Proximal femoral reconstruction with impaction bone grafting and circumferential metal mesh.

INTRODUCTION: Impaction bone grafting (IBG) using a circumferential metal mesh is one of the options that allow restoration of the femoral bone stock and stability of the implant in revision hip arthroplasty. Here we examine the clinical and radiographic outcome of this procedure using a cemented stem, including experimental analysis of the initial stability of mesh-grafted bone-cemented stem complexes. METHODS: We retrospectively reviewed six hips (six patients) that had undergone femoral revisions with a circumferential metal mesh, impacted bone allografts, and a cemented stem. The mean follow-up period was 3.9 years (range 2.4-4.8 years). Hip joint function was evaluated using the Japanese Orthopaedic Association hip score, and radiographic changes were determined from radiographs. The initial resistance of mesh-grafted bone-cemented stem complexes to axial and rotational force was measured in a composite bone model with various segmental losses of the proximal femur. RESULTS: The hip score improved from 50 (range 10-84) preoperatively to a mean of 74 (range 67-88) at the final follow-up. The overall implant survival rate was 100 % at five years when radiological loosening or revision for any reason was used as the endpoint. No stem subsided more than 3 mm vertically within one year after implantation. Computed tomography showed reconstitution of the femoral canal in a metal mesh. In mechanical analyses, there was no relationship between IBG reconstruction rates under axial compression and stem subsidence or failure load. In contrast, under rotational load, the rotation angles of the stem to the stainless steel mesh were strongly affected by the IBG reconstruction rate. CONCLUSIONS: The short-term results show good outcomes for reconstruction of proximal bone loss with IBG and a circumferential mesh. The procedure should be applied in cases where the circumferential proximal bone loss is less than half the length of the implanted stem.

Comparison of the efficacy of ribavirin plus peginterferon alfa-2b for chronic hepatitis C infection in patients with and without coagulation disorders.

Many patients with coagulation disorders are infected with hepatitis C virus (HCV) that advances to end stage liver disease, resulting in an increased number of deaths. The efficacy of ribavirin and peginterferon combination therapy for chronic HCV infection in patients with coagulation disorders has not been clarified fully. The aim of this study was to evaluate the efficacy and tolerability of combination therapy in this patient population compared with patients who are infected with HCV and do not have coagulation disorders. A total of 226 consecutive chronic hepatitis C patients were treated with combination therapy and divided into two groups: patients with (n = 23) and without coagulation disorders (n = 203). Clinical characteristics, sustained virological response rates obtained by an intention-to-treat analysis, and combination therapy discontinuation rates were compared between the two groups. The sustained virological response rates did not differ significantly between patients with and without coagulation disorders (65.2% vs. 47.8% by intention-to-treat analysis). According to a multivariate analysis, age, alanine aminotransferase, gamma-glutamyltransferase, and HCV genotype were associated significantly with a sustained virological response, whereas whether a patient had a coagulation disorder did not affect the sustained virological response. In conclusion, combination therapy for chronic hepatitis C was comparably effective between patients with and without coagulation disorders and did not result in adverse bleeding.

In-vitro characteristics of cemented titanium femoral stems with a smooth surface finish.

BACKGROUND: In cemented total hip arthroplasty (THA), a polished tapered femoral stem with a design based on the taper-slip concept enables extremely reliable and durable fixation. In contrast, cemented femoral stems made from titanium alloys are not favored because of reports describing insufficient clinical outcomes. However, we have reported excellent clinical and radiological outcomes for cemented titanium stems made using the composite-beam concept. This study examines the characteristics of cemented titanium femoral stems with a smooth surface. METHODS: The bonding strength between titanium alloys with different surface finishes and bone cement was evaluated by use of push-out and detachment tests. Torsional stability tests were performed to evaluate the initiation and propagation of disruption of the fixation of cemented stems at the cement-implant interface. The wear resistance was investigated by use of wear-friction tests performed using a multidirectional pin-on-disc machine. The bone strain loaded on to the femoral cortex was measured by use of an implanted Sawbone and analyzed by use of the finite element method. RESULTS: The push-out and detachment tests revealed increasing cement adhesion strength with increasing degree of roughness of the metal surface. The torsional stability tests indicated that a load >1,000 N led to progressive debonding between the cement and the implant with a smooth surface finish. Interestingly, wear-friction tests revealed the wear rate for polished titanium surfaces was clearly higher than for smooth surfaces. In addition, the greater elasticity of titanium stems compared with cobalt-chromium stems transmitted the external load to the proximal side of the femur more effectively. CONCLUSIONS: The smooth surface finish of the stems is an important factor for the satisfactory clinical and radiological outcomes of cemented titanium femoral stems. The greater elasticity of a titanium stem effectively transmits the external load to the medial side of the femur.

