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  • 1.
    Borg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Outcome 5 years after surgical treatment of acetabular fractures: a prospective clinical and radiographic follow-up of 101 patients2015In: Archives of Orthopaedic and Trauma Surgery, ISSN 0936-8051, E-ISSN 1434-3916, Vol. 135, no 2, p. 227-233Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    The aim of this study was to evaluate functional outcome after surgically treated acetabular fracture using radiography and patient-reported outcome measures, and to determine predictors of hip joint failure 5 years post-surgery.

    PATIENTS AND METHODS:

    All patients with acetabular fractures treated with open reduction and internal fixation (ORIF) at our unit are prospectively entered into a local register. 101 acetabular fractures in 112 patients treated from 2004 to 2007 were eligible for analysis 5 years after surgery. Radiographs and questionnaires regarding physical function (Short Form[SF]-36) and pelvic discomfort index (PDI, 100 % = worst outcome) were obtained. The primary outcome measure was "joint failure" defined as either secondary total hip arthroplasty (THA) or a Girdlestone situation. Univariable analysis was used to compare patients with joint failure to those without, and binary logistic regression analysis was performed to identify risk factors of joint failure.

    RESULTS:

    77 % of 101 followed patients had a preserved hip joint 5 years after surgery, and failure of the hip joint most often occurred within the first 2 years after injury. Patients with preserved hip joints had higher scores in the SF-36 physical function domain (median 75 vs. 48; p = 0.004) and better PDI (28 vs. 43 %, p = 0.03). Femoral head impaction was associated with an increased risk of joint failure [relative risk (RR) = 15.2, 95 % CI 3-95; p = 0.002], as was an age of ≥60 years at the time of injury (RR = 4.2, CI 1.3-15; p = 0.02).

    CONCLUSIONS:

    Patients with failed hip joints after surgery for acetabular fracture have inferior global and disease-specific functional outcomes, even after secondary arthroplasty surgery. We suggest that patients with predictors of joint failure could benefit from other treatment strategies than ORIF, and primary insertion of THA may be an alternative treatment strategy for this subgroup.

  • 2.
    Borg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hernefalk, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Acute total hip arthroplasty combined with internal fixation for displaced acetabular fractures in the elderly: A short-term comparison with internal fixation alone after a minimum of two years2019In: The Bone & Joint Journal, ISSN 2049-4394, E-ISSN 2049-4408, Vol. 101B, no 4, p. 478-483Article in journal (Refereed)
    Abstract [en]

    Aims

    Displaced, comminuted acetabular fractures in the elderly are increasingly common, but there is no consensus on whether they should be treated non-surgically, surgically with open reduction and internal fixation (ORIF), or with acute total hip arthroplasty (THA). A combination of ORIF and acute THA, an approach called 'combined hip procedure' (CHP), has been advocated and our aim was to compare the outcome after CHP or ORIF alone.

    Patients and Methods

    A total of 27 patients with similar acetabular fractures (severe acetabular impaction with or without concomitant femoral head injury) with a mean age of 72.2 years (50 to 89) were prospectively followed for a minimum of two years. In all, 14 were treated with ORIF alone and 13 were treated with a CHP. Hip joint and patient survival were estimated. Operating times, blood loss, radiological outcomes, and patient-reported outcomes were assessed.

    Results

    No patient in the CHP group required further hip surgery, giving THA a survival rate of 100% (95% confidence interval (CI) 100 to 100) after three years, compared with 28.6% hip joint survival in the ORIF group (95% CI 12.5 to 65.4; p = 0.001). No dislocations or deep infections occurred in the CHP group. No patient died within the first year after index surgery, but patient survival was lower in the CHP group after three years. There were no relevant differences in patient-reported outcomes.

    Conclusion

    The CHP confers a considerably reduced need of further surgery when compared with ORIF alone in elderly patients with complex acetabular fractures. These findings encourage both further use of, and larger prospective studies on, the CHP.

  • 3.
    Brüggemann, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fredlund, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Are porous tantalum cups superior to conventional reinforcement rings?: A retrospective cohort study of 207 acetabular revisions2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 1, p. 35-40Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Porous tantalum cups have been introduced as an alternative to various reinforcement rings in revision hip surgery. We hypothesized that porous tantalum cups would be superior to muller acetabular roof reinforcement rings (MARRs) in revision hip surgery with re-revision for aseptic loosening as the primary outcome measure. Patients and methods - 207 hips operated with either a porous tantalum cup (TM cup, n = 111) or a MARR (n = 96) at index procedure were identified in our local arthroplasty register. Acetabular defects were classified according to Paprosky. There were 96 men and 111 women with a median age of 71 (35-95) years, presenting acetabular defect size type I in 39 cases, IIA in 22, IIB in 27, IIC in 43, IIIA in 32, and IIIB in 37 cases. Analysis of medical records identified all patients with subsequent re-revision and reasons for re-revisions. Kaplan-Meier survival functions were used to estimate implant survival. Results - With re-revision for aseptic loosening as the end-point, the 6-year unadjusted cumulative survival was 97% (95% CI: 94-100) for TM cups and 96% (CI: 92-100) for MARR (p = 0.6). Using re-revision for any reason as the endpoint, 6-year survival was 87% (CI: 81-94) for TM cups and 95% (CI: 90-99) for MARR (p = 0.06). The main reason for re-revision in the TM group was dislocation (n = 10), followed by loosening (n = 3), whereas the main reason for re-revision in the MARR group was aseptic loosening (n = 8). Duration of the index procedure and perioperative blood loss were lower in the TM group. Interpretation - Both TM and MARR lead to good 6-year results in acetabular revision surgery. The methods differ in their respective failure mechanisms. We conclude that TM cups are a valuable treatment option in acetabular revision surgery, but the reasons underlying dislocations after the use of TM cups must be analyzed further.

  • 4.
    Brüggemann, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Do dual-mobility cups cemented into porous tantalum shells reduce the risk of dislocation after revision surgery?: A retrospective cohort study on 184 patients2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 2, p. 156-162Article in journal (Refereed)
    Abstract [en]

    Background and purpose Dual-mobility cups (DMCs) reduce the risk of dislocation and porous tantalum (TM) shells show favorable osseointegration after acetabular revision surgery, yet the combination of these implants has not been studied. We hypothesized that (1) cementing a DMC into a TM shell decreases the risk of dislocation; (2) DMCs cemented into TM shells are not at greater risk of re-revision; (3) liberation of tantalum ions is marginal after use of this combined technique.Patients and methods We investigated the outcome in 184 hips (184 patients) after acetabular revision surgery with TM shells, fitted either with DMCs (n = 69), or with standard polyethylene (PE) liners (n = 115). Chart follow-up was complete for all patients, and the occurrence of dislocations and re-revisions was recorded. 20 were deceased, 50 were unable to attend follow-up, leaving 114 for assessment of hip function after 4.9 (0.5-8.9) years, radiographs were obtained in 99, and tantalum concentrations in 84 patients.Results 1 patient with a DMC had a dislocation, whereas 14 patients with PE liners experienced at least 1 dislocation. 11 of 15 re-revisions in the PE group were necessitated by dislocations, whereas none of the 2 re-revisions in the DMC group was performed for this reason. Hence, dislocation-free survival after 4 years was 99% (95% CI 96-100) in the DMC group, whereas it was 88% (CI 82-94, p = 0.01) in the PE group. We found no radiographic signs of implant failure in any patient. Mean tantalum concentrations were 0.1 mu l/L (CI 0.05-0.2) in the DMC group and 0.1 mu g/L (CI 0.05-0.2) in the PE group.Interpretation Cementing DMCs into TM shells reduces the risk of dislocation after acetabular revision surgery without jeopardizing overall cup survival, and without enhancing tantalum release.

  • 5.
    Clewemar, Pantelis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Yasmin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Klar, Joakim
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Stattin, Eva-Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Expanding the phenotypic spectrum of osteogenesis imperfecta type V including heterotopic ossification of muscle origins and attachments2019In: Molecular Genetics & Genomic Medicine, ISSN 2324-9269, Vol. 7, no 7, article id e00723Article in journal (Refereed)
    Abstract [en]

    Background

    Osteogenesis imperfecta (OI) is a clinical and genetic heterogeneous group of connective tissue disorders, characterized by bone fragility and a propensity to fracture.

    Methods

    In this report we describe the clinical phenotype of two patients, a 28‐year‐old woman and her mother (54 years old), both with a history of short stature and multiple fractures.

    Results

    Exome sequencing revealed the recurring IFITM5:c.‐14 C>T variant causing OI type V. Both patients had several fractures during childhood. CT‐scan and scintigraphy showed ossification of the origin and attachment of muscles and hypertrophic callus formation.

    Conclusion

    Ossification of the origin and attachment of muscles seems to be part of the phenotype in patients with OI type V.

  • 6.
    Dahlstrand, Henrik
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Sect Orthopaed & Sports Med, Dept Mol Med & Surg, Stockholm, Sweden..
    Stark, Andre
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Wick, Marius C.
    Karolinska Univ Hosp, Karolinska Inst Stockholm, Funct Unit Musculoskeletal Radiol Funct Imaging &, Stockholm, Sweden..
    Anissian, Lucas
    Oregon Hlth & Sci Univ, Dept Orthopaed Surg, Portland, OR USA..
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Weiss, Rudiger J.
    Karolinska Univ Hosp, Karolinska Inst, Sect Orthopaed & Sports Med, Dept Mol Med & Surg, Stockholm, Sweden..
    Comparison of metal ion concentrations and implant survival after total hip arthroplasty with metal-on-metal versus metal-on-polyethylene articulations: a 16-year follow-up of a prospective randomized study2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 5, p. 490-495Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Large metal-on-metal (MoM) articulations are associated with metal wear and corrosion, leading to increased metal ion concentrations and unacceptable revision rates. There are few comparative studies of 28-mm MoM articulations with conventional metal-on-polyethylene (MoP) couplings. We present a long-term follow-up of a randomized controlled trial comparing MoM versus MoP 28-mm articulations, focused on metal ions and implant survival. Patients and methods - 85 patients with a mean age of 65 years at surgery were randomized to a MoM (Metasul) or a MoP (Protasul) bearing. After 16 years, 38 patients had died and 4 had undergone revision surgery. 13 patients were unavailable for clinical follow-up, leaving 30 patients (n = 14 MoM and n = 16 MoP) for analysis of metal ion concentrations and clinical outcome. Results - 15-year implant survival was similar in both groups (MoM 96% [95% CI 88-100] versus MoP 97% [95% CI 91-100]). The mean serum cobalt concentration was 4-fold higher in the MoM (1.5 mu g/L) compared with the MoP cohort (0.4 mu g/L, p < 0.001) and the mean chromium concentration was double in the MoM (2.2 mu g/L) compared with the MoP cohort (1.0 mu g/L, p = 0.05). Mean creatinine levels were similar in both groups (MoM 93 mu mol/L versus MoP 92 mu mol/L). Harris hip scores differed only marginally between the MoM and MoP cohorts. Interpretation - This is the longest follow-up of a randomized trial on 28-mm MoM articulations, and although implant survival in the 2 groups was similar, metal ion concentrations remained elevated in the MoM cohort even in the long term.

