Relationship between Stress Shielding and Optimal Femoral Canal Contact Regions for Short, Tapered-Wedge Stem Analyzed by 2D and 3D Systems in Total Hip Arthroplasty.

Although tapered-wedge short stem has been widely employed with its availability for minimally invasive surgeries in total hip arthroplasty (THA), post-operative stress shielding matter remains unresolved in cementless procedures. This study aimed to clarify the most optimal femoral canal contact regions of the stem design taking stress shielding incidence into consideration. This investigation included 60 joints from 60 patients (mean age at operation: 65.9 years), of which follow-up duration after primary THA had been more than 2 years. Frequencies of spot welds, subsidence, and stress shielding were examined 2 years after surgery. The most suitable femoral canal contact regions were evaluated by plain radiograph (2D) and 3D-computed tomography analyses according to Nakata's division for fitting manners. Spot welds were observed in 38 cases (63.3%), and no subsidence case was seen. Respective number of stress shielding cases, based on Engh's classification, categorized as degree 0, 1, and 2, were 2 (3.3%), 31 (51.7%), and 27 (45.0%), while no cases for degree 3 or 4 were found. When assessed by 3D fitting analysis, 27 cases of stress shielding degree 2 were constituted by 13/42 cases of mediolateral (ML) fit, 2/4 cases of flare fit, and 12/14 cases of multi point fit. In 42 cases of ML fitting, stem contact rate of the most proximedial region in stress shielding degree 0 and 1 was significantly higher compared to stress shielding degree 2 cases. Meanwhile, the rates of distal regions were significantly lower or absent in stress shielding degree 0 and 1 cases. The initial fixation of this stem design was very good in our cohort regardless of fitting manners. This study successfully revealed that ML fitting with femoral component, especially the most proximedial calcar site restricted fitting, would be optimal for reducing stress shielding occurrence in cementless short, tapered-wedge stem THA. Thus, the ideal stem contact region should be considered during THA procedures in light of the reduction of stress shielding development.

The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage.

Organ transplantation has progressed with the comprehension of the major histocompatibility complex (MHC). It is true that the outcome of organ transplantation largely relies on how well rejection is managed. It is no exaggeration to say that to be well acquainted with MHC is a shortcut to control rejection. In human beings, MHC is generally recognized as human leukocyte antigens (HLA). Under the current circumstances, the number of alleles is still increasing, but the function is not completely understood. Their roles in organ transplantation are of vital importance, because mismatches of HLA alleles possibly evoke both cellular and antibody-mediated rejection. Even though the control of cellular rejection has improved by recent advances of immunosuppressants, there is no doubt that antibody-mediated rejection (AMR), which is strongly correlated with donor-specific anti-HLA antibodies (DSA), brings a poor outcome. Thus, to diagnose and treat AMR correctly is a clear proposition. In this review, we would like to focus on the detection of intra-graft DSA as a recent trend. Overall, here we will review the current knowledge regarding MHC, especially with intra-graft DSA, and future perspectives: HLA epitope matching; eplet risk stratification; predicted indirectly recognizable HLA epitopes etc. in the context of organ transplantation.

An easy and novel method for safer brachytherapy: real-time fluoroscopic verification of high-dose-rate 192Ir source position using a flat-panel detector.

Real-time fluoroscopic verification of the active source position during actual treatment is the only established method to prevent high-dose-rate (HDR) brachytherapy events. The challenge is spurious signals from an HDR 192Ir source that result in image halation, making source positions indiscernible when using a non-modified image intensifier fluoroscope. We have previously reported a method for observing an HDR 192Ir source by using an elaborately modified image intensifier system. The newly developed flat-panel detector fluoroscope is, by contrast, inherently halation-free thanks to the wider dynamic range (12-14 bits), compared with image intensifier fluoroscopes (8 bits). To explore the feasibility, we applied a commercially available flat-panel detector fluoroscope without modification to actual treatment. We successfully observed source positions without halation for all 107 patients, with a total of 522 HDR treatment sessions during a 3-year period from 2014 to 2017. Actual source positions were compared with planned positions on the planning hard copy. With this method, we detected a total of 1 error (0.2%) among the 522 sessions, at a similar detection rate of 0.1% with our previous experience using a modified image intensifier fluoroscope. We found that a commercially available flat-panel detector fluoroscope is ready for use for real-time verification and outweighs the need for elaborate modifications of an image intensifier fluoroscope. A flat-panel detector fluoroscope will help the global radiation oncology community promote real-time verification programs, leading to safer HDR brachytherapy.