Using the Novel "3D-Ortho" Concept to Achieve a Beautiful Asian Face.

It has become more common for adult patients to seek conflicting orthodontic results, such as the reduction of the buccal corridors by arch form expansion and achieving esthetic-line (E-line) harmony by moving the anterior teeth backward using the extraction space. Therefore, the author devised and implemented the novel "3D-Ortho" concept to achieve the abovementioned conflicting results and solve the requirement of facial beauty. The patient was a 23-year-old female with mouth protrusion. The author used the 3D-Ortho concept to provide orthodontic treatment. A maxillary skeletal expander appliance and the extraction of the maxillary first premolar were performed, and a multi-bracket device was placed on the buccal aspect to decrease Mx1 to point A-pogonion line (APo) by full class II molar relationship finishing. Postoperatively, the nasolabial angle was increased from 83.4° to 93.1°, the E-line to upper lip distance decreased from 2.6 mm to -1.1 mm, the Mx1 to Apo distance decreased from 13.6 mm to 7.5 mm, the distance between the mesial buccal cusp of the mandibular first molars increased from 41.2 mm to 45.2 mm, the inclination of the mandibular first molar incisor changed from 21° to 11° on the right side and from 21° to 9° on the left side, and the improvement of the buccal corridors was observed; thus, significant improvement was observed in these parameters. Therefore, the novel orthodontic treatment method showed good results in solving problems unique to Asians, incorporating occlusal stability and facial beauty harmony.

An in vitro study of the effects of Phellodendron bark extract and berberine chloride on periodontal pathogenic bacteria in the oral microbiome.

OBJECTIVES: Periodontal disease is triggered by oral microbiome dysbiosis. Thus, to prevent its onset, it is important to maintain relative abundance of periodontal pathogenic bacteria in the oral microbiome at a low level. While Phellodendron bark extract (PBE) and its active ingredient, berberine, exert antibacterial effects on periodontal pathogenic bacteria, such as Porphyromonas gingivalis, their effects on the oral microbiome as a whole remain unknown. Therefore, we aimed to clarify the potential of PBE and berberine chloride (BC) in regulating the relative abundance of periodontal pathogenic bacteria in the oral microbiome. METHODS: Saliva was collected from 20 participants. Each participant's saliva was combined separately with P. gingivalis suspension and either PBE or BC in a modified basal medium. The samples were then incubated under anaerobic conditions for 24 h. After cultivation, we determined the total bacterial concentration using quantitative polymerase chain reaction analysis and the bacterial composition using 16 S ribosomal RNA gene sequencing. RESULTS: The total bacterial concentration was reduced because of treatment with PBE and BC. Bacterial 16 S ribosomal RNA gene sequencing confirmed that treatment with PBE and BC significantly reduced the relative abundance of periodontal pathogenic bacteria, including red and orange complex bacteria. CONCLUSIONS: Our findings suggest that PBE and BC reduce the relative abundance of periodontal pathogenic bacteria in the oral microbiome. Thus, PBE and BC can aid in preventing periodontal disease, given their ability to regulate the oral microbiome composition and their anti-inflammatory effects.

Two types of two-component gels formed from pseudoenantiomeric ethynylhelicene oligomers.

