Impact of Positive Cultures During the Second Stage of a Two-Stage Exchange: Systematic Review and Meta-Analysis.

BACKGROUND: Two-stage exchange is a frequently performed procedure in patients who have a periprosthetic joint infection. Positive cultures when performing the second stage are perceived as a risk factor for reinfection. This study aimed to determine the impact of positive cultures during the second stage on the outcome of patients undergoing a 2-stage septic exchange and the impact of stopping the antibiotic treatment before reimplantation. METHODS: We systematically searched four databases. We performed a meta-analysis on the risk of complications after positive cultures during second stage and a subgroup analysis by antibiotic holiday period. We included 24 studies. RESULTS: Failure in the positive group was 37.0% and in the negative group was 13.7% with an odds ratio (OR) of 4.05. In the subgroup analysis by antibiotic holidays, failure rate without holidays was 15% and with holidays was 17.3% (P = .21). Failure in each group was higher when cultures were positive (without holidays, 25 versus 12.2%, P = .0003, and with holidays 41.1 versus 12.7%, P < .0001), but the risk of failure when cultures were positive was higher in the holiday group (OR 4.798) than in the nonholiday group (OR 2.225) in comparison to those patients who were culture negative at the second stage. CONCLUSIONS: Microbiological eradication at second stage was not obtained in 18% of cases and it was associated with a higher failure rate. In patients with positive cultures, withholding antibiotic treatment was associated with lower failure rate. Further studies to define the antibiotic strategy in 2-stage exchange procedure are necessary.

Clinical and laboratory predictors for prosthetic joint infection within the first postoperative days following primary total hip and knee arthroplasty.

PURPOSE: To identify clinical and laboratory predictors for low- and high-grade prosthetic joint infection (PJI) within the first postoperative days following primary total hip/knee arthroplasty (THA/TKA). METHODS: Institutional bone and joint infection registry of a single osteoarticular infection referral centre was reviewed to identify all osteoarticular infections treated between 2011 and 2021. Among them were 152 consecutive PJI (63 acute high-grade PJI, 57 chronic high-grade PJI, and 32 low-grade PJI) who also had primary THA/TKA performed at the same institution, which were retrospectively analyzed with multivariate logistic regression and covariables. RESULTS: For each additional day of wound discharge, persistent wound drainage (PWD) predicted PJI in the acute high-grade PJI group with odds ratio (OR) 39.4 (p = 0.000, 95%CI 1.171-1.661), in the low-grade PJI group with OR 26.0 (p = 0.045, 95%CI 1.005-1.579), but not in the chronic high-grade PJI group (OR 16.6, p = 0.142, 95%CI 0.950-1.432). The leukocyte count product of pre-surgery and POD2 >100 predicted PJI in the acute high-grade PJI group (OR 2.1, p = 0.025, 95%CI 1.003-1.039) and in the chronic high-grade PJI group (OR 2.0, p = 0.018, 95%CI 1.003-1.036). Similar trend was also seen in the low-grade PJI group, but was not statistically significant (OR 2.3, p = 0.061, 95%CI 0.999-1.048). CONCLUSIONS: The most optimal threshold value for predicting PJI was observed only in the acute high-grade PJI group, where PWD >three days after index surgery yielded 62.9% sensitivity and 90.6% specificity, whereby the leukocyte count product of pre-surgery and POD2 >100 showed 96.9% specificity. Glucose, erythrocytes, hemoglobin, thrombocytes, and CRP showed no significant value in this regard.

The Sinus Tract in Bone and Joint Infection: Minimally Invasive Salvation or Prolonged Suffering? A Multicenter Study.

