Influence of surgical quality (according to postoperative radiography) on mortality, complications and recovery of walking ability in 1425 hip fracture patients.

PURPOSE: To evaluate the influence of surgical quality (as evaluated in the post-surgical radiographic control) on mortality, complications and recovery of walking ability in patients older than 64 years with hip fracture. PATIENTS AND METHODS: Retrospective observational study of a single-center, consecutive cohort of 1425 patients operated from December/2012 to March/2018. Average age was 85.66±7.13 (65-108) years and 966 (67.86%) were female. Extracapsular fractures (811 cases, 56.91%) were fixed with trochanteric nails (Affixus-DePuy / PFNA-Synthes) (795 cases) or sliding-hip-screw-plates (Biomet) (16 patients). Intracapsular fractures (614, 43.09%) were treated with cannulated screws (Smith-Nephew) (134 cases) or with arthroplasty (472 bipolar and 8 total hip, Furlong-JRI or Exeter-Stryker). Postoperative radiographs were used to determine surgical quality (reduction, compression, screw position, tip-apex, stem position, Voss, intraoperative fracture). Patients were followed clinically and radiographically in outpatient clinic after 1, 3, 6, and 12 months. STATISTICAL ANALYSIS: Bivariate analysis (Pearson, Fischer, Mann-Whitney, Wilcoxon) was applied to study statistically significant relations, and Relative Risks (RR) were calculated. RESULTS: 196 patients (13.75%) died along follow-up, and poor reduction was found to be a risk factor for mortality both in trochanteric nail group (p=0.0495) (RR 1.510, 1.01-2.26) and in cannulated screw group (p=0.0023) (RR 6.48, 2.40-17.53); this is a previously non-published risk factor. Surgical complications included 33 infections (2.36%), 12 non-unions (1.27%), 12 cut-outs (1.47%), 7 broken nails (0.86%), 21 hemiarthroplasty dislocations (4.37%), and 8 ischemic necrosis of the femoral head (5.97%). The significant risk factors were: poor reduction for trochanteric nail breakage (p=0.041) (RR 4.47, 1.13-17.67), poor reduction for non-union in cannulated screws (p=0.035) (RR 10.91, 1.70-70.09), as well as "tip-apex distance" over 25mm in trochanteric fractures for "cut-out" type of fixation failure (p=0.0159) (RR 3.84, 1.19-12.40). Previous walking ability was restored in 564 patients (39.58%) and worsened in 581 (40.77%), but statistical relationships were not found, although follow-up data were inadequate in 212 cases (14.88%). CONCLUSIONS: Appropriate reduction of hip fractures is a significant step to reduce mortality, nail breakage and non-union. Adequate position of sliding screw (avoiding tip-apex distances over 25mm) is important to reduce "cut-out" in trochanteric fractures.

Diagnostic Accuracy of Magnetic Resonance Images and Weight-Bearing Radiographs in Patients With Arthroscopic-Proven Medial Osteoarthritis of the Knee.

AIMS: The aim of this study is to analyze the diagnostic value of weight-bearing radiographs, magnetic resonance images (MRI), and the combination of both in osteoarthritic knees when using arthroscopic findings as the "gold standard" to compare with. METHODS: A total of 59 patients were studied because of chronic pain in 1 of their knees. Radiographs were classified according to Kellgren-Lawrence scale. Magnetic resonance images were classified according to Vallotton, and arthroscopic findings according to Outerbridge criteria. RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were, respectively, 75.0%, 60.0%, 56.2%, 77.8%, and 66.1% for weight-bearing radiographs, and 70.8%, 88.6%, 81.0%, 81.6%, and 81.4% for MRI. Logistic regression analysis showed that a weight-bearing radiograph added to MRI offered no additional diagnostic value compared with MRI alone (P < .001). CONCLUSIONS: Magnetic resonance images presented higher specificity, positive and negative predictive values, and accuracy than weight-bearing radiographs for knee osteoarthritis. The combination of radiographs and MRI did not improve the diagnostic accuracy, compared with MRI alone.

Early efficacy evaluation of mesenchymal stromal cells (MSC) combined to biomaterials to treat long bone non-unions.