Two-component gels formed from pseudoenantiomeric ethynylhelicene oligomers in toluene exhibited two different properties depending on difference in numbers of helicenes in the two components. The combinations (M)-5/(P)-4, (M)-6/(P)-4, and (M)-7/(P)-4, which contained oligomers with comparable numbers of helicenes, formed transparent gels (Type I gels). The combinations (M)-6/(P)-3, (M)-7/(P)-3, and (M)-8/(P)-3, which contained oligomers with considerably different numbers of helicenes, formed turbid gels (Type II gels). Negative Cotton effects were observed for the Type I gels in the region between 350 and 450 nm, and were positive for the Type II gels, despite the use of (M)-oligomers for the longer components. UV/vis exhibited absorption maxima at 350 nm for the Type I gels and at 338 nm for the Type II gels. Different behaviors in gel formation processes were observed by fluorescence studies. Atomic force microscopy analysis showed fiber structures of 25-50 nm diameter for Type I gels and bundles of 100-150 nm diameter for Type II gels. The stoichiometry in gel formation also differed: The Type I gels showed 1:1 stoichiometry of the two components; the Type II gels showed no 1:1 stoichiometry, likely 1:2 stoichiometry. Using the Type I and II gels, two-layer gel systems were constructed.

Novel Approach for Midface Attractiveness.

We previously reported the Point A-Koji method, which uses a titanium plate to move the soft tissue Subnasale (Sn) point forward. This method improves the nasolabial angle, but it is not effective in nasal ala base depression. Various treatments for midface depression have been devised; however, each method has its own disadvantages. Therefore, we developed a minimally invasive method (A-10 surgery), in which an artificial dermis is inserted into the nasal ala base in combination with the Point A-Koji method, and performed it on a patient who has midface depression. Methods: The patient was a 34-year-old woman with midface depression and mouth protrusion' and her Sn point was located posteriorly. We provided A-10 surgery for this patient. Results: Six months after A-10 surgery, the following results were obtained: (1) the facial convexity increased by 3.7 degrees preoperative and postoperative surgery, (2) the soft tissue thickness at the nasal ala base increased by 2.15 mm from 7.42 mm preoperatively to 9.57 mm postoperatively, and (3) the postoperative computed tomography values of the tissue in the same area ranged from -11 to 250 Hounsfield units, suggesting that the inserted artificial dermis was established as dermal-like tissue. A-10 surgery improved the esthetic appearance of the midface. Conclusions: With A-10 surgery, which utilizes a titanium plate as a frame, the facial morphology of the patient changed owing to autologous tissue filling. In addition to being safe and minimally invasive, A-10 surgery yielded a three-dimensional appearance of the midface.

Novel Approach for Midface Depression.

Background: Although Le Fort type II, prosthesis detainment, and orthodontic treatment are considered for the management of midface retraction, they may be limited by their high cost, infection risk, and excessive amount of tooth movement. Therefore, the Point A-Koji method was devised as a novel treatment in patients with midface retraction. Methods: This is a case report of a 26-year-old woman who presented with a feeling of depressed midface and protrusion of the mouth. Preoperatively, the position of the lip and line connecting the nasal apex and mental muscles (E-line) were normal, but the subnasale was located posteriorly. The patient had a narrow nasolabial angle of 74 degrees and the subnasale-Pog' to the upper lip of 6.5 mm. After insertion of a metallic-plate implant under the periosteum, the plate was screwed and fixed to the bone. The Point A-Koji method was used for treatment in this patient. This is characterized by the A-point anterior migration technique in which the periosteum of hard tissue A-point circumferential attachment was shifted anteriorly, thereby preventing the return of soft tissue. Results: The following changes with respect to preoperative findings were noted 5 months postsurgery: facial convexity from 3.3 degrees to 7.6 degrees; nasolabial angle from 74 degrees to 90.2 degrees; true horizontal line from 50 degrees to 73 degrees; and subnasale-Pog' to the upper lip from 6.5 mm to 4.7 mm. This resulted in an improved midface retraction. Conclusion: The Point A-Koji method may be an ideal method to improve the midface retraction in patients.

Cemented total hip arthroplasty with subtrochanteric femoral shortening transverse osteotomy for severely dislocated hips: outcome with a 3- to 10-year follow-up period.

