRSA when found, and this strategy is to verify whether it's effective for preventing orthopedic surgical infections. METHODS: Subjects were 4148 patients who underwent preoperative screening for nasal carrier and subsequently underwent orthopedic surgery during a 7-year period between April 2007 and March 2014. The incidence of SSI among patients who were operated in our department was investigated, and the rates were compared between patients with and without nasal carriage to reveal the effect of preoperative nasal carriage on SSI. RESULTS: In total, 1036 patients were nasal carriers of S. aureus (carriage rate, 25.0%), whereas 140 patients carried MRSA (carriage rate, 3.4%). SSI developed in 24 patients [incidence, 0.58% (24/4148)] consisting of 12 non-carriers [0.39% (12/3112)] and 12 carriers [1.16% (12/1036)] with a significant difference in the incidence between the groups. Among 24 cases of SSI, more than half (13 cases) were caused by bacterial species other than S. aureus or those that could not be detected by the tests used. Only 7 patients out of 24 SSI patients, S. aureus was the bacterium detected in preoperative nasal cultures and the causal bacterium for SSI (concordance rate of 29.2%). CONCLUSIONS: It was difficult to reduce the incidence rate of SSI in eradication group to the same level as nasal culture negative group. However, nasal carriage of S. aureus or MRSA may be a risk factor for SSI in orthopedic surgery.

Failure rates of Asian-type anatomic medullary locking stemmed metal-on-metal total hip replacement: A cause for adverse tissue reactions to metal debris (ARMD).

BACKGROUND: Adverse tissue reaction to metal debris (ARMD) as a secondary complication of Metal-on-metal total hip replacement (MoM THR) has been of concern. We have been performing cementless MoM THR using an Asian-type anatomic medullary locking (AML) stem. The purpose of this study is to examine the incident rate of ARMD, and the implant survival rate. METHODS: The study included 187 patients (211 hip joints) who underwent MoM THR between February 2007 and November 2009 at our hospital and who were followed up for a minimum of 6 years. The cases included 174 female joints and 37 male joints. The average age at the time of surgery was 68.4 years. The average postoperative follow-up period was 87.5 months. RESULTS: ARMD was observed in 23 joints postoperatively, and the incidence rate was 10.9%. Most of the instances occurred within the first 30 months postoperatively. Revision surgery was performed for 14 joints after conservative treatment failed, and we changed the bearing surface. During the intraoperative observation, black-colored deposition of metal debris on the head-neck junction was observed in 13 cases. Kaplan-Meier analysis using the replacement surgery as the end point showed that this implant has a survival rate of 93.8% 7 years after the primary surgery. CONCLUSIONS: We conclude that the major cause of failure of Asian-type AML stemmed MoM THR is likely the breakage of the fixation between the taper neck and metal head at the head-neck junction.

Single-Cell Memory Regulates a Neural Circuit for Sensory Behavior.

Unveiling the molecular and cellular mechanisms underlying memory has been a challenge for the past few decades. Although synaptic plasticity is proven to be essential for memory formation, the significance of "single-cell memory" still remains elusive. Here, we exploited a primary culture system for the analysis of C. elegans neurons and show that a single thermosensory neuron has an ability to form, retain, and reset a temperature memory. Genetic and proteomic analyses found that the expression of the single-cell memory exhibits inter-individual variability, which is controlled by the evolutionarily conserved CaMKI/IV and Raf pathway. The variable responses of a sensory neuron influenced the neural activity of downstream interneurons, suggesting that modulation of the sensory neurons ultimately determines the behavioral output in C. elegans. Our results provide proof of single-cell memory and suggest that the individual differences in neural responses at the single-cell level can confer individuality.

Subchondral cysts in dysplastic osteoarthritic hips communicate with the joint space: analysis using three-dimensional computed tomography.

