Session 4: YODA Best Paper

Carsten Ulrich Strømmen¹, Mads Radmer Jensen², Lene Simonsen², Krassimir Kostadinov¹, Jesper Hvolris4, Susanne Lind², Lars Friberg², Søren Overgaard¹ ³
Department of Orthopaedic Surgery and Traumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg¹; Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Bispebjerg and Frederiksberg²; University of Copenhagen, Department of Clinical Medicine, Faculty of Health and Medical Sciences³; Speciallægeklinikken Søbjærggaard4

Background: Infection and/or loosening are serious complications after total knee- and hip arthroplasty (TKA/THA). Bone scintigraphy (planar and SPECT/CT) may yield important information in the diagnosis, but the overall clinical value is limited by poor accuracy. Studies using 18F-sodium fluoride Positron Emission Tomography/Computed Tomography (18F-NaF PET/CT) have shown promising results; however, these findings need validation in larger populations.
Aim: To assess diagnostic accuracy of 18F-NaF PET/CT in patients suspected of infection and/or loosening of total knee- or hip arthroplasty.
Materials and Methods: The study was a prospective descriptive study. Included patients were examined with laboratory tests, conventional x-ray, SPECT/CT and 18F-NaF PET/CT. Here we only report results from the PET/CT part of the study. The PET/CT scans were interpreted by nuclear medicine specialists blinded to clinical findings. Patients with clinically suspected infection and/or loosening in TKA/THA were surgically revised. Perioperative findings or clinical follow up at 12 months for those that were not revised were considered the diagnostic gold standard.
Results: Our study included 58 patients (m:f 20:38) with a mean age of 67 years. Infection and/or loosening was suspected clinically in 15 TKA and 43 THA prior to the examinations. 18F-NaF PET/CT showed a sensitivity of 63% for finding infection and/or loosening and a specificity of 90% for correctly identifying those without infection and/or loosening. The fraction of true infection and/or loosening of the positive patients comprised the positive predictive value (PPV) of 71%. The negative predictive value (NPV) was 86%, thus showing the fraction of patients without infection and/or loosening with negative findings.
Interpretation / Conclusion: Our study shows good clinical value of 18F- NaF PET/CT for ruling out infection and/or loosening of total knee- and hip arthroplasty. 18F-NaF PET/CT was best to diagnose patients without infection and/or loosening meaning that a scan without typical uptake in 90% of the cases is correct. Low sensitivity and PPV show that a positive 18F-NaF PET/CT need to be assessed in conjunction with other examinations before a decision of revision is made.

Sara Kousgaard Tøstesen, Maiken Stilling, Pelle Hanberg, Theis Muncholm Thillemann, Thomas Falstie-Jensen, Mikkel Tøttrup, Martin Knudsen, Emil Toft Petersen, Mats Bue
Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic Research Laboratory, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Aalborg University Hospital; Department of Clinical Medicine, Aarhus University; AutoRSA Research Group, Orthopaedic Research Laboratory, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital

Background: Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI).
Aim: This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (fT > MIC (4 µg/mL)).
Materials and Methods: In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected as a reference. Cefuroxime was administered according to weight (20 mg/kg).
Results: During the two dosing intervals, mean fT > MIC (4 µg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 µg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval.
Interpretation / Conclusion: In conclusion, weight-adjusted cefuroxime fT > MIC (4 µg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI.

Ibrahim El Haddouchi, MS¹, Anders Brøgger Overgård, MD¹, Per Hölmich MD, Professor, DMSc¹, Kristoffer Weisskirchner Barfod, MD, PhD¹
1. Sports Orthopedic Research Center – Copenhagen (SORC-C), Department of Orthopedic Surgery, Copenhagen University Hospital Amager-Hvidovre, Denmark.