BACKGROUND AND STUDY AIM: Advanced therapy medicinal products (ATMP) frequently lack of clinical data on efficacy to substantiate a future clinical use. This study aims to evaluate the efficacy to heal long bone delayed unions and non-unions, as secondary objective of the EudraCT 2011-005441-13 clinical trial, through clinical and radiological bone consolidation at 3, 6 and 12 months of follow-up, with subgroup analysis of affected bone, gender, tobacco use, and time since the original fracture. PATIENTS AND METHODS: Twenty-eight patients were recruited and surgically treated with autologous bone marrow derived mesenchymal stromal cells expanded under Good Manufacturing Practices, combined to bioceramics in the surgical room before implantation. Mean age was 39 ± 13 years, 57% were males, and mean Body Mass Index 27 ± 7. Thirteen (46%) were active smokers. There were 11 femoral, 4 humeral, and 13 tibial non-unions. Initial fracture occurred at a mean ± SD of 27.9 ± 31.2 months before recruitment. Efficacy results were expressed by clinical consolidation (no or mild pain if values under 30 in VAS scale), and by radiological consolidation with a REBORNE score over 11/16 points (value of or above 0.6875). Means were statistically compared and mixed models for repeated measurements estimated the mean and confidence intervals (95%) of the REBORNE Bone Healing scale. Clinical and radiological consolidation were analyzed in the subgroups with Spearman correlation tests (adjusted by Bonferroni). RESULTS: Clinical consolidation was earlier confirmed, while radiological consolidation at 3 months was 25.0% (7/28 cases), at 6 months 67.8% (19/28 cases), and at 12 months, 92.8% (26/28 cases including the drop-out extrapolation of two failures). Bone biopsies confirmed bone formation surrounding the bioceramic granules. All locations showed similar consolidation, although this was delayed in tibial non-unions. No significant gender difference was found in 12-month consolidation (95% confidence). Higher consolidation scale values were seen in non-smoking patients at 6 (p = 0.012, t-test) and 12 months (p = 0.011, t-test). Longer time elapsed after the initial fracture did not preclude the occurrence of consolidation. CONCLUSION: Bone consolidation was efficaciously obtained with the studied expanded hBM-MSCs combined to biomaterials, by clinical and radiological evaluation, and confirmed by bone biopsies, with lower consolidation scores in smokers.

Editorial. The Challenges of Orthopaedic Trauma in Spain.

Spain is considered the healthiest nation in the world, due to lifepromoting aspects such as good diet, care facilities and a favourable family environment. However, although increased life expectancy is an indicator of development, it may have a negative impact on the other two variables of health service efficiency, namely health expenditure per capita and its relative weight in Gross Domestic Product.

Validation of a long bone fracture non-union healing score after treatment with mesenchymal stromal cells combined to biomaterials.

The available scores to clinically evaluate fracture consolidation encounter difficulties to interpret progression towards consolidation in long-bone non-union, particularly when incorporating biomaterials in the surgical treatment. The aims of this study were to validate the REBORNE bone healing scale in tibia, humerus and femur non-unions treated by a combination of mesenchymal stromal cells (MSCs) and biomaterials, through the interclass correlation (ICC) among raters, and to define reliability and concordance in anteroposterior and lateral radiographs, compared to computed tomography (CT). METHODS: Twenty-six cases from the EudraCT 2011-005441-13 clinical trial underwent bone healing evaluation, if at least 3 out of 4 cortical views clearly identified. Three senior orthopaedic surgeons evaluated radiographs and CTs at 3 and 6 months FU. All cases included preoperative imaging and radiographs at 12 months. The 4-stage scale score was obtained from each cortical view in orthogonal radiographs or CTs. A score of 0.6875 (11/16) was set as a threshold for bone healing. Statistically, ICC evaluated agreement among raters. Cronbach's alpha coefficient tested reliability. Lin's concordance correlation coefficients (CCC) were estimated between mean CT scores and mean radiographic scores. Bland and Altman graphs provided the limits of agreement between both imaging techniques. Sensitivity and specificity were assessed in radiographs (against CT), and the Area Under the Receiver Operating Characteristics (ROC) Curve was estimated. The probability to predict bone consolidation with REBORNE scores obtained from radiographs was modelled. RESULTS: An ICC of 0.88 and 0.91 (CT and radiographs) confirmed agreement in the REBORNE score for non-union bone healing, with an inter-rater reliability of 0.92 and 0.95. Scores through the radiographic evaluation were found equivalent to the CTs at 6 months FU. A CCC of 0.79 was detected against CT. The radiographic scores in the REBORNE bone healing scale correctly classified bone consolidation in 77%, with an accuracy of 83% based on ROC curves. CONCLUSIONS: The REBORNE score measured with CT or radiographic images was reliable among raters at a follow-up time above 6 months for long bone non-union fractures. The REBORNE scale measured with radiographs proved valid to assess consolidation against CT measurements.