This study assessed the quality of life (QOL) and the functional outcome in daily living in patients with a chronic, treatment-resistant periprosthetic joint infection (PJI) or osteomyelitis, living with a natural or iatrogenic sinus tract. METHODS: A follow-up examination in three national reference centers for septic bone and joint surgery was performed utilizing the Hospital Anxiety and Depression Scale (HADS-D/A), the Visual Analogue Scale (VAS), and the Short Form-36 (SF-36) score, including patients with a chronic sinus tract due to treatment-resistant PJI or osteomyelitis. RESULTS: In total, 48 patients were included, with a mean follow-up time of 43.1 ± 23.9 months. The mean SF-36 Mental Component Summary (MCS) was 50.2 (±12.3) and the Physical Component Summary (PCS) was 33.9 (±11.3). The mean HADS-D was 6.6 (±4.4) and HADS-A was 6.2 (±4.6), and the VAS was 3.4 (±2.6). The SF-36 MCS showed no significant differences between the study group and the standard population (47.0, p = 0.10), as well as the HADS-A. The PCS in the study population was significantly worse (50.0, p < 0.001), as was the HADS-D. CONCLUSIONS: A sinus tract represents a treatment option in selected cases with an acceptable QOL. The treatment should be considered for multimorbid patients with a high perioperative risk or if the bone or soft tissue quality prevents surgery.

Zirconia-Toughened Alumina Ceramic Wear Particles Do Not Elicit Inflammatory Responses in Human Macrophages.

Ten percent of patients undergoing total hip arthroplasty (THA) require revision surgery. One of the reasons for THA are wear particles released from the implants that can activate the immune defense and cause osteolysis and failure of the joint implant. The discrepancies between reports on toxicity and immunogenicity of the implant materials led us to this study in which we compared toxicity and immunogenicity of well-defined nanoparticles from Al2O3, zirconia-toughened alumina (ZTA), and cobalt chrome (CoCr), a human THP-1 macrophage cell line, human PBMCs, and therefrom-derived primary macrophages. None of the tested materials decreased the viability of THP-1 macrophages nor human primary macrophages at the 24 h time point, indicating that at concentrations from 0.05 to 50 µm3/cell the tested materials are non-toxic. Forty-eight hours of treatment of THP-1 macrophages with 5 µm3/cell of CoCr and Al2O3 caused 8.3-fold and 4.6-fold increases in TNF-α excretion, respectively, which was not observed for ZTA. The comparison between THP-1 macrophages and human primary macrophages revealed that THP-1 macrophages show higher activation of cytokine expression in the presence of CoCr and Al2O3 particles than primary macrophages. Our results indicate that ZTA is a non-toxic implant material with no immunogenic effects in vitro.

60 years of Charnley-Muller Alivium hip prosthesis: the revision percentage and tribo-corrosion sequelae after a mean of 27 years.

INTRODUCTION: The main aim was to analyse the series of 29 collected cemented Charnley-Muller Alivium retrievals with the meantime in situ of 27 years. In addition, the revision rate of 1425 Alivium prostheses implanted at our institution between 1977 and 1992 was calculated. MATERIALS AND METHODS: The revision percentage of the Alivium cohort was calculated up to 45 years of follow-up and compared to that of all total hip arthroplasties (THAs) implanted in the same period (No. 5535). Metal and polyethylene retrieved components were inspected in 29 cases for wear damage and roughness. Wear particles were retrieved from periprosthetic tissue using digestion protocols and their composition, morphology, and size distribution were investigated. Periprosthetic tissue was analysed histologically. RESULTS: The revision percentage of the Alivium cohort was 16% at 45 years of follow-up. It was comparable to all the THAs implanted at the same time (18%). The shape of polyethylene particles isolated from periprosthetic tissue corresponded to the wear pattern on polyethylene cups. Polyethylene particles were the main wear product, with the majority (68%) of particles smaller than 0.1 µm. Metal particles were rare with two types: CoCr and Cr based. Histological analysis showed that in 14 out of 18 specimens, the metal particles were graded + 1, reflecting that the metal loading in the periprosthetic tissue was low. CONCLUSIONS: Our study represents valuable data not reported previously on the survival rate of Charnley-Muller prostheses at 45 years of follow-up and a unique insight into the collected retrievals from the materials' point of view.