BACKGROUND: Total hip arthroplasty (THA) for the treatment of severe dislocation of the hip is a technically demanding procedure. In most previous reports, techniques and clinical outcomes using cementless prostheses are widely reported, but there have been few reports on the technique and outcomes using cemented prostheses. The purpose of this study was to evaluate the outcomes of a cemented THA with a simultaneous subtrochanteric femoral shortening transverse osteotomy in patients with Crowe type III or IV developmental dysplasia of the hip. METHODS: We retrospectively reviewed 15 hips in 11 patients who underwent cemented THA with subtrochanteric femoral shortening transverse osteotomy and with placement of the acetabular component at the level of the anatomic hip center. Patients were evaluated preoperatively and postoperatively with the Merle d'Aubigné and Postel hip score. Radiographic examination was performed to evaluate the level of the femoral osteotomy site, of the radiographic leg lengthening, and of bone union. RESULTS: The clinical evaluation by the Merle d'Aubigné and Postel hip score was improved from 8.1 ± 2.5 preoperatively to 15.1 ± 1.3 at the time of final follow-up. Radiographic evidence of bone union at the osteotomy site appeared at more than 6 months after operation. Moreover, there were 3 (20%) nonunions that needed reoperation. No acetabular and femoral components exhibited radiological loosening at the time of final follow-up. In addition, one delayed union causing thigh pain was treated with low-intensity pulsed ultrasound that accelerated bone formation. CONCLUSION: Our results in this study indicate that we should prevent instability at the transverse osteotomy site and an adequate intercalary cortical bone graft is needed to prevent nonunion in cemented THA combined with a subtrochanteric femoral shortening transverse osteotomy. We should apply this procedure with caution in patients, especially those who show less potential bone formation activity.

The long-term in vivo behavior of polymethyl methacrylate bone cement in total hip arthroplasty.

BACKGROUND AND PURPOSE: The long-term success of cemented total hip arthroplasty (THA) has been well established. Improved outcomes, both radiographically and clinically, have resulted mainly from advances in stem design and improvements in operating techniques. However, there is concern about the durability of bone cement in vivo. We evaluated the physical and chemical properties of CMW1 bone cements retrieved from patients undergoing revision THA. METHODS: CMW1 cements were retrieved from 14 patients who underwent acetabular revision because of aseptic loosening. The time in vivo before revision was 7-30 years. The bending properties of the retrieved bone cement were assessed using the three-point bending method. The molecular weight and chemical structure were analyzed by gel permeation chromatography and Fourier-transform infrared spectroscopy. The porosity of the bone cements was evaluated by 3-D microcomputer tomography. RESULTS: The bending strength decreased with increasing time in vivo and depended on the density of the bone cement, which we assume to be determined by the porosity. There was no correlation between molecular weight and time in vivo. The infrared spectra were similar in the retrieved cements and in the control CMW1 cements. INTERPRETATION: Our results indicate that polymer chain scission and significant hydrolysis do not occur in CMW1 cement after implantation in vivo, even in the long term. CMW1 cement was stable through long-term implantation and functional loading.

Rationale and design of a randomised, double-blind, placebo-controlled, parallel-group, investigator-initiated phase 2a study to investigate the efficacy and safety of elobixibat in combination with cholestyramine for non-alcoholic fatty liver disease.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) pathogenesis involves abnormal metabolism of cholesterol and hepatic accumulation of toxic free-cholesterol. Elobixibat (EXB) inhibits the ileal bile acid (BA) transporter. EXB and cholestyramine (CTM) facilitate the removal of free cholesterol from the liver by decreasing BA recirculation to the liver, thereby stimulating novel BA synthesis from cholesterol. In this randomised, double-blind, placebo-controlled, parallel-group, phase IIa study, we aim to provide a proof-of-concept assessment by evaluating the efficacy and safety of EXB in combination with CTM in patients with NAFLD. METHODS AND ANALYSIS: A total of 100 adult patients with NAFLD, diagnosed based on low-density lipoprotein cholesterol (LDL-C) level of >120 mg/dL and liver fat content of ≥8% by MRI-based proton density fat fraction (MRI-PDFF), who meet the inclusion/exclusion criteria will be enrolled. The patients will be randomly assigned to receive the combination therapy of 10 mg EXB and 9 g CTM powder (4 g CTM), 10 mg EXB monotherapy, 9 g CTM powder monotherapy or a placebo treatment (n=25 per group). Blood tests and MRIs will be performed 16 weeks following treatment initiation. The primary study endpoint will be the absolute LDL-C level change at week 16 after treatment initiation. The exploratory endpoint will include absolute changes in the liver fat fraction as measured by MRI-PDFF. This proof-of-concept study will determine whether the combination therapy of EXB and CTM is effective and safe for patients with NAFLD. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of Yokohama City University Hospital before participant enrolment. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences. TRIAL REGISTRATION NUMBER: NCT04235205.