  • 7.
    Eriksson, Hannah K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ahadpour, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lazarinis, Stergios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Linezolid in the treatment of periprosthetic joint infection caused by coagulase-negative staphylococci2019In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 51, no 9, p. 683-690Article in journal (Refereed)
    Abstract [en]

    Background: Periprosthetic joint infection (PJI) caused by coagulase-negative staphylococci (CoNS) is increasingly common and is sometimes treated with off-label use of linezolid.

    Methods: We conducted a retrospective study of patients with PJI caused by CoNS treated with surgical intervention and orally administrated linezolid during the period 1995-2014 (n = 28). Clinical outcomes and adverse events related to linezolid administration were evaluated. Mean time to follow-up was 4.3 years (range: 0.2-12).

    Results: Twenty-two of 28 patients were infection-free at follow-up. No CoNS strain was resistant to vancomycin, but 16 of 28 were resistant to rifampicin, 23 of 28 to clindamycin and 20 of 27 to quinolones. The mean duration of linezolid treatment was 4.2 weeks (range: 1-12). Eleven of 28 patients had an adverse event related to the antimicrobial treatment, and four had to discontinue linezolid, but all adverse events were reversible within 2 months after discontinuation.

    Conclusions: Oral linezolid administration combined with adequate surgical treatment may be useful for the treatment of PJIs caused by CoNS.

  • 8.
    Eriksson, Hannah K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nordström, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lazarinis, Stergios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Does the Alpha-defensin Immunoassay or the Lateral Flow Test Have Better Diagnostic Value for Periprosthetic Joint Infection?: A Systematic Review2018In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 476, no 5, p. 1065-1072Article, review/survey (Refereed)
    Abstract [en]

    Background: Measuring alpha-defensin concentrations in synovial fluid may help to diagnose periprosthetic joint infection (PJI). There are two commercially available methods for measuring alpha-defensin in synovial fluid: the enzyme-linked immunosorbent assay-based Synovasure (R) alpha-defensin immunoassay, which gives a numeric readout within 24 hours, and the Synovasure lateral flow test, which gives a binary readout within 20 minutes. There is no compilation of the existing literature to support the use of one of these two tests over the other.

    Questions/purposes: Does the immunoassay or the lateral flow test have better diagnostic value (sensitivity and specificity) in diagnosing PJI?

    Methods: We followed PRISMA guidelines and identified all studies on alpha-defensin concentration in synovial fluid as a PJI diagnostic marker, indexed to April 14, 2017, in PubMed, JSTOR, Google Scholar, and OVID databases. The search retrieved 1578 records. All prospective and retrospective studies on alpha-defensin as a PJI marker (PJI classified according to the criteria of the Musculoskeletal Infection Society) after THA or TKA were included in the analysis. All studies used only one of the two commercially available test methods, but none of them was comparative. After excluding studies with overlapping patient populations, four studies investigating the alpha-defensin immunoassay and three investigating the lateral flow test remained. Alpha-defensin immunoassay studies included 482 joints and lateral flow test studies included 119. The quality of the trials was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The heterogeneity among studies was evaluated by the I-2 index, indicating that the heterogeneity of the included studies was low. Pooled sensitivity, specificity, positive and negative likelihood ratios, and receiver operating curves were calculated for each method and compared with each other.

    Results: The alpha-defensin immunoassay had superior overall diagnostic value compared with the lateral flow test (area under the curve, 0.98 versus 0.75) with higher sensitivity (96% [90%-98%] versus 71% [55%-83%], p < 0.001), but no difference in specificity with the numbers available (96% [93%-97%] versus 90% [81%-95%], p = 0.060).

    Conclusions: Measurement of alpha-defensin in synovial fluid is a valuable complement to existing diagnostic criteria, and the immunoassay test detects PJI more accurately than the lateral flow test. The lateral flow test has lower sensitivity, making it difficult to rule out infection, but its relatively high specificity combined with the advantage of a quick response time can make it useful to rule in infection perioperatively.

    Level of Evidence: Level III, diagnostic study.

  • 9.
    Garland, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gordon, Max
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Danderyd Hosp, Swedish Hip Arthroplasty Register, Stockholm, Sweden.; Danderyd Hosp, Karolinska Inst, Stockholm, Sweden..
    Garellick, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Swedish Hip Arthroplasty Register, Gothenburg, Sweden..
    Kärrholm, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Swedish Hip Arthroplasty Register, Gothenburg, Sweden.; Univ Gothenburg, Gothenburg, Sweden..
    Sköldenberg, Olof
    Danderyd Hosp, Swedish Hip Arthroplasty Register, Stockholm, Sweden.; Danderyd Hosp, Karolinska Inst, Stockholm, Sweden..
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Risk of early mortality after cemented compared with cementless total hip arthroplasty: a nationwide matched cohort study2017In: The Bone & Joint Journal, ISSN 2049-4394, E-ISSN 2049-4408, Vol. 99-B, no 1, p. 37-43Article in journal (Refereed)
    Abstract [en]

    Aims It has been suggested that cemented fixation of total hip arthroplasty (THA) is associated with an increased peri-operative mortality compared with cementless THA. Our aim was to investigate this through a nationwide matched cohort study adjusting for age, comorbidity, and socioeconomic background. Patients and Methods A total of 178 784 patients with osteoarthritis who underwent either cemented or cementless THA from the Swedish Hip Arthroplasty Register were matched with 862 294 controls from the general population. Information about the causes of death, comorbidities, and socioeconomic background was obtained. Mortality within the first 90 days after the operation was the primary outcome measure. Results Patients who underwent cemented THA had an increased risk of death during the first 14 days compared with the controls (hazard ratio (HR) 1.3, confidence interval (CI) 1.11 to 1.44), corresponding to an absolute increase in risk of five deaths per 10 000 observations. No such early increase of risk was seen in those who underwent cementless THA. Between days 15 and 29 the risk of mortality was decreased for those with cemented THA (HR 0.7, CI 0.62 to 0.87). Between days 30 and 90 all patients undergoing THA, irrespective of the mode of fixation, had a lower risk of death than controls. Patients selected for cementless fixation were younger, healthier and had a higher level of education and income than those selected for cemented THA. A supplementary analysis of 16 556 hybrid THAs indicated that cementation of the femoral component was associated with a slight increase in mortality up to 15 days, whereas no such increase in mortality was seen in those with a cemented acetabular component combined with a cementless femoral component. Conclusion This nationwide matched cohort study indicates that patients receiving cemented THA have a minimally increased relative risk of early mortality that is reversed from day 15 and thereafter. The absolute increase in risk is very small. Our findings lend support to the idea that cementation of the femoral component is more dangerous than cementation of the acetabular component.

  • 10.
    Garland, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Visby Hosp, Dept Orthopaed, Visby, Sweden; Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Rolfson, Ola
    Swedish Hip Arthroplasty Register, Gothenburg, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden; Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Lab, Boston, MA 02115 USA.
    Garellick, Göran
    Swedish Hip Arthroplasty Register, Gothenburg, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden.
    Kärrholm, Johan
    Swedish Hip Arthroplasty Register, Gothenburg, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Early postoperative mortality after simultaneous or staged bilateral primary total hip arthroplasty: an observational register study from the swedish Hip arthroplasty register2015In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 16, article id 77Article in journal (Refereed)
    Abstract [en]

    Background: Approximately a fifth of all total hip arthroplasty (THA) patients suffers from bilateral osteoarthritis of the hip. It is unclear whether mortality risks differ between simultaneous bilateral THA and staged bilateral THA. We investigated mortality after simultaneous THA compared with staged bilateral THA in the largest cohort hitherto reported. Methods: The 42,238 patients reported to have received bilateral primary THA from 1992 to 2012 in the Swedish Hip Arthroplasty Register were included. Tumours and fractures as underlying diagnoses were excluded. The time interval between the first and second THA was divided into four categories or treated as a continuous variable. Unadjusted survival was calculated according to Kaplan-Meier and adjusted Cox regression models were fitted in order to calculate crude and adjusted hazard ratios (HR) for the risk of death within different time frames. Results: Patients selected for simultaneous bilateral surgery were younger, more often male, and had lower ASA (American Society of Anesthesiologists) class than patients receiving staged procedures. The adjusted 90-day mortality after the second procedure did not differ between the four investigated groups (simultaneous bilateral [HR 1.3, CI 0.5-3.3], surgeries within 6 months [HR 1.1, CI 0.6-2.0], surgeries between 7 and 12 months [HR 0.7, CI 0.4-1.2], with second surgery after > 12 months as the reference group). For patients older than 75 years, men, patients with ASA class 3 or above, and for patients with rheumatoid arthritis (RA) the 90-day mortality was increased. The unadjusted risk of implant revision of any hip was slightly higher for patients with simultaneous bilateral THA compared to those with staged procedure within one year, but after adjustment for age, gender, diagnosis and implant fixation these differences were no longer statistically significant. Conclusion: There were no clinically relevant differences in early postoperative mortality between simultaneous and staged bilateral surgery in healthy patients. Advanced age, RA, a high ASA class and male sex increased the risk of death within 90 days. There may be an issue with enhanced risk of implant revision in patients with simultaneous bilateral THA that needs to be explored further.

  • 11.
    Garland, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rolfsson, Ola
    Institute of clinical sciencesSahlgrenska Academy, University of Gothenburg.
    Garellick, Göran
    Swedish Hip Artroplasty Register, Institute of clinical sciencesSahlgrenska Academy, University of Gothenburg.
    Kärrholm, Johan
    Swedish Hip Arthroplasty Register, Institute of clinical sciencesSahlgrenska Academy, University of Gothenburg.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Erratum to:Early postoperative mortality after simultaneous or staged bilateral primary total hip arthroplasty: an observational register study from the Swedish Hip Arthroplasty Register2015In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 16, p. 263-263Article in journal (Refereed)
  • 12.
    Gordon, Max
    et al.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Rysinska, Agata
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Garland, Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rolfson, Ola
    Registerctr VGR, Swedish Hip Arthroplasty Register, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Dept Orthoped, Inst Clin Sci, Gothenburg, Sweden.;Massachusetts Gen Hosp, Harris Orthoped Lab, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Boston, MA USA..
    Aspberg, Sara
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Eisler, Thomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Garellick, Goran
    Registerctr VGR, Swedish Hip Arthroplasty Register, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Dept Orthoped, Inst Clin Sci, Gothenburg, Sweden..
    Stark, Andre
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sköldenberg, Olof
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Increased Long-Term Cardiovascular Risk After Total Hip Arthroplasty A Nationwide Cohort Study2016In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 95, no 6, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Total hip arthroplasty is a common and important treatment for osteoarthritis patients. Long-term cardiovascular effects elicited by osteoarthritis or the implant itself remain unknown. The purpose of the present study was to determine if there is an increased risk of late cardiovascular mortality and morbidity after total hip arthroplasty surgery. A nationwide matched cohort study with data on 91,527 osteoarthritis patients operated on, obtained from the Swedish Hip Arthroplasty Register. A control cohort (n = 270,688) from the general Swedish population was matched 1:3 to each case by sex, age, and residence. Mean follow-up time was 10 years (range, 7-21). The exposure was presence of a hip replacement for more than 5 years. The primary outcome was cardiovascular mortality after 5 years. Secondary outcomes were total mortality and re-admissions due to cardiovascular events. During the first 5 to 9 years, the arthroplasty cohort had a lower cardiovascular mortality risk compared with the control cohort. However, the risk in the arthroplasty cohort increased over time and was higher than in controls after 8.8 years (95% confidence interval [CI] 7.0-10.5). Between 9 and 13 years postoperatively, the hazard ratio was 1.11 (95% CI 1.05-1.17). Arthroplasty patients were also more frequently admitted to hospital for cardiovascular reasons compared with controls, with a rate ratio of 1.08 (95% CI 1.06-1.11). Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation when compared with controls.

