Stig Jakobsen - Academia.edu (original) (raw)

Papers by Stig Jakobsen

Insertion of metal implants is associated with a possible change in the delicate balance between ... more Insertion of metal implants is associated with a possible change in the delicate balance between pro-and antiinflammatory proteins, probably leading to an unfavourable predominantly pro-inflammatory milieu. The most likely cause is an inappropriate activation of macrophages in close relation to the metal implant and wear-products. The aim of the present study was to compare surfaces of as-cast and wrought Cobalt-Chrome-Molybdenum (CoCrMo) alloys and Titanium-Aluminium-Vanadium (TiAlV) alloy when incubated with mouse macrophage J774A.1 cell cultures. Changes in pro-and anti-inflammatory cytokines [TNF-α, IL-6, IL-1α, IL-1β, IL-10] and proteins known to induce proliferation [M-CSF], chemotaxis [MCP-1] and osteogenesis [TGF-β, OPG] were determined by ELISA and Real Time reverse transcriptase-PCR (Real Time rt-PCR). Lactate dehydrogenase (LDH) was measured in the medium to asses the cell viability. Surface properties of the discs were characterised with a profilometer and with energy dispersive X-ray spectroscopy. We here report, for the first time, that the prosthetic material surface (nonphagocytable) of as-cast high carbon CoCrMo reduces the pro-inflammatory cytokine IL-6 transcription, the chemokine MCP-1 secretion, and M-CSF secretion by 77 %, 36 %, and 62 %, respectively. Furthermore, we found that reducing surface roughness did not affect this reduction. The results suggest that as-cast CoCrMo alloy is more inert than wrought CoCrMo and wrought TiAlV alloys and could prove to be a superior implant material generating less inflammation which might result in less osteolysis.

Journal of Biomaterials Science-polymer Edition, 2009

Hydroxyapatite (Ca(10)(PO(2))(6)(OH)(2), HA) coatings are widely used in un-cemented total hip ar... more Hydroxyapatite (Ca(10)(PO(2))(6)(OH)(2), HA) coatings are widely used in un-cemented total hip arthroplasties because it increases implant fixation and bone in-growth. HA adsorbs high levels of proteins (e.g., fibronectin) and adhering macrophages release higher levels of BMP-2 compared to non-coated surfaces. Inflammation, however, can block the BMP-2 production from macrophages and it has been suggested that roughened surfaces activate macrophages. Therefore, the aim of the present study was to investigate whether commercially available 3D surfaces would generate increased BMP-2 and TGF-beta production and establish how this production is affected by macrophage activation. A mouse macrophage cell line (J774A.1) was incubated with 3D coatings resembling clinically used protestic surfaces, i.e., plasmaspray TiAlV coating with or without HA and porous TiAlV coating with or without HA. BMP-2 and TGF-beta production was determined after 24 h with ELISA and real time-reverse transcriptase-PCR (real time RT-PCR). Changes in pro-inflammatory response were established with ELISA after 6 and 24 h. The increased surface roughness of HA-coated surfaces was characterized with confocal microscopy. HA coating on plasmasprayed TiAlV coating was not found to induce BMP-2 and TGF-beta secretion in the J774A.1 macrophage cell line. In contrast, LPS-activated macrophages increased their TGF-beta, but not BMP-2, secretion when exposed to the prosthetic surfaces. These results imply that the well-known bone-inductive effects of HA may not be dependent on macrophage BMP-2 and TGF-beta secretion. Surface topography and protein adhesion may play a more pivotal role.

BMJ Open, Sep 1, 2022

To cite: Jacobsen JS, Thorborg K, Nielsen RØ, et al. Comparing exercise and patient education wit... more To cite: Jacobsen JS, Thorborg K, Nielsen RØ, et al. Comparing exercise and patient education with usual care in the treatment of hip dysplasia: a protocol for a randomised controlled trial with 6-month follow-up (MovetheHip trial). BMJ Open 2022;12:e064242.

