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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 60 - 60
1 Dec 2022
Martin RK Wastvedt S Pareek A Persson A Visnes H Fenstad AM Moatshe G Wolfson J Lind M Engebretsen L
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External validation of machine learning predictive models is achieved through evaluation of model performance on different groups of patients than were used for algorithm development. This important step is uncommonly performed, inhibiting clinical translation of newly developed models. Recently, machine learning was used to develop a tool that can quantify revision risk for a patient undergoing primary anterior cruciate ligament (ACL) reconstruction (https://swastvedt.shinyapps.io/calculator_rev/). The source of data included nearly 25,000 patients with primary ACL reconstruction recorded in the Norwegian Knee Ligament Register (NKLR). The result was a well-calibrated tool capable of predicting revision risk one, two, and five years after primary ACL reconstruction with moderate accuracy. The purpose of this study was to determine the external validity of the NKLR model by assessing algorithm performance when applied to patients from the Danish Knee Ligament Registry (DKLR).

The primary outcome measure of the NKLR model was probability of revision ACL reconstruction within 1, 2, and/or 5 years. For the index study, 24 total predictor variables in the NKLR were included and the models eliminated variables which did not significantly improve prediction ability - without sacrificing accuracy. The result was a well calibrated algorithm developed using the Cox Lasso model that only required five variables (out of the original 24) for outcome prediction. For this external validation study, all DKLR patients with complete data for the five variables required for NKLR prediction were included. The five variables were: graft choice, femur fixation device, Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life subscale score at surgery, years from injury to surgery, and age at surgery. Predicted revision probabilities were calculated for all DKLR patients. The model performance was assessed using the same metrics as the NKLR study: concordance and calibration.

In total, 10,922 DKLR patients were included for analysis. Average follow-up time or time-to-revision was 8.4 (±4.3) years and overall revision rate was 6.9%. Surgical technique trends (i.e., graft choice and fixation devices) and injury characteristics (i.e., concomitant meniscus and cartilage pathology) were dissimilar between registries. The model produced similar concordance when applied to the DKLR population compared to the original NKLR test data (DKLR: 0.68; NKLR: 0.68-0.69). Calibration was poorer for the DKLR population at one and five years post primary surgery but similar to the NKLR at two years.

The NKLR machine learning algorithm demonstrated similar performance when applied to patients from the DKLR, suggesting that it is valid for application outside of the initial patient population. This represents the first machine learning model for predicting revision ACL reconstruction that has been externally validated. Clinicians can use this in-clinic calculator to estimate revision risk at a patient specific level when discussing outcome expectations pre-operatively. While encouraging, it should be noted that the performance of the model on patients undergoing ACL reconstruction outside of Scandinavia remains unknown.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 47 - 47
1 Mar 2021
Martin K Persson A Moatshe G Fenstad A Engebretsen L Visnes H
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Surgery performed in low-volume centres has been associated with longer operating time, longer hospital stays, lower functional outcomes, and higher rates of revision surgery, complications, and mortality. This has been reported consistently in the arthroplasty literature, but there is a paucity of data regarding the relationship between surgical volume and outcome following anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare the ACL reconstruction failure rate between hospitals performing different annual surgical volumes. The hypothesis was that ACL reconstructions performed at low-volume hospitals would be associated with higher failure rates than those performed at high-volume centres.

This level-II cohort study included all patients from the Norwegian Knee Ligament Registry that underwent isolated primary autograft ACL reconstruction between 2004 and 2016. Hospital volume was divided into quintiles based on the number of ACL reconstructions performed annually, defined arbitrarily as: 1–12 (V1), 13–24 (V2), 25–49 (V3), 50–99 (V4), and ≥100 (V5) annual procedures. Kaplan-Meier estimated survival curves and survival percentages were calculated with revision ACL reconstruction as the end point. Mean change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life and Sport subsections from pre-operative to two-year follow-up were compared using t-test.

19,204 patients met the inclusion criteria and 1,103 (5.7%) underwent subsequent revision ACL reconstruction over the study period. Patients in the lower volume categories (V1-3) were more often male (58–59% vs. 54–55% p=<0.001) and older (27 years vs. 24–25 years, p=<0.001) compared to the higher volume hospitals (V4-5). Concomitant meniscal injuries (52% vs. 40%) and participation in pivoting sports (63% vs. 56%) were most common in V5 compared with V1 (p=<0.001). Median operative time decreased as hospital volume increased, ranging from 90 minutes at V1 hospitals to 56 minutes at V5 hospitals (p=<0.005). Complications occurred at a rate of 3.8% at low-volume (V1) hospitals versus 1.9% at high-volume (V5) hospitals (p=<0.001). Unadjusted 10-year survival with 95% confidence intervals for each hospital volume category were: V1 – 95.1% (93.7–96.5%), V2 – 94.1% (93.1–95.1%), V3 – 94.2% (93.6–94.8%), V4 – 92.6% (91.8–93.4%), and V5 – 91.9% (90.9–92.9%). There was no difference in improvement between pre-operative and two-year follow-up KOOS scores between hospital volume categories.