  • 13.
    Gudnason, Asgeir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Adalberth, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, Kjell-Gunnar
    Univ Umea, Dept Surg & Perioperat Sci, Umea, Sweden..
    Hailer, Nils P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Tibial component rotation around the transverse axis measured by radiostereometry predicts aseptic loosening better than maximal total point motion: A follow-up of 116 total knee arthroplasties after at least 15 years2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 3, p. 282-287Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Maximal total point motion (MTPM) measured by radiostereometry (RSA) is widely used as a predictor of total knee arthroplasty (TKA) loosening. We compared the ability of different RSA measurements at different time points to predict loosening of tibial TKA components in the long term. Patients and methods - 116 TKAs in 116 patients were included in our analysis. 16 (14.8-17.4) years after surgery, 5 tibial components had been revised due to aseptic loosening. Receiver operating characteristic curves were calculated in order to investigate the specificity and sensitivity of different RSA parameters at different thresholds. Results - Rotation around the transverse (x-) axis measured 2 years postoperatively had the best predictive value of all parameters, with an area under the curve (AUC) of 80%. Using a threshold of 0.8 degrees, a specificity of 85% and a sensitivity of 50% were reached. The AUC for tibial component distal translation was 79% and it was 77% for proximal translation, whereas it was only 68% for MTPM. Interpretation - Rotation of the cemented tibial component around the transverse axis, proximal translation, and distal translation are slightly better at predicting aseptic loosening than MTPM, and tibial component migration measured after 2 years gives a good prediction of aseptic loosening up to 15 years.

  • 14.
    Gudnason, Asgeir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    W-Dahl, Annette
    Sundberg, Martin
    Robertsson, Otto
    All-Polyethylene Versus Metal-Backed Tibial Components: An Analysis of 27,733 Cruciate-Retaining Total Knee Replacements from the Swedish Knee Arthroplasty Register2014In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 96, no 12, p. 994-999Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Currently, the use of metal-backed tibial components is more common than the use of all-polyethylene components in total knee arthroplasty. However, the available literature indicates that all-polyethylene tibial components are not inferior to the metal-backed design. We hypothesized that there would be no difference in the ten-year survival rate between all-polyethylene and metal-backed tibial components of a specific design in a large nationwide cohort.

    METHODS:

    In the Swedish Knee Arthroplasty Register, we identified 27,733 cruciate-retaining total knee replacements using the press-fit condylar prosthesis with either metal-backed or all-polyethylene tibial components inserted from 1999 to 2011. Unadjusted survival functions were calculated with the end points of revision for any reason, revision due to infection, and revision due to reasons other than infection, and the differences between the groups were investigated with the log-rank test. Cox proportional hazard models were fitted to analyze the influence of various covariates on the adjusted relative risk of revision.

    RESULTS:

    The median duration of follow-up was 4.5 years (range, zero to 12.9 years). Of all total knee replacements, 16,896 (60.9%) were in women and 10,837 (39.1%) were in men. Metal-backed components were used in 16,011 total knee arthroplasties (57.7%) and all-polyethylene in 11,722 total knee arthroplasties (42.3%). With revision for any reason as the end point, the all-polyethylene tibial component had slightly superior, unadjusted ten-year survival compared with the metal-backed component: 97.2% (95% confidence interval [CI], 96.7% to 97.7%) compared with 96.6% (95% CI, 96.2% to 96.9%; p = 0.002). Cox multiple regression analysis adjusting for age group, sex, and patellar resurfacing showed that all-polyethylene components had a reduced risk of revision for any reason (relative risk = 0.75; 95% CI, 0.64 to 0.89) and a reduced risk of revision due to infection (relative risk = 0.63; 95% CI, 0.46 to 0.86). Patellar resurfacing and male sex increased the risk of revision due to infection (relative risk = 2.22 [95% CI, 1.37 to 3.62] and 2.21 [95% CI, 1.66 to 2.94], respectively).

    CONCLUSIONS:

    These all-polyethylene tibial components were at least as good as or superior to metal-backed tibial components with respect to implant survivorship at ten years in cruciate-retaining total knee replacements. We concluded that these less expensive all-polyethylene tibial components can be safely and effectively used in total knee arthroplasty.

    LEVEL OF EVIDENCE:

    Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

  • 15.
    Gudnason, Asgeir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Implant survival and outcome after rotating-hinge total knee revision arthroplasty: a minimum 6-year follow-up2011In: Archives of Orthopaedic and Trauma Surgery, ISSN 0936-8051, E-ISSN 1434-3916, Vol. 131, no 11, p. 1601-1607Article in journal (Refereed)
    Abstract [en]

    Introduction: Data on long-time survival and clinical function of rotating hinge knee prostheses used in revision total knee arthroplasty (TKA) are scarce.

    Method: We evaluate the outcome of 42 revision TKA in 38 patients using the Endo-model rotating hinge total knee prosthesis after a minimum of 6 years, with 10-year implant survival as our primary outcome measure. Only revision TKAs performed due to aseptic loosening were included, and the Swedish Knee Arthroplasty Register was consulted in order to ensure that patients unavailable for clinical follow-up had not been revised elsewhere. Mean follow-up was after 8.8 (6-18) years, mean age at revision surgery was 72 (55-88) years, and most patients had severe medical comorbidities (n = 31).

    Results: At follow-up, four knees had been re-revised due to aseptic loosening, and five further knees underwent re-revision due to other reasons. With implant revision due to aseptic loosening as the endpoint, 10-year survival was 89.2%, and with implant revision due to any reason 10-year survival was 65.1%. 11 patients (13 knees) eligible for clinical follow-up were evaluated according to the Hospital for Special Surgery score (HSSS), the Knee Society scores (KSS), and by plain radiography. Mean HSSS was 67 (36-90), mean KSS-knee was 85 (73-96), and mean KSS-function was 29 (0-100). Radiography showed that no implant was in need of revision.

    Conclusion: Our results indicate that revision arthroplasty of the knee with this rotating hinge prosthesis can be performed with satisfactory or good results in an elderly population with severe comorbidities.

  • 16.
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    20 years of porous tantalum in primary and revision hip arthroplasty-time for a critical appraisal2018In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 89, no 3, p. 254-255Article in journal (Other academic)
  • 17.
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    The innovation trap2016In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 87, no 2, p. 91-92Article in journal (Refereed)
    Abstract [en]

    Without innovation, we would still be performing resection arthroplasties for end-stage osteoarthritis instead of well-functioning joint replacements. But the road towards successful joint replacement has been paved with failures, and innovation has sometimes resulted in disasters.

  • 18.
    Hailer, Nils
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Adalberth, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Compartment syndrome of the calf following total knee arthroplasty: a case report of a highly unusual complication2007In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 78, no 2, p. 293-295Article in journal (Refereed)
  • 19.
    Hailer, Nils
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hänni, Mari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Widerström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Chronic obstructive pulmonary disease, younger age and impaired preoperative flexion increase the risk of stiffness after total knee arthroplasty: a retrospective case–control study2013In: European orthopaedics and traumatology, ISSN 1867-4577, Vol. 4, no 3, p. 137-145Article in journal (Refereed)
    Abstract [en]

    Introduction

    Knee stiffness after total knee arthroplasty (TKA) impairs patient satisfaction and can necessitate mobilisation under anaesthesia (MUA). We investigated what factors predispose towards the need for MUA after TKA.

    Patients and methods

    The study population was extracted from our local arthroplasty register. Within the setting of a retrospective case/control study, we compared patients who underwent MUA after TKA (n = 35) with a randomly selected control group that did not need MUA after TKA (n = 122) using binary logistic regression analysis.

    Results

    We found that the risk of MUA due to flexion below 90° was increased in patients suffering from chronic obstructive pulmonary disease (COPD) with a risk ratio (RR) of 12 (95 % confidence interval [CI] 1.7–84, p = 0.01). Increasing age decreased the risk of developing stiffness with a RR of 0.88 (CI 0.81–0.95, p < 0.001) per year. Greater preoperative flexion decreased the risk of stiffness with a RR of 0.97 (CI 0.94–1.0, p  = 0.03) per degree of flexion. Gender, body mass index, medical and psychiatric comorbidities, rheumatoid arthritis, the Insall–Salvati index, and the increase in sagittal femoral diameter induced by prosthesis insertion did not significantly affect the risk of stiffness. A certain type of knee prosthesis (Natural Knee 2) was overrepresented among patients requiring MUA.

    Discussion and conclusion

    We conclude that stiffness after TKA is more frequent in younger patients and in those with limited preoperative flexion. It is also suggested that postoperative stiffness may be associated with COPD and with the choice of certain implants.  

  • 20.
    Hailer, Nils P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Orthopedic registry research - limitations and future perspectives.2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 1Article in journal (Refereed)
  • 21.
    Hailer, Nils P
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bengtsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lundberg, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    High Metal Ion Levels After Use of the ASR™ Device Correlate With Development of Pseudotumors and T Cell Activation2014In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 472, no 3, p. 953-961Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Pseudotumors and immunologic alterations are reported in patients with elevated metal ion levels after resurfacing arthroplasty of the hip. A direct association of increased cobalt and chromium concentrations with the development of pseudotumors has not been established.

    QUESTIONS/PURPOSE

     We hypothesized that (1) patients with higher blood cobalt and chromium concentrations are more likely to have pseudotumors develop, (2) elevated cobalt and chromium concentrations correlate with increased activation of defined T cell populations, and (3) elevated metal ion levels, small implant size, cup inclination angle, and patient age are risk factors for the development of pseudotumors.

    METHODS

    A single-surgeon cohort of 78 patients with 84 Articular Surface Replacement(®) implants was retrospectively investigated. Between 2006 and 2010, we performed 84 THAs using the Articular Surface Replacement(®) implant; this represented 2% (84/4950) of all primary hip replacements performed during that period. Of the procedures performed using this implant, we screened 77 patients (99%) at a mean of 43 months after surgery (range, 24-60 months). Seventy-one patients were investigated using ultrasound scanning, and cobalt and chromium concentrations in whole blood were determined by high-resolution inductively coupled plasma mass spectrometry. Differential analysis of lymphocyte subsets was performed by flow cytometry in 53 patients. Results of immunologic analyses were investigated separately for patients with and without pseudotumors. Pseudotumors were found in 25 hips (35%) and were more common in women than in men (p = 0.02). Multivariable regression analysis was performed to identify risk factors for the development of pseudotumors.

