Total joint replacement in inhibitor-positive haemophilia: Long-term outcome analysis in fifteen patients.

AIM: To collect data from joint replacement in inhibitor patients, evaluate haemostatic and patient outcomes, and analyse the costs. METHODS: We report our 21-year, single-centre cumulative experience of 15 joint arthroplasties in six inhibitor patients. RESULTS: Two low responder inhibitor patients were in the early days treated with FVIII, whereas bypassing agents were used in the rest of the high responder patients. The primary haemostatic outcome was good in 8/15, fair in 4/15 and poor in 3/15 operations. The overall patient outcome, including joint health and patient satisfaction, was good in 10/15, fair 4/15 and poor in 1/15. No deep infections were observed. Cost analysis was most beneficial in low responders and in two immune-tolerized, high responder patients. In all cases, factor replacement comprised the main treatment costs. CONCLUSION: Our experience supports the initial use of bypassing agents as well as preoperative immune-tolerance induction when possible. Despite the challenges of haemostasis and severe joint disease, total joint arthroplasty can reach a good outcome, even in inhibitor patients. The risk for deep infection might be smaller than previously reported. Individual planning, intense multidisciplinary teamwork and execution of operations should be centralised in a professional unit.

Soluble biglycan: a potential mediator of cartilage degradation in osteoarthritis.

BACKGROUND: Soluble biglycan (sBGN) and soluble decorin (sDCN), are two closely related essential components of extracellular matrix which both have been shown to possess proinflammatory properties. We studied whether sBGN or sDCN were present in synovial fluid (SF) of osteoarthritis (OA) or rheumatoid arthritis (RA) patients and studied sBGN or sDCN potential role in the degradation of OA cartilage. METHODS: SF obtained from meniscus tear, OA, and RA patients were analysed for sBGN and sDCN using enzyme-linked immunosorbent assays. OA chondrocytes and cartilage explants were stimulated for 48 h with 5 µg/ml sBGN or 1 µg/ml lipopolysaccharide. Messenger RNA (mRNA) levels of Toll-like receptors (TLRs), proteinases and cartilage matrix molecules were determined using quantitative real-time polymerase chain reaction. Protein levels of matrix metalloproteinases (MMPs) and cytokines were measured using Luminex xMap technology. Production of nitric oxide (NO), release of proteoglycans and soluble collagen were measured from conditioned culture media using biochemical assays. OA cartilage explant proteoglycans were stained for Safranin O and quantified using image analysis. TLR4 activation by sBGN and sDCN was studied in engineered HEK-293 cells with TLR4 signalling genes inserted together with a reporter gene. RESULTS: sBGN was found in meniscus tear SF (14 ± 2 ng/ml), OA SF (582 ± 307 ng/ml) and RA SF (1191 ± 482 ng/ml). Low levels of sDCN could also be detected in SF of meniscus tear (51 ± 4) ng/ml, OA (52 ± 3 ng/ml), and RA (49 ± 4 ng/ml). Stimulation of chondrocytes with sBGN increased significantly the mRNA and protein expression of catabolic MMPs, including MMP1, MMP9 and MMP13, and of inflammatory cytokines interleukin (IL)-6 and IL-8, whereas the expression of anabolic markers aggrecan and collagen type II was decreased. sBGN induced release of proteoglycans, collagen and NO from chondrocytes and cartilage explants. The catabolic response in explants was dependent of OA cartilage degradation stage. The mechanism of action of sBGN was mainly mediated through the TLR4-nuclear factor-κB pathway. CONCLUSIONS: High levels of sBGN was found in advanced OA and RA SF. sBGN activates chondrocytes mainly via TLR4, which results in net loss of cartilage. Thus, sBGN can be a mediator of OA cartilage degradation and also a potential biomarker for arthritis.

Back-side wear in HexLoc cups clinico-radiological, immunohistopathological, finite element, and retrieval analysis studies.