Chronological Changes in Axial Alignment of the Ipsilateral Hip and Knee After Total Hip Arthroplasty.

BACKGROUND: Internal rotation of the hip and lateral patellar tilt increases after total hip arthroplasty (THA). However, it remains unknown whether these parameters change with time after the index THA. METHODS: A total of 91 patients undergoing 2-stage bilateral primary THAs between January 2008 and May 2014 were included to assess the association of chronological changes in internal rotation of the hip or lateral patellar tilt with anthropometric and perioperative parameter and changes in alignment after the index THA. Chronological changes were assessed as changes between postoperative computed tomography on the index surgery and the preoperative computed tomography on the contralateral THA. Internal rotation of the hip was defined as the angle between the posterior intercondylar line and a line passing through the posterior inferior iliac spines. Lateral patellar tilt was defined as the angle between the posterior intercondylar line and a line joining the medial and lateral edges of the patella. RESULTS: Internal rotation of the hip and lateral patellar tilt changed until 2 years after the index surgery by a mean of -2° (range -17.3° to 17.7°) and -2° (range -18.2° to 5.3°), respectively. Adductor tenotomy was associated with increasing internal rotation of the hip with time (adjusted R2 0.076); leg lengthening and larger preoperative femorotibial angle were associated with decreasing lateral patellar tilt with time (adjusted R2 0.159). CONCLUSION: Both internal rotation of the hip at rest and lateral patellar tilt decreased by approximately 2° until 2 years after surgery and there was a large variation in chronological change.

The recipient CXCL10 + 1642C>G variation predicts survival outcomes after HLA fully matched unrelated bone marrow transplantation.

CXCL10 is a chemoattractant for immune cells that is involved in several immune-inflammatory disorders. This study retrospectively examined the impact of a single nucleotide variation (rs3921, +1642C>G) in the CXCL10 gene on transplant outcomes in a cohort of 652 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies. The recipient C/G or G/G genotype was found to be associated with a significantly better 5-year overall survival (OS) rate and a lower transplant-related mortality (TRM) rate than the recipient C/C genotype. The recipient C/G or G/G genotype also predicted a reduced incidence of death due to organ failure. The multivariate analysis showed the recipient C/G or G/G genotype to exhibit statistical trends toward beneficial effects on OS but not on TRM. CXCL10 genotyping could therefore be useful in predicting prognoses and creating therapeutic strategies for improving the final outcomes of patients who undergo allogeneic BMT.

Human microRNA-1245 down-regulates the NKG2D receptor in natural killer cells and impairs NKG2D-mediated functions.

BACKGROUND: NKG2D is an activating receptor expressed by natural killer and T cells, which have crucial functions in tumor and microbial immunosurveillance. Several cytokines have been identified as modulators of NKG2D receptor expression. However, little is known about NKG2D gene regulation. In this study, we found that microRNA 1245 attenuated the expression of NKG2D in natural killer cells. DESIGN AND METHODS: We investigated the potential interactions between the 3'-untranslated region of the NKG2D gene and microRNA as well as their functional roles in the regulation of NKG2D expression and cytotoxicity in natural killer cells. RESULTS: Transforming growth factor-ß1, a major negative regulator of NKG2D expression, post-transcriptionally up-regulated mature microRNA-1245 expression, thus down-regulating NKG2D expression and impairing NKG2D-mediated immune responses in natural killer cells. Conversely, microRNA-1245 down-regulation significantly increased the expression of NKG2D expression in natural killer cells, resulting in more efficient NKG2D-mediated cytotoxicity. CONCLUSIONS These results reveal a novel NKG2D regulatory pathway mediated by microRNA-1245, which may represent one of the mechanisms used by transforming growth factor-ß1 to attenuate NKG2D expression in natural killer cells.

A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation.

