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Background and Purpose: Pain in the sacroiliac joint may be caused by abnormal joint motion. Diagnosis is mainly based on clinical tests. The aims of this study were to examine whether low-dose computed tomography with provocation of the hip could detect sacroiliac joint motion, and to study whether provocation of the hip results in greater sacroiliac joint motion in the ipsilateral than in the contralateral sacroiliac joint., Patients and Methods: 12 patients with sacroiliac joint pain were examined with low-dose computed tomography scans of the sacroiliac joint, one with the hips in the neutral position, and one each in provocation with the left or the right hip in a figure-of-4 position. Accuracy was tested by comparing internal rotation of the sacrum with internal rotation in the sacroiliac joint. Motion in the sacroiliac joint was assessed by comparing the position of each of the ilia with the reference, the sacrum. Data is shown as mean with 95% confidence interval (CI)., Results: We observed greater motion in the sacroiliac joint than internally in the sacrum, i.e., 0.57° (CI 0.43-0.71) vs. 0.20° (CI 0.11-0.28). The motion of the geometric center of the moving object for the sacroiliac joint was larger on the provoked side; mean difference 0.17 mm (CI 0.01-0.33), P = 0.04. Corresponding figures for rotation were mean difference 0.19° (CI 0.10-0.28), P < 0.001. Compared with the sacrum, the largest motion was seen at the anterior superior iliac spine; mean difference 0.38 mm (CI 0.10-0.66), P = 0.001., Conclusion: Provocation in the figure-of-4 position of the hip results in sacroiliac joint motion measurable with computed tomography motion analysis. Provocation of the hip induces larger motion on the ipsilateral than on the contralateral sacroiliac joint.

Background: Volar locking plate fixation (VLPF) is the most common method for operative fixation of distal radius fractures (DRF). The dorsal ulnar corner (DUC) can be difficult to stabilize as the fragment is small and not exposed when using the volar approach. The purpose of this study was to study fracture fragment migration after VLPF of AO type C DRF, using a volume registration technique of paired CT scans with special focus on the DUC fragment., Materials and Methods: This pilot study included ten patients with AO type C DRF, all operated with VLPF. The primary outcome was radiographic outcome. Postoperative and 1-year scans were compared and analyzed. Fragment migration was assessed with CT-based micromotion analysis (CTMA), a software technique used for volume registration of paired CT scans., Results: All plates were stable over time. Two patients showed signs of screw movement (0.2-0.35 mm and 0.35- > 1 mm respectively). Postoperative reduction was maintained, and there was no fragment migration at the 1-year follow-up except for one case with increased dorsal tilt. The DUC fragment was found in 8/10 cases, fixated in 7/8 cases, and not dislocated in any case at the 1-year follow-up., Conclusion: The CTMA results indicate that variable-angle VLPF after AO type C DRF can yield and maintain a highly stable reduction of the fracture fragments. The DUC fragment remained stable regardless of the number of screws through the fragment. CT volume registration can be a valuable tool in the detailed assessment of fracture fragment migration following volar plate fixation of DRFs., Competing Interests: Conflict of InterestDr Olivecrona is occasionally engaged by Sectra as an independent consultant for software development. The authors declared no other potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Purpose: High-energy pelvic fractures are complex injuries often requiring surgical treatment. Different radiological methods exist to evaluate the reduction and healing process postoperatively but with certain limitations. The aim of this study was to evaluate Computed Tomography Micromotion Analysis (CTMA) in a clinical setting for follow-up of surgically treated pelvic fracture patients., Methods: 10 patients surgically treated for a pelvic fracture were included and prospectively followed with Computed Tomography (CT) at 0, 6, 12 and 52 weeks postoperatively. CTMA was used to measure postoperative translation and rotation of the pelvic fracture during the 52 weeks follow-up. Clinical outcomes were collected through the questionnaires EQ-5D index score and Majeed score., Results: 10 patients were included with mean age (± SD, min-max) 52 (16, 31-80) years and 70% (n = 7) were males. The median (IQR, min-max) global translation from 0 to 52 weeks was 6.0 (4.6, 1.4-12.6) millimeters and median global rotation was 2.6 (2.4, 0.7-4.7) degrees. The general trend was a larger translation between 0 and 6 weeks postoperatively compared to 6-12 and 12-52 weeks. For the clinical outcomes, the general trend was that all patients started from high scores which decreased in the first postoperative follow-up and recovered to different extent during the study period., Conclusion: CTMA was successfully used in the follow-up of surgically treated pelvic fracture patients. Movement in the pelvic fractures after surgical fixation was largest between 0 and 6 weeks., (© 2023. The Author(s).)