The HexLoc locking system was designed to prevent back-side wear of the polyethylene liner in the modular cementless metal-backed acetabular cup, but failed. Back-side wear was analyzed using clinico-radiological data, immunohistopathology, finite element modeling (FEM, and retrieval analysis. Screw holes allowed entry of titanium oxide and exit of polyethylene particles. Birefringent polyethylene wear particles were found behind the metal cup in macrophages containing pro-inflammatory tumor necrosis factor-α and interleukin-1ß, whereas fibroblast-like cells stained for osteoclastogenic receptor activator of nuclear factor kappa B ligand (RANKL). Computerized tomography revealed granulomas (83% versus 17 %) and cortical destruction (50% versus 5%) better than radiographs. In FEM, a change of the abduction angle from 45 to 60 deg, and liner thickness from 4.8 mm to 2.5 mm, increased the back-side wear by 90% and 120%, respectively. Screw holes were stress concentration areas; their removal decreased wear by 40%. Modeling results were validated in retrieved implants, which demonstrated extensive back-side wear damage of liners with a high abduction angle. Combined clinico-radiological, immunohistopathological, FEM, and retrieval analysis disclosed that back-side wear in the HexLoc design is sensitive to the abduction angle, liner thickness, and presence of screw holes.

Toll-like receptors in human chondrocytes and osteoarthritic cartilage.

BACKGROUND AND PURPOSE: Degenerating cartilage releases potential danger signals that react with Toll-like receptor (TLR) type danger receptors. We investigated the presence and regulation of TLR1, TLR2, and TLR9 in human chondrocytes. METHODS: We studied TLR1, TLR2, TLR4, and TLR9 mRNA (qRT-PCR) and receptor proteins (by immunostaining) in primary mature healthy chondrocytes, developing chondrocytes, and degenerated chondrocytes in osteoarthritis (OA) tissue sections of different OARSI grades. Effects of a danger signal and of a pro-inflammatory cytokine on TLRs were also studied. RESULTS: In primary 2D-chondrocytes, TLR1 and TLR2 were strongly expressed. Stimulation of 2D and 3D chondrocytes with a TLR1/2-specific danger signal increased expression of TLR1 mRNA 1.3- to 1.8-fold, TLR2 mRNA 2.6- to 2.8-fold, and TNF-α mRNA 4.5- to 9-fold. On the other hand, TNF-α increased TLR1 mRNA] expression 16-fold, TLR2 mRNA expression 143- to 201-fold, and TNF-α mRNA expression 131- to 265-fold. TLR4 and TLR9 mRNA expression was not upregulated. There was a correlation between worsening of OA and increased TLR immunostaining in the superficial and middle cartilage zones, while chondrocytes assumed a CD166(×) progenitor phenotype. Correspondingly, TLR expression was high soon after differentiation of mesenchymal stem cells to chondrocytes. With maturation, it declined (TLR2, TLR9). INTERPRETATION: Mature chondrocytes express TLR1 and TLR2 and may react to cartilage matrix/chondrocyte-derived danger signals or degradation products. This leads to synthesis of pro-inflammatory cytokines, which stimulate further TLR and cytokine expression, establishing a vicious circle. This suggests that OA can act as an autoinflammatory disease and links the old mechanical wear-and-tear concept with modern biochemical views of OA. These findings suggest that the chondrocyte itself is the earliest and most important inflammatory cell in OA.

Do changing toll-like receptor profiles in different layers and grades of osteoarthritis cartilage reflect disease severity?

