Mild aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL)-type reactions also present in patients with failed knee prostheses.

Aims: Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Methods: Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia. Results: Median metal concentrations were as follows: cobalt: 0.69 µg/g (interquartile range (IQR) 0.10 to 6.10); chromium: 1.1 µg/g (IQR 0.27 to 4.10); and titanium: 1.6 µg/g (IQR 0.90 to 4.07). Moderate ALVAL scores were found in 30% (n = 39) of the revised knees. There were ten patients with an ALVAL score of 6 or more who were revised for suspected periprosthetic joint infection (PJI), aseptic loosening, or osteolysis. R2 varied between 0.269 and 0.369 for the ordinal regression models. The most important variables were model type, indication for revision, and cobalt and chromium in the ordinal regression models. Conclusion: We found that metal particles released from the knee prosthesis can accumulate in the periprosthetic tissues. Several patients revised for suspected culture-negative PJI had features of an ALVAL reaction, which is a novel finding. Therefore, ALVAL-type reactions can also be found around knee prostheses, but they are mostly mild and less common than those found around metal-on-metal prostheses.

Clinical Outcomes After Revision Hip Arthroplasty due to Prosthetic Joint Infection-A Single-Center Study of 369 Hips at a High-Volume Center With a Minimum of One Year Follow-Up.

BACKGROUND: Prosthetic joint infection (PJI) treatment decisions are traditionally based on treatment algorithms. There is, however, a lack of evidence to support the choice of these treatment algorithms. Therefore, we aimed to assess the one-year survival after PJI revision and compared different surgical strategies in a single-center setting. METHODS: Revisions of the hip due to PJI performed at our institution between January 2008 and September 2021 with at least one-year of follow-up were identified. In total, 134 debridement, antibiotics, and implant retentions (DAIRs), 114 one-stage revisions, and 121 two-stage revisions were performed. Infections were classified as early, acute hematogenous, and chronic. Survival was calculated using the Kaplan-Meier method and cumulative incidence function. Predictors of outcomes were examined with Fine-Gray regressions and Cox proportional hazards regressions. Subdistribution hazard ratios and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. RESULTS: At one-year follow-up, 26.6% (CI 22.2 to 31.2%) of the patients had undergone reoperation and 7.9% (CI 5.4 to 10.9%) had died. The risk for reoperation was highest after DAIR (36.6%, CI 28.5 to 44.7%) and lowest after one-stage revision (20.2%, CI 13.4 to 28%). Within the early infections, the one-stage revision almost halved the risk of reoperation (HR 0.51, CI 0.31 to 0.84) with no added mortality risk (HR 1.05, CI 0.5 to 2.2), when compared to DAIR. CONCLUSION: By utilizing 1-stage revision over DAIR in early infections, it might be possible to improve the prognosis by decreasing the risk of reoperation without increasing mortality. However, as the patient selection is undeniably difficult, more research is warranted.

KLIC Score Does Not Predict Failure After Early Prosthetic Joint Infection: An External Validation With 153 Knees and 130 Hips.

BACKGROUND: A preoperative risk score, the KLIC score (chronic renal failure [K], liver cirrhosis [L], indication of the index surgery [I], cemented prosthesis [C], and C-reactive protein >115 mg/L), has been developed to predict the risk of treatment failure after early prosthetic joint infection (PJI). This study aimed to validate the KLIC score for the debridement, antibiotics, and implant retention (DAIR) procedure and one-stage revisions in a Northern European cohort. METHODS: Revisions due to early PJI of the hip or knee between January 1, 2008, and September 12, 2021, were identified retrospectively. The primary outcome was early failure, which was considered when the patient needed an unscheduled surgery, the patient died, or the patient was prescribed long-term suppressive antibiotics. To examine the association between KLIC score and failure risk, univariable logistic regression with area under the curve (AUC) was used. In addition, models were calibrated to assess prognostic ability and clinical utility was examined with decision-curve analyses. RESULTS: An increase in KLIC score had a moderate predictive value for early failure after DAIR (odds ratio [OR] 1.45; confidence interval [CI] 1.13 to 1.90). For one-stage revision, it was only slightly predictive of failure (OR 1.20; CI 0.93 to 1.56). After 60 days, the AUC for DAIR was 0.63 (CI 0.55 to 0.72) and 0.56 (CI 0.46 to 0.66) for one-stage revisions, indicating poor discriminative ability. The decision-curve analyses revealed that the model did not offer a remarkable net benefit across a range of threshold probabilities. CONCLUSIONS: We demonstrated that the KLIC score is not a reliable predictor of early failure after early PJI in a Northern European cohort. Using the model to guide treatment decisions does not provide any additional clinical utility beyond the baseline strategies.