    RESULTS

    Cobalt and chromium concentrations were greater in patients with pseudotumors than in those without (cobalt, median 8.3 versus median 1.0 μg/L, p < 0.001; chromium, median 5.9 versus median 1.3 μg/L, p < 0.001). The percentage of HLA-DR(+)CD4(+) T cells was greater in patients with pseudotumors than in those without (p = 0.03), and the proportion of this lymphocyte subtype was positively correlated with cobalt concentrations (r = 0.3, p = 0.02). Multivariable regression analysis indicated that increasing cobalt levels were associated with the development of pseudotumors (p < 0.001), and that patients with larger implants were less likely to have them develop (p = 0.04); age and cup inclination were not risk factors.

    CONCLUSIONS

    We found a distinct association of elevated metal ion concentrations with the presence of pseudotumors and a correlation of increased cobalt concentrations with the proportion of activated T helper/regulator cells. Thus, the development of soft tissue masses after metal-on-metal arthroplasty could be accompanied by activation of T cells, indicating that this complication may be partly immunologically mediated. Further investigations of immunologic parameters in larger cohorts of patients with metal-on-metal arthroplasties are warranted.

    LEVEL OF EVIDENCE

    Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

  • 22.
    Hailer, Nils P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Blaheta, Roman A.
    Dahlstrand, Henrik
    Stark, André
    Elevation of circulating HLA DR+ CD8+ T-cells and correlation with chromium and cobalt concentrations 6 years after metal-on-metal hip arthroplasty: a randomized trial2011In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 82, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    Background and purpose Following metal-on-metal hip arthroplasty (THA), immunological reactions including changes in lymphocyte populations, aseptic loosening, and lymphocytic pseudotumors occur. We hypothesized that changes in lymphocyte subpopulations would be associated with elevated metal ion concentrations. Methods A randomized trial involving 85 patients matched for age and sex and randomized to receiving metal-on-metal (n = 41) or metal-on-polyethylene total hip arthroplasty (n = 44) was conducted. 36 patients were eligible for follow-up after mean 7 (6-8) years. Concentrations of chromium and cobalt were analyzed by high-resolution inductively coupled plasma mass spectrometry. Leukocyte subpopulations and immunoglobulins in patient blood were measured using standard laboratory methods. Results Patients with a metal-on-metal hip had higher serum concentrations of chromium (1.05 vs. 0.36 μg/L; p < 0.001) and cobalt (0.86 vs. 0.24 μg/L; p < 0.001) than those with metal-on-polyethylene. The percentage of HLA DR(+) CD8(+) T-cells was higher in the metal-on-metal group (10.6 vs. 6.7%; p = 0.03) and correlated positively with chromium and cobalt concentrations in patient blood (Pearson's correlation coefficient: 0.39, p = 0.02; 0.36, p = 0.03, respectively). The percentage of B-cells was lower in the metal-on-metal group (p = 0.01). The two groups were similar with respect to immunoglobulin concentrations and Harris hip scores, and there were no radiographic signs of loosening. Interpretation We conclude that immunological alterations appear to be associated with increased cobalt and chromium concentrations. It is tempting to speculate that HLA DR(+) CD8(+) T-cells are involved in the pathogenesis of allergic reactions, implant loosening, and lymphocytic pseudotumors.

  • 23.
    Hailer, Nils P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Garellick, Göran
    Kärrholm, Johan
    Uncemented and cemented primary total hip arthroplasty in the Swedish Hip Arthroplasty Register: Evaluation of 170,413 operations2010In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, no 1, p. 34-41Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Since the introduction of total hip arthroplasty (THA) in Sweden, both components have most commonly been cemented. A decade ago the frequency of uncemented fixation started to increase, and this change in practice has continued. We therefore analyzed implant survival of cemented and uncemented THA, and whether the modes of failure differ between the two methods of fixation. PATIENTS AND METHODS: All patients registered in the Swedish Hip Arthroplasty Register between 1992 and 2007 who received either totally cemented or totally uncemented THA were identified (n = 170,413). Kaplan-Meier survival analysis with revision of any component, and for any reason, as the endpoints was performed. Cox regression models were used to calculate risk ratios (RRs) for revision for various reasons, adjusted for sex, age, and primary diagnosis. RESULTS: Revision-free 10-year survival of uncemented THA was lower than that of cemented THA (85% vs. 94%, p < 0.001). No age or diagnosis groups benefited from the use of uncemented fixation. Cox regression analysis confirmed that uncemented THA had a higher risk of revision for any reason (RR = 1.5, 95% CI: 1.4-1.6) and for aseptic loosening (RR = 1.5, CI: 1.3-1.6). Uncemented cup components had a higher risk of cup revision due to aseptic loosening (RR = 1.8, CI: 1.6-2.0), whereas uncemented stem components had a lower risk of stem revision due to aseptic loosening (RR = 0.4, CI: 0.3-0.5) when compared to cemented components. Uncemented stems were more frequently revised due to periprosthetic fracture during the first 2 postoperative years than cemented stems (RR = 8, CI: 5-14). The 5 most common uncemented cups had no increased risk of revision for any reason when compared with the 5 most commonly used cemented cups (RR = 0.9, CI: 0.6-1.1). There was no significant difference in the risk of revision due to infection between cemented and uncemented THA. INTERPRETATION: Survival of uncemented THA is inferior to that of cemented THA, and this appears to be mainly related to poorer performance of uncemented cups. Uncemented stems perform better than cemented stems; however, unrecognized intraoperative femoral fractures may be an important reason for early failure of uncemented stems. The risk of revision of the most common uncemented cup designs is similar to that of cemented cups, indicating that some of the problems with uncemented cup fixation may have been solved.

  • 24.
    Hailer, Nils P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Garland, Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Gordon, Max
    Karolinska Inst, Danderyd Hosp, Div Orthopaed, Dept Clin Sci, Stockholm, Sweden;Danderyd Univ Hosp Corp, Dept Orthopaed, Stockholm, Sweden.
    Karrholm, Johan
    Swedish Hip Arthroplasty Register, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden.
    Skoldenberg, Olof
    Karolinska Inst, Danderyd Hosp, Div Orthopaed, Dept Clin Sci, Stockholm, Sweden;Danderyd Univ Hosp Corp, Dept Orthopaed, Stockholm, Sweden.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    No generally increased risk of cancer after total hip arthroplasty performed due to osteoarthritis2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Article in journal (Refereed)
    Abstract [en]

    Previous studies on the risk of cancer after total hip arthroplasty (THA) contradict each other, and many are hampered by small cohort sizes, residual confounding, short observation times or a mix of indications underlying the THA procedure. We evaluated the risk of cancer after total hip arthroplasty due to osteoarthritis in a nationwide cohort by comparing cancer incidences in individuals exposed to total hip arthroplasty due to osteoarthritis and in unexposed, sex-, age- and residence matched individuals. To address some previous studies' shortcomings, information on comorbidity and socioeconomic background were obtained and adjusted for. We included 126,276 patients exposed to a cemented THA between 1992 and 2012, and 555,757 unexposed individuals. Follow-up started on the day of surgery for exposed individuals and respective date for matched, unexposed individuals, and ended on the day of death, emigration, censuring or December 31st, 2012, whichever came first. The Swedish Hip Arthroplasty Registry (SHAR), the Swedish Cancer Registry, the Swedish National Patient Registry and Statistics Sweden were accessed to obtain information on procedural details of the THA, cancer diagnoses, comorbidities, and socioeconomic background. The primary outcome measure was the occurrence of any cancer after the index date. Exposed individuals had a slightly lower adjusted risk of developing any cancer than unexposed individuals (hazard ratio [HR] 0.97; CI 0.95-0.99). The only cancer with a statistically significant risk increase in exposed individuals was skin melanoma (HR 1.15; CI 1.05-1.24). We attained similar risk estimates in analyses stratified by sex, in individuals with minimum 5 years of follow-up, in an analysis including individuals with a history of previous cancer, and in patients with cementless THA. In this study on a large and well-defined population with long follow-up, we found no increased overall risk of cancer after THA. These reassuring findings could be included in the guidelines on preoperative information given to THA patients.

  • 25.
    Hailer, Nils P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Garland, Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rogmark, Cecilia
    Garellick, Göran
    Kärrholm, Johan
    Early mortality and morbidity after total hip arthroplasty in patients with femoral neck fracture2016In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 87, no 6, p. 560-566Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Early postoperative mortality is relatively high after total hip arthroplasty (THA) that has been performed due to femoral neck fracture. However, this has rarely been investigated after adjustment for medical comorbidity and comparison with the mortality in an age-matched population. We therefore assessed early mortality in hip fracture patients treated with a THA, in the setting of a nationwide matched cohort study.

    Patients and methods - 24,699 patients who underwent THA due to a femoral neck fracture between 1992 and 2012 were matched with 118,518 controls. Kaplan-Meier survival analysis was used to calculate cumulative unadjusted survival, and Cox regression models were fitted to compute hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustment for age, sex, comorbidity, and socioeconomic background.

    Results - 90-day survival was 96.3% (95% CI: 96.0-96.5) for THA cases and 98.7% (95% CI: 98.6-98.8) for control individuals, giving an adjusted HR of 2.2 (95% CI: 2.0-2.4) for THA cases compared to control individuals. Comorbidity burden increased in THA cases over time, but the adjusted risk of death within 90 days did not differ statistically significantly between the time periods investigated (1992-1998, 1999-2005, and 2006-2012). A Charlson comorbidity index of 3 or more, an American Society of Anesthesiologists (ASA) grade of 3 and above, male sex, an age of 80 years and above, an income below the first quartile, and a lower level of education were all associated with an increased risk of 90-day mortality.

    Interpretation - The adjusted early mortality in femoral neck fracture patients who underwent THA was about double that in a matched control population. Patients with femoral neck fracture but with no substantial comorbidity and an age of less than 80 years appear to have a low risk of early death. Patients older than 80 years and those with a Charlson comorbidity index of more than 2 have a high risk of early death, and such patients would perhaps benefit from treatment strategies other than THA, but this should be investigated further.

  • 26.
    Hailer, Nils P
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lazarinis, Stergios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mäkelä, Keijo T
    Eskelinen, Antti
    Fenstad, Anne M
    Hallan, Geir
    Havelin, Leif
    Overgaard, Søren
    Pedersen, Alma B
    Mehnert, Frank
    Kärrholm, Johan
    Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!: An analysis of 116,069 THAs in the Nordic Arthroplasty Register Association (NARA) database2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 1, p. 18-25Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival.

    Patients and methods

    We identified 152,410 THA procedures using uncemented stems that were performed between 1995 and 2011 and registered in the Nordic Arthroplasty Register Association (NARA) database. We excluded 19,446 procedures that used stem brands less than 500 times in each country, procedures performed due to diagnoses other than osteoarthritis or pediatric hip disease, and procedures with missing information on the type of coating. 22 stem brands remained (which were used in 116,069 procedures) for analysis of revision of any component. 79,192 procedures from Denmark, Norway, and Sweden were analyzed for the endpoint stem revision. Unadjusted survival rates were calculated according to Kaplan-Meier, and Cox proportional hazards models were fitted in order to calculate hazard ratios (HRs) for the risk of revision with 95% confidence intervals (CIs).