Electromagnetic Navigation Assisted Patient-Personalized Femoral Osteotomy for Acute Correction of Posttraumatic Residual Multiplanar Femoral Deformity with Shortening.

Improper healing of a femoral shaft fracture can result in posttraumatic residual multiplanar femoral deformity and limb shortening, which can be restored with a corrective osteotomy. Predominantly in complex posttraumatic circumstances, the use of computer assistance in orthopaedic surgery may facilitate meticulous preoperative planning, and further improve the accuracy and safety of such procedures, potentially resulting in better clinical outcomes. Herein, we present a unique case of electromagnetic navigation assisted patient-personalized femoral osteotomy for acute correction of posttraumatic residual multiplanar femoral deformity with shortening.

Effects of early home-based strength and sensory-motor training after total hip arthroplasty: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Total hip arthroplasty (THA) is very effective in alleviating pain, but functional deficits persist up to a year following surgery. Regardless of standard physiotherapy programs, significant additional muscular atrophy and weakness occur. Deficits in strength have serious adverse consequences for these patients with respect to physical function, the maintenance of independence, and the requirement for revision surgery. Progressive resistance training in rehabilitation following THA has been shown to significantly enhance muscle strength and function. The fundamental principle is to progressively overload the exercised muscle as it becomes stronger. Different strength training protocols have been used at different times in the postoperative phase, in group or individual practices, with major differences being in center-based and home-based programs with or without supervision. The primary objective of our study is to evaluate whether an early postoperative home-based strength training protocol can improve patient functional outcomes at 3 months and 1 year following surgery. Secondary objectives are the feasibility of the presented protocol for all elective THA patients and its safety. METHODS/DESIGN: This study is a prospective multicenter randomized clinical trial to be conducted in the orthopedic departments of two Slovenian hospitals. In each hospital, 124 patients aged 60 or older with unilateral osteoarthritis, an ASA score between 1 and 3, a signed informed consent form, and no terminal illness disabling rehabilitation participation will be randomly assigned to the intervention or control group. THA with an anterior approach will be performed. All patients will receive current standard physiotherapy during hospitalization. Patients in the intervention group will also learn strength and sensory-motor training exercises. Upon discharge, all will receive USB drives with exercise videos, written exercise instructions, and a training diary. Physiotherapists will perform the assessments (physical tests and the maximal voluntary isometric contraction assessment), and patients will fill out outcome assessment questionnaires (the Harris Hip Score and 36-Item Short Form Health Survey) at baseline and 1, 3, and 12 months after surgery. DISCUSSION: The main purpose of our study is to design a new standardized rehabilitation protocol with videos that will be effective, safe, and accessible to all Slovenian THA patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04061993 . Registered on 07 November 2019. Protocol ID: PRT_PhD. Version 1.

The Surgical Treatment of Osteoarthritis.

Osteoarthritis is a degenerative condition affecting the whole joint with the underlying bone, representing a major source of pain, disability, and socioeconomic cost worldwide. Age is considered the strongest risk factor, albeit abnormal biomechanics, morphology, congenital abnormality, deformity, malalignment, limb-length discrepancy, lifestyle, and injury may further increase the risk of the development and progression of osteoarthritis as well. Pain and loss of function are the main clinical features that lead to treatment. Although early manifestations of osteoarthritis are amenable to lifestyle modification, adequate pain management, and physical therapy, disease advancement frequently requires surgical treatment. The symptomatic progression of osteoarthritis with radiographical confirmation can be addressed either with arthroscopic interventions, (joint) preservation techniques, or bone fusion procedures, whereas (joint) replacement is preferentially reserved for severe and end-stage disease. The surgical treatment aims at alleviating pain and disability while restoring native biomechanics. Miscellaneous surgical techniques for addressing osteoarthritis exist. Advanced computer-integrated surgical concepts allow for patient personalization and optimization of surgical treatment. The scope of this article is to present an overview of the fundamentals of conventional surgical treatment options for osteoarthritis of the human skeleton, with emphasis on arthroscopy, preservation, arthrodesis, and replacement. Contemporary computer-assisted orthopaedic surgery concepts are further elucidated.