Early implant migration is an indicator of the long-term survival/failure of implants. CT-based radio-stereometric analysis (CT-RSA) is a precise method for measuring and visualizing implant migration in vivo using image processing of CT scans. This makes the method widely applicable to orthopedic researcher. Since its development in the early 2000s, CT-RSA has benefited from breakthroughs in CT and computing technology. These advancements have allowed for the acquisition of images with higher resolution at a much lower radiation dose. As a result, the measurement precision of CT-RSA is now comparable to that of the current gold standard technology while still compatible with most ethical considerations regarding radiation exposure. In this review we present bests practices for the successful execution of CT-RSA research projects. These practices are based on experience from projects on the hip, knee, shoulder, lower back, cervical spine, foot, pelvis, and wrist.

Background and Purpose: Inducible displacement CT compares 2 CTs acquired in series but with alternated rotation of the femur. This provides visual and quantitative clues as to the mechanical situation, i.e., loosening, of a total hip arthroplasty. We report the accuracy of this method as well as the experience of integrating it into a clinical workflow., Patients and Methods: This was a retrospective single centre study of 72 cases of suspected aseptic loosening were the surgeon after reviewing a standard plain radiograph saw a need for more information. The displacement CT and plain radiograph were compared either to intraoperative findings or a 1-3 year follow up questionnaire for patients that did not have revision surgery. Patients reporting degradation in status since the time of the displacement CT were called for a follow up plain radiograph. Sensitivity and specificity were assessed, and user experience gathered., Results: Of 72 enrolled patients 15 were lost to follow up. Of the remaining 57, 17 were judged by in-traoperative findings or follow-up to have had loose implants. For plain radiography the sensitivity and specificity were 59% (95% CI 35-82) and 85% (74-96). For displacement CT the corresponding values were 77% (56-97), and 100% (100-100) respectively. The tool was adaptable to clinical routine., Conclusion: Displacement CT with alternated rotations of the femur is a viable option to improve the diagnostic process for identifying aseptic loosening in a total hip arthroplasty.

Background: Photochemical internalization (PCI) is a novel technology for light-induced enhancement of the local therapeutic effect of cancer drugs, utilizing a specially designed photosensitizing molecule (fimaporfin). The photosensitizing molecules are trapped in endosomes along with macromolecules or drugs. Photoactivation of fimaporfin disrupts the endosomal membranes so that drug molecules are released from endosomes inside cells and can reach their therapeutic target in the cell cytosol or nucleus. Compared with photodynamic therapy, the main cytotoxic effect with PCI is disruption of the endosomal membrane resulting in delivery of chemotherapy drug, and not to the photochemical reactions per se. In this study we investigated the effect of PCI with gemcitabine in patients with inoperable perihilar cholangiocarcinoma (CCA)., Methods: The in vitro cytotoxic effect of PCI with gemcitabine was studied on two CCA-derived cell lines. In a fimaporfin dose-escalation phase I clinical study, we administered PCI with gemcitabine in patients with perihilar CCA (n = 16) to establish a safe and tolerable fimaporfin dose and to get early signals of efficacy. The patients enrolled in the study had tumors in which the whole length of the tumor could be illuminated from the inside of the bile duct, using an optical fiber inserted via an endoscope (Fig. 1). Fimaporfin was administered intravenously at day 0; gemcitabine (i.v.) and intraluminal biliary endoscopic laser light application on day 4; followed by standard gemcitabine/cisplatin chemotherapy., Results: Preclinical experiments showed that PCI enhanced the effect of gemcitabine. In patients with CCA, PCI with gemcitabine was well tolerated with no dose-limiting toxicities, and no unexpected safety signals. Disease control was achieved in 10 of 11 evaluable patients, with a clearly superior effect in the two highest dose groups. The objective response rate (ORR) was 42%, including two complete responses, while ORR at the highest dose was 60%. Progression-free survival at 6 months was 75%, and median overall survival (mOS) was 15.4 months, with 22.8 months at the highest fimaporfin dose., Conclusion: Photochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA., (© The Author(s) 2022. Published by Oxford University Press. The data published online to support this summary are the property of the authors. Please contact the authors about reuse rights of the original data.)

Background and Purpose: CT micromotion analysis (CTMA) has been considered as an alternative to radiostereometry (RSA) for assessing early implant migration of orthopedic implants. We investigated the feasibility of CTMA to assess early migration and the progression of radiolucent lines in shoulder arthroplasties over 24 months using sequential low-dose CT scans., Patients and Methods: 7 patients were included and underwent 9 primary total shoulder arthroplasties. We made CT scans preoperatively, within 1 week postoperatively, and after 3, 6, 12, and 24 months. At each follow-up, postoperative glenoid migration and any development of radiolucent lines were assessed. Clinical outcomes were recorded at all time points except within 1 week postoperatively., Results: For the glenoid component, the median translation and median rotation were 0.00-0.10 mm and -1.53° to 1.05° at 24 months. Radiolucent lines could be observed around all glenoid components. The radiolucent lines developed from the periphery to the center of the implant for 6 glenoid components during follow-up. The Constant Score improved from a mean of 30 (21-51) preoperatively to 69 (41-88) at 24 months., Interpretation: CTMA can be used to identify early migration and the development of radiolucent lines over time in glenoid components. Clinical trials with a larger sample size and longer follow-up are needed to establish the relationship between migration, radiolucent lines, loosening, and clinical outcome.