OBJECTIVE: Cartilage degeneration in osteoarthritis (OA) leads to release of potential danger signals. The aim of our study was to profile OA cartilage for the Toll-like receptor (TLR) danger signal receptors. METHODS: Osteochondral cylinders from total knee replacements were graded using OA Research Society International score and stained for proteoglycans, collagenase-cleaved type II collagen, and TLR 1-10, which were analyzed histomorphometrically. RESULTS: Grade 1 OA lesions contained 22%-55% TLR 1-9-positive cells in the surface zone, depending on the TLR type. In Grade 2 TLR, immunoreactivity was 60%-100% (p < 0.01) and it was even higher in Grades 3 and 4 (p < 0.01 vs Grade 1). TLR-positive cells in Grade 1 middle zone were low, 0-19.9%, but were 5.1%-32.7% in Grade 2 (p < 0.01) and 34%-83% in Grades 3-4 samples (p < 0.001). TLR values in Grade 5 were low (14.3%-28.7%; p < 0.001). In Grades 3-4 OA, cartilage matrix stained strongly for TLR. In Grade 1, COL2-3/4M was restricted to chondrocytes, but was increasingly seen in matrix upon progress of OA to Grade 4, and then declined. CONCLUSION: Cells in the gliding surface zone are fully equipped with TLR in mild OA. Their proportion increases and extends to the middle or even the deep zone, reflecting OA progression. COL2A-3/4M staining suggests Endo180-mediated intake for intralysosomal degradation by cathepsins in Grade 1, but in higher grades this chondrocyte-mediated clearance fails and the matrix demonstrates extensive collagenase-induced damage. Detached and/or partially degraded matrix components can then act as endogenous danger signals (damage-associated molecular patterns or DAMP) and stimulate increasingly TLR-equipped chondrocytes to inflammation. At the peak inflammatory response, soluble TLR may exert negative feedback, explaining in part the low TLR levels in Grade 5 OA.

Results of total knee replacement with a cruciate-retaining model for severe valgus deformity--a study of 48 patients followed for an average of 9 years.

The objectives of the present study were to find out the results and the factors affecting survival after primary knee arthroplasty with a cruciate-retaining prosthesis in severe valgus deformity. Forty-eight patients (52 knees) participated in the current follow-up study. All patients were followed at least 5 years or to first revision. Mean follow-up time was 9 years (range, 1 to 17 years).The Kaplan-Meier analysis revealed 79% (95% CI 68% to 91%) survival rate with revision for any reason and 81% (95% CI 70% to 93%) survival rate with revision for instability as an endpoint at 10 years. Preoperatively TFA was 23° (range, 15°-51°) in valgus and 7° (range, 21° valgus-4° varus) in valgus postoperatively. Of the 14 re-operated patients, eight were revised because of progressive postoperative medial collateral ligament instability. All re-operations were performed during the first 4 years of the follow-up. The mean TFA was 15.5° valgus postoperatively for those eight and the odds ratio for a revision was 2 (95% CI 1-3, p = 0.025) when compared to the rest of the study population. The residual valgus deformity increases the risk of re-operation and it should be avoided. If proper soft-tissue balance cannot be achieved or there is no functional medial collateral ligament present more constrained implants should be used. In selected cases where both bony correction and ligament balancing have properly been achieved the use of a cruciate-retaining type of prosthesis is justified.

Cementless total hip arthroplasty in patients with severely dysplastic hips and a previous Schanz osteotomy of the femur: techniques, pitfalls, and long-term outcome.

BACKGROUND AND PURPOSE: Historically, a Schanz osteotomy of the femur has been used to reduce limp in patients with severely dysplastic hips. In such hips, total hip arthroplasty is a technically demanding operation. We report the long-term results of cementless total hip arthroplasty in a group of patients who had all undergone a Schanz osteotomy earlier. PATIENTS AND METHODS: From 1988 through 1995, 68 total hip replacements were performed in 59 consecutive patients previously treated with a Schanz osteotomy. With the cup placed at the level of the true acetabulum, a shortening osteotomy of the proximal part of the femur and distal advancement of the greater trochanter were performed in 56 hips. At a mean of 13 (9-18) years postoperatively, we evaluated these patients clinically and radiographically. RESULTS: The mean Harris hip score had increased from 51 points preoperatively to 93 points. Trendelenburg sign was negative and there was good or slightly reduced abduction strength in 23 of 25 hips that had not been revised. There were 12 perioperative complications. Only 1 cementless press-fit porous-coated cup was revised for aseptic loosening. However, the 12-year survival rate of these cups was only 64%, as 18 cups underwent revision for excessive wear of the polyethylene liner and/or osteolysis. 6 CDH femoral components had to be revised due to technical errors. INTERPRETATION: Our results suggest that cementless total hip arthroplasty combined with a shortening osteotomy of the femur and distal advancement of the greater trochanter can be recommended for most patients with a previous Schanz osteotomy of the femur. Because of the high incidence of liner wear and osteolysis of modular cementless cups in this series, nowadays we use hard-on-hard articulations in these patients.