INTRODUCTION: Bone cyst formation in hips increases as osteoarthritis worsens. Although bone cysts in hips have been described in many studies, their etiology remains unclear and under debate. The purpose of this study was to investigate the communication between a bone cyst and the joint space, as well as the relationship between the severity of osteoarthritis and the formation of subchondral bone cysts in dysplastic hips. METHOD: We studied bone cysts from 150 dysplastic hips in 97 patients by computed tomography (CT) and plain radiography. We investigated the distribution of the bone cysts and the presence or absence of a communication path between the cysts and the joint space by three-dimensional (3D) CT. RESULT: Of the 150 hips, 94 acetabula and 55 femoral heads were found to contain cysts. Of the 94 hips containing acetabular cysts, 89 and 5 hips showed black lines and gray lines connecting the cyst and the joint space, respectively, on 3D-CT. The rate of cyst presentation in the hip increased as the joint space became narrower. The number of hips that possessed cysts in the anterior and/or middle portion was significantly higher than that in the posterior portions. CONCLUSION: Bone cysts in dysplastic osteoarthritic hips were found to communicate with the joint space in all cases. This suggests that the formation and enlargement of the cysts in dysplastic hips may be greatly influenced by the joint fluid. Cyst formation was initially observed in the anterior acetabulum, gradually progressing to involve the entire joint, including the posterior acetabulum and the femoral head, with worsening of the osteoarthritis.

Clinical outcomes of spinal surgery in patients treated with hemodialysis.

STUDY DESIGN: Retrospective study. OBJECTIVE: The purpose of this study is to review clinical outcomes, including survival rate, and to discuss the potential benefit of surgical treatments for spinal disorders in patients treated with long-term hemodialysis (HD). SUMMARY OF BACKGROUND DATA: Long-term HD is known to possibly cause destructive spondyloarthropathy (DSA) with spinal canal stenosis. There have been few reports, however, regarding clinical outcomes and patient survival rates after spinal surgeries in this population. METHODS: We retrospectively reviewed 33 chronic HD patients who underwent 21 cervical and 13 lumbar spinal surgeries. According to the radiologic findings, we divided them into the non-DSA and the DSA groups. In general, only decompression was performed for the non-DSA patients, whereas spinal fusion was added for the DSA patients. We analyzed the following data, respectively: male-female ratio, age, operative time, estimated blood loss, duration of HD, follow-up duration, preoperative and postoperative Japanese Orthopaedic Association score, improvement ratio of the Japanese Orthopaedic Association score, amyloid deposition characteristics, and survival rate. RESULTS: All patients improved neurologically and functionally after surgery. There were significant differences in the operative time between the DSA and the non-DSA groups in patients with cervical spinal lesions, whereas in patients with lumbar spinal lesions, there were significant differences in sex, operative time, and estimated blood loss. Amyloid deposition was found signficantly more commonly in DSA than in non-DSA patients and was associated with a longer duration of HD. Nine patients died within 49 months of the surgery because of HD-related complications, but there was no surgery-related morbidity. Kaplan-Meier analysis showed a trend toward decreased survival rate in non-DSA patients more than 40 months after the index surgery. CONCLUSIONS: Even in patients treated with long-term HD, spinal surgeries reliably obtain neurological and functional improvement if surgeons judge the preoperative inclusion criteria correctly. However, if surgeries are necessary for these patients, surgeons should consider the patients' comorbidity-related survival rate after the spinal surgeries.

Retrospective study of deep surgical site infections following spinal surgery and the effectiveness of continuous irrigation.

Surgical site infection (SSI) is an unfortunate and unpreventable complication of any surgical intervention including spinal surgery. Early deep SSI (EDSSI) after instrumented spinal fusion are particularly difficult to manage due to the implanted, and possibly infected, instrumentation. The purpose of this study is to retrospectively review patients who underwent spinal surgery, investigate the rate of EDSSI, identify patient-related and surgery-related risk factors and to assess the effectiveness of continuous indwelling irrigation on the eradication of these infections. A total of 814 patients (319 women and 495 men) who underwent spinal surgery were enrolled. Mean age at the initial surgery was 57.4 years old. Infections that penetrated the deep fascia within 1 month after the initial operation were considered as EDSSI. The rate of EDSSI, causal organisms, infection management and resolution were studied. Furthermore, we examined the patient-related and the operation-related risk factors. An overall incidence of EDSSI of 1.1% was found. In 177 patients with diabetes mellitus (DM), two patients (1.1%) developed EDSSI. In 28 patients receiving chronic haemodialysis (HD), two patients with infections (7.1%) were identified, which was statistically significantly greater than the other patient populations. Both operative time and intraoperative blood loss were significantly greater in patients with EDSSI than in non-infected patients. Furthermore, the rate of EDSSI in patients undergoing instrumented spinal fusion (3.8%) was significantly higher than that in the other patients. In the nine patients who developed EDSSI, the causal organisms were identified and treated by surgical debridement, antibiotic therapy and continuous indwelling surgical site irrigation. All infections resolved, and no recurrence has been observed at final follow-up. Removal of the instrumentation was required in only one patient. Based on our results, we believe that continuous surgical site irrigation is an effective adjunct in the surgical treatment for early SSI following spinal surgery.