Acute Femoral Lengthening in Adults Using Step-Cut Osteotomy, Traction Table, and Proximal Femoral Locking Plate Fixation: Surgical Technique and Report of Three Cases.

Introduction: Leg-length discrepancy (LLD) can cause distinct gait and posture disorders that may lead to lifestyle-limiting disability and premature joint degeneration. The purpose of this study was to describe a novel surgical method for acute femoral lengthening in adults with symptomatic structural LLD using step-cut osteotomy, traction table, and proximal femoral locking plate fixation. Materials and methods: We retrospectively evaluated three consecutive adult patients that underwent the procedure at our institution between 2011 and 2019, describing the surgical technique and presenting a report of three cases, including complications assessment. Results: The average age was 47 years (range 38-58), average BMI was 28.1 kg/m2 (range 26.8-29.9), average ASA score was 2 (range 1-3). The mean pre-operative shortening (2 congenital, 1 posttraumatic) was 21 mm (range 20-23). The average elongation achieved was 18 mm (range 15-20). The average surgery duration was 142 min (range 120-165) and the average estimated blood loss was 558 mL (range 375-900). Symptoms were relieved after the lengthening in all three cases. We observed no complications after the mean 68 months (range 22-125) of follow-up. Conclusions: Successful correction of structural LLD is challenging, depends on patient selection, meticulous planning, surgical technique and experience. Therefore, it should be considered case-by-case. In the hands of an experienced surgeon, our method of acute femoral lengthening seems safe and suitable for carefully selected cases of structural LLD correction, where the final lengthening goal remains within the critical limits of one-stage leg lengthening and principles of traction table use.

Survival rate of total hip replacements with matched and with mixed components with 10.7 years mean follow-up.

BACKGROUND: Mixing and matching components from different manufacturers in total hip arthroplasty is a frequently used off-label praxis. The clinical consequences of this procedure have not been studied in detail. METHODS: 860 patients with matched and 1067 patients with mixed primary total hip replacement (THR) components carried out between 1 January 2002 and 31 December 2004, were selected from our Institution registry. The analysis endpoint was set at 1 January 2016. THRs with poorly performing components were excluded from study groups. Kaplan-Meier survival curves for both groups were calculated and compared using the Log-Rank test and the demographic data using the chi-square test. Correlations between demographic data and revisions were calculated using bivariate correlation. RESULTS: 28 revisions were carried out in the matched group and 67 in the mixed group. The 14-year overall survival probability was significantly better in the former (96.0%) than in the mixed group (92.7%) (p = 0.002). Survival, free of aseptic and septic failures, was statistically, significantly higher in the matched group (p = 0.026 and p = 0.007, respectively).The survival of the mixed subgroup with heads and stems from the same manufacturer did not differ statistically from that of the matched group (p = 0.079). CONCLUSIONS: In contrast to the results listed in the National Joint Registry and the New Zealand Joint Registry, the survival probability in our study was, statistically, significantly higher in total hip replacements using components of the same manufacturer. Importantly, mixing and matching the components of different manufacturers led to similar survival providing the head and the stem were from the same manufacturer.

The efficacy of suppressive antibiotic treatment in patients managed non-operatively for periprosthetic joint infection and a draining sinus.