Medial unicompartmental knee arthroplasty with Miller-Galante II prosthesis: mid-term clinical and radiographic results.

AIM: The purpose of our study was to evaluate retrospectively the mid-term results of the Miller-Galante II (Zimmer, Warsaw, USA) unicondylar knee arthoplasty (UKA). METHOD: The study included 46 patients with medial UKAs. Mean follow-up time was 7.0 years (range 2.7-13.1 years). RESULTS: Survival rate of the prosthesis was 86.6% (95% CI 73.7-99.6) at 7 years. The mean clinical and functional Knee Society Scores had increased from 51 and 62 points preoperatively to 76 and 93 points (P < 0.001) postoperatively. Five of the 46 knees were revised because of excessive wear of the polyethylene liner, and three due to progression of the osteoarthritis in the lateral compartment of the knee. CONCLUSION: Survival of this fixed-bearing UKA was not as good as previously reported and polyethylene wear seems to be a more common problem than previously assumed.

Similar results with 21 Kudo and 21 Souter-Strathclyde total elbow arthroplasties in patients with rheumatoid arthritis.

INTRODUCTION: The results of different prostheses used for total elbow arthroplasty (TEA) in rheumatoid arthritis (RA) have been reported in only a few studies. Small differences in survival or function between implants have been reported. We retrospectively evaluated the results of 42 Souter-Strathclyde and Kudo TEAs. MATERIALS AND METHODS: Between 1988 and 1994, 21 consecutive patients with RA and severe elbow destruction underwent a Souter-Strathclyde TEA. Between 1994 and 1998, another group comprising 21 consecutive patients with RA with severe elbow destruction underwent a Kudo TEA. RESULTS: There were six revisions for the groups combined, including four aseptic loosenings, one fracture and one liner wear and metallosis. The 5-year survival for the Souter-Strathclyde and the Kudo were 85% (95% CI 69-100) and 95% (95% CI 85-100), respectively. The difference between the groups was not statistically significant as tested by the Cox regression analysis. The majority of the patients were free of pain at follow-up. More than half of the patients were able to perform only light housekeeping tasks and a considerable proportion even had difficulties in maintaining personal hygiene. The elbow range of motion improved only slightly after the operation. CONCLUSION: Both the Souter-Strathclyde and the Kudo TEAs provide good pain relief in the arthritic elbow leading to high patient satisfaction despite the residual disabilities. Only small differences in the results between the Souter-Strathclyde and the Kudo TEAs were found. More than half of the patients were able to perform only light housekeeping tasks and a considerable proportion even had difficulties in maintaining personal hygiene. The elbow range of motion improved only slightly after the operation.

Late hardware-induced sciatic nerve lesions after acetabular revision.

UNLABELLED: We encountered late hardware-induced sciatic nerve lesions after acetabular revision in six patients. There were five female patients and one male patient. The mean age of the patients at the time of index acetabular revision was 59.3 years (range, 42-76 years). The interval from the index acetabular revision to the onset of sciatic nerve symptoms averaged 9.4 months (range, 4-16 months) and that from the onset of symptoms to nerve release was 11.3 months (range, 8-13 months), except in two patients with intermittent symptoms in which it was 9 and 10.5 years, respectively. Sciatic nerve release was successful in two patients, but in four patients, the nerve had been partly or entirely cut by the metallic hardware resulting in a permanent deficit. The minimum followup was 2 years (mean, 4 years; range, 2-7 years). Mechanical irritation should be suspected in the case of any late sign of peroneal neuropathy after acetabular revision with a macrocup or antiprotrusion device, and plate fixation of the posterior column. We recommend exploration and nerve release before a permanent lesion of the nerve has developed. LEVEL OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Arthrography for the diagnosis of abductor avulsion after total hip arthroplasty: a comparison of arthrographic and surgical findings in 33 patients.