Does choice of bearings influence the survival of cementless total hip arthroplasty in patients aged 20-55 years? Comparison of 21,594 patients reported to the Nordic Arthroplasty Register Association dataset 2005-2017.

BACKGROUND AND PURPOSE: The bearings with the best survivorship for young patients with total hip arthroplasty (THA) should be identified. We compared hazard ratios (HR) of revision of primary stemmed cementless THAs with metal-on-metal (MoM), ceramic-on-ceramic (CoC), and ceramic-on-highly-crosslinked-polyethylene (CoXLP) with that of metal-on-highly-crosslinked-polyethylene (MoXLP) bearings in patients aged 20-55 years with primary osteoarthritis or childhood hip disorders. PATIENTS AND METHODS: From the Nordic Arthroplasty Register Association dataset we included 1,813 MoM, 3,615 CoC, 5,947 CoXLP, and 10,219 MoXLP THA in patients operated on between 2005 and 2017 in a prospective cohort study. We used the Kaplan-Meier estimator for THA survivorship and Cox regression to estimate HR of revision adjusted for confounders (including 95% confidence intervals [CI]). MoXLP was used as reference. HRs were calculated during 3 intervals (0-2, 2-7, and 7-13 years) to meet the assumption of proportional hazards. RESULTS: Median follow-up was 5 years for MoXLP, 10 years for MoM, 6 years for CoC, and 4 years for CoXLP. 13-year Kaplan-Meier survival estimates were 95% (CI 94-95) for MoXLP, 82% (CI 80-84) for MoM, 93% (CI 92-95) for CoC, and 93% (CI 92-94) for CoXLP bearings. MoM had higher 2-7 and 7-13 years' adjusted HRs of revision (3.6, CI 2.3-5.7 and 4.1, CI 1.7-10). MoXLP, CoC, and CoXLP had similar HRs in all 3 periods. The 7-13-year adjusted HRs of revision of CoC and CoXLP were statistically non-significantly higher. CONCLUSION: In young patients, MoXLP for primary cementless THA had higher revision-free survival and lower HR for revision than MoM bearings. Longer follow-up is needed to compare MoXLP, CoC, and CoXLP.

Increasing risk of revision due to infection after primary total hip arthroplasty: results from the Nordic Arthroplasty Register Association.

BACKGROUND AND PURPOSE: The incidence of periprosthetic joint infection after total hip arthroplasty (THA) may be increasing. We performed time-trend analyses of risk, rates, and timing of revision due to infection after primary THAs in the Nordic countries from the period 2004-2018. PATIENTS AND METHODS: 569,463 primary THAs reported to the Nordic Arthroplasty Register Association from 2004 to 2018 were studied. Absolute risk estimates were calculated by Kaplan-Meier and cumulative incidence function methods, whereas adjusted hazard ratios (aHR) were assessed by Cox regression with the first revision due to infection after primary THA as primary endpoint. In addition, we explored changes in the time span from primary THA to revision due to infection. RESULTS: 5,653 (1.0%) primary THAs were revised due to infection during a median follow-up time of 5.4 (IQR 2.5-8.9) years after surgery. Compared with the period 2004-2008, the aHRs for revision were 1.4 (95% confidence interval [CI] 1.3-1.5) for 2009-2013, and 1.9 (CI 1.7-2.0) for 2014-2018. The absolute 5-year rates of revision due to infection were 0.7% (CI 0.7-0.7), 1.0% (CI 0.9-1.0), and 1.2% (CI 1.2-1.3) for the 3 time periods respectively. We found changes in the time span from primary THA to revision due to infection. Compared with 2004-2008, the aHR for revision within 30 days after THA was 2.5 (CI 2.1-2.9) for 2009-2013, and 3.4 (CI 3.0-3.9) for 2013-2018. The aHR for revision within 31-90 days after THA was 1.5 (CI 1.3-1.9) for 2009-2013, and 2.5 (CI 2.1-3.0) for 2013-2018, compared with 2004-2008. CONCLUSION: The risk of revision due to infection after primary THA almost doubled, both in absolute cumulative incidence and in relative risk, throughout the period 2004-2018. This increase was mainly due to an increased risk of revision within 90 days of THA. This may reflect a "true" increase (i.e., frailer patients or more use of uncemented implants) and/or an "apparent" increase (i.e., improved diagnostics, changed revision strategy, or completeness of reporting) in incidence of periprosthetic joint infection. It is not possible to disclose such changes in the present study, and this warrants further research.