Otx-dependent expression of proneural bHLH genes establishes a neuronal bilateral asymmetry in C. elegans.

Bilateral asymmetry in Caenorhabditis elegans arises in part from cell lineages that differ on the left and right sides of the animal. The unpaired MI neuron descends from the right side of an otherwise left-right symmetric cell lineage that generates the MI neuron on the right and the e3D epithelial cell on the left. We isolated mutations in three genes that caused left-right symmetry in this normally asymmetric cell lineage by transforming MI into an e3D-like cell. These genes encode the proneural bHLH proteins NGN-1 and HLH-2 and the Otx homeodomain protein CEH-36. We identified the precise precursor cells in which ceh-36 and ngn-1 act, and showed that CEH-36 protein is asymmetrically expressed and is present in an MI progenitor cell on the right but not in its bilateral counterpart. This asymmetric CEH-36 expression promotes asymmetric ngn-1 and hlh-2 expression, which in turn induces asymmetric MI neurogenesis. Our results indicate that this left-right asymmetry is specified within the two sister cells that first separate the left and right branches of the cell lineage. We conclude that the components of an evolutionarily conserved Otx/bHLH pathway act sequentially through multiple rounds of cell division on the right to relay an initial apparently cryptic asymmetry to the presumptive post-mitotic MI neuron, thereby creating an anatomical bilateral asymmetry in the C. elegans nervous system.

Arthroplasty using a custom-made cemented total hip prosthesis for an extensive giant cell tumor of the proximal femur: report of a patient followed up for over 30 years.

We report the case of a 26-year-old man who had a pathologic transtrochanteric fracture of the left femur due to a grade II giant cell tumor affecting the neck and the trochanteric area. This patient underwent complete resection of the tumor and arthroplasty using a custom-made cemented total hip prosthesis. The good radiologic and functional results of the surgery have been maintained for over 30 years without local recurrence or lung metastasis. Moreover, new bone formation was observed at the reattachment sites of abductors, iliopsoas tendons and vastus lateralis to the femoral component of the prosthesis although local bone resorption was detected at the upper lateral part of the femoral stem and zone I of the cup side.

Life expectancies of Japanese patients with rheumatoid arthritis: a review of deaths over a 20-year period.

We investigated trends in life expectancy in rheumatoid arthritis (RA) patients, reviewing records for 286 patients (204 female, 82 male) who had died over the past 20 years. The average age at death was 68.8 years before 1990, increasing to 72.1 years after 2001. Trends in disease modifying anti-rheumatic drugs (DMARDs) saw gold preparations (45.2%) predominate before 1990, sulphydryl donor agents (53.6%) from 1991 to 2000, then methotrexate (43.0%) after 2001. The most common causes of death were infectious diseases up to 1995, rheumatic disease 1996-2000, and cardiovascular events and malignancies after 2001. Major advances in surgical interventions, such as joint replacement surgery, occurred after 1990. Surgical intervention followed by a period of rehabilitation maintained a favourable level of activities of daily living (ADLs), The requirements for favourable life expectancy are control of RA inflammation and maintenance of a favourable level of ADLs. Although recently developed DMARDs and biological agents show promise, caution is required to avoid serious adverse reactions. Optimum care of patients with RA will require preventive measures and early intervention for infections and rheumatic diseases, as well as for lifestyle diseases, osteoporosis and malignancies.

Treatment of dysplastic osteoarthritis with labral tear by Chiari pelvic osteotomy: outcomes after more than 10 years follow-up.