BACKGROUND: Weakness of the abductor muscles--or even their avulsion--is a potential risk when total hip arthroplasty (THA) is performed using the anterolateral approach. Avulsion of the re-attached gluteus medius leads to a limp, but can also provide an open canal for joint fluid to escape to the trochanteric region. Thus, our hypothesis was that arthrography can be used to diagnose such detachment. METHODS: We compared THA arthrographies with peroperative findings retrospectively in 33 patients who had undergone surgical exploration for a muscle reattachment because of a strong suspicion of abductor avulsion at physical examination. RESULTS: After a mean follow-up time of 22 (2-57) months after THA, 14/33 patients had a positive (pathological) arthrogram whereas 19 had a negative (normal) result. All 14 patients with a positive arthrogram were verified to have an avulsion of the abductor muscle at the operation. 10 of the 19 patients with a negative arthrogram had an intact abductor insertion, but 9 had an avulsion. All of these 9 patients with the peroperatively disclosed avulsion had a fibrous capsule, which obstructed the fistula leading from the joint cavity to the trochanteric bursa region. INTERPRETATION: Arthrography is a valuable diagnostic aid in the evaluation of patients with abductor weakness and with Trendelenburg's gait appearing after a THA performed using the anterolateral approach. A positive finding helps in the operative decision making, but a negative arthrogram is not a reliable predictor.

Cementless total hip arthroplasty in patients with high congenital hip dislocation.

BACKGROUND: The optimal surgical treatment for patients with high congenital dislocation of the hip remains controversial. The purpose of our study was to evaluate the mid-term to long-term results of cementless total hip arthroplasty in such patients. METHODS: The study included sixty-eight total hip replacements performed between 1989 and 1994 in fifty-six consecutive patients with high congenital hip dislocation at our hospital. The cup was placed at the level of the true acetabulum, and a shortening osteotomy of the proximal part of the femur and distal advancement of the greater trochanter were performed in 90% of the hips. At the time of final follow-up, at a mean of 12.3 years postoperatively, fifty-two patients (sixty-four hips) were evaluated by us with a physical examination, determination of Harris hip scores, and radiographs. RESULTS: The mean Harris hip score increased from 54 points preoperatively to 84 points at the time of final follow-up (p < 0.001). There was a negative Trendelenburg sign in fifty-nine (92%) of the sixty-four hips. There were thirteen perioperative complications (19%): three peroneal nerve palsies, one femoral nerve palsy, one superior gluteal nerve palsy, four nondisplaced fractures of the proximal part of the femur, one malpositioned stem perforating the posteromedial cortex of the femur, one superficial wound infection, and two early dislocations. With revision because of aseptic loosening as the end point, the ten-year survival rate for press-fit, porous-coated acetabular components was 94.9% (95% confidence interval, 89.3% to 100%). Eight of nine threaded acetabular components were revised, and the ninth was radiographically loose at the time of the last follow-up examination. The rate of survival for the CDH femoral components, with revision because of aseptic loosening as the end point, was 98.4% (95% confidence interval, 96.8% to 100%) at ten years. CONCLUSIONS: Total hip arthroplasty, with placement of the cup at the level of the true acetabulum, distal advancement of the greater trochanter, and femoral shortening osteotomy, can be recommended for patients with high congenital hip dislocation. Complications such as wear, osteolysis, and cup revision were secondary to the suboptimal design of the acetabular components used in this series.