Formation of filamentous appendages by Acinetobacter sp. Tol 5 for adhering to solid surfaces.

The toluene-degrading bacterium Acinetobacter sp. Tol 5 is highly adhesive to solid surfaces owing to two filamentous cell appendages, namely, anchors and peritrichate fibrils. When growing this bacterium in the presence of a carrier made of polyurethane foam, almost all the cells adhered to the surface of the carrier. In contrast, when Tol 5 cells were grown in the absence of the polyurethane carrier, the cells were suspended as aggregated cells or individually dispersed cells. The aggregated cells possessed the cell appendages and showed an adhesiveness similar to that of cells grown in the presence of the carrier, while the dispersed cells scarcely produced the cell appendages and showed a low level of adhesiveness. The dispersed cells started to adhere to the polyurethane carrier by producing the filamentous appendages within 30 min of the addition of the carrier as a substratum and toluene as a carbon source. Peritrichate fibrils just sprouting and growing anchors longer than 3 microm were observed when the cells started to adhere. This suggests that the presence of surface areas sufficient for adhesion might trigger cell appendage formation in Tol 5 cells for adhesion by increasing the amount of cell contact with the surfaces.

Time-dependent changes in adhesive force between chondrocytes and silk fibroin substrate.

In tissue engineering for cartilage repair using scaffold, initial chondrocyte-material interactions are significantly important for the following cell behaviors such as phenotypic expression and matrix synthesis. Silk fibroin scaffold is considered to be one of the useful materials in/on which chondrocytes can proliferate without dedifferentiating into fibroblast-like cells and can organize a hyaline-like tissue. For the purpose of seeking some useful aspects for designing scaffold, initial adhesive force of chondrocytes to the surface of fibroin substrate was measured by using a lab-made apparatus applying the cantilever beam method. It was found that the adhesive force per unit spreading area of chondrocytes on fibroin substrate had a clear peak between 6 and 12h after seeding. From the results of immunofluorescence staining for actin and vinculin during this period, it could be thought that an immature formation of actin fibers which was uniquely observed at the periphery of cells attaching to fibroin substrate did not contribute to the increase of adhesive force. Results in this study suggested that surface of the fibroin substrate was gradually covered with some substances which inhibit the adhesion during this period. These cell-material interactions have a possibility to be useful information for designing the adhesive performance of scaffold surface in cartilage regeneration.

Strontium and magnesium ions released from bioactive titanium metal promote early bone bonding in a rabbit implant model.

We have previously developed the "alkali and heat treatment" method to confer bioactivity (bone-bonding ability) to titanium metal (Ti). As strontium (Sr) and magnesium (Mg) ions reportedly promote osteoblastic cell proliferation and differentiation and accelerate bone formation, we improved this method to induce the release of Sr (Sr-Ti) or Mg (Mg-Ti) ions from Ti in a previous study. Here, we evaluated the bioactivity of these novel surface treatments, Sr-Ti and Mg-Ti. In vitro evaluation of cell viability, expression of integrin ß1, ß catenin, and cyclin D1, osteogenic gene expression, alkaline phosphatase activity, and extracellular mineralization using MC3T3-E1 cells revealed that Sr-Ti and Mg-Ti enhanced proliferation and osteogenic differentiation. In rabbit in vivo studies, Sr-Ti and Mg-Ti also provided greater biomechanical strength and bone-implant contact than the positive control Ti (Ca-Ti), especially at the early stage (4-8weeks), and maintained these properties for a longer period (16-24weeks). Advantages of the improved method include process simplicity, applicability for any implant shape, and lack of adverse effects on implant composition and structure. Therefore, our treatment is promising for clinical applications to achieve early bone bonding. STATEMENT OF SIGNIFICANCE: Implantation into osteoporotic bone constitutes a challenging problem because of early migration or loosening of the implant, which is primarily due to insufficient initial fixation in porotic bone. Therefore, it is desirable to provide implants with a capacity for early bone bonding. We have achieved conferring early bone bonding ability to titanium metal by releasing strontium ions or magnesium ions. Our treatment is promising for clinical applications to achieve early bone bonding of orthopedic or dental Ti-based implants.