Trends in Revision Knee Arthroplasty for Prosthetic Joint Infection: A Single-Center Study of 384 Knees at a High-Volume Center Between 2008 and 2021.

BACKGROUND: Prosthetic joint infection (PJI) is one of the most devastating complications after total knee arthroplasty (TKA), and comorbidities increase the risk. We examined whether a temporal change has occurred in the demographics, especially regarding comorbidities, of patients who have PJI and were treated at our institution over a 13-year study period. In addition, we assessed the surgical methods used and the microbiology of the PJIs. METHODS: Revisions (n = 384, 377 patients) due to PJI of the knee performed at our institution between 2008 and September 2021 were identified. All included PJIs fulfilled the 2013 International Consensus Meeting diagnostic criteria. The surgeries were categorized into one of the following categories: debridement, antibiotics, and retention (DAIR), 1-stage revision, and 2-stage revision. Infections were classified as early, acute hematogenous, and chronic. RESULTS: No changes in the median age of the patients nor comorbidity burden were observed during the study period. However, the proportion of 2-stage revisions decreased remarkably from 57.6% in 2008 to 2009 to 6.3% in 2020 to 2021. A DAIR was the most used treatment strategy, but the proportion of 1-stage revisions increased the most. In 2008 to 2009, 12.1% of the revisions were 1-stage, but in 2020 to 2021, the proportion was 43.8%. The most common pathogen was Staphylococcus aureus (27.8%). CONCLUSION: The comorbidity burden remained at the same level with no trends. A DAIR was the most used strategy, but the proportion of 1-stage revisions rose to almost the same level. The incidence of PJI varied between the years, but remained relatively low.

Risk factors for revision due to prosthetic joint infection following total knee arthroplasty based on 62,087 knees in the Finnish Arthroplasty Register from 2014 to 2020.

BACKGROUND AND PURPOSE: Periprosthetic joint infection (PJI) is the commonest reason for revision after total knee arthroplasty (TKA). We assessed the risk factors for revision due to PJI following TKA based on the Finnish Arthroplasty Register (FAR). PATIENTS AND METHODS: We analyzed 62,087 primary condylar TKAs registered between June 2014 and February 2020 with revision for PJI as the endpoint. Cox proportional hazards regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for the first PJI revision using 25 potential patient- and surgical-related risk factors as covariates. RESULTS: 484 knees were revised for the first time during the first postoperative year because of PJI. The HRs for revision due to PJI in unadjusted analysis were 0.5 (0.4-0.6) for female sex, 0.7 (0.6-1.0) for BMI 25-29, and 1.6 (1.1-2.5) for BMI > 40 compared with BMI < 25, 4.0 (1.3-12) for preoperative fracture diagnosis compared with osteoarthritis, and 0.7 (0.5-0.9) for use of an antimicrobial incise drape. In adjusted analysis the HRs were 2.2 (1.4-3.5) for ASA class III-IV compared with class I, 1.7 (1.4-2.1) for intraoperative bleeding ≥ 100 mL, 1.4 (1.2-1.8) for use of a drain, 0.7 (0.5-1.0) for short duration of operation of 45-59 minutes, and 1.7 (1.3-2.3) for long operation duration > 120 min compared with 60-89 minutes, and 1.3 (1.0-1.8) for use of general anesthesia. CONCLUSION: We found increased risk for revision due to PJI when no incise drape was used. The use of drainage also increased the risk. Specializing in performing TKA reduces operative time and thereby also the PJI rate.