Scaphoid and lunate mobility has been suggested to be minimal during the dart-throwing motion in studies based on serial computed tomography (CT) scans and cadaver studies. This study analyzes the direct motion between the scaphoid and the lunate during the dart-throwing motion in vivo . We examined nine individuals with standard CT scans of the wrist in radial extension and ulnar flexion. The paired CT scans were analyzed with a volume registration technique. The lunate was registered as fixed and the scaphoid as the mobile element. The motion of the scaphoid relative the lunate between the positions of radial extension and ulnar flexion was measured. There was considerable motion between the scaphoid and the lunate with both a distal to proximal translation and rotation during the dart-throwing motion, regardless of whether the scapholunate ligament was intact or not. These results suggest that aggressive dart-throwing exercises should not be implemented early on during rehabilitation following scapholunate repair.

Background and purpose - CT (computed tomography) based methods have lately been considered an alternative to radiostereometry (RSA) for assessing early implant migration. However, no study has directly compared the 2 methods in a clinical setting. We estimated the precision and effective radiation dose of a CT-based method and compared it with marker-based RSA in 10 patients with hip arthroplasty.Patients and methods - We included 10 patients who underwent total hip replacement with a cemented cup. CT and RSA double examinations were performed postoperatively, and precision and effective dose data were compared. The CT data was analyzed with CT micromotion analysis (CTMA) software both with and without the use of bone markers. The RSA images were analyzed with RSA software with the use of bone markers.Results - The precision of CTMA with bone markers was 0.10-0.16 mm in translation and 0.31°-0.37° in rotation. Without bone markers, the precision of CTMA was 0.10-0.16 mm in translation and 0.21°-0.31° in rotation. In comparison, the precision of RSA was 0.09-0.26 mm and 0.43°-1.69°. The mean CTMA and RSA effective dose was estimated at 0.2 mSv and 0.04 mSv, respectively.Interpretation - CTMA, with and without the use of bone markers, had a comparable precision to RSA. CT radiation doses were slightly higher than RSA doses but still at a considerably low effective dose.

Adverse events in total hip replacement (THR) may have several origins, one being lack of precision in diagnosis and/or during surgery. This study describes the pattern and frequency of avoidable injuries in THR and the potential value of a new tool for early diagnosis of implant loosening. This retrospective study was based on all ( n  = 1 456) settled claims regarding THR in the Swedish National Patient Insurance database from 2010 to 2017. The claims and medical records were analyzed for root causes, with special focus on adverse events where lack of precision could be the cause. In a second stage, we assessed in 10 patients (20 implants) the diagnostic precision of a new software tool based on provocation-CT. These were all patients where the implant loosening diagnosis was deemed as inconclusive after a first plain X-ray. The findings from the provocation-CT and plain X-ray were compared to the surgical findings at revision. While 3 of 20 implants were correctly diagnosed with plain X-ray, for dynamic CT, this number was 14 of 20 implants. The retrospective study showed that the most common types of injuries were infections (34%), nerve injury (29%), mechanical problems (14.5%), dislocation (6%), and miscellaneous complications (16.5%). Of the patients with mechanical complications, one-third had aseptic implant loosening. Statement of clinical significance: we estimated that almost 200 patients in our registry study had mechanical complications after THR, mainly implant loosening. A third of these could potentially have been diagnosed and treated if CT examination with a dedicated image analysis tool to assess implant loosening after THR had been available., Competing Interests: OS is a full-time employee at Sectra AB, a company commercializing a diagnostic tool for implant loosening diagnosis. HO has worked as a consultant for the aforementioned company., (Copyright © 2021 Olof Sandberg et al.)