Background: Treatment of acute Achilles tendon rupture (ATR) is a subject of discussion. Individual treatment selection has been proposed as the key to optimized treatment for patients with an acute ATR.
Aim: The purpose of the present study was to investigate if calf muscle atrophy and Achilles tendon elongation measured on magnetic resonance imaging (MRI) was less affected when comparing patients treated according to Copenhagen Achilles Rupture Treatment Algorithm (CARTA) – an individualized treatment algorithm utilizing surgical or non-surgical treatment depending on ultrasound findings – to patients treated non-surgically or surgically.
Materials and Methods: 60 patients with ATR were randomized 1:1:1 in a three-armed design: 1) intervention group; patients treated according to CARTA, 2) control group; patients treated non-surgically, and 3) control group; patients treated surgically. Investigators were blinded to the intervention. At 1 year MRI of both lower limbs was performed and muscle volumes were calculated for the medial and the lateral head of the gastrocnemius muscle, the soleus muscle, and the deep flexors muscles (flexor hallucis longus, flexor digitorum longus and tibialis posterior). Length of the different parts of the Achilles tendon was measured from the top of the talus to each of the three muscle bellies in the triceps surae. Calf muscle atrophy and Achilles tendon elongation were investigated using the limb symmetry index (LSI) (injured / uninjured x 100%).
Results: One hundred and fifty-six patients were assessed for eligibility, 60 patients were included and 54 patients contributed data for the MRI analysis: 19 intervention group, 17 non-surgical treatment and 18 surgical treatment. No statistically significant differences were found between the intervention group and the two control groups regarding both calf muscle atrophy and Achilles tendon elongation. Comparison between the injured and the uninjured limb revealed significantly lower muscle volume of the triceps surae and significant tendon elongation of the injured leg.
Interpretation / Conclusion: The individualized treatment algorithm CARTA did not reduce calf muscle atrophy and Achilles tendon elongation compared to usual treatment.

Simone Elmholt ¹ , Torsten Nielsen ¹ , Martin Lind ¹
¹ Department of Orthopedics, Aarhus University Hospital

Background: Button implants with an Adjustable-Loop Device (ALD) are now used more often in Anterior Cruciate Ligament Reconstruction (ACLR). Clinical research comparing ALDs to Fixed-Loop Device (FLD) has mainly been investigated in small patient populations with short follow-up time. To investigate if ALDs are safe to use in ACLR a non-inferiority study with a large study population and long follow-up time would be beneficial.
Aim: This study investigated if ALDs demonstrated non-inferior revision surgery rates, knee stability and Patient-Reported Outcomes (PROMs) in ACLR compared to FLDs.
Materials and Methods: This was non-inferiority register-based cohort study, with data from the Danish Knee Ligament Reconstruction Registry (DKRR). 12.722 patients of >15 years of age with primary ACLR using hamstring tendon autografts and either a FLD or ALD for femoral fixation were included: 9.719 in the FLD group and 3.014 in the ALD group. The primary outcome was revision ACLR with a non-inferiority margin set to 2% difference. Secondary outcomes were anterior and rotatory knee stability and as well as PROMs with the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 1- year follow-up. The non-inferiority margin for anterior stability was set to a difference of 2mm in the side-to-side difference, and for PROMs the non-inferiority margin was set to a 10 points difference.
Results: The crude cummulative revision rates for ALD implants at 2 and 5 years was 2.1% (95% CI: 1.62-2.68) and 5.0% (95% CI: 4.22-5.96). In the FLD group this was 2.2% (95% CI: 1.89-2.48) and 4.7% (95% CI: 4.31-5.20). The 1-year side-to-side difference was 0.97mm (95% CI: 0.90 – 1.03) in the ALD group and 1.45mm (95% CI: 1.41-1.49) in the FLD group. 13% had a positive pivot shift in the FLD group, and 6% in the ALD group. There were no differences in KOOS.
Interpretation / Conclusion: ALDs are non-inferior compared to FLDs regarding revision rates, knee stability and patient reported outcomes, and are therefore safe to use for femoral fixation in ACLR.