    Results

    Unadjusted 10-year survival with the endpoint revision of any component for any reason was 92.1% (CI: 91.8-92.4). Unadjusted 10-year survival with the endpoint stem revision due to aseptic loosening varied between the stem brands investigated and ranged from 96.7% (CI: 94.4-99.0) to 99.9% (CI: 99.6-100). Of the stem brands with the best survival, stems with and without HA coating were found. The presence of HA coating was not associated with statistically significant effects on the adjusted risk of stem revision due to aseptic loosening, with an HR of 0.8 (CI: 0.5-1.3; p = 0.4). The adjusted risk of revision due to infection was similar in the groups of THAs using HA-coated and non-HA-coated stems, with an HR of 0.9 (CI: 0.8-1.1; p = 0.6) for the presence of HA coating. The commonly used Bimetric stem (n = 25,329) was available both with and without HA coating, and the adjusted risk of stem revision due to aseptic loosening was similar for the 2 variants, with an HR of 0.9 (CI: 0.5-1.4; p = 0.5) for the HA-coated Bimetric stem.

    Interpretation

    Uncemented HA-coated stems had similar results to those of uncemented stems with porous coating or rough sand-blasted stems. The use of HA coating on stems available both with and without this surface treatment had no clinically relevant effect on their outcome, and we thus question whether HA coating adds any value to well-functioning stem designs.

  • 27.
    Hailer, Nils P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Weiss, Rudiger J.
    Stark, Andre
    Karrholm, Johan
    Dual-mobility cups for revision due to instability are associated with a low rate of re-revisions due to dislocation 228 patients from the Swedish Hip Arthroplasty Register2012In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 6, p. 566-571Article in journal (Refereed)
  • 28.
    Hailer, Nils P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Weiss, Rudiger J.
    Stark, Andre
    Karrholm, Johan
    The risk of revision due to dislocation after total hip arthroplasty depends on surgical approach, femoral head size, sex, and primary diagnosis An analysis of 78,098 operations in the Swedish Hip Arthroplasty Register2012In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 5, p. 442-448Article in journal (Refereed)
    Abstract [en]

    Background and purpose The effects of patient-related and technical factors on the risk of revision due to dislocation after primary total hip arthroplasty (THA) are only partly understood. We hypothesized that increasing the femoral head size can reduce this risk, that the lateral surgical approach is associated with a lower risk than the posterior and minimally invasive approaches, and that gender and diagnosis influence the risk of revision due to dislocation. Patients and methods Data on 78,098 THAs in 61,743 patients performed between 2005 and 2010 were extracted from the Swedish Hip Arthroplasty Register. Inclusion criteria were a head size of 22, 28, 32, or 36 mm, or the use of a dual-mobility cup. The covariates age, sex, primary diagnosis, type of surgical approach, and head size were entered into Cox proportional hazards models in order to calculate the adjusted relative risk (RR) of revision due to dislocation, with 95% confidence intervals (CI). Results After a mean follow-up of 2.7 (0-6) years, 399 hips (0.5%) had been revised due to dislocation. The use of 22-mm femoral heads resulted in a higher risk of revision than the use of 28-mm heads (RR = 2.0, CI: 1.2-3.3). Only 1 of 287 dual-mobility cups had been revised due to dislocation. Compared with the direct lateral approach, minimally invasive approaches were associated with a higher risk of revision due to dislocation (RR = 4.2, CI: 2.3-7.7), as were posterior approaches (RR = 1.3, CI: 1.1-1.7). An increased risk of revision due to dislocation was found for the diagnoses femoral neck fracture (RR = 3.9, CI: 3.1-5.0) and osteonecrosis of the femoral head (RR = 3.7, CI: 2.5-5.5), whereas women were at lower risk than men (RR = 0.8, CI: 0.7-1.0). Restriction of the analysis to the first 6 months after the index procedure gave similar risk estimates. Interpretation Patients with femoral neck fracture or osteonecrosis of the femoral head are at higher risk of dislocation. Use of the minimally invasive and posterior approaches also increases this risk, and we raise the question of whether patients belonging to risk groups should be operated using lateral approaches. The use of femoral head diameters above 28 mm or of dual-mobility cups reduced this risk in a clinically relevant manner, but this observation was not statistically significant.

  • 29.
    Hailer, Nils
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Soykaner, L
    Ackermann, H
    Rittmeister, M
    Triple osteotomy of the pelvis for acetabular dysplasia: age at operation and the incidence of nonunions and other complications influence outcome.2005In: J Bone Joint Surg Br, ISSN 0301-620X, Vol. 87, no 12, p. 1622-6Article in journal (Refereed)
  • 30.
    Hailer, Nils
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Vogt, Cornelia
    Korf, Horst-Werner
    Dehghani, Faramarz
    Interleukin-1beta exacerbates and interleukin-1 receptor antagonist attenuates neuronal injury and microglial activation after excitotoxic damage in organotypic hippocampal slice cultures.2005In: Eur J Neurosci, ISSN 0953-816X, Vol. 21, no 9, p. 2347-60Article in journal (Other scientific)
  • 31.
    Hailer, Yasmin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Is Legg-Calve-Perthes Disease a Local Manifestation of a Systemic Condition?2018In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 476, no 5, p. 1055-1064Article in journal (Refereed)
    Abstract [en]

    Background: Osteochondrosis includes numerous diseases that occur during rapid growth, characterized by disturbances of endochondral ossification. One example, Legg-Calvé-Perthes disease, is characterized by disruption of the blood supply to the femoral head epiphysis, and a systemic etiology often has been suggested. If this were the case, secondary osteochondroses at locations other than the hip might be expected to be more common among patients with Legg-Calvé-Perthes disease, but to our knowledge, this has not been evaluated in a nationwide sample.

    Questions/purposes: (1) Do patients with Legg-Calvé-Perthes disease have an increased prevalence of secondary osteochondroses at locations other than the hip? (2) Is the concept of Legg-Calvé-Perthes disease a systemic etiology supported by a higher prevalence of the metabolic diseases obesity and hypothyroidism?

    Methods: We designed a retrospective population-based cohort study with data derived from the Swedish Patient Registry (SPR). The SPR was established in 1964 and collects information on dates of hospital admission and discharge, registered diagnoses (categorized along the International Classification of Diseases [ICD]), and applied treatments during the entire lifetime of all Swedish citizens with high validity. Analyzing the time span from 1964 to 2011, we identified 3183 patients with an ICD code indicative of Legg-Calvé-Perthes disease and additionally sampled 10 control individuals per patient with Legg-Calvé-Perthes disease, matching for sex, age, and residence, resulting in 31,817 control individuals. The prevalence of secondary osteochondroses, obesity, and hypothyroidism was calculated separately for patients with Legg-Calvé-Perthes disease and control individuals based on the presence of ICD codes indicative of these conditions. Using logistic regression analysis, we compared the adjusted relative risk of having either of these conditions develop between patients with Legg-Calvé-Perthes disease and their matched control subjects. The mean followup was 26.1 years (range, 2.8-65 years).

    Results: The prevalence of secondary osteochondroses was greater among patients with Legg-Calvé-Perthes disease (3.11%) than among control subjects (0.31%), resulting in an increased adjusted risk of an association with such lesions in the patients (relative risk [RR], 10.3; 95% confidence interval [CI], 7.7-13.6; p < 0.001). When stratified by sex, we attained a similarly increased risk ratio for females (RR, 12.5; 95% CI, 6.1-25.8; p < 0.001) as for males (RR, 9.9; 95% CI, 7.3-13.5; p < 0.001). Patients with Legg-Calvé-Perthes disease had an increased adjusted risk of an association with obesity (RR, 2.8; 95% CI, 1.9-4.0; p < 0.001) or hypothyroidism (RR, 2.6; 95% CI, 1.7-3.8; p < 0.001) when compared with control subjects.

    Conclusions: To our knowledge, this is the first population-based description of a robust association of Legg-Calvé-Perthes disease with osteochondroses at locations other than the hip, and we also found increased risk estimates for an association with obesity and hypothyroidism in patients with Legg-Calvé-Perthes disease. Our findings strengthen the hypothesis that Legg-Calvé-Perthes disease is the local manifestation of a systemic disease, indicative of an underlying common disease pathway that requires further investigation. Physicians should be aware that patients with Legg-Calvé-Perthes disease may present with secondary osteochondroses and metabolic comorbidities.

  • 32.
    Johansson, Lisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rahme, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    High incidence of periprosthetic joint infection with propionibacterium acnes after the use of a stemless shoulder prosthesis with metaphyseal screw fixation: a retrospective cohort study of 241 patients propionibacter infections after eclipse TSA2017In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 18, article id 203Article in journal (Refereed)
    Abstract [en]

    Background: A stemless shoulder prosthesis with humeral metaphyseal screw fixation was introduced in order to save bone-stock and to facilitate reconstruction of biomechanics (Eclipse (R)). The aim of this study was to analyze whether the risk of infection is different with this implant compared to conventional shoulder prosthesis.

    Methods: Two hundred and forty-one patients (54.8% females) were operated with a shoulder arthroplasty and followed for median 2.0 (0.1-5.7) years. One hundred and two (42.3%) had received an Eclipse (R) prosthesis, the remaining patients were operated with other implants. There was an overrepresentation of males in the Eclipse (R) group (63.7% males) when compared with the control group (31.7% males).

    Results: In the Eclipse (R) group 10 (9.8%) patients developed a periprosthetic joint infection, as opposed to 1 (0.7%) in the control group. The most common bacteria was Propionibacterium acnes. Unadjusted infection-free survival after 4 years was 88.8% (CI 82.5-95.7) for Eclipse (R) patients and 95.7% (CI 87.7-100.0) for controls (p = 0.002). After adjustment for age, gender, diagnosis, and type of shoulder prosthesis (total or hemi), the risk ratio for revision due to infection was 4.3 (CI 0.5-39.1) for patients with the Eclipse (R) prosthesis.

    Conclusions: Deep infections seem to be more common after the use of the metaphyseally fixed Eclipse (R) prosthesis than after conventional shoulder implants, but a predominance of male gender and younger age in the Eclipse group may have biased our findings. Future studies on larger cohorts and in vitro investigations on bacterial adherence and biofilm formation are needed.

  • 33.
    Lazarinis, Stergios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kärrholm, Johan
    Swedish Hip arthroplasty Register and Department of Orthopaedics, Institute of Clinical Sciences, The Sahlgrenska Akademy, University of Gothenburg, Gothenburg, Sweden.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Effects of hydroxyapatite coating of cups used in hip revisionarthroplasty: A Swedish Hip Arthroplasty Register study of 1,780 revisions2012In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 5, p. 427-435Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    Coating of acetabular revision implants with hydroxyapatite (HA) has been proposed to improve ingrowth and stability. We investigated whether HA coating of revision cups can reduce the risk of any subsequent re-revision.