Objectives: Patients with prosthetic joint infections (PJIs) not suitable for curative surgery may benefit from suppressive antibiotic therapy (SAT). However, the usefulness of SAT in cases with a draining sinus has never been investigated. Methods: A multicentre, retrospective observational cohort study was performed in which patients with a PJI and a sinus tract were eligible for inclusion if managed conservatively and if sufficient follow-up data were available (i.e. at least 2 years). SAT was defined as a period of >  6 months of oral antibiotic therapy. Results: SAT was initiated in 63 of 72 (87.5 %) included patients. Implant retention during follow-up was the same in patients receiving SAT vs. no SAT (79.4 % vs. 88.9 %; p = 0 .68). In total, 27 % of patients using SAT experienced side effects. In addition, the occurrence of prosthetic loosening in initially fixed implants, the need for surgical debridement, or the occurrence of bacteremia during follow-up could not be fully prevented with the use of SAT, which still occurred in 42 %, 6.3 %, and 3.2 % of cases, respectively. However, the sinus tract tended to close more often (42 % vs. 13 %; p = 0 .14), and a higher resolution of pain was observed (35 % vs. 14 %; p = 0 .22) in patients receiving SAT. Conclusions: SAT is not able to fully prevent complications in patients with a draining sinus. However, it may be beneficial in a subset of patients, particularly in those with pain or the hindrance of a draining sinus. A future prospective study, including a higher number of patients not receiving SAT, is needed.

Bernese peri-acetabular osteotomy performed with navigation and patient-specific templates is a reproducible and safe procedure.

PURPOSE: To present a novel surgical technique for the Bernese peri-acetabular osteotomy (PAO) using electromagnetic navigation (EMN) and patient-specific templates (PST), and to evaluate it against the traditional fluoroscopic technique. METHODS: We included 40 dysplastic hips. All PAOs were performed using PST and EMN. We recorded learning-related complications. For the purpose of acetabular fragment correction analysis, patients were divided into two groups. In the study group (EMN group, 30 hips), the acetabular fragment was reoriented with the help of EMN. In the control group (XR group, 10 hips), the acetabular fragment was reoriented using fluoroscopy. We compared the difference between the planned and achieved position of the acetabular fragment and outcomes between both groups. RESULTS: Two major complications occurred in four PAOs in the XR group only (first ten PAOs). The average absolute difference in planned and achieved lateral centre -edge angle (LCEA) and acetabular index (AI) was 1.2° ± 1.5° and 1.1° ± 2° for the EMN and 7° ± 6.1° and 6.3° ± 6.3° for the XR group (p = 0.02; p = 0.03). The average surgery duration was 183 ± 32 minutes for the EMN and 203 ± 42 minutes for the XR group (p = 0.19). At the last follow-up, the average Harris Hip Score (HHS) value was 88 ± 12 in the EMN and 86 ± 14 in the XR group (p = 0.84). CONCLUSIONS: Our study indicates that PAO performed with EMN and PST seems to be a safe and reproducible procedure with a short learning curve. Additionally, navigated reorientation of the acetabular fragment is significantly more accurate than the fluoroscopic technique.

Patient-specific template and electromagnetic navigation assisted bilateral periacetabular osteotomy for staged correction of bilateral injury-induced hip dysplasia: a case report.

Periacetabular osteotomy (PAO) for pelvic fracture sequelae presents a challenge in hip preservation surgery due to a combination of complex conditions involving post-traumatic altered anatomy and technically demanding procedure, with high surgical risk involved. To address these challenging conditions and evade potential devastating complications, a combination of patient-specific template (PST) and electromagnetic navigation (EMN) guidance can be used to increase the safety of the procedure and the accuracy of the acetabular reorientation. Herein we report our experience utilizing a combined PST- and EMN-assisted bilateral PAO for staged correction of bilateral severe, injury-induced hip dysplasia. The presented case report describes a unique method of successful surgical treatment of severe, bilateral injury-induced hip dysplasia with combined 3-D printing technology (PST) and intra-operative electromagnetic computer-assisted navigation (EMN) aided technically demanding surgical procedure (PAO), which emphasizes the benefits of PST and EMN use in hip preservation surgery in patients with complex pathoanatomic circumstances.

A novel concept of cam-type femoroacetabular impingement treatment with patient-specific template guided osteochondral deformity ablation.