Bioactivity of sol-gel-derived TiO2 coating on polyetheretherketone: In vitro and in vivo studies.

A polyetheretherketone (PEEK) surface was modified using a sol-gel-derived TiO2 coating in order to confer bone-bonding ability. To enhance the bonding strength of the coating layer, pretreatment with either O2 plasma or sandblasting was performed prior to sol-gel coating. Additionally, post-treatment with acid was carried out to confer apatite (calcium phosphate)-forming ability to the surface. Biomechanical and histological analyses performed using an in vivo rabbit tibia model showed that PEEK surfaces modified with sol-gel-derived TiO2 and acid post-treatment had better bone-bonding properties than uncoated PEEK surfaces. These modified surfaces also performed well in terms of their in vitro cell responses due to their modified surface chemistries and topographies. Although O2 plasma or sandblasting treatment were, for the most part, equivocal in terms of performance, we conclude that sol-gel-derived TiO2 coating followed by acid post-treatment significantly improves the bone bonding ability of PEEK surfaces, thus rendering them optimal for their use in surgical implants. STATEMENT OF SIGNIFICANCE: The role of polyetheretherketone (PEEK) as an alternative biomaterial to conventional metallic implant materials has become increasingly important. However, its low bone bonding ability is yet to be resolved. This in vivo and in vitro investigation on the functionalization of PEEK surfaces highlights the utility of this material in clinical interventions that require implants, and may extend range of applications of PEEK.

Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25.

Sox9 is a direct transcriptional activator of cartilage-specific extracellular matrix genes and has essential roles in chondrogenesis. Mutations in or around the SOX9 gene cause campomelic dysplasia or Pierre Robin Sequence. However, Sox9-dependent transcriptional control in chondrogenesis remains largely unknown. Here we identify Wwp2 as a direct target of Sox9. Wwp2 interacts physically with Sox9 and is associated with Sox9 transcriptional activity via its nuclear translocation. A yeast two-hybrid screen using a cDNA library reveals that Wwp2 interacts with Med25, a component of the Mediator complex. The positive regulation of Sox9 transcriptional activity by Wwp2 is mediated by the binding between Sox9 and Med25. In zebrafish, morpholino-mediated knockdown of either wwp2 or med25 induces palatal malformation, which is comparable to that in sox9 mutants. These results provide evidence that the regulatory interaction between Sox9, Wwp2 and Med25 defines the Sox9 transcriptional mechanisms of chondrogenesis in the forming palate.

Effect of RGDS-expressing fibroin dose on initial adhesive force of a single chondrocyte.

Initial chondrocyte-material interactions are important for cell behaviors such as proliferation, phenotypic expression and matrix synthesis. Previously, we showed that chondrocytes cultured in/on silk fibroin scaffolds proliferate without dedifferentiating into fibroblast-like cells and that RGDS sequences genetically interfused in the fibroin light chain protein enhance cartilage tissue formation. In the present study, the adhesive force of chondrocytes was measured on fibroin substrates containing RGDS-expressing fibroin molecules produced by transgenic silkworms at the different densities of 0, 0.6, 1.5 and 3.0 mol%. The degree of chondrocyte attachment to fibroin substrates increased with the number of RGDS-expressing fibroin molecules. Moreover, the adhesive force per unit spreading area of a single cultured chondrocyte exhibited a peak that was higher with increased RGDS concentrations. The results of this study indicate that the RGDS sequences genetically interfused in the fibroin light chain protein exert effects on chondrocytes' adhesive behavior and can enhance cartilage tissue organization.