Effect of non-cephalosporin antibiotic prophylaxis on the risk of periprosthetic joint infection after total joint replacement surgery: a retrospective study with a 1-year follow-up.

Background: Cephalosporins are recommended as first-line antibiotic prophylaxis in total joint replacement surgery. Studies have shown an increased risk for periprosthetic joint infection (PJI) when non-cephalosporin antibiotics have been used. This study examines the effect of non-cephalosporin antibiotic prophylaxis on the risk for PJI. Methods: Patients with a primary hip or knee replacement performed from 2012 to 2020 were identified (27 220 joint replacements). The primary outcome was the occurrence of a PJI in a one-year follow-up. The association between perioperative antibiotic prophylaxis and the outcome was examined using logistic regression analysis. Discussion: Cefuroxime was used as prophylaxis in 26,467 operations (97.2%), clindamycin in 654 (2.4%) and vancomycin in 72 (0.3%). The incidence of PJI was 0.86% (228/26,467) with cefuroxime and 0.80% (6/753) with other prophylactic antibiotics. There was no difference in the risk for PJI with different prophylactic antibiotics in the univariate (OR 1.06, 95% CI 0.47-2.39) or multivariable analysis (OR 1.02, 95% CI 0.45-2.30). Conclusion: Non-cephalosporin antibiotic prophylaxis in primary total joint replacement surgery was not associated with an increased risk for PJI.

Venous thromboembolism is rare after total hip and knee joint arthroplasty with long thromboprophylaxis in Finnish fast-track hospitals.

INTRODUCTION: Pharmacological thromboprophylaxis effectively prevents venous thromboembolism (VTE) after total knee (TKA) and total hip arthroplasty (THA). Less is known about the influence of fast-track arthroplasty on VTE risk. We conducted a register-based study to determine the incidence of VTE after fast-track TKA and THA in Finland using long thromboprophylaxis. MATERIALS AND METHODS: All primary TKAs and THAs operated during 2015-2016 in 3 fast-track hospitals were identified from the Finnish Arthroplasty Register. Pulmonary embolism (PE) and deep vein thrombosis (DVT) diagnosed in this patient cohort within 90 days of surgery were identified from the Finnish Hospital Discharge Register. The recommended length of thromboprophylaxis was 10 to 14 days for TKA and 28 days for THA during study period. RESULTS: During the study period, 3 831 THAs, 4 394 TKAs and 286 bilateral TKAs (BTKAs) were performed. Of all these patients, 60% were females. Venous thromboembolism (VTE) incidence within 90 days of surgery was 0.3% (95% CI 0.2-0.4). These VTEs comprised 10 PEs and 15 DVTs. None of the VTE patients´ died within the 90-day period. CONCLUSION: VTE incidence is low in Finnish fast-track TKA and THA patients with long thromboprophylaxis.

Trends in Revision Hip Arthroplasty for Prosthetic Joint Infection: A Single-Center Study of 423 Hips at a High-Volume Center Between 2008 and 2021.

BACKGROUND: Prosthetic joint infection (PJI) is one of the most devastating complications after total hip arthroplasty (THA), and comorbidities increase the risk. We examined whether there was a temporal change in the demographics, especially regarding comorbidities, of patients who have PJIs and were treated over a 13-year study period at a high-volume academic joint arthroplasty center. In addition, the surgical methods used and the microbiology of the PJIs were assessed. METHODS: Revisions (n = 423, 418 patients) due to PJI of the hip performed at our institution between 2008 and September 2021 were identified. All included PJIs fulfilled the 2013 International Consensus Meeting diagnostic criteria. The surgeries were categorized into one of the following categories: debridement, antibiotics, and implant retention, 1-stage revision, and 2-stage revision. Infections were classified as early, acute hematogenous, and chronic infections. RESULTS: There was no change in the median age of the patients, but the proportion of ASA-class 4 patients increased from 10.5% to 20%. The incidence of early infections increased from 0.11 per 100 primary THAs in 2008 to 1.09 in 2021. The incidence of 1-stage revisions increased the most, rising from 0.10 per 100 primary THAs in 2010 to 0.91 per 100 primary THAs in 2021. Furthermore, the proportion of infections caused by Staphylococcus aureus increased from 26.3% in 2008 to 2009 to 40% in 2020 to 2021. CONCLUSION: The comorbidity burden of PJI patients increased during the study period. This increase may present a treatment challenge, as comorbidities are known to have a negative effect on PJI treatment outcomes.