PURPOSE: To present a novel surgical concept for the cam-type femoroacetabular impingement (FAI) treatment and to assess and report the clinical outcomes. METHODS: We performed a retrospective study of a single-surgeon case series of six hips in five consecutive male patients with symptomatic cam-type FAI, treated with the mini-open anterior hip approach with a patient-specific template (PST)-guided deformity ablation between 2015 and 2018. We assessed the hip range of motion, iHOT-33, Tegner, and EQ-5D before surgery and after a minimum follow-up of 30 months. RESULTS: The average age was 37 ± 13.3 years, average BMI was 31.1 ± 3.3 kg/m2, and average pre-surgery Tönnis hip osteoarthritis (OA) grade was 1 ± 1. The average surgery duration was 71 ± eight minutes. The average estimated blood loss was 83 ± 26 ml. After a mean follow-up of 50 ± 12 months, we observed no OA progression with no change in Tönnis hip OA grades. Hip flexion and internal rotation significantly improved (p = 0.007; p = 0.048) from mean 98° ± 9° and 14° ± 11° to mean 113° ± 8° and 23° ± 8°, respectively. iHOT-33, Tegner, and EQ-5D improved significantly (p = < 0.001; p = 0.004; p = < 0.001) from mean 44.7 ± 12.2, 3 ± 1, and 0.513420 ± 0.101389 to mean 94 ± 2.7, 5 ± 1, and 1.000000 ± 0, respectively. One patient needed revision surgery for heterotopic ossification removal, with no sequelae at the last follow-up. CONCLUSION: Mini-open anterior hip approach with the PST-guided cam-type FAI deformity ablation presents an accurate and reproducible solution for cam-type FAI surgical treatment, with promising clinical outcomes. Using a PST in the cam-type FAI surgery may present a powerful additional tool in the existing open techniques armamentarium.

Synovial fluid interleukin-6 is not superior to cell count and differential in the detection of periprosthetic joint infection.

AIMS: Synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells (%PMN) are elevated at periprosthetic joint infection (PJI). Leucocytes produce different interleukins (IL), including IL-6, so we hypothesized that synovial fluid IL-6 could be a more accurate predictor of PJI than synovial fluid WBC count and %PMN. The main aim of our study was to compare the predictive performance of all three diagnostic tests in the detection of PJI. METHODS: Patients undergoing total hip or knee revision surgery were included. In the perioperative assessment phase, synovial fluid WBC count, %PMN, and IL-6 concentration were measured. Patients were labeled as positive or negative according to the predefined cut-off values for IL-6 and WBC count with %PMN. Intraoperative samples for microbiological and histopathological analysis were obtained. PJI was defined as the presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in a minimum of two or more samples out of at least four taken. RESULTS: In total, 49 joints in 48 patients (mean age 68 years (SD 10; 26 females (54%), 25 knees (51%)) were included. Of these 11 joints (22%) were infected. The synovial fluid WBC count and %PMN predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 82%, 97%, 94%, 90%, and 95%, respectively. Synovial fluid IL-6 predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 73%, 95%, 90%, 80%, and 92%, respectively. A comparison of predictive performance indicated a strong agreement between tests. CONCLUSIONS: Synovial fluid IL-6 is not superior to synovial fluid WBC count and %PMN in detecting PJI.Level of Evidence: Therapeutic Level IICite this article: Bone Jt Open 2020;1-12:737-742.

Reactive Arthritis Provoked by Campylobacter jejuni Enterocolitis Mimicking Prosthetic Joint Infection: A Case Report.

CASE: A 59-year-old man with previously well-functioning partial knee replacement was admitted with a warm, swollen, and painful knee. The clinical presentation was consistent with prosthetic joint infection (PJI), but the synovial fluid analysis was negative for microbial growth. Further discussion revealed earlier Campylobacter jejuni enterocolitis that subsequently provoked reactive arthritis (ReA) mimicking PJI. The patient was treated with oral naproxen and intra-articular injection of triamcinolone and recovered completely without antibiotics or surgery. After 29 months, the knee is functioning normally. CONCLUSION: ReA is rare but should be included in the differential diagnosis of PJI.