Interleukin IL-17 is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. The single nucleotide polymorphism (SNP), rs2275913, in the promoter region of the IL-17 gene is associated with susceptibility to ulcerative colitis. When we examined the impact of rs2275913 in a cohort consisting of 438 pairs of patients and their unrelated donors transplanted through the Japan Marrow Donor Program, the donor IL-17 197A allele was found to be associated with a higher risk of acute graft-versus-host disease (GVHD; hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00 to 2.13; P = 0.05). Next, we investigated the functional relevance of the rs2275913 SNP. In vitro stimulated T cells from healthy individuals possessing the 197A allele produced significantly more IL-17 than those without the 197A allele. In a gene reporter assay, the 197A allele construct induced higher luciferase activity than the 197G allele, and the difference was higher in the presence of T cell receptor activation and was abrogated by cyclosporine treatment. Moreover, the 197A allele displayed a higher affinity for the nuclear factor activated T cells (NFAT), a critical transcription factor involved in IL-17 regulation. These findings substantiate the functional relevance of the rs2275913 polymorphism and indicate that the higher IL-17 secretion by individuals with the 197A allele likely accounts for their increased risk for acute GVHD and certain autoimmune diseases.

Genetic variants of human granzyme B predict transplant outcomes after HLA matched unrelated bone marrow transplantation for myeloid malignancies.

Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G), the A and G alleles represent wild type QPY and RAH mutant variants, respectively. In this study, we analyzed the impact of granzyme B polymorphisms on transplant outcomes in recipients undergoing unrelated HLA-fully matched T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The granzyme B genotypes were retrospectively analyzed in a cohort of 613 pairs of recipients with hematological malignancies and their unrelated donors. In patients with myeloid malignancies consisting of acute myeloid leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41-0.89; P = 0.01) as well as transplant related mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27-0.86, P = 0.01). The recipient G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI, 0.47-0.99; P = 0.05) and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI, 0.35-1.06; P = 0.08). Granzyme B polymorphism did not have any effect on the transplant outcomes in patients with lymphoid malignancies consisting of acute lymphoid leukemia and malignant lymphoma. These data suggest that there is an association between the granzyme B genotype and better clinical outcomes in patients with myeloid malignancies after unrelated BMT.

A clinical comparative study of the direct anterior with mini-posterior approach: two consecutive series.

We classified 182 consecutive patients (195 hips) treated by primary cementless minimally invasive total hip arthroplasty (MIS-THA) into 2 groups via the surgical approaches: direct anterior approach (DAA, 99 hips) and a mini-posterior approach (MPA, 96 hips). Ninety-nine percent of the cups in the DAA group and 91% in the MPA group had been implanted within the safe zone (P = .008). Patients in the DAA group could get single-leg stance of more than 5 seconds by 16.6 days (P = .0004), had positive Tredelenburg's sign by 29%, got 50-m walking time of 52.3 seconds (P = .017), and showed improvement in the use of assistive walking aids (P = .031) at 3 weeks postoperatively. The results of this study suggest more rapid recovery for hip function and gait ability after MIS-THA via a DAA when compared to an MPA.

Comparison between bipolar hemiarthroplasty and THA for osteonecrosis of the femoral head.

It is controversial whether bipolar hemiarthroplasty or total hip arthroplasty should be done for Ficat Stage III osteonecrosis of the femoral head. A prospective comparative study was done using the same cementless femoral components for both procedures. Forty cementless bipolar hemiarthroplasties and 31 cementless total hip arthroplasties were done in 54 patients with Ficat Stage III osteonecrosis of the femoral head. Age, gender, and followup were matched between patients having bipolar hemiarthroplasty and total hip arthroplasty. Treatment with total hip arthroplasty increased the total hip score more than treatment with bipolar hemiarthroplasty. The final pain score especially showed a significant difference between patients who had a bipolar hemiarthroplasty (5.5) and patients who had a total hip arthroplasty (5.9). Thigh pain occurred in four patients (four hips) from the bipolar hemiarthroplasty group and in six patients (six hips) from the total hip arthroplasty group. In the bipolar hemiarthroplasty group, gluteal pain occurred in six patients (six hips, 15%) and groin pain occurred in eight patients (eight hips, 20%). Dislocation occurred in two hips (two patients) in each group. The outer head migrated superiorly in nine hips (nine patients) (23%) from the bipolar hemiarthroplasty group. Because of the incidence of gluteal and groin pain and migration, total hip arthroplasty is a better procedure than bipolar hemiarthroplasty for patients with Ficat Stage III osteonecrosis of the femoral head.