Background and Aims: Photochemical internalization (PCI) is a technology for inducing release of endocytosed antigens into the cell cytosol via a light-induced process. Preclinical experiments have shown that PCI improves MHC class I antigen presentation, resulting in strongly enhanced CD8+ T-cell responses to polypeptide antigens. In PCI vaccination a mixture of the photosensitizing compound fimaporfin, vaccine antigens, and an adjuvant is administered intradermally followed by illumination of the vaccination site. This work describes an open label, phase I study in healthy volunteers, to assess the safety, tolerability, and immune response to PCI vaccination in combination with the adjuvant poly-ICLC (Hiltonol) (ClinicalTrials.gov Identifier: NCT02947854)., Methods: The primary objective of the study was to assess the safety and local tolerance of PCI mediated vaccination, and to identify a safe fimaporfin dose for later clinical studies. A secondary objective was to analyze the immunological responses to the vaccination. Each subject received 3 doses of HPV16 E7 peptide antigens and two doses of Keyhole Limpet Hemocyanin (KLH) protein. A control group received Hiltonol and vaccine antigens only, whereas the PCI groups in addition received fimaporfin + light. Local and systemic adverse effects were assessed by standard criteria, and cellular and humoral immune responses were analyzed by ELISpot, flow cytometry, and ELISA assays., Results: 96 healthy volunteers were vaccinated with fimaporfin doses of 0.75-50 µg. Doses below 17.5 µg were safe and tolerable, higher doses exhibited local tolerability issues in some study subjects, mainly erythema, and pain during illumination. There were few, and only mild and expected systemic adverse events. The employment of PCI increased the number of subjects exhibiting a T-cell response to the HPV peptide vaccine about 10-fold over what was achieved with the antigen/Hiltonol combination without PCI. Moreover, the use of PCI seemed to result in a more consistent and multifunctional CD8+ T-cell response. An enhancement of the humoral immune response to KLH vaccination was also observed., Conclusions: Using PCI in combination with Hiltonol for intradermal vaccination is safe at fimaporfin doses below 17.5 µg, and gives encouraging immune responses to peptide and protein based vaccination., Competing Interests: TO and AH are employees of PCI Biotech AS and own shares and share options in the Company. AH and PS are inventors on several patents and patent Applications on the PCI Technology. HO and SJ work as consultants for PCI Biotech, and SJ is working for ZellNet Consulting, Inc. VE is an employee of PCI Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Otterhaug, Janetzki, Welters, Håkerud, Nedberg, Edwards, Boekestijn, Loof, Selbo, Olivecrona, van der Burg and Høgset.)

Photochemical internalization (PCI) is a technology to induce a localized, intracellular enhancement of therapeutics that are processed through endosomal pathways, including gemcitabine in malignant cells. In addition to a direct phototoxic and tumoricidal effect, PCI specifically disrupts endosomal membranes and, thereby, the compartmentalization of certain cytotoxic compounds to enhance a drug's intended intracellular target reach within the tissue treated. Non-resectable extrahepatic cholangiocarcinoma (eCCA) is a common primary tumor and gemcitabine/cisplatin chemotherapy is widely considered standard of care for it. PCI is well suited as an endoscopic intervention, and clinical observations in three subjects participating in a phase I/IIa dose escalation safety trial are described. The trial included patients with perihilar, non-resectable CCA suitable for standard-of-care chemotherapy. Per protocol, a single endoscopic PCI procedure with gemcitabine was conducted at the initiation of standard gemcitabine/cisplatin therapy. Sixteen patients enrolled in the initial dose escalation phase of the trial, which later was extended to explore the safety of a second PCI procedure during chemotherapy. While limited to a case series, the various clinical observations described here serve to illustrate the effects of localized, perihilar tumor targeting in appropriate patients by any safe methodology, including PCI. As previously indicated by clinical data using other localized treatment modalities, adding a directed, tumor-targeting treatment to systemic therapy to ameliorate the progressively expanding extrahepatic tumor burden can have important effects on the overall outcome of systemic treatment in many patients who have incurable eCCA., Competing Interests: Competing interests Dr. Olivecrona is a consultant for PCI Biotech AS. Drs. Dechêne, Kasper, Schirra, and Trojan participated as investigators in the study PCI A202/12., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and purpose - Early postoperative implant migration predicts failure of joint replacements. Bone mineral density reflects bone quality and bone-graft incorporation. Implant migration and bone densitometry analysis usually require special equipment. We investigated cup migration and bone mineral density changes simultaneously with low-dose CT scans after acetabular revision hip arthroplasty using impaction bone grafting.Patients and methods - We performed a low-dose CT postoperatively, after 6 weeks, and after 2 years in 17 patients, all revised using impaction bone grafting and a graft-compressing titanium shell in the acetabulum. 6 patients had combined segmental and cavitary acetabular defects. Cup migration was analyzed using CT-based micromotion analysis (CTMA). Bone mineral density was determined in the graft and in surrounding native bone using volumetric quantitative computed tomography (QCT). The bone graft volume was calculated from 3D reconstructions.Results - At 2 years, the translations were 1.5 (95% CI 0.4-2.6) mm in proximal direction, -0.6 (CI -1.6 to 0.4) in the medial direction and 0.3 (CI 0.0-0.6) in the anterior direction. The mean volume of impacted bone graft was 40 cm³ (CI 28-52). In the graft bone mineral density increased 14% after 6 weeks and 23% after 2 years. There was 1 mechanical failure.Interpretation - Proximal migration of the acetabular component was low and comparable to previous reports. There was a rapid increase of bone mineral density in the bone graft. Low-dose CT scans make migration analysis and bone densitometry measurements possible in the same setting, offering great diagnostic potential for hip arthroplasty patients.