Electromagnetic navigation system for acetabular component placement in total hip arthroplasty is more precise and accurate than the freehand technique: a randomized, controlled trial with 84 patients.

Background and purpose - The accuracy of conventional navigation systems depends on precise registration of bony landmarks. We investigated the clinical use of electromagnetic navigation (EMN), with a unique device for precise determination of the anterior pelvic plane. Patients and methods - We randomly allocated patients scheduled for total hip arthroplasty into 2 groups of 42 patients each. In the study group, cups were placed at the predetermined target angles (inclination: 42.5°; anteversion: 15°) with the support of EMN. In the control group, cups were placed freehand aiming at the same target angles. Postoperatively the true position of the cup was determined using computed tomography scan of the pelvis. Precision (root mean squared error, RMSE) bias (mean bias error, ME), accuracy, and duration of surgery were compared between the methods. Results - Cup anteversion was more accurate and precise in the navigated group. The ME in the navigated and freehand group was -1.7° (95% CI -2.4 to 1.1) and -4.5° (CI -6.5 to 2.5), respectively. The RMSE in the navigated and freehand group was 2.8° (CI 2.3-3.2) and 8.0° (CI 6.3-9.5), respectively. The inclination was also more precise in the navigated group, with the RMSE in the navigated and freehand group at 4.6° (CI 3.4-5.9) and 6.5° (CI 5.4-7.5), respectively. The accuracy of the inclination and the duration of surgeries were similar between the groups. Interpretation - Cup placement with the help of EMN is more precise than the freehand technique and it does not affect the duration of surgery.

Comprehensive analysis of skeletal muscle- and bone-derived mesenchymal stem/stromal cells in patients with osteoarthritis and femoral neck fracture.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) can replenish the aged cells of the musculoskeletal system in adult life. Stem cell exhaustion and decrease in their regenerative potential have been suggested to be hallmarks of aging. Here, we investigated whether muscle- and bone-derived MSCs of patients with osteoarthritis and osteoporosis are affected by this exhaustion, compared to healthy donors. METHODS: Patients with primary osteoarthritis, femoral neck fractures due to osteoporosis, and healthy donors (controls) were included. MSCs were isolated from the skeletal muscle and subchondral bone from each patient and compared using ex vivo and in vitro analyses, including immunophenotyping, colony-forming unit fibroblast assays, growth kinetics, cell senescence, multilineage potential, and MSC marker gene expression profiling. RESULTS: Freshly isolated cells from muscle from patients with osteoarthritis showed a lower proportion of CD45/CD19/CD14/CD34-negative cells compared to patients with osteoporosis and healthy donors. Freshly isolated muscle cells from patients with osteoarthritis and osteoporosis also showed higher clonogenicity compared to healthy donors. MSCs from both tissues of osteoarthritis patients showed significantly reduced osteogenesis and MSCs from the bone also reduced adipogenesis. Chondrogenic pellet diameter was reduced in bone-derived MSCs from both patient groups compared to healthy donors. A significant positive correlation was observed between adipogenesis and CD271 expression in muscle-derived MSCs. CD73 was significantly lower in bone-derived MSCs from osteoarthritis patients, compared to osteoporosis patients. Gene expression profiling showed significantly lower expression of MSC marker gene leptin receptor, LEPR, previously identified as the major source of the bone and adipocytes in the adult bone marrow, in bone-derived MSCs from patients with osteoarthritis in comparison with osteoporotic patients and healthy donors. CONCLUSIONS: Our results show deficient ex vivo and in vitro properties of both skeletal muscle- and bone-derived MSCs in osteoarthritis and osteoporosis patients, compared to healthy donors. In bone-derived MSCs from patients with osteoarthritis, we also identified a lower expression of the leptin receptor, a marker of MSCs that present a major source of MSCs in the adult bone marrow. This suggests that exhaustion of skeletal muscle- and bone-derived MSCs is a hallmark of osteoarthritis and osteoporosis, which defines the need for further clinical trials of stem cell transplantation in these patients.