Long-term changes in blood metal ion levels in patients with hip resurfacing implants: implications for patient surveillance after 10 years follow-up.

BACKGROUND: Studies investigating changes in blood metal ion levels during the second decade of the implant lifetime in MoM hip resurfacing patients are scarce. METHODS: Patients implanted with either Birmingham Hip Resurfacing (BHR) or Articular Surface Replacement (ASR) hip resurfacings with >10 years follow-up and repeated blood metal ion measurements were identified at 2 large specialist European arthroplasty centres. After excluding patients with initial metal ion levels >7 ppb, the proportion of patients with an increase in blood metal ion levels above previously validated implant-specific thresholds (cobalt 2.15 ppb for unilateral implants, cobalt or chromium 5.5 ppb for bilateral) was assessed. RESULTS: We included 2743 blood metal ion measurements from 457 BHR patients (555 hips) and 216 ASR patients (263 hips). Of patients with initial metal ion levels below implant specific thresholds, increases in cobalt or chromium level, respectively, to above these thresholds during the second decade were seen as follows: unilateral BHR (cobalt = 15.6%), unilateral ASR (cobalt = 13.8%), bilateral BHR (cobalt = 8.2%, chromium = 11.8%), bilateral ASR (cobalt = 8.5%, chromium = 4.3%). Measurement-to-measurement changes exceeding +2.15 ppb or +5.5 ppb were, however, uncommon during the second decade. Subgroup results with small diameter (<50 mm) implants were similar. CONCLUSIONS: We recommend less frequent blood metal ion measurements are needed (every 3 to 5 years) for hip resurfacing patients if initial values were below 7ppb.

Thicker polyethylene inserts (≥ 13 mm) increase the risk for early failure after primary cruciate-retaining total knee arthroplasty (TKA): a single-centre study of 7643 TKAs.

PURPOSE: This study investigates whether thicker (PE) inserts lead to a greater risk for revision after TKA. The differences between the TKA designs of three manufacturers (NexGen, PFC Sigma, Triathlon) are also compared. METHODS: A total of 7643 primary TKA surgeries were included. PE inserts were divided into two groups-"thick PE inserts" with a thickness of 13 mm (mm) or more and "standard PE inserts" with a thickness of less than 13 mm. Three cruciate-retaining (CR) TKA designs (NexGen, PFC Sigma, Triathlon) were included in the study. The differences in failure rates between groups were investigated using Kaplan-Meier survival curves and Cox regression model with hazard ratios (HR). Failure rates were investigated short-term (< 2 years) and long-term (the whole follow-up period). The TKA designs were analysed both together and separately. RESULTS: During the whole follow-up period, there were 184 (2.4%) aseptic revisions. The thick PE insert group showed an increased risk for revision compared to the standard PE insert group in both short-term (< 2 years; HR 2.0, CI 1.3 to 3.2) and long term (> 2 years; HR 1.6, CI 1.1 to 2.3) follow-up. The highest revision rate was observed in patients who received the Triathlon TKA with a thicker PE insert (HR 2.6, CI 1.2 to 5.7). CONCLUSION: The results indicate that thicker PE inserts are associated with increased risk for revision in primary TKA. Further research is required to ascertain whether more conformed PE inserts or constrained knee designs instead of thick CR inserts will ultimately lead to better clinical outcomes. LEVEL OF EVIDENCE: III.