Background: Radiostereometric analysis (RSA) is the gold standard to measure early implant migration which is a predictive factor for implant survival., Purpose: To validate an alternative computed tomography (CT) technique to measure implant migration in shoulder arthroplasty., Material and Methods: A cadaver proximal humerus and a scapula, which had tantalum beads incorporated within them, were prepared to accept a short-stemmed humeral component and a two-pegged glenoid component of a commercial total shoulder arthroplasty (TSA) system. A five degree of freedom micrometer and goniometer equipped rig was used to translate and rotate the implant components relative to the respective bone to predetermined positions. Double CT examinations were performed for each position and CT motion analysis software (CTMA) was used to assess these movements. The accuracy and precision of the software was estimated using the rig's micrometers and goniometers as the gold standard. The technique's effective dose was also assessed., Results: The accuracy was in the range of 0.07-0.23 mm in translation and 0.22-0.71° in rotation. The precision was in the range of 0.08-0.15 mm in translation and 0.23-0.54° in rotation. The mean effective dose for the CT scans was calculated to be 0.27 mSv., Conclusion: In this experimental setting, accuracy, precision, and effective dose of the CTMA technique were found to be comparable to that of RSA. Therefore, we believe clinical studies are warranted to determine if CTMA is a suitable alternative to traditional RSA for migration measurements in TSA.

Background and purpose - Early implant migration is known to be a predictive factor of clinical loosening in total hip arthroplasty (THA). Radiostereometric analysis (RSA) is the gold standard used to measure early migration in patients. However, RSA requires costly, specialized imaging equipment and the image process is complex. We determined the precision of an alternative, commercially available, CT method in 3 ongoing clinical THA studies, comprising 3 different cups.Materials and methods - 24 CT double examinations of 24 hip cups were selected consecutively from 3 ongoing prospective studies: 2 primary THA (1 cemented and 1 uncemented) and 1 THA (cemented) revision study. Precision of the CT-based implant motion analysis (CTMA) system was calculated separately for each study, using both the surface anatomy of the pelvis and metal beads placed in the pelvis.Results - For the CTMA analysis using the surface anatomy of the pelvis, the precision ranged between 0.07 and 0.31 mm in translation and 0.20° and 0.39° for rotation, respectively. For the CTMA analysis using beads the precision ranged between 0.08 and 0.20 mm in translation and between 0.20° and 0.43° for rotations. The radiation dose ranged between 0.2 and 2.3 mSv.Interpretation - CTMA achieved a clinically relevant and consistent precision between the 3 different hip cups studied. The use of different hip cup types, different CT scanners, or registration method (beads or surface anatomy) had no discernible effect on precision. Therefore, CTMA without the use of bone markers could potentially be an alternative to RSA to measure early migration.

Purpose: Lunocapitate arthrodesis is a motion-preserving salvage procedure for painful wrist osteoarthritis. Because the arthrodesis is limited to the capitate and the lunate, the adaptive motion of the triquetrum is theoretically maintained. We aimed to examine whether triquetral motion is sustained in vivo after lunocapitate arthrodesis., Methods: We examined 7 patients after lunocapitate arthrodesis at least 1 year earlier, with computed tomography at 2 wrist positions: maximal radial extension and maximal ulnar flexion. Triquetral motion in vivo was analyzed using volume registration technique of the paired computed tomography scans and compared with the contralateral side., Results: The triquetrum moved in all patients, but the degree of motion was small compared with the nonsurgical wrist. A minor degree of motion of the hamate relative to the fused lunocapitate could also be demonstrated., Conclusions: Triquetral motion is limited after lunocapitate arthrodesis., Type of Study/level of Evidence: Therapeutic IV., (© 2019 The Authors.)

This case report follows a woman who had a total hip replacement in 1992 when she was 45 years old. Six serial computed tomography (CT) examinations over a period of 13 years provided information that allowed her revision surgery to be limited to liner replacement as opposed to replacement of the entire prosthesis. Additionally, they provided data that ruled out the presence of osteolysis and indeed none was found at surgery. In 2004, when the first CT was performed, the 3D distance the femoral head had penetrated into the cup was determined to be 2.6 mm. By 2017, femoral head penetration had progressed to 5.0 mm. The extracted liner showed wear at the thinnest part to be 5.5 mm, as measured with a micrometer. The use of modern CT techniques can identify problems, while still correctable without major surgery. Furthermore, the ability of CT to assess the direction of wear revealed that the liner wear changed from the cranial to dorsal direction.