Patients having ACL reconstruction at lower volume hospitals did not have inferior clinical or patient reported outcomes, and actually demonstrated a lower revision rate. Complications occurred more frequently however, and operative duration was longer. The decreased revision rate is an interesting finding that may be partly explained by the fact that patients being treated in these small, often rural hospitals, may be of lower demand as suggested by the increased age and decreased participation in pivoting sports. In addition, patients with more complicated pathology such as meniscal tears were more commonly treated in the larger volume hospitals. The most significant limitation of this study is that provider volume was not assessed, and the number of surgeons dividing up the surgical volume at each hospital is not known.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 133 - 134
1 May 2011
Ackermann P Schizas N Oystein L Frihagen F Engebretsen L Bahr R
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Introduction: Tendinopathy entails pain and degenerative tissue proliferation such as tenocyte transformation and increased numbers of sensory nerves and microvessels. Pain and tissue proliferation are suggested to be modulated via nerve transmitters, including substance P (SP) and glutamate, both detected in tendinopathy. Substance P and glutamate are known to activate glutamate receptors in a variety of pain conditions and additionally to be implicated in cell transformation. However, the presence of different glutamate receptors, eg. ionotropic (NMDA) and metabotropic (mGlu), and whether they are up- or downregulated in tendinopathy is still unknown. In this study we assessed the

presence,

the tissue density and

the co-existence of different glutamate receptors together with glutamate in tendinopathic biopsies and controls.

Methods: All procedures were conducted with local ethical committee approval and patient consent. Human patellar tendon biopsies of tendinopathic patients (n=10) and controls (n=8) were single- and double-stained immunohistochemically for glutamate, glutamate receptors NMDAR1, mGluR1, mGluR5 and mGluR6,7, the nerve marker PGP9.5 and SP and assessed subjectively and semi-quantitatively with image analysis. Images were taken using an epifluorescence microscope with camera and were subjectively assessed by two independent observers blinded with regard to the identity of the slides. Tenocyte density and morphologic characteristics were assessed. Non-parametric Mann-Whitney U-tests for independent samples were used, and the level for significance was set at p< 0.05.

Results: Of the glutamate receptors tested all except mGluR1 was identified in the tendons, however only NMDAR1 was found significantly altered between both groups. The chronic painful tendons exhibited a significant elevation of NMDAR1 (9-fold) and also of glutamate (10-fold). This up-regulation of NMDAR1 and glutamate was found to be co-localized on sensory nerve fibers, blood vessels as well as on transformed tenocytes. None of the controls exhibited neuronal co-existence of glutamate with NMDAR1.

Conclusions: This study establishes for the first time that patients with tendinopathy exhibit an elevation of peripheral glutamate receptor NMDAR1, morphologically co-localized with increased glutamate expression. The up-regulated NMDAR1/glutamate system may represent hyper-excitability of the cells – leading to cell proliferative effects observed as angiogenesis, tenocyte transformation, and nerve sprouting. Moreover, the neuronal co-existence of glutamate and NMDAR1 observed in painful tendinosis, but not seen in any of the controls, strongly suggests a role in pain signalling. Future studies will focuse on interventional approaches to investigate if modulation of NMDAR1 pathways can ameliorate the symptoms of tendinopathic patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 2 | Pages 259 - 263
1 Feb 2009
Dimmen S Nordsletten L Engebretsen L Steen H Madsen JE

Conventional non-steroidal anti-inflammatory drugs (NSAIDs) and newer specific cyclo-oxygenase-2 (cox-2) inhibitors are commonly used in musculoskeletal trauma and orthopaedic surgery to reduce the inflammatory response and pain. These drugs have been reported to impair bone metabolism. In reconstruction of the anterior cruciate ligament the hamstring tendons are mainly used as the graft of choice, and a prerequisite for good results is healing of the tendons in the bone tunnel. Many of these patients are routinely given NSAIDs or cox-2 inhibitors, although no studies have elucidated the effects of these drugs on tendon healing in the bone tunnel.