Alexander Madrid¹, Shoaib Afzal² ³ 4, Stig Boiesen² ³ 4 5
Department of Orthopedic Surgery, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark¹; Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark²,The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark³; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark4; The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark5

Background: Abnormal levels of thyroid stimulating hormone (TSH) and thyroid status is thought to be associated with increased risk of hip fracture and other fractures.
Aim: The aim of the present study was to test the association of abnormal levels of TSH and thyroid hormones with hip fracture, fragility fracture, and all fracture.
Materials and Methods: In total, 108,000 participants with measured TSH were included from the Copenhagen General Population study. Thyroid hormones were automatically measured if TSH was outside of reference range (0.4-4.5 mIU). Risk of fracture was estimated using proportional hazard models. Primary outcome was hip fracture. Multiple events analysis was performed for both fragility fracture and all fractures.
Results: Among 107,996 participants, 524(0.5%) had hypothyroidism, 3,279(3%) had subclinical hypothyroidism, 2,262(2%) had subclinical hyperthyroidism, 393(0.4%) had hypothyroidism. During 988,323 person years of follow-up 1,939 participants sustained a hip fracture, 6,639 had fragility fractures, and 11,522 had any fracture. Subclinical hyperthyroidism showed a strong association with increased risk of hip fracture, fragility fractures, and any fracture with multiple adjusted hazard ratios of 1.33 (95% Confidence Interval (95%CI) 1.08 - 1.64 ), 1.21(95%CI 1.06-1.39), and 1.31(95%CI 1.16- 1.47), respectively. Consistently, a TSH below reference range was associated with multifactorially adjusted hazard ratio of 1.31(1.05-1.62) for hip fracture, 1.23(1.07- 1.41) for fragility fracture, and 1.30 (95% 1.15- 1.47) for any fracture. However, TSH did not follow a linear relationship with fracture risk. Severely depressed TSH (<0.10 mIU) was not associated with an increased risk of hip, fragility fracture, and any fracture.
Interpretation / Conclusion: Results from the present study indicated that subclinical hyperthyroidism is associated with an increased risk of hip, fragility, or any fracture. However, TSH did not follow a linear relationship with fracture risk.

Britt Aaen Olesen, Susanne Faurholt Närhi, Thomas Giver Jensen, Søren Overgaard, Henrik Palm, Michala Skovlund Sørensen
Department of Orthopaedic Surgery and Traumatology, Copenhagen University Hospital, Bispebjerg

Background: Several factors might be associated with risk of dislocating following uncemented hemiarthroplasty (uHA) due to hip fracture. Current evidence is limited with great variance in reported incidence of dislocation (1-15%).
Aim: Aim of this study was to calculate the true cumulative incidence of dislocation following uHA and to identify the associated risk factors.
Materials and Methods: We performed a retrospective cohort study of patients receiving an uHA (BFX Biomet stem) at Copenhagen University Hospital, Bispebjerg, in 2010-2016. Patients were followed until death or end of study (dec 2018). Dislocation was identified by code extraction from the Danish National Patient Registry. Variables included in the multivariate model was defined pre-analysis to include: age, sex and variables with a p-value <0.1 in univariate analysis. A regression model was fitted for 90 days dislocation as the assumption of proportional hazard rate (HR) was not met here after.
Results: We identified 772 stems with a mean follow- up of 24 mo (range 0-102). 58 stems suffered 90 dislocations during the observation period resulting in a 7% (CI 5-9) incidence of dislocation. 55 of the 58 stems (95%) experienced the first dislocation within 90 days after surgery. Dementia and residence status were found as independent risk factors in the subdistribution model (dementia: HR 0.46 (CI 0.22-0.92), residence other than home: HR 2.04 (CI 1.00-4.14)). Only absence of dementia was identified as an independent protective factor in the cause-specific model (HR 0.46 (CI 0.23-0.89)) resulting in a 2.4- fold cumulative risk of experiencing a dislocation in case of dementia. Several other variables such as age, sex, various medical conditions, surgery delay and surgical experience were eliminated as statistical risk factors.
Interpretation / Conclusion: The incidence of dislocation of uHA in patients with a hip fracture is found to be 7%. Due to the non-existing attribution bias, we claim it to be the true incidence. Dementia is among several variables identified as the only risk factor for dislocation. In perspective, we may consider treating patients with cognitive impairment by other methods than HA.