As part of the 14-year follow-up of a prospectively randomized radiostereometry (RSA) study on uncemented cup fixation, two pairs of stereo radiographs and a CT scan of 46 hips were compared. Tantalum beads, inserted during the primary operation, were detected in the CT volume and the stereo radiographs and used to produce datasets of 3D coordinates. The limit of agreement between the combined CT and RSA datasets was calculated in the same way as the precision of the double RSA examination. The precision of RSA corresponding to the 99% confidence interval was 1.36°, 1.36°, and 0.60° for X -, Y -, and Z -rotation and 0.40, 0.17, and 0.37 mm for X -, Y -, and Z -translation. The limit of agreement between CT and RSA was 1.51°, 2.17°, and 1.05° for rotation and 0.59, 0.56, and 0.74 mm for translation. The differences between CT and RSA are close to the described normal 99% confidence interval for precision in RSA: 0.3° to 2° for rotation and 0.15 to 0.6 mm for translation. We conclude that measurements using CT and RSA are comparable and that CT can be used for migration studies for longitudinal evaluations of patients with RSA markers., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Objective: Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report., Methods: A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports., Results: In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs., Conclusion: In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation., Trial Registration: ClincialTrials.gov, clinicaltrials.gov, NCT00069329., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Computed tomography (CT) plays an important role in evaluating wear and periacetabular osteolysis (PAO) in total hip replacements. One concern with CT is the high radiation exposure since standard pelvic CT provides approximately 3.5 millisieverts (mSv) of radiation exposure, whereas a planar radiographic examination with three projections totals approximately 0.5 mSv. The objective of this study was to evaluate the lowest acceptable radiation dose for dual-energy CT (DECT) images when measuring wear and periacetabular osteolysis in uncemented metal components., Materials and Methods: A porcine pelvis with bilateral uncemented hip prostheses and with known linear wear and acetabular bone defects was examined in a third-generation multidetector DECT scanner. The examinations were performed with four different radiation levels both with and without iterative reconstruction techniques. From the high and low peak kilo voltage acquisitions, polychrmoatic images were created together with virtual monochromatic images of energies 100 kiloelectron volts (keV) and 150 keV., Results: We could assess wear and PAO while substantially lowering the effective radiation dose to 0.7 mSv for a total pelvic view with an accuracy of around 0.5 mm for linear wear and 2 mm to 3 mm for PAO., Conclusion: CT for detection of prosthetic wear and PAO could be used with clinically acceptable accuracy at a radiation exposure level equal to plain radiographic exposures.Cite this article: B. Sandgren, M. Skorpil, P. Nowik, H. Olivecrona, J. Crafoord, L. Weidenhielm, A. Persson. Assessment of wear and periacetabular osteolysis using dual energy computed tomography on a pig cadaver to identify the lowest acceptable radiation dose. Bone Joint Res 2016;5:307-313. DOI: 10.1302/2046-3758.57.2000566., Competing Interests: ICMJE conflict of interest:None declared., (© 2016 Sandgren et al.)

Background: Radiostereometric analysis (RSA) is often used for evaluating implanted devices over time. Following patients who have had tantalum beads implanted as markers in conjunction with joint replacements is important for longitudinal evaluation of these patients and for those with similar implants. As doing traditional RSA imaging is exacting and limited to specialized centers, it is important to consider alternative techniques for this ongoing evaluation. This paper studies the use of computed tomography (CT) to evaluate over time tantalum beads which have been implanted as markers., Methods: The project uses both a hip model implanted with tantalum beads, acquired in several orientations, at two different CT energy levels, and a cohort of seven patients. The model was evaluated twice by the same observer with a 1-week interval. All CT volumes were analyzed using a semi-automated 3D volume fusion (spatial registration) tool which provides landmark-based fusion of two volumes, registering a target volume with a reference volume using a rigid body 3D algorithm. The mean registration errors as well as the accuracy and repeatability of the method were evaluated., Results: The mean registration error, maximum value of repeatability, and accuracy for the relative movement in the model were 0.16 mm, 0.02° and 0.1 mm, and 0.36° and 0.13 mm for 120 kVp and 0.21 mm, 0.04° and 0.01 mm, and 0.39° and 0.12 mm for 100 kVp. For the patients, the mean registration errors per patient ranged from 0.08 to 0.35 mm. These results are comparable to those in typical clinical RSA trials. This technique successfully evaluated two patients who would have been lost from the cohort if only RSA were used., Conclusions: The proposed technique can be used to evaluate patients with tantalum beads over time without the need for stereoradiographs. Further, the effective dose associated with CT is decreasing.

Background and Purpose. The gold standard for detection of implant wear and migration is currently radiostereometry (RSA). The purpose of this study is to compare a three-dimensional computed tomography technique (3D CT) to standard RSA as an alternative technique for measuring migration of acetabular cups in total hip arthroplasty. Materials and Methods. With tantalum beads, we marked one cemented and one uncemented cup and mounted these on a similarly marked pelvic model. A comparison was made between 3D CT and standard RSA for measuring migration. Twelve repeated stereoradiographs and CT scans with double examinations in each position and gradual migration of the implants were made. Precision and accuracy of the 3D CT were calculated. Results. The accuracy of the 3D CT ranged between 0.07 and 0.32 mm for translations and 0.21 and 0.82° for rotation. The precision ranged between 0.01 and 0.09 mm for translations and 0.06 and 0.29° for rotations, respectively. For standard RSA, the precision ranged between 0.04 and 0.09 mm for translations and 0.08 and 0.32° for rotations, respectively. There was no significant difference in precision between 3D CT and standard RSA. The effective radiation dose of the 3D CT method, comparable to RSA, was estimated to be 0.33 mSv. Interpretation. Low dose 3D CT is a comparable method to standard RSA in an experimental setting.