    Methods

    We studied uncemented cups either with or without HA coating that were used at a primary acetabular revision and registered in the Swedish Hip Arthroplasty Register (SHAR). 2 such cup designs were identified: Harris-Galante and Trilogy, both available either with or without HA coating. These cups had been used as revision components in 1,780 revisions of total hip arthroplasties (THA) between 1986 and 2009. A Cox proportional hazards model including the type of coating, age at index revision, sex, cause of cup revision, cup design, the use of bone graft at the revision procedure, and the type of cup fixation at primary THA were used to calculate adjusted risk ratios (RRs with 95% CI) for re-revision for any reason or due to aseptic loosening.

    Results

    71% of the cups were coated with HA and 29% were uncoated. At a mean follow-up time of 6.9 (0–24) years, 159 (9%) of all 1,780 cups had been re-revised, mostly due to aseptic loosening (5%), dislocation (2%), or deep infection (1%). HA coating had no significant influence on the risk of re-revision of the cup for any reason (RR = 1.4, CI: 0.9–2.0) or due to aseptic loosening (RR = 1.1, 0.6–1.9). In contrast, HA coating was found to be a risk factor for isolated liner re-revision for any reason (RR = 1.8, CI: 1.01–3.3). Age below 60 years at the index cup revision, dislocation as the cause of the index cup revision, uncemented cup fixation at primary THA, and use of the Harris-Galante cup also increased the risk of re-revision of the cup. In separate analyses in which isolated liner revisions were excluded, bone grafting was found to be a risk factor for re-revision of the metal shell due to aseptic loosening (RR = 2.1, CI: 1.05–4.2).

    Interpretation

    We found no evidence to support the notion that HA coating improves the performance of the 2 studied cup designs in revision arthroplasty. In contrast, patient-related factors such as younger age and dislocation as the reason for cup revision, and technical factors such as the choice of revision cup were found to influence the risk of subsequent re-revision of the cup. The reason for inferior results after revision of uncemented cups is not known, but it is possible that these hips more often had pronounced bone loss at the index cup revision.

  • 34.
    Lazarinis, Stergios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kärrholm, Johan
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Increased risk of revision of acetabular cups coated with hydroxyapatite: A Swedish Hip Arthroplasty Register study involving 8,043 total hip replacements2010In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 81, no 1, p. 53-59Article in journal (Refereed)
    Abstract [en]

    Background Hydroxyapatite (HA) is the main inorganic component of bone, and HA coating is widely used on acetabular cups in hip arthroplasty. It has been suggested that this surface finish improves cup survival. Methods All patients registered in the Swedish Hip Arthroplasty Register between 1992 and 2007 with an uncemented acetabular implant that was available either with or without HA coating were identified. 8,043 total hip arthroplasties (THAs) with the most common cup types (Harris-Galante, Romanus, and Trilogy) were investigated. A Cox regression model including type of coating, age, sex, primary diagnosis, cup type, and type of stem fixation was used to calculate adjusted risk ratios (RRs) for the risk of revision. Results HA coating was a risk factor for cup revision due to aseptic loosening (adjusted RR 1.7; 95% CI: 1.3-2). Age at primary arthroplasty of < 50 years, a diagnosis of pediatric hip disease, the use of a cemented stem, and the Romanus and Harris-Galante cup types were also associated with statistically significantly increased risk of cup revision due to aseptic loosening. Interpretation Our findings question the routine use of HA-coated cups in primary total hip arthroplasty. With some designs, this practice may even increase the risk of loosening-resulting in revision surgery.

  • 35.
    Lazarinis, Stergios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mattsson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    A prospective cohort study on the short collum femoris preserving (CFP) stem using RSA and DXA: Primary stability but no prevention of proximal bone loss in 27 patients followed for 2 years2013In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 84, no 1, p. 32-39Article in journal (Refereed)
    Abstract [en]

    Background and purpose Short femoral stems have been introduced in total hip arthroplasty in order to save proximal bone stock. We hypothesized that a short stem preserves periprosthetic bone mineral density (BMD) and provides good primary stability. Methods We carried out a prospective cohort study of 30 patients receiving the collum femoris-preserving (CFP) stem. Preoperative total hip BMD and postoperative periprosthetic BMD in Gruen zones 1-7 were investigated by dual-energy x-ray absorptiometry (DXA), stem migration was analyzed by radio-stereometric analysis (RSA), and the Harris hip score (HHS) was determined. Results 2 patients were excluded intraoperatively and 1 patient was revised due to a deep infection, leaving 27 patients for analysis. The mean HHS increased from 49 (24-79) preoperatively to 99 (92-100) after 2 years. DXA after 1 year showed substantial loss of BMD in Gruen zone 7 (-31%), zone 6 (-19%), and zone 2 (-13%, p < 0.001) compared to baseline BMD determined immediately postoperatively. The bone loss in these regions did not recover after 2 years, whereas the more moderate bone loss in Gruen zones 1, 3, and 5 partially recovered. There was a correlation between low preoperative total hip BMD and a higher amount of bone loss in Gruen zones 2, 6 and 7. RSA showed minor micromotion of the stem: mean subsidence was 0.13 (95% CI: -0.28 to 0.01) mm and mean rotation around the longitudinal axis was 0.01 (95% CI: -0.1 to 0.39) after 2 years. Interpretation We conclude that substantial loss in proximal periprosthetic BMD cannot be prevented by the use of a novel type of short, curved stem, and forces appear to be transmitted distally. However, the stems showed very small migration-a characteristic of stable uncemented implants.

  • 36.
    Lazarinis, Stergios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mattsson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bone loss around a stable, partly threaded hydroxyapatite-coated cup: a prospective cohort study using RSA and DXA2014In: HIP International, ISSN 1120-7000, E-ISSN 1724-6067, Vol. 24, no 2, p. 155-166Article in journal (Refereed)
    Abstract [en]

    Study purpose: Aseptic loosening of the acetabular component is the most common reason for revision after primary THA, and periprosthetic demineralisation has been described as a potential cause for this process. The trabeculae-oriented pattern (TOP)-cup is a flat, hydroxyapatite (HA)-coated titanium shell with a threaded rim that was developed in order to minimise periprosthetic bone loss. We hypothesised that this cup provides good primary stability and improves preservation of periprosthetic bone mineral density (BMD). Basic procedures: A prospective cohort study on 30 patients receiving the TOP cup was carried out. Preoperative total hip BMD and postoperative periprosthetic BMD in five periprosthetic regions of interest were investigated by dual energy radiographic absorptiometry (DXA), cup migration was analysed by radiostereometry (RSA), and the Harris hips score (HHS) was determined. Main findings: Mean HHS increased from 49 (24-79) preoperatively to 99 (92-100) after two years. DXA after one year demonstrated substantial BMD loss in the proximal periprosthetic zones 1 (-18%), zone 2 (-16%) and zone 3 (-9%, all p<0.001 when compared with baseline BMD determined immediately postoperatively). The bone loss in these regions did not recover after two years. RSA (performed on 16 patients) showed that only very limited micromotion of the implant occurred: Mean cranial migration was 0.01 mm (95% confidence interval (CI): -0.09-0.12) and mean inclination decreased by 0.02 degrees (CI: -0.43-0.39) after two years. Conclusion: We conclude that the TOP cup provides good primary stability in the short-term. However, substantial BMD loss in proximal periprosthetic areas indicates that the design of this cup cannot prevent periprosthetic bone loss that has also been observed around other uncemented cups.

  • 37.
    Lazarinis, Stergios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mattsson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Demineralization around a stable uncemented modular cup: A prospective cohort study on a hemispherical, partly threaded and hydroxyapatite-coated cup using RSA and DXAManuscript (preprint) (Other academic)
  • 38.
    Lazarinis, Stergios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Univ Gothenburg, Swedish Hip Arthroplasty Register, Gothenburg, Sweden.; Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden.
    Mäkelä, K T
    Department of Orthopaedics and Traumatology, Turku University Hospital, Turku, Finland.
    Eskelinen, A
    Coxa Hospital for Joint Replacement, Tampere, Finland.
    Havelin, L
    The Norwegian Arthroplasty Register, Department of Orthopaedic Surgery, Haukeland University Hospital, Bergen, Norway.
    Hallan, G
    The Norwegian Arthroplasty Register, Department of Orthopaedic Surgery, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
    Overgaard, S
    The Danish Hip Arthroplasty Register, Denmark.; Department of Orthopaedic Surgery and Traumatology, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
    Pedersen, A B
    The Danish Hip Arthroplasty Register, Denmark.; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Kärrholm, J
    Univ Gothenburg, Swedish Hip Arthroplasty Register, Gothenburg, Sweden.; Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden.
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Univ Gothenburg, Swedish Hip Arthroplasty Register, Gothenburg, Sweden.; Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden.
    Does hydroxyapatite coating of uncemented cups improve long-term survival?: An analysis of 28,605 primary total hip arthroplasty procedures from the Nordic Arthroplasty Register Association (NARA)2017In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 25, no 12, p. 1980-1987, article id S1063-4584(17)31137-8Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: It is unclear whether hydroxyapatite (HA) coating of uncemented cups used in primary total hip arthroplasty (THA) improves bone ingrowth and reduces the risk of aseptic loosening. We therefore investigated survival of different uncemented cups that were available with or without HA coating.

    METHOD: We investigated three different cup types used with or without HA coating registered in the Nordic Arthroplasty Register Association (NARA) database that were inserted due to osteoarthritis (n = 28,605). Cumulative survival rates and adjusted hazard ratios (HRs) for the risk of revision were calculated.

    RESULTS: Unadjusted 13-year survival for cup revision due to aseptic loosening was 97.9% (CI: 96.5-99.4) for uncoated and 97.8% (CI: 96.3-99.4) for HA-coated cups. Adjusted HRs were 0.66 (CI 0.42-1.04) for the presence of HA coating during the first 10 years and 0.87 (CI 0.14-5.38) from year 10-13, compared with uncoated cups. When considering the endpoint cup revision for any reason, unadjusted 13-year survival was similar for uncoated (92.5% [CI: 90.1-94.9]) and HA-coated (94.7% [CI: 93.2-96.3]) cups. The risk of revision of any component due to infection was higher in THA with HA-coated cups than in THA with uncoated cups (adjusted HR 1.4 [CI 1.1-1.9]).

    CONCLUSIONS: HA-coated cups have a similar risk of aseptic loosening as uncoated cups, thus the use of HA coating seems to not confer any added value in terms of implant stability. The risk of infection seemed higher in THA with use of HA-coated cups, an observation that must be investigated further.

  • 39.
    Marsell, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Successful treatment of a humeral capitulum osteonecrosis with bone morphogenetic protein-7 combined with autologous bone grafting2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 287-289Article in journal (Refereed)
    Abstract [en]

    We present the case of a 27-year-old female with subcortical osteonecrosis of the humeral capitulum. Percutaneous retrograde drilling of the lesion and application of recombinant human bone morphogenetic protein (BMP)-7 were combined with autologous bone grafting. At follow-up the patient was almost pain-free, had normalized her range of motion, and radiography showed consolidation of the lesion without any heterotopic bone formation. By timing surgery prior to subchondral collapse, biomechanical stability of the subchondral bone was maintained. To our knowledge, this is the first report on the treatment of an osteonecrosis in this location with a BMP, and this strategy could potentially be applied in other locations with juxta-articular osteonecrosis.