No difference in implant survival between 28-mm M2a RingLoc metal-on-metal and metal-on-polyethylene total hip arthroplasty: results from the Finnish Arthroplasty Register.

BACKGROUND AND PURPOSE: Long-term outcome of small head (28 mm) metal-on-metal (MoM) total hip arthroplasty (THA) is available mainly for Metasul devices (Sulzer Medica, Winterthur, Switzerland). Biomet MoM THA was frequently used in Finland. Therefore, we assessed long-term survivorship of the M2a 28-mm RingLoc MoM THA (Biomet, Warsaw, IN, USA) and compared it with the metal-on-polyethylene (MoP) RingLoc THA from the same manufacturer. PATIENTS AND METHODS: We conducted a register study based on THAs from the Finnish Arthroplasty Register performed between January 1, 2000 and December 31, 2007. 290 28-mm head M2a MoM THAs and 1,647 28-mm head MoP THAs (reference group) were included. The endpoint was revision for any reason, or revision for aseptic loosening, osteolysis, liner wear, or metallosis as one group. Kaplan-Meier survival estimates were calculated, and revision risks were assessed using a Cox multiple regression model, both with 95% confidence intervals (CI). RESULTS: No difference was found in the 15-year Kaplan-Meier survivorship between the 28-mm head M2a RingLoc MoM THA and the reference group for any reason for revision (87.7% [82.9-92.1] and 83.3% [81.0-85.3], respectively). The adjusted hazard ratio (HR) for any reason for revision for the MoM THA group compared with the reference group was at least equal or better (0.70 [0.48-1.02]). Both groups presented similar survival for revision for aseptic loosening of the cup, osteolysis, liner wear, or metallosis, at 96.2% (92.7-98.0) and 95.4% (93.9-96.5), respectively. INTERPRETATION: In the long-term survival there was no difference between the M2a 28-mm RingLoc MoM THA and 28-mm MoP THA. Further follow-up regimens for M2a 28-mm RingLoc THA patients may be unnecessary, but long-term metal ion and radiological data is needed before any formal suggestions.

Impact of Nordic Arthroplasty Register Association (NARA) collaboration on demographics, methods and revision rates in knee arthroplasty: a register-based study from NARA 2000-2017.

BACKGROUND AND PURPOSE: We have previously observed differences in treatment and outcome of knee arthroplasties in the Nordic countries. To evaluate the impact of Nordic collaboration in the last 15 years we aimed to compare patient demographics, methods, and revision rates in primary knee arthroplasties among the 4 Nordic countries. PATIENTS AND METHODS: We included 535,051 primary knee arthroplasties reported 2000-2017 from the Nordic Arthroplasty Register Association (NARA) database. Kaplan-Meier analysis (KM) and restricted mean survival time (RMST) analysis were used to evaluate the cumulative revision rate (CRR) and RMST estimates with 95% confidence intervals (CI) and to compare countries in relation to risk of revision for any reason. RESULTS: After 2010, the increase in incidence of knee arthroplasty plateaued in Sweden and Denmark but continued to increase in Finland and Norway. In 2017 the incidence was highest in Finland with 226 per 105 person-years, while it was less than 150 per 105 in the 3 other Nordic countries. In total knee arthroplasties performed for osteoarthritis (OA), overall CRR at 15 years for revision due to any reason was higher in Denmark (CRR 9.6%, 95% CI 9.2-10), Norway (CRR 9.1%, CI 8.7-9.5), and Finland (CRR 7.0%, CI 6.8-7.3) compared with Sweden (CRR 6.6%, CI 6.4-6.8). There were differences among the countries in use of implant brand and type, fixation, patellar component, and use of unicompartmental knee arthroplasty. INTERPRETATION: We evinced a slowing growth of incidence of knee arthroplasties in the Nordic countries after 2010 with Finland having the highest incidence. We also noted substantial differences among the 4 Nordic countries, with Sweden having a lower risk of revision than the other countries. No impact of NARA could be demonstrated and CRR did not improve over time.

Prediction model for an early revision for dislocation after primary total hip arthroplasty.