Object: Artificial disc replacement (ADR) devices are unlike implants used in cervical fusion in that they are continuously exposed to stress not only within the implant site but also at their site of attachment to the adjacent vertebra. An imaging technique with higher accuracy than plain radiography and with the possibility of 3D visualization would provide more detailed information about the motion quality and stability of the implant in relation to the vertebrae. Such high-accuracy studies have previously been conducted with radiostereometric analysis (RSA), which requires implantation of tantalum markers in the adjacent vertebrae. The aim of this study was to evaluate in vivo motion and stability of implanted artificial discs. A noninvasive analysis was performed with CT, with an accuracy higher than that of plain radiographs and almost as high as RSA in cervical spine., Methods: Twenty-eight patients with ADR were included from a larger cohort of a randomized controlled trial comparing treatment of cervical radiculopathy with ADR or anterior cervical decompression and fusion. Surgical levels included C4-7; 18 patients had 1-level surgery and 10 patients had 2-level surgery. Follow-up time ranged from 19 to 50 months, with an average of 40 months. Two CT volumes of the cervical spine, 1 in flexion and 1 in extension, were obtained in each patient and then spatially registered using a customized imaging tool, previously used and validated for the cervical spine. Motion between the components in the artificial disc, as well as motion between the components and adjacent vertebrae, were calculated in 3 planes. Intraclass correlation (ICC) between independent observers and repeatability of the method were also calculated., Results: Intrinsic motion, expressed as degrees in rotation and millimeters in translation, was detectable in a majority of the ADRs. In the sagittal plane, in which the flexion/extension was performed, sagittal rotation ranged between 0.2° and 15.8° and translation between 0.0 and 5.5 mm. Eight percent of the ADRs were classified as unstable, as motion between at least 1 of the components and the adjacent vertebra was detected. Five percent were classified as ankylotic, with no detectable motion, and another 8% showed very limited motion due to heterotopic ossification. Repeatability for the motion in the sagittal plane was calculated to be 1.30° for rotation and 1.29 mm for translation (95% confidence level), ICC 0.99 and 0.84, respectively. All 3 patients with unstable devices had undergone 1-level ADRs at C5-6. They all underwent revision surgery due to increased neck pain, and instability was established during the surgery., Conclusions: The majority of the artificial discs in this study showed intrinsic mobility several years after implantation and were also shown to be properly attached. Implant instability was detected in 8% of patients and, as all of these patients underwent revision surgery due to increasing neck pain, this might be a more serious problem than heterotopic bone formation.

This study describes a 3D-CT method for analyzing facet joint motion and vertebral rotation in the lumbar spine after TDR. Ten patients were examined before and then three years after surgery, each time with two CT scans: provoked flexion and provoked extension. After 3D registration, the facet joint 3D translation and segmental vertebral 3D rotation were analyzed at the operated level (L5-S1) and adjacent level (L4-L5). Pain was evaluated using VAS. The median (±SD) 3D movement in the operated level for the left facet joint was 3.2 mm (±1.9 mm) before and 3.5 mm (±1.7 mm) after surgery and for the right facet joint was 3.0 mm (±1.0 mm) before and 3.6 mm (±1.4 mm) after surgery. The median vertebral rotation in the sagittal plane at the operated level was 5.4° (±2.3°) before surgery and 6.8° (±1.7°) after surgery and in the adjacent level was 7.7° (±4.0°) before and 9.2° (±2.7°) after surgery. The median VAS was reduced from 6 (range 5-8) to 3 (range 2-8) in extension and from 4 (range 2-6) to 2 (range 1-3) in flexion.

Background: Determination of the amount of wear in a polyethylene liner following total hip arthroplasty (THA) is important for both the clinical care of individual patients and the development of new types of liners., Patients and Methods: We measured in vivo wear of the polyethylene liner using computed tomography (CT) (obtained in the course of regular clinical care) and compared it to coordinate-measuring machine (CMM) readings. Also, changes in liner thickness of the same retrieved polyethylene liner were measured using a micrometer, and were compared to CT and CMM measurements. The distance between the centers of the acetabular cup and femoral head component was measured in 3D CT, using a semi-automatic analysis method. CMM readings were performed on each acetabular liner and data were analyzed using 3D computer-aided design software. Micrometer readings compared the thickest and thinnest regions of the liner. We analyzed 10 THA CTs and retrievals that met minimal requirements for CT slice thickness and explanted cup condition. RESULTS - For the 10 cups, the mean difference between the CT readings and the CMM readings was -0.09 (-0.38 to 0.20) mm. This difference was not statistically significant (p = 0.6). Between CT and micrometer, the mean difference was 0.11 (-0.33 to 0.55) mm. This difference was not statistically significant (p = 0.6). INTERPRETATION - Our results show that CT imaging is ready to be used as a tool in clinical wear measurement of polyethylene liners used in THA.