  • 40.
    Nyström, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kiritopoulos, Demostenis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ullmark, Gösta
    Department of Orthopedics, Gävle Hospital, Gävle, Sweden.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Petrén-Mallmin, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Denosumab Prevents Early Periprosthetic Bone Loss After Uncemented Total Hip Arthroplasty: Results from a Randomized Placebo-Controlled Clinical Trial2019In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681Article in journal (Refereed)
    Abstract [en]

    Implant loosening is the most common indication for revision surgery after total hip arthroplasty (THA). Although bone resorption around the implants plays a pivotal role in the pathophysiology of loosening, it is unknown whether potent early inhibition of osteoclasts could mitigate this process and thus reduce the need for revision surgery. We performed a randomized, double-blind, placebo-controlled phase 2 trial in 64 patients aged 35 to 65 years with unilateral osteoarthritis of the hip. They underwent surgery with an uncemented THA and were randomized to either two subcutaneous doses of denosumab (n = 32) or placebo (n = 32) given 1 to 3 days and 6 months after surgery. Patients were followed for 24 months. Primary outcome was periprosthetic bone mineral density (BMD) of the hip at 12 months as measured by dual-energy X-ray absorptiometry (DXA). In addition, [18 F] sodium fluoride positron emission tomography/CT (F-PET) was performed in half of the patients for analysis of periprosthetic standardized uptake value (SUV). Analyses were made according to intention-to-treat principles. The trial was registered at ClinicalTrials.gov 2011-001481-18, NCT01630941. Denosumab potently inhibited early periprosthetic bone loss. After 12 months, BMD in the denosumab group was 32% (95% confidence interval [CI] 22-44) higher in Gruen zone 7 and 11% (95% CI 8-15) higher in zones 1 to 7. After 24 months, the difference in BMD between groups had decreased to 15% (95% CI 4-27) in zone 7 and 4% (95% CI 0-8) in zones 1 to 7. In both groups, SUV increased after surgery, but the increase was less pronounced in the denosumab group. Biochemical markers of bone metabolism decreased in the denosumab group in the first 12 months, but a rebound effect with marker concentrations above baseline was observed after 24 months. Denosumab potently prevents early periprosthetic bone loss after uncemented THA; however, the effect diminishes after discontinuation of treatment. Further research is needed to determine whether this bone loss will prove to be of clinical importance and, if so, whether the positive effect observed in this study could be preserved by either prolonged treatment with denosumab or additional antiresorptive treatment. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

  • 41. Rittmeister, Markus E
    et al.
    Manthei, Lilian
    Hailer, Nils
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Prosthetic replacement in secondary Girdlestone arthroplasty has an unpredictable outcome.2005In: Int Orthop, ISSN 0341-2695, Vol. 29, no 3, p. 145-8Article in journal (Refereed)
  • 42.
    Rysinska, Agata
    et al.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Skoldenberg, Olof
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Garland, Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rolfson, Ola
    Swedish Hip Arthroplasty Register, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden;Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA;Harvard Med Sch, Boston, MA USA.
    Aspberg, Sara
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Eisler, Thomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Garellick, Goran
    Swedish Hip Arthroplasty Register, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden;Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA;Harvard Med Sch, Boston, MA USA.
    Stark, Andreas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gordon, Max
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Aseptic loosening after total hip arthroplasty and the risk of cardiovascular disease: A nested case-control study2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 11, article id e0204391Article in journal (Refereed)
    Abstract [en]

    Background: Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation compared with controls. Our hypothesis is that this increased risk after total hip arthroplasty (THA) is mediated by development of periprosthetic osteolysis leading to aseptic loosening of the implant.

    Methods: We conducted a nation-wide, nested, case-control study consisting of patients receiving a cemented THA due to osteoarthritis between the years 1992 and 2005. Our study population included a total of 14,430 subjects identified in the Swedish hip arthroplasty register and linked to the Swedish National Patient Register. The case group consisted of patients (n = 2,886) who underwent reoperation of the treated hip due to osteolysis or aseptic loosening at any time within five years after the index surgery. Each case was matched with four controls (n = 11,544) who had not undergone reoperation. The main outcomes were cardiovascular events i.e. myocardial infarction, heart failure and cerebral infarction according to ICD-codes and time to the first cardiovascular event during the exposure period. Outcomes were subgrouped into cardiac and cerebral events. We used regression models to calculate the incidence rates and adjusted our results for confounders.

    Findings: Overall, 5.1% of patients had cardiac events, with slightly more overall cardiovascular events occurring in the control group (8.1% vs. 6.7%, odds ratio 0.8, 95% confidence interval (CI) 0.7 to 1.0). After adjusting for confounders, the case group had an increased relative risk of 1.3 (95% confidence interval (CI) 1.1 to 1.3) for total number of cardiovascular events. Similar effect sizes were observed for time to first event.

    Interpretation: Patients with osteoarthritis who received THA and subsequently underwent a revision operation due to loosening had a higher relative risk of developing cardiovascular events than controls. Thus there is an association which could be explained by a common inflammatory disease pathway that requires further experimental research.

  • 43.
    Schizas, Nikos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Andersson, Brittmarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Interleukin-1 Receptor Antagonist Promotes Survival of Ventral Horn Neurons and Suppresses Microglial Activation in Mouse Spinal Cord Slice Cultures2014In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 92, no 11, p. 1457-1465Article in journal (Refereed)
    Abstract [en]

    Secondary damage after spinal cord injury (SCI) induces neuronal demise through neurotoxicity and inflammation, and interleukin (IL)-1 beta is a key inflammatory mediator. We hypothesized that IL-1 beta is released in spinal cord slice cultures (SCSC) and aimed at preventing the potentially neurotoxic effects of IL-1 beta by using interleukin-1 receptor antagonist (IL1RA). We hypothesized that IL1RA treatment enhances neuronal survival and suppresses microglial activation. SCSC were cultured up to 8 days in vitro (DIV) in the presence of IL1RA or without, either combined with trophic support using neurotrophin (NT)-3 or not. Four groups were studied: negative control, IL1RA, NT-3, and IL1RA1NT-3. IL-1 beta concentrations in supernatants were measured by ELISA. SCSC were immunohistochemically stained for NeuN and a-neurofilament, and microglial cells were visualized with isolectin B-4. After 8 DIV, ventral horn neurons were significantly more numerous in the IL1RA, NT-3, and IL1RA1NT-3 groups compared with negative controls. Activated microglial cells were significantly less numerous in the IL1RA, NT-3, and IL1RA1NT-3 groups compared with negative controls. Axons expanded into the collagen matrix after treatment with IL1RA, NT-3, or IL1RA1NT-3, but not in negative controls. IL-1 beta release from cultures peaked after 6 hr and was lowest in the IL1RA1NT-3 group. We conclude that IL-1 beta is released in traumatized spinal cord tissue and that IL1RA could exert its neuroprotective actions by blocking IL-1-receptors. IL1RA thereby sustains neuronal survival irrespective of the presence of additional trophic support. Microglial activation is suppressed in the presence of IL1RA, suggesting decreased inflammatory activity. IL1RA treatment approaches may have substantial impact following SCI.

  • 44.
    Schizas, Nikos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    König, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Andersson, Brittmarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Vasylovska, Svitlana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hoeber, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Kozlova, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Neural crest stem cells protect spinal cord neurons from excitotoxic damage and inhibit glial activation by secretion of brain-derived neurotrophic factor2018In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 372, no 3, p. 493-505Article in journal (Refereed)
    Abstract [en]

    The acute phase of spinal cord injury is characterized by excitotoxic and inflammatory events that mediate extensive neuronal loss in the gray matter. Neural crest stem cells (NCSCs) can exert neuroprotective and anti-inflammatory effects that may be mediated by soluble factors. We therefore hypothesize that transplantation of NCSCs to acutely injured spinal cord slice cultures (SCSCs) can prevent neuronal loss after excitotoxic injury. NCSCs were applied onto SCSCs previously subjected to N-methyl-d-aspartate (NMDA)-induced injury. Immunohistochemistry and TUNEL staining were used to quantitatively study cell populations and apoptosis. Concentrations of neurotrophic factors were measured by ELISA. Migration and differentiation properties of NCSCs on SCSCs, laminin, or hyaluronic acid hydrogel were separately studied. NCSCs counteracted the loss of NeuN-positive neurons that was otherwise observed after NMDA-induced excitotoxicity, partly by inhibiting neuronal apoptosis. They also reduced activation of both microglial cells and astrocytes. The concentration of brain-derived neurotrophic factor (BDNF) was increased in supernatants from SCSCs cultured with NCSCs compared to SCSCs alone and BDNF alone mimicked the effects of NCSC application on SCSCs. NCSCs migrated superficially across the surface of SCSCs and showed no signs of neuronal or glial differentiation but preserved their expression of SOX2 and Krox20. In conclusion, NCSCs exert neuroprotective, anti-apoptotic and glia-inhibitory effects on excitotoxically injured spinal cord tissue, some of these effects mediated by secretion of BDNF. However, the investigated NCSCs seem not to undergo neuronal or glial differentiation in the short term since markers indicative of an undifferentiated state were expressed during the entire observation period.

  • 45.
    Schizas, Nikos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Perry, Sharn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Andersson, Brittmarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wählby, Carolina
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Kullander, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Differential neuroprotective effects of interleukin-1 receptor antagonist on spinal cord neurons after excitotoxic injury2017In: Neuroimmunomodulation, ISSN 1021-7401, E-ISSN 1423-0216, Vol. 24, p. 220-230Article in journal (Refereed)
  • 46.
    Schizas, Nikos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rojas, Ramiro
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Kootala, Sujit
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Andersson, Brittmarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pettersson, Jennie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Hailer, Nils P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hyaluronic acid-based hydrogel enhances neuronal survival in spinal cord slice cultures from postnatal mice2014In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 28, no 6, p. 825-836Article in journal (Refereed)
    Abstract [en]

    Numerous biomaterials based on extracellular matrix-components have been developed. It was our aim to investigate whether a hyaluronic acid-based hydrogel improves neuronal survival and tissue preservation in organotypic spinal cord slice cultures. Organotypic spinal cord slice cultures were cultured for 4 days in vitro (div), either on hyaluronic acid-based hydrogel (hyaluronic acid-gel group), collagen gel (collagen group), directly on polyethylene terephthalate membrane inserts (control group), or in the presence of soluble hyaluronic acid (soluble hyaluronic acid group). Cultures were immunohistochemically stained against neuronal antigen NeuN and analyzed by confocal laser scanning microscopy. Histochemistry for choline acetyltransferance, glial fibrillary acidic protein, and Griffonia simplicifolia isolectin B4 followed by quantitative analysis was performed to assess motorneurons and different glial populations. Confocal microscopic analysis showed a 4-fold increase in the number of NeuN-positive neurons in the hyaluronic acid-gel group compared to both collagen (p < 0.001) and control groups (p < 0.001). Compared to controls, organotypic spinal cord slice cultures maintained on hyaluronic acid-based hydrogel showed 5.9-fold increased survival of choline acetyltransferance-positive motorneurons (p = 0.008), 2-fold more numerous resting microglial cells in the white matter (p = 0.031), and a 61.4% reduction in the number of activated microglial cells within the grey matter (p = 0.05). Hyaluronic acid-based hydrogel had a shear modulus (G') of ≈1200 Pascals (Pa), which was considerably higher than the ≈25 Pa measured for collagen gel. Soluble hyaluronic acid failed to improve tissue preservation. In conclusion, hyaluronic acid-based hydrogel improves neuronal and - most notably - motorneuron survival in organotypic spinal cord slice cultures and microglial activation is limited. The positive effects of hyaluronic acid-based hydrogel may at least in part be due to its mechanical properties.