Dislocation is one of the most common complications after primary total hip arthroplasty (THA). Several patient-related risk factors for dislocation have been reported in the previous literature, but only few prediction models for dislocation have been made. Our aim was to build a prediction model for an early (within the first 2 years) revision for dislocation after primary THA using two different statistical methods. The study data constituted of 37 pre- or perioperative variables and postoperative follow-up data of 16 454 primary THAs performed at our institution in 2008-2021. Model I was a traditional logistic regression model and Model II was based on the elastic net method that utilizes machine learning. The models' overall performance was measured using the pseudo R2 values. The discrimination of the models was measured using C-index in Model I and Area Under the Curve (AUC) in Model II. Calibration curves were made for both models. At 2 years postoperatively, 95 hips (0.6% prevalence) had been revised for dislocation. The pseudo R2 values were 0.04 in Model I and 0.02 in Model II indicating low predictive capability in both models. The C-index in Model I was 0.67 and the AUC in Model II was 0.73 indicating modest discrimination. The prediction of an early revision for dislocation after primary THA is difficult even in a large cohort of patients with detailed data available because of the reasonably low prevalence and multifactorial nature of dislocation. Therefore, the risk of dislocation should be kept in mind in every primary THA, whether the patient has predisposing factors for dislocation or not. Further, when conducting a prediction model, sophisticated methods that utilize machine learning may not necessarily offer significant advantage over traditional statistical methods in clinical setup.

Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen.

Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide-drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human bone marrow-derived MSCs (BMSCs) and how these drugs affect BMSC proliferation. We established co-cultures of BMSCs with MM.1S myeloma cells to see if BMSCs increase or decrease the cytotoxicity of melflufen, melphalan, bortezomib and doxorubicin. We evaluated how the drugs affect BMSC differentiation into adipocytes and osteoblasts and the BMSC-supported formation of vascular networks. Our results showed that BMSCs were more sensitive to melflufen than to melphalan. The cytotoxicity of melflufen in myeloma cells was not affected by the co-culture with BMSCs, as was the case for melphalan, bortezomib and doxorubicin. Adipogenesis, osteogenesis and BMSC-mediated angiogenesis were all affected by melflufen. Melphalan and doxorubicin affected BMSC differentiation in similar ways. The effects on adipogenesis and osteogenesis were not solely because of effects on proliferation, seen from the differential expression of differentiation markers normalized by cell number. Overall, our results indicate that melflufen has a significant impact on BMSCs, which could possibly affect therapy outcome.

Low incidence of clinically relevant bleeding complications after fast-track arthroplasty: a register study of 8,511 arthroplasties.

BACKGROUND AND PURPOSE: Fast-track total joint replacement (TJR) has become increasingly common. Routine thromboprophylaxis for pulmonary embolism and deep venous thrombosis prevention lasts from 2 to 5 weeks. This retrospective registry study focused on clinically relevant bleeding complications 90 days after fast-track primary TJR. PATIENTS AND METHODS: All primary fast-track total hip (THA) and knee arthroplasties (TKA) performed between 2015 and 2016 were extracted from the Finnish Arthroplasty Register and Finnish Hospital Discharge Register. Type of arthroplasty and indication for the operation were combined with diagnoses of clinically relevant bleeding complications within 90 days of surgery. The incidence of these bleedings was the primary outcome measure. RESULTS: Of the total of 8,511 patients (mean age 67 years (SD 10); 60% female), 45% underwent unilateral THA, 52% unilateral TKA, and 3% bilateral TKA. The incidence of clinically relevant bleeding complications within 90 days was 1% (95% CI 0.8-1.3). No difference was observed in bleeding incidence between the groups. The 87 bleedings comprised 57 operative site bleedings, 17 gastrointestinal bleedings, 6 intracranial non-traumatic bleedings, 5 bleedings from the nose or another undetermined site, and 2 intraocular bleedings. 1 death due to intracranial bleeding was recorded, and hence clinically relevant bleeding-specific 90-day mortality was 0.01%. INTERPRETATION: The incidence of clinically relevant bleeding complications was low. However, they cause patient discomfort, increase the use of healthcare services, and can be life-threatening and even fatal.