Staphylococcus aureus Prosthetic Joint Infection Is Prevented by a Fluorine- and Phosphorus-Doped Nanostructured Ti-6Al-4V Alloy Loaded With Gentamicin and Vancomycin.

Prosthetic joint infection (PJI) is one of the most devastating complications in orthopedic surgery. One approach used to prevent PJI is local antibiotic therapy. This study evaluates the antibiotic release, in vitro cytocompatibility and in vivo effectiveness in preventing PJI caused by Staphylococcus aureus (S. aureus) of the fluorine- and phosphorus-doped, bottle-shaped, nanostructured (bNT) Ti-6Al-4V alloy loaded with a mixture of gentamicin and vancomycin (GV). We evaluated bNT Ti-6Al-4V loading with a mixture of GV, measuring the release of these antibiotics using high-performance liquid chromatography. Further, we describe bNT Ti-6Al-4V GV cytocompatibility and its efficacy against S. aureus using an in vivo rabbit model. GV was released from bNT Ti-6Al-4V following a Boltzmann non-linear model and maximum release values were obtained at 240 min for both antibiotics. The cell proliferation of MCT3T3-E1 osteoblastic cells significantly increased at 48 (28%) and 168 h (68%), as did the matrix mineralization (52%) of these cells and the gene expression of three of the most important markers related to bone differentiation (more than threefold for VEGF and BGLAP, and 65% for RunX) on bNT Ti-6Al-4V GV compared with control. In vivo study results show that bNT Ti-6Al-4V GV can prevent S. aureus PJI according to histopathological and microbiological results. According to our results, bNT Ti-6Al-4V loaded with a mixture of GV using the soaking method is a promising biomaterial with favorable cytocompatibility and osteointegration, demonstrating local bactericidal properties against S. aureus. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:588-597, 2020.

Urine Aluminum Concentration as a Possible Implant Biomarker of Pseudomonas aeruginosa Infection Using a Fluorine- and Phosphorus-Doped Ti-6Al-4V Alloy with Osseointegration Capacity.

Joint prosthesis failure is mainly related to aseptic loosening and prosthetic joint infections, both associated with high morbidity and a substantial cost burden for patients and health systems. The development of a biomaterial capable of stimulating bone growth while minimizing bacterial adhesion would reduce the incidence of prosthetic failure. Using an in vivo rabbit model, this study evaluates the osseointegration effect of the fluorine (F)- and phosphorus (P)-doped bottle-shaped nanostructured (bNT) Ti-6Al-4V alloy and effectiveness of monitoring urine aluminum concentration to determine the presence of Pseudomonas aeruginosa infection in Ti-6Al-4V implants. Unlike chemically polished (CP) Ti-6Al-4V alloy implants, bNT Ti-6Al-4V alloy implants promoted osseointegration and showed effectiveness as a biomaterial marker. The bNT Ti-6Al-4V alloy implants were associated with a twofold increase in bone thickness and up to 15% greater bone density compared to the CP alloy. Additionally, bNT Ti-6Al-4V alloy implants allowed for discrimination between P. aeruginosa-infected and noninfected animals for 15 days postoperatively, as indicated by the decrease of aluminum concentration in urine, while this difference was only appreciable over the first 7 days when CP Ti-6Al-4V alloy implants were used. Therefore, bNT Ti-6Al-4V alloys could have clinical applications by detecting the infection and by avoiding aseptic loosening.

Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial.

BACKGROUND: ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. METHODS: Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. FINDINGS: With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). INTERPRETATION: Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. FUNDING: EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).

Proximal Femoral Bone Regeneration After an Uncemented Hydroxyapatite-coated Long-stem in Revision Hip Surgery.