INTRODUCTION: The presence of a damaged labrum is one of many factors influencing the outcomes of Chiari pelvic osteotomy. However, there are few previous papers describing the long-term outcomes of Chiari pelvic osteotomy with labrectomy. The purpose of this study was to evaluate the long-term clinical and radiological outcomes of Chiari pelvic osteotomy for dysplastic hips with labral tears. We compared outcomes between labrectomy (+) and labrectomy (-) groups. PATIENTS AND METHODS: Chiari pelvic osteotomies were performed by one surgeon on 34 dysplastic hips with labral tears between 1983 and 1996, in which labrectomy was performed on 23 hips but not on 11 hips. Three patients undergoing labrectomy were lost to follow-up evaluation within 5 years after surgery. The average age of the remaining 31 patients was 35.5 years (range, 16-54 years). The clinical and radiographic surveillance averaged 16.0 years (range, 10-23.3 years). RESULTS: In all patients, pain disappeared after the operation. At the end of the study, 8 of the 31 patients displayed clinical deterioration. Progression of osteoarthritis (OA) was observed in 11 hips. Patients with poor results have not opted for revision surgery except for one patient. In the labrectomy (+) group, 10 of the 20 hips showed progression of OA and the clinical outcomes of 6 patients deteriorated. In the labrectomy (-) group, 1 of the 11 hips showed progression of OA and 2 patients deteriorated clinically. Radiological outcomes differed significantly between the two groups. CONCLUSION: Labrectomy accompanying Chiari pelvic osteotomy is an acceptable procedure for relieving pain caused by the damaged labrum, but the outcomes have a tendency to deteriorate after 10 or more years postoperatively.

Replication of reported genetic associations of PADI4, FCRL3, SLC22A4 and RUNX1 genes with rheumatoid arthritis: results of an independent Japanese population and evidence from meta-analysis of East Asian studies.

We conducted population-based association tests for the four selected SNPs (rs2240340/padi4_94, rs7528684/fcrl3_3, rs3792876/slc2F2 and rs2268277/runx1) previously reported to be associated with rheumatoid arthritis (RA). The study population consisted of 950 unrelated Japanese subjects with RA and 507 controls, none of whom had previously been tested for these variants. Only the SNP rs2240340/padi4_94 was modestly associated with RA [allele odds ratio (OR) 1.22, 95% confidence interval (CI) 1.04-1.43, P=0.012]. The most significant association effect was found for genotype contrast between minor and major allele homozygotes (OR 1.53, 95% CI 1.10-2.12, P=0.010). No other SNPs showed a statistically significant association with RA in our population. Meta-analysis of published studies and our new data confirmed a highly significant association between PADI4 gene SNPs and increased risk of RA in East Asian populations (allele fixed-effects summary OR 1.31, 95% CI 1.22-1.41, P<0.0001). We found some evidence for an association of either rs7528684/fcrl3_3 or rs3792876/slc2F2 with RA; however, because the magnitudes of effects were apparently much weaker than those reported in the initial positive reports, and there were substantial levels of inter-study OR heterogeneity, we concluded that additional studies are needed to fully understand the present results.

PKC412 (CGP41251) modulates the proliferation and lipopolysaccharide-induced inflammatory responses of RAW 264.7 macrophages.

PKC412 (CGP41251) is a multitarget protein kinase inhibitor with anti-tumor activities. Here, we investigated the effects of PKC412 on macrophages. PKC412 inhibited the proliferation of murine RAW 264.7 macrophages through induction of G2/M cell cycle arrest and apoptosis. At non-toxic drug concentrations, PKC412 significantly suppressed the lipopolysaccharide (LPS)-induced release of TNF-alpha and nitric oxide, while instead enhancing IL-6 secretion. PKC412 attenuated LPS-induced phosphorylations of MKK4 and JNK, as well as AP-1 DNA binding activities. Furthermore, PKC412 suppressed LPS-induced Akt and GSK-3beta phosphorylations. These results suggest that the anti-proliferative and immunomodulatory effects of PKC412 are, at least in part, mediated through its interference with the MKK4/JNK/AP-1 and/or Akt/GSK-3beta pathways. Since macrophages contribute significantly to the development of both acute and chronic inflammation, PKC412 may have therapeutic potential and applications in treating inflammatory and/or autoimmune diseases.

Total hip arthroplasty in osteopetrosis using computer-assisted fluoroscopic navigation.

Hybrid total hip arthroplasty with computer-assisted fluoroscopic navigation was performed on a patient with osteoarthritis due to an autosomal dominant form of osteopetrosis. The surgical procedures were difficult because the bone was extremely hard and brittle with obliteration of the medullary cavity. Especially, preparation of a femoral canal for the stem was technically challenging and required changes from a conventional surgical procedure. Therefore, we used a computer-assisted fluoroscopic navigation system to create the femoral cavity for the stem, and an accurate placement of the prosthesis was achieved. Navigation guidance can be a useful tool when performing arthroplasty in patients with hip osteoarthritis associated with osteopetrosis.