  • 47. Stavridis, Stavros I
    et al.
    Dehghani, Faramarz
    Korf, Horst-Werner
    Hailer, Nils
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Characterisation of transverse slice culture preparations of postnatal rat spinal cord: preservation of defined neuronal populations.2005In: Histochem Cell Biol, ISSN 0948-6143, Vol. 123, no 4-5, p. 377-92Article in journal (Refereed)
  • 48.
    Tsikandylakis, Georgios
    et al.
    Univ Gothenburg, Dept Orthopaed, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden; Sahlgrens Univ Hosp, Registerctr Västra Götaland, Gothenburg, Sweden; Swedish Hip Arthroplasty Register, Gothenburg, Sweden; Univ Gothenburg, Dept Orthopaed, Inst Clin Sci, Sahlgrenska Acad,Sahlgrenska Univ Hospital, Mölndal, Gothenburg, Sweden; Swedish Hip Arthroplasty Register, Registerctr Västra Götaland, Mölndal, Sweden.
    Kärrholm, Johan
    Univ Gothenburg, Dept Orthopaed, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden; Sahlgrens Univ Hosp, Registerctr Västra Götaland, Gothenburg, Sweden; Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Eskelinen, Antti
    Coxa Hosp Joint Replacement, Tampere, Finland; Finnish Arthroplasty Register, Helsinki, Finland.
    Mäkelä, Keijo T.
    Finnish Arthroplasty Register, Helsinki, Finland; Turku Univ Hosp, Dept Orthoped & Traumatol, Turku, Finland.
    Hallan, Geir
    Haukeland Hosp, Norwegian Arthroplasty Register, Dept Orthoped Surg, Bergen, Norway; Univ Bergen, Dept Clin Med, Fac Med, Bergen, Norway.
    Furnes, Ove Nord
    Haukeland Hosp, Norwegian Arthroplasty Register, Dept Orthoped Surg, Bergen, Norway; Univ Bergen, Dept Clin Med, Fac Med, Bergen, Norway.
    Pedersen, Alma B.
    Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark; Danish Hip Arthroplasty Register, Aarhus, Denmark.
    Overgaard, Søren
    Danish Hip Arthroplasty Register, Aarhus, Denmark; Odense Univ Hosp, Dept Orthopaed Surg & Traumatol, Odense, Denmark; Univ Southern Denmark, Inst Clin Res, Odense, Denmark.
    Mohaddes, Maziar
    Univ Gothenburg, Dept Orthopaed, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden; Sahlgrens Univ Hosp, Registerctr Västra Götaland, Gothenburg, Sweden; Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    No Increase in Survival for 36-mm versus 32-mm Femoral Heads in Metal-on-polyethylene THA: A Registry Study2018In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 476, no 12, p. 2367-2378Article in journal (Refereed)
    Abstract [en]

    Background During the past decade, the 32-mm head has replaced the 28-mm head as the most common head size used in primary THA in many national registries, and the use of 36-mm heads has also increased. However, it is unclear whether 32-mm and 36-mm heads decrease the revision risk in metal-on-polyethylene (MoP) THA compared with 28-mm heads.

    Questions/purposes (1) In the setting of the Nordic Arthroplasty Register Association database, does the revision risk for any reason differ among 28-, 32-, and 36-mm head sizes in patients undergoing surgery with MoP THA? (2) Does the revision risk resulting from dislocation decrease with increasing head diameter (28-36 mm) in patients undergoing surgery with MoP THA in the same registry?

    Methods Data were derived from the Nordic Arthroplasty Register Association database, a collaboration among the national arthroplasty registries of Denmark, Finland, Norway, and Sweden. Patients with primary osteoarthritis who had undergone primary THA with a 28-, 32-, or 36-mm MoP bearing from 2003 to 2014 were included. Patients operated on with dual-mobility cups were excluded. In patients with bilateral THA, only the first operated hip was included. After applying the inclusion criteria, the number of patients and THAs with a complete data set was determined to be 186,231, which accounted for 51% of all hips (366,309) with primary osteoarthritis operated on with THA of any head size and bearing type during the study observation time. Of the included patients, 60% (111,046 of 186,231) were women, the mean age at surgery was 70 (± 10) years, and the median followup was 4.5 years (range, 0-14 years). A total of 101,094 patients had received a 28-mm, 57,853 a 32-mm, and 27,284 a 36-mm head with 32 mm used as the reference group. The revision of any component for any reason was the primary outcome and revision for dislocation was the secondary outcome. Very few patients are estimated to be lost to followup because emigration in the population of interest (older than 65-70 years) is rare. A Kaplan-Meier analysis was used to estimate THA survival for each group, whereas Cox regression models were fitted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for THA revision comparing the 28- and 36-mm head diameters with the 32-mm head diameters adjusting for age, sex, year of surgery, type of cup and stem fixation, polyethylene type (crosslinked versus conventional), and surgical approach.

    Results In the adjusted Cox regression model, there was no difference in the adjusted risk for revision for any reason between patients with 28-mm (HR, 1.06; 95% CI, 0.97–0.16) and 32-mm heads, whereas the risk of revision was higher for patients with 36-mm heads (HR, 1.14; 95% CI, 1.04–1.26) compared with patients with 32-mm heads. Patients with 28-mm heads had a higher risk of revision for dislocation (HR, 1.67; 95% CI, 1.38–1.98) compared with 32 mm, whereas there was no difference between patients with 36-mm (HR, 0.85; 95% CI, 0.70–1.02) and 32-mm heads.

    Conclusions After adjusting for relevant confounding variables, we found no benefits for 32-mm heads against 28 mm in terms of overall revision risk. However, when dislocation risk is considered, 32-mm heads would be a better option, because they had a lower risk of revision resulting from dislocation. There were no benefits with the use of 36-mm heads over 32 mm, because the transition from 32 to 36 mm was associated with a higher risk of revision for all reasons, which was not accompanied by a decrease in the risk of revision resulting from dislocation. The use of 32-mm heads appears to offer the best compromise between joint stability and other reasons for revision in MoP THA. Further studies with longer followup, especially of 36-mm heads, as well as better balance of confounders across head sizes and better control of patient-related risk factors for THA revision are needed.

    Level of Evidence Level III, therapeutic study.

  • 49.
    Tyson, Yosef
    et al.
    Uppsala Univ Hosp, Dept Surg Sci, Sect Orthoped Surg, Uppsala, Sweden;Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Rolfson, Ola
    Swedish Hip Arthroplasty Register, Gothenburg, Sweden;Sahlgrens Univ Hosp, Sahlgrenska Acad, Inst Clin Sci, Dept Orthoped, Molndal, Sweden.
    Karrholm, Johan
    Swedish Hip Arthroplasty Register, Gothenburg, Sweden;Sahlgrens Univ Hosp, Sahlgrenska Acad, Inst Clin Sci, Dept Orthoped, Molndal, Sweden.
    Hailer, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mohaddes, Maziar
    Swedish Hip Arthroplasty Register, Gothenburg, Sweden;Sahlgrens Univ Hosp, Sahlgrenska Acad, Inst Clin Sci, Dept Orthoped, Molndal, Sweden.
    Uncemented or cemented revision stems?: Analysis of 2,296 first-time hip revision arthroplasties performed due to aseptic loosening, reported to the Swedish Hip Arthroplasty Register2019In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 90, no 5, p. 421-426Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Uncemented stems are increasingly used in revision hip arthroplasty, but only a few studies have analyzed the outcomes of uncemented and cemented revision stems in large cohorts of patients. We compared the results of uncemented and cemented revision stems. Patients and methods - 1,668 uncemented and 1,328 cemented revision stems used in first-time revisions due to aseptic loosening between 1999 and 2016 were identified in the Swedish Hip Arthroplasty Register. Kaplan-Meier analysis was used to investigate unadjusted implant survival with re-revision for any reason as the primary outcome. Hazard ratios (HR) for the risk of re-revision were calculated using a Cox regression model adjusted for sex, age, head size, concomitant cup revision, surgical approach at primary and at index revision surgery, and indication for primary total hip arthroplasty. Results - Unadjusted 10-year survival was 85% (95% CI 83-87) for uncemented and 88% (CI 86-90) for cemented revision stems. The adjusted HR for re-revision of uncemented revision stems during the first year after surgery was 1.3 (CI 1.0-1.6), from the second year the HR was 1.1 (CI 0.8-1.4). Uncemented stems were most often re-revised early due to infection and dislocation, whereas cemented stems were mostly re-revised later due to aseptic loosening. Interpretation - Both uncemented and cemented revision stems had satisfactory long-term survival but they differed in their modes of failure. Our conclusions are limited by the fact that femoral bone defect size could not be investigated within the setting of the current study.

  • 50. Weiss, Rudiger J.
    et al.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Stark, Andre
    Karrholm, Johan
    Survival of uncemented acetabular monoblock cups: Evaluation of 210 hips in the Swedish Hip Arthroplasty Register2012In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 3, p. 214-219Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    Monoblock acetabular cups represent a subtype of uncemented cups with the polyethylene liner molded into a metal shell, thus eliminating-or at least minimizing-potential backside wear. We hypothesized that the use of mono block cups could reduce the incidence of osteolysis and aseptic loosening, and thus improve survival compared to modular designs.

    Patients and methods

    We identified all 210 primary total hip arthroplasty (THA) procedures in the Swedish Hip Arthroplasty Register that used uncemented monoblock cups during the period 1999-2010. Kaplan-Meier and Cox regression analyses with adjustment for age, sex, and other variables were used to calculate survival rates and adjusted hazard ratios (HRs) of the revision risk for any reason. 1,130 modular cups, inserted during the same time period, were used as a control group.

    Results

    There was a nearly equal sex distribution in both groups. Median age at the index operation was 47 years in the monoblock group and 56 years in the control group (p < 0.001). The cumulative 5-year survival with any revision as the endpoint was 95% (95% CI: 91-98) for monoblock cups and 97% (CI: 96-98) for modular cups (p = 0.6). The adjusted HR for revision of monoblock cups compared to modular cups was 2 (CI: 0.8-6; p = 0.1). The use of 28-mm prosthesis heads rather than 22-mm heads reduced the risk of cup revision (HR = 0.2, CI: 0.1-0.5; p = 0.001).

    Interpretation

    Both cups showed good medium-term survival rates. There was no statistically significant difference in revision risk between the cup designs. Further review of the current patient population is warranted to determine the long-term durability and risk of revision of monoblock cup designs.

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