Archives of Orthopaedic and Trauma Surgery, Feb 21, 2023

Introduction Dual mobility implants have been successful in reducing postoperative hip dislocatio... more Introduction Dual mobility implants have been successful in reducing postoperative hip dislocation but mid-term results of cup migration and polyethylene wear are missing in the literature. Therefore, we measured migration and wear at 5-year follow-up using radiostereometric analysis (RSA). Materials and methods A cohort of 44 patients (mean age 73, 36 female) with heterogeneous indications for hip arthroplasty but all with a high risk of hip dislocation received total hip replacement (THA) with The Anatomic Dual Mobility X3 monoblock acetabular construct and a highly crosslinked polyethylene liner. RSA images and Oxford Hip Scores were obtained perioperatively and 1, 2, and 5 years postoperatively. Cup migration and polyethylene wear were calculated using RSA. Results Mean 2-year proximal cup translation was 0.26 mm (95% CI 0.17; 0.36). Proximal cup translation was stable from 1-to 5-year follow-up. Mean 2-year cup inclination (z-rotation) was 0.23° (95% CI − 0.22; 0.68) and was greater in patients with osteoporosis compared to patients without osteoporosis (p = 0.04). Using 1-year follow-up as baseline, the 3D polyethylene wear rate was 0.07 mm/year (0.05; 0.10). Oxford hip scores improved 19 (95% CI 14; 24) points from mean 21 (range 4; 39) at baseline, to 40 (9; 48) 2 years postoperatively. There were no progressive radiolucent lines > 1 mm. There was 1 revision for offset correction. Conclusions Anatomic Dual Mobility monoblock cups were well-fixed, the polyethylene wear rate was low, and the clinical outcomes were good until 5-year follow-up suggesting good implant survival in patients of different age groups and with heterogeneous indications for THA.

The Open Orthopaedics Journal, Sep 3, 2012

Interaction between implant surface and surrounding bone influences implant fixation. We attempte... more Interaction between implant surface and surrounding bone influences implant fixation. We attempted to improve the bone-implant interaction by 1) adding surface micro scale topography by acid etching, and 2) removing surface-adherent pro-inflammatory agents by plasma cleaning. Implant fixation was evaluated by implant osseointegration and biomechanical fixation. The study consisted of two paired animal sub-studies where 10 skeletally mature Labrador dogs were used. Grit blasted titanium alloy implants were inserted press fit in each proximal tibia. In the first study grit blasted implants were compared with acid etched grit blasted implants. In the second study grit blasted implants were compared with acid etched grit blasted implants that were further treated with plasma sterilization. Implant performance was evaluated by histomorphometrical investigation (tissue-to-implant contact, peri-implant tissue density) and mechanical push-out testing after four weeks observation time. Neither acid etching nor plasma sterilization of the grit blasted implants enhanced osseointegration or mechanical fixation in this press-fit canine implant model in a statistically significant manner.

Acta Orthopaedica, May 21, 2014

Bone & Joint Open, 2021

Aims Femoral bone preparation using compaction technique has been shown to preserve bone and impr... more Aims Femoral bone preparation using compaction technique has been shown to preserve bone and improve implant fixation in animal models. No long-term clinical outcomes are available. There are no significant long-term differences between compaction and broaching techniques for primary total hip arthroplasty (THA) in terms of migration, clinical, and radiological outcomes. Methods A total of 28 patients received one-stage bilateral primary THA with cementless femoral stems (56 hips). They were randomized to compaction on one femur and broaching on the contralateral femur. Overall, 13 patients were lost to the ten-year follow-up leaving 30 hips to be evaluated in terms of stem migration (using radiostereometry), radiological changes, Harris Hip Score, Oxford Hip Score, and complications. Results Over a mean follow-up period of 10.6 years, the mean stem subsidence was similar between groups, with a mean of -1.20 mm (95% confidence interval (CI) -2.28 to -0.12) in the broaching group and...