Mild knee osteoarthritis predicts dissatisfaction after total knee arthroplasty: a prospective study of 186 patients aged 65 years or less with 2-year follow-up.

BACKGROUND AND AIMS: The incidence of total knee arthroplasty (TKA) is increasing, especially among younger working-age patients. However, dissatisfaction rates in this population are higher than among older patients. The aim of this study was to assess the rates of dissatisfaction and persistent pain after TKA and to evaluate those factors that predict these outcomes. MATERIAL AND METHODS: In total, 186 patients undergoing unilateral TKA aged 65 years or less were enrolled into this prospective observational study with 2-year follow-up. To assess the outcome, the visual analogue scales regarding satisfaction and persistent pain at rest and during exercise were used. In addition, the association between patients´ demographics, radiographic severity of knee osteoarthritis (OA), patient-reported outcome measures (PROMs) and dissatisfaction and persistent pain were tested by univariate logistic regression analysis. Mild OA was defined as Kellgren-Lawrence (KL) grade 2 and severe OA as KL grade 3-4. Furthermore, multiple logistic regression analysis was also conducted to test statistically significant relations. RESULTS: After 2 years, 12 % (n = 23) of patients were dissatisfied with the outcome of TKA, 27 % (n = 50) reported persistent pain during exercise and 10 % (n = 18) at rest. Patients with mild knee OA were significantly more dissatisfied (28.6 %) than patients with more severe OA (8.7 %) (p = 0.003). Younger patients had an increased risk for both dissatisfaction and persistent pain. Apart from KOOS Quality of Life, poor preoperative KOOS subscores were also predictive for these outcomes. CONCLUSION: Mild radiographic knee OA was the main predicting factor for dissatisfaction after TKA. Thus, performing TKA for such patients should be carefully considered. Furthermore, these patients should be informed about the increased risk for dissatisfaction and the same seems to apply to younger patients. Interestingly, when TKA is performed for patients with more severe knee OA, the satisfaction rates seem to be somewhat higher than those previously reported. TRIAL REGISTRATION: The study was retrospectively registered with ClinicalTrials.gov (registration number NCT03233620 ) on 28 July 2017.

Implant survival of 662 dual-mobility cups and 727 constrained liners in primary THA: small femoral head size increases the cumulative incidence of revision.

Background and purpose - In total hip arthroplasty (THA), the risk for dislocation can be reduced using either dual-mobility cups (DMCs) or constrained liners (CLs). There are few studies comparing these concepts in primary THA. Therefore, we compared the cumulative incidence of revision in primary THA patients treated with DMC or CL with varying head sizes with conventional THA patients as reference group.Patients and methods - We performed a cohort study based on the Finnish arthroplasty register, comparing DMCs and CLs operated over the period 2000-2017. DMCs were divided into 2 groups based on the implant design: "DMC Trident" group (n = 399) and "DMC Others" group (n = 263). CLs were divided based on the femoral head size: "CL 36 mm" group (n = 425) and "CL < 36 mm" group (n = 302). All conventional primary THAs operated on in 2000-2017 with 28-36 mm femoral head were included as control group ("Conventional THA" group, n = 102,276). Implant survival was calculated by the corresponding cumulative incidence function with revision as the endpoint and death as competing event. Also, the prevalence of different reasons for revision was compared.Results - The 6-year cumulative incidence function estimates for the first revision were 6.9% (95% CI 4.0-9.7) for DMC Trident, 5.0% (CI 1.5-8.5) for DMC Others, 13% (CI 9.3-17) for CL < 36 mm, 6.3% (3.7-8.9) for CL 36 mm, and 4.7% (CI 4.5-4.8) for control group (conventional THA). The prevalence of dislocation revision was high (5.0%, CI 2.9-8.2) in the CL < 36 mm group compared with other groups.Interpretation - The DMC and CL 36 mm groups had promising mid-term survival rates, comparable to those of primary conventional THA group. The revision rate of CLs with < 36 mm head was high, mostly due to high prevalence of dislocation revisions. Therefore, CLs with 36 mm femoral head should be preferred over smaller ones.