Monitoring and quantifying bone remodeling are of interest, for example, in correction osteotomies, delayed fracture healing pseudarthrosis, bone lengthening, and other instances. Seven patients who had operations to attach an Ilizarov-derived Taylor Spatial Frame to the tibia gave informed consent. Each patient was examined by Na(18)F PET/CT twice, at approximately six weeks and three months after the operation. A validated software tool was used for the following processing steps. The first and second CT volumes were aligned in 3D and the respective PET volumes were aligned accordingly. In the first PET volume spherical volumes of interest (VOIs) were delineated for the crural fracture and normal bone and transferred to the second PET volume for SUVmax evaluation. This method potentially provides clinical insight into questions such as, when has the bone remodeling progressed well enough to safely remove the TSF? and when is intervention required, in a timelier manner than current methods? For example, in two patients who completed treatment, the SUVmax between the first and second PET/CT examination decreased by 42% and 13%, respectively. Further studies in a larger patient population are needed to verify these preliminary results by correlating regional Na(18)F PET measurements to clinical and radiological findings.

As the most advantageous total hip arthroplasty (THA) operation is the first, timely replacement of only the liner is socially and economically important because the utilization of THA is increasing as younger and more active patients are receiving implants and they are living longer. Automatic algorithms were developed to infer liner wear by estimating the separation between the acetabular cup and femoral component head given a computed tomography (CT) volume. Two series of CT volumes of a hip phantom were acquired with the femoral component head placed at 14 different positions relative to the acetabular cup. The mean and standard deviation (SD) of the diameter of the acetabular cup and femoral component head, in addition to the range of error in the expected wear values and the repeatability of all the measurements, were calculated. The algorithms resulted in a mean (± SD) for the diameter of the acetabular cup of 54.21 (± 0.011) mm and for the femoral component head of 22.09 (± 0.02) mm. The wear error was ± 0.1 mm and the repeatability was 0.077 mm. This approach is applicable clinically as it utilizes readily available computed tomography imaging systems and requires only five minutes of human interaction.

Osteolysis is a silent disease leading to aseptic loosening. This has not been studied in a cohort of asymptomatic patients. The aim of this study was to detect factors that might be associated with the development of periacetabular osteolysis and wear around an uncemented cup. We assessed 206 patients with an uncemented cup, measuring wear and periacetabular osteolysis using computed tomography with a median follow-up of 10 years after surgery (range 7-14 years). EQ5D, pain from the hip, and satisfaction were assessed. The association between periacetabular osteolysis and wear, age, gender, activity, BMI, cup type, cup age, positioning of the cup, and surface coating was investigated with a proportional odds model. Wear and male gender were associated with an increased risk for periacetabular osteolysis. There was no association with periacetabular osteolysis for time from operation, patient age, UCLA Activity Score, liner thickness at time of operation, BMI, cup positioning, and type of implant. A thin liner at time of operation is correlated to increased wear. Linear wear rate was 0.18 mm/year and 46 of 206 patients had large periacetabular osteolysis. Asymptomatic patients with these implants should be followed up on a regular basis with a sensitive method such as CT in order to detect complications early.

Digital radiographic images in the anterior-posterior and lateral view have been gold standard for evaluation of peri-acetabular osteolysis for patients with an uncemented hip replacement. We compared digital radiographic images and computer tomography in detection of peri-acetabular osteolysis and devised a classification system based on computer tomography. Digital radiographs were compared with computer tomography on 206 hips, with a mean follow up 10 years after surgery. The patients had no clinical signs of osteolysis and none were planned for revision surgery. On digital radiographs, 192 cases had no osteolysis and only 14 cases had osteolysis. When using computer tomography there were 184 cases showing small or large osteolysis and only 22 patients had no osteolysis. A classification system for peri-acetabular osteolysis is proposed based on computer tomography that is easy to use on standard follow up evaluation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Accurately estimating polyethylene wear in 3 dimensions, without the need for additional procedures or equipment, is of significant interest. We investigated the use of a high-resolution clinical computed tomographic (CT) scanner to estimate femoral head displacement relative to the cup as an indirect method of estimating polyethylene wear. A hip phantom was used to simulate the 3-dimensional displacement of a femoral head. The phantom was imaged in a high-resolution CT scanner. The mean difference between the true phantom displacement as positioned by micrometers and the calculated displacement based on the CT images was as follows: for the x-axis, 0 mm (SD, 0.213; SE, 0.058); y-axis, 0.039 mm (SD, 0.035; SE, 0.026); and z-axis, 0.039 mm (SD, 0.051; SE, 0.020)., (Copyright © 2012 Elsevier Inc. All rights reserved.)