BACKGROUND: Bone remodelling with lateral femoral cortex thinning is a major concern after extensively porous-coated long-stem in revision surgery. Extensive hydroxyapatite coated long-stems were introduced to improve osseointegration, but bone remodelling changes have not been quantified. OBJECTIVE: The question of whether bone remodelling changes from extensive hydroxyapatite-coated long stems influence the durability of femoral revision, clinical outcome is assessed in follow-up radiographs. METHODS: Uncemented straight monoblock hydroxyapatite-coated long-stems used in revision hip surgery for aseptic loosening were assessed in a consecutive series of 64 hips (60 patients). Mean follow-up was 8.6 years and the mean age at surgery was 70 years (27-91). The pre-operative bone defect was classified according to Paprosky. Cortical struts were not used in this series. Cortical index and femoral cortical width were measured at three different levels at different periods. RESULTS: Four patients with pain under level 4 due to stem loosening needed an exchange surgery of their femoral component, but two patients rejected re-surgery. The cumulative probability of not having aseptic loosening was 91.2% (95% confidence interval 73.5-96.9) at 10 years according to Kaplan and Meier. Twenty-seven of 35 osteolytic lesions had disappeared or decreased at the last follow-up. The thickness of the lateral and medial cortex increased over the course of the study at different levels. Increases of femoral cortex thickness were greater in men and in cases with mild bone defects. CONCLUSION: Although clinical outcome of the hydroxyapatite-coated long stem in revision surgery is good but not outstanding, most osteolytic lesions heal and the femoral cortex thickness increases at different levels.

One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies.

One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6-20.7) and 32.3 (95% CI 27.3-38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58-5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip.

A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol.

ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

Ruminococcus gnavus infection of a metal-on-metal hip arthroplasty resembling a pseudo-tumour in a 72 year-old woman with no intestinal symptoms / Infección por Ruminococcus gnavus de prótesis de cadera metal-metal asemejando un pseudotumor, en una mujer de 72 años sin síntomas intestinales

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Effect of different agents with potential antibiofilm activity on antimicrobial susceptibility of biofilms formed by Staphylococcus spp. isolated from implant-related infections.

An in vitro study aimed to evaluate the effect of N-acetyl cysteine (NAC) or sub-ICs of erythromycin on antimicrobial susceptibility of staphylococcal biofilms was performed. Staphylococcus aureus and Staphylococcus epidermidis strains were isolated from patients with prosthetic joint infections using a previously published sonication procedure. Conventional susceptibility studies were performed using microdilution according to the CLSI procedures. Biofilm susceptibility was performed using the Calgary methodology. The addition of NAC showed no effect with the S. aureus strains, and a strain-dependent effect with the S. epidermidis strains. No effect was detected with erythromycin for almost all tested strains.

Prevalence of asymptomatic bacteriuria in knee arthroplasty patients and subsequent risk of prosthesis infection.

INTRODUCTION: The risk of knee arthroplasty infection and appropriateness of antibiotic treatment are not clearly established in patients with preoperative asymptomatic bacteriuria. It has been the purpose to analyze the prevalence of preoperative asymptomatic bacteriuria in knee arthroplasty patients, as well as the incidence of prosthetic joint infection in those with asymptomatic bacteriuria treated and not with specific antibiotics. PATIENTS AND METHODS: This prospective study included 215 consecutive knee arthroplasty patients (73 ± 6 years, 168 females) with neither urinary symptoms nor perioperative urethral catheterization. A "clean-catch" urinalysis was obtained from all patients before surgery and an urine culture if urinalysis was abnormal. Asymptomatic bacteriuria was diagnosed if >100,000 colony-forming units/ml were cultured. Patients were treated (Group A) or not (Group B) with additional specific antibiotics for urine bacteria according to surgeon criteria. Minimum follow-up reached 48 months. No patient was lost to follow-up. RESULTS: Asymptomatic bacteriuria was diagnosed in 11/215 patients (5.1 %) (11/11 females), and four of these 11 were treated with specific antibiotics (Group A). Only one patient in Group A suffered a prosthesis infection along the first 3 months (1/125, 0.5 %), but bacteria cultured from the wound were absolutely different to those in urine culture. No patient in Group B suffered a prosthesis infection. CONCLUSIONS: Asymptomatic bacteriuria presents a low prevalence. We have not found any case of arthroplasty infection from urinary focus in patients with asymptomatic bacteriuria whether they received or not specific antibiotics.