Journal of Bone and Joint Infection, 2021

Introduction. Systemic perioperative vancomycin may not provide sufficient prophylactic target-si... more Introduction. Systemic perioperative vancomycin may not provide sufficient prophylactic target-site concentrations in the prevention of prosthetic joint infections. Intraosseous vancomycin potentially provides high target-site concentrations. The objective of the present study was to evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model. Methods. Eight pigs received 500 mg diluted vancomycin (50 mg/mL) through an intraosseous cannula into the proximal tibial cancellous bone. No tourniquet was applied. Microdialysis was applied for sampling of vancomycin concentrations in adjacent tibial cancellous bone, in cortical bone, in the intramedullary canal of the diaphysis, in the synovial fluid of the knee joint, and in the subcutaneous tissue. Plasma samples were obtained as a systemic reference. Samples were collected for 12 h. Results. High vancomycin concentrations were found in the tibial cancellous bone with a mean peak drug concentration of 1236 (range 28-5295) µg/mL, which remained high throughout the sampling period. The mean (standard deviation) peak drug concentration in plasma was 19 (2) µg/mL, which was obtained immediately after administration. Peak drug concentration, time to peak drug concentration, and area under the concentration-time curve were within the same range in the intramedullary canal, the synovial fluid of the knee, and the subcutaneous tissue. Conclusion. Tibial intraosseous administration of vancomycin provided high concentrations in tibial cancellous bone throughout a 12 h period but with an unpredictable and wide range of peak concentration. The systemic absorption was high and immediate, thus mirroring an intravenous administration. Low mean concentrations were found in all the remaining compartments.

BMJ Open, 2019

IntroductionPeriacetabular osteotomy (PAO) is an established treatment for adolescent and adult p... more IntroductionPeriacetabular osteotomy (PAO) is an established treatment for adolescent and adult patients with hip dysplasia. However, the efficacy of PAO has not been tested against another surgical intervention or conservative treatment in a randomised controlled trial before. We suggest that progressive resistance training (PRT) could be an alternative to PAO. The primary aim of this trial is therefore to examine the efficacy of PAO followed by 4 months of usual care followed by 8 months of PRT compared to 12 months of solely PRT in patients with hip dysplasia eligible for PAO in terms of patient-reported pain measured by The Copenhagen Hip and Groin Outcome Score (HAGOS).Methods and analysisThis trial is a single-blinded multicentre randomised controlled clinical trial, where patients with hip dysplasia, who are eligible for PAO, will be randomised to either PAO followed by usual care and PRT or PRT only. Primary outcome is patient-reported pain, measured on the subscale pain on ...

Acta Orthopaedica, 2019

Stilling (2019): Higher early proximal migration of hemispherical cups with electrochemically app... more Stilling (2019): Higher early proximal migration of hemispherical cups with electrochemically applied hydroxyapatite (BoneMaster) on a porous surface compared with porous surface alone: a randomized RSA study with 53 patients, Acta Orthopaedica,

Journal of Orthopaedics, 2019

Two-stage revision with 'StageOne™ Select Hip Cement Spacer' is used as treatment of periprosthet... more Two-stage revision with 'StageOne™ Select Hip Cement Spacer' is used as treatment of periprosthetic hip joint infection. The aim is to evaluate complications and restoration the joint with the StageOne Select Spacer. From 2013 to 2018 twenty-nine StageOne Select Spacers was inserted. Data was obtained through medical records and radiographs. 3.5% dislocated the spacer, 6.9% sustained a femoral fracture, 6.9% got reinfected and 6.9% failed to control the infection. Leg length discrepancy was 1.5 mm (−4,25-5.25) and offset discrepancy was 4 mm (−0.5-9). The spacer shows promising results with a low reinfection and dislocation rate and allowance of restoration of the joint.

Journal of Clinical Medicine, 2019

Metal release from total hip replacements (THRs) is associated with aseptic loosening (AL). It ha... more Metal release from total hip replacements (THRs) is associated with aseptic loosening (AL). It has been proposed that the underlying immunological response is caused by a delayed type IV hypersensitivity-like reaction to metals, i.e., metal allergy. The purpose of this study was to investigate the immunological response in patients with AL in relation to metal release and the prevalence of metal allergy. THR patients undergoing revision surgery due to AL or mechanical implant failures were included in the study along with a control group consisting of primary THR patients. Comprehensive cytokine analyses were performed on serum and periimplant tissue samples along with metal analysis using inductive coupled plasma mass spectrometry (ICP-MS). Patient patch testing was done with a series of metals related to orthopedic implant. A distinct cytokine profile was found in the periimplant tissue of patients with AL. Significantly increased levels of the proinflammatory cytokines IL-1β, IL-...