Increased Exhaustion of the Subchondral Bone-Derived Mesenchymal Stem/ Stromal Cells in Primary Versus Dysplastic Osteoarthritis.

Mesenchymal stem/ stromal cell (MSC) exhaustion has been suggested to be a hallmark of aging. Osteoarthritis has a complex etiology that comprises several factors. Dysplasia has been shown to be an individual risk factor for osteoarthritis. Subchondral bone changes are often the first detectable alterations in osteoarthritis. In this study, we aimed to determine whether skeletal MSCs are differentially affected in patients with primary versus dysplastic osteoarthritis. Patients undergoing hip arthroplasty due to primary osteoarthritis (n = 11) and osteoarthritis with hip dysplasia (n = 10) were included in the study. Femoral head subchondral bone was used for isolation of MSCs. The cells were compared using detailed ex-vivo and in-vitro analyses, which included immunophenotyping, colony-forming-unit fibroblast assay, growth kinetics, senescence, multilineage potential, immunophenotyping, and MSC marker-gene expression profiling. Isolated cells from primary osteoarthritis patients showed decreased viability in comparison with those from dysplasia patients, with similar mesenchymal fractions (i.e., CD45/ CD19/ CD14/ CD34-negative cells). In-vitro expanded MSCs from primary osteoarthritis patients showed reduced osteogenic and chondrogenic potential in comparison with dysplasia patients. There were no differences in clonogenicity, growth kinetics, senescence, adipogenic potential, and immunophenotype between these groups. Gene expression profiling showed well-known marker of bone marrow MSCs, the leptin receptor, to be significantly lower for primary osteoarthritis patients. Our study shows that the pathology of primary osteoarthritis is accompanied by bone MSC exhaustion, while biomechanical dysfunction associated with hip dysplasia can induce secondary osteoarthritis without this MSC impairment. Our study suggests that subchondral bone MSC exhaustion is implicated in the pathology of primary osteoarthritis.

Lower Success Rate of Débridement and Implant Retention in Late Acute versus Early Acute Periprosthetic Joint Infection Caused by Staphylococcus spp. Results from a Matched Cohort Study.

BACKGROUND: Surgical débridement, antibiotics and implant retention (DAIR) is currently recommended by international guidelines for both early acute (postsurgical) and late acute (hematogenous) periprosthetic joint infections (PJIs). However, due to a different pathogenesis of infection, a different treatment strategy may be needed. QUESTIONS/PURPOSES: (1) Compared with early acute PJIs, are late acute PJIs associated with a higher risk of DAIR failure? (2) When stratified by microorganism, is the higher risk of failure in late acute PJI associated with Staphylocococcus aureus infection? (3) When analyzing patients with S. aureus infection, what factors are independently associated with DAIR failure? METHODS: In this multicenter observational study, early acute and late acute PJIs treated with DAIR were retrospectively evaluated and matched according to treating center, year of diagnosis, and infection-causing microorganism. If multiple matches were available, the early acute PJI diagnosed closest to the late acute PJI was selected. A total of 132 pairs were included. Treatment success was defined as a retained implant during follow-up without the need for antibiotic suppressive therapy. RESULTS: Late acute PJIs had a lower treatment success (46% [60 of 132]) compared with early acute PJIs (76% [100 of 132]), OR 3.9 [95% CI 2.3 to 6.6]; p < 0.001), but the lower treatment success of late acute PJIs was only observed when caused by Staphylococcus spp (S. aureus: 34% versus 75%; p < 0.001; coagulase-negative staphylococci: 46% versus 88%; p = 0.013, respectively). On multivariable analysis, late acute PJI was the only independent factor associated with an unsuccessful DAIR when caused by S. aureus (OR 4.52 [95% CI 1.79 to 11.41]; p < 0.001). CONCLUSIONS: Although DAIR seems to be a successful therapeutic strategy in the management of early acute PJI, its use in late acute PJI should be reconsidered when caused by Staphylococcus spp. Our results advocate the importance of isolating the causative microorganism before surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.