In our study 60 female Wistar rats were randomly allocated into three groups of 20. One received parecoxib, one indometacin and one acted as a control. In all the rats the tendo-Achillis was released proximally from the calf muscles. It was then pulled through a drill hole in the distal tibia and sutured anteriorly. The rats were given parecoxib, indometacin or saline intraperitoneally twice daily for seven days. After 14 days the tendon/bone-tunnel interface was subjected to mechanical testing.

Significantly lower maximum pull-out strength (p < 0.001), energy absorption (p < 0.001) and stiffness (p = 0.035) were found in rats given parecoxib and indometacin compared with the control group, most pronounced with parecoxib.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 5 - 5
1 Mar 2006
Engebretsen L Johansen S Ludvigsen T
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As a level I trauma hospital, OOU receives an increasing number of knee dislocations. This study evaluates acute knee dislocations seen at OOU from May 1. 1996 through Dec 2004.

Patients and methods: 136 patients with 137 dislocated knees were admitted in the periode. All patients were students or working prior to the injury and all had a high functional level. 50% of the dislocations occured in conjunction with major traffic accidents- the majority of which were motorbikecyklists, while the remaining injuries were sustained during sports. 4 patients had a complete injury of the peroneal nerve on admittance, while an additional 4 had decreased motor strength and \or sensory dysfunction.

In addition one patient had a ruptur of the patellar tendon and one a patella dislocation. Two of the patients in this group had a vascular injury. On admittance the patients underwent a diagnostic exam in the emergency room.. All the patients then had a MRI. The patients were the placed in a brace and on a CPM 2 hours 2 times a day for 7 days, and the vascular status was monitored closely. After 7–10 days the patients underwent surgery including arthroscopic reconstruction of the ACL and PCL with auto or preferably, if available allograft. Results for patient with a followup for more than 6 months are presented including IKDS, Cincinatti, Tegner and a clinical exam with KT1000.

Results:. No serious complication occurred in conjuntion with surgery or the hospital stay. One infection with staf occurred successfully treated. Two patients underwent secondary arthroscopic debridement for arthrofibrosis All the patients have returned to work, but the majority have had to reduce or change their sports activities.

Conclusion:. We have designed a treatment protocol for this difficult patient group. So far the complication frequency has been low.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 120 - 120
1 Feb 2003
Hoiness P Andreassen G Skramm I Engebretsen L Granlund O
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Screw stripping in osteoporotic bone and bone of otherwise poor quality represents a common problem. Treatment alternatives, such as using a larger diameter screw or a longer plate, may add time, increase morbidity, be impractical, or simply be ineffective. Alternatively, the stripped screw can be augmented with a bone cement. A new injectable synthetic cortical bone void filler (Cor-toSSTM) is based on a resin system, resulting in a very strong, radiopaque, extensively crosslinked, biocompatible composite that does not resorb. We tested the safety and efficacy of the new bone cement in augmenting stripped screws until bone healing.

Of a total of 143 screws implanted in 24 patients with ankle fractures (average age 66. 8 years), 61 became stripped and were augmented. The primary efficacy endpoint was successful intraoperative screw augmentation. The secondary endpoint was whether screw fixation, determined radiologically, remained effective during the 3-month follow-up required for the fracture to heal.

All the stripped screws were successfully augmented. During follow-up at 24 hours, 7 days, and 1 month, none showed any movement relative to either the plate or the bone. At 3 months, one augmented screw in a patient with severe osteoporosis showed gross movement above the plate, which did not affect healing. Serial radiographic analysis did not show the development of any lucencies or cracks in the cement. All fractures healed within 3 months following surgery.

Screw augmentation allowed successful reduction and fixation of the fractures. No adverse events directly attributable to the device were observed. The new bone void filler represents a safe, simple, and reliable method by which to achieve stable internal fixation constructs in patients in whom bone screws fail to gain purchase due to poor bone quality or overtightening.


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 5 | Pages 817 - 822
1 Sep 1996
Grøntvedt T Engebretsen L Bredland T

In 100 consecutive patients with chronic deficiency of the anterior cruciate ligament we reconstructed the ligament using a bone-patellar tendon-bone autograft either with or without a Kennedy ligament augmentation device. The patients had an aggressive rehabilitation programme supervised by two physiotherapists.

They were followed prospectively for at least two years by one surgeon, and assessed after six months and at one and two years. No significant functional or clinical difference was found between the two groups and the stability of the knees did not deteriorate with time in either group. The addition of a Kennedy ligament augmentation device gave no better results than the bone-patellar tendon-bone technique alone.