Journal of Hip Preservation Surgery, 2019

Symptomatic hip dysplasia is primarily treated surgically with periacetabular osteotomy (PAO). It... more Symptomatic hip dysplasia is primarily treated surgically with periacetabular osteotomy (PAO). It is unclear whether changes in quality of life (QoL) and changes in hip function follow the same pattern of improvement as pain following PAO. The aim of the study is to investigate whether changes in pain were associated with changes in QoL and hip function 2 years after PAO. Furthermore, to examine patient satisfaction 2 years after PAO. This is a follow-up study with data from Aarhus University Hospital Denmark. Pain was measured using the Visual Analogue Scale, QoL with Short-Form 36 and hip function with Hip disability and Osteoarthritis Outcome Score both preoperatively and 2 years after PAO in 321 patients. Multiple linear regressions were applied. Significant mean improvements in pain, QoL and hip function were found (P < 0.05). Significant associations between changes in pain and changes in physically related QoL and changes in hip function, respectively were found (P < 0.05). A non-significant association between changes in pain and changes in mentally-related QoL was found (P ¼ 0.13). The majority of patients (84%) reported satisfaction with the result of PAO and would undergo PAO again if they had known the results in advance. The study had a loss to follow-up of 26%. Decreased pain was significantly associated with increased physically related QoL and improved hip function 2 years after PAO. A nonsignificant association between decreased pain and increased mentally related QoL was found. Patients were in general satisfied with treatment and results 2 years after PAO.

Journal of Hip Preservation Surgery, 2018

Periacetabular osteotomy (PAO) corrects underlying anatomical anomalies, reduces pain and may pos... more Periacetabular osteotomy (PAO) corrects underlying anatomical anomalies, reduces pain and may postpone or even prevent osteoarthritis onset in patients with symptomatic acetabular dysplasia. Current evidence is based on immediate post-operative pain levels, but knowledge on pain levels in the period after PAO is scarce, and the association between pain score and acetabular angles at PAO is unknown. This study had two aims. First, we studied pain level and patient-reported outcome scores pre-and postoperatively; second, we analysed the association between acetabular angles and pain level. From our database, 426 patients operated from June 2012 to November 2015 were analysed; 127 were excluded. Patients were invited to complete standardized questionnaires preoperatively and postoperatively at 6 and 24 months. Pain was measured using visual analogue scale (VAS). Multiple regression analysis was used to investigate the association between change in centre edge (CE) and acetabular index (AI) angle and pre/postoperative pain levels. Mean (standard deviation, SD) VAS pain at rest before surgery and at the 6-and 24-month follow-up were 35 (24), 14 (20) and 14 (19), respectively. Mean (SD) VAS pain at activity were 69 (22), 41 (29) and 41 (30), respectively. Both VAS pain at rest and at activity fell from the preoperative level to 6 months post-surgery with no further change at 24 months. Patients reported significant improvement in outcomes after 6 months and no further change at the 24-month follow-up. There was no significant association between change in CE/AI angles and VAS pain, either during rest or activity.

Journal of hip preservation surgery, 2018

The primary aim was to identify muscle-tendon-related pain in 100 patients with hip dysplasia. Th... more The primary aim was to identify muscle-tendon-related pain in 100 patients with hip dysplasia. The secondary aim was to test whether muscle-tendon-related pain is associated with self-reported hip disability and muscle strength in patient with hip dysplasia. One hundred patients (17 men) with a mean age of 29 years (SD 9) were included. Clinical entity approach was carried out to identify muscle-tendon-related pain. Associations between muscle-tendon-related pain and self-reported hip disability and muscle strength were tested with multiple regression analysis, including adjustments for age and gender. Self-reported hip disability was recorded with the Copenhagen Hip and Groin Outcome Score (HAGOS), and muscle strength was assessed with a handheld dynamometer. Iliopsoas- and abductor-related pain were most prevalent with prevalences of 56% (CI 46; 66) and 42% (CI 32; 52), respectively. Adductor-, hamstrings- and rectus abdominis-related pain were less common. There was a significant...

European Cells and Materials, 2007