Are IDH1 R132 Mutations Associated With Poor Prognosis in Patients With Chondrosarcoma of the Bone?

BACKGROUND: Because chondrosarcomas vary widely in their behavior, and because anticipating their behavior based on histology alone can be challenging, genetic markers represent an appealing area of inquiry that may help us refine our prognostic approaches. Isocitrate dehydrogenase (IDH) mutations are involved in the pathogenesis of a variety of neoplasms, and recently, IDH1/2 mutations have been found in the tissue of benign cartilage tumors as well as in conventional chondrosarcomas and highly aggressive dedifferentiated chondrosarcomas. However, their association with patient survival is still controversial. QUESTIONS/PURPOSES: (1) What proportion of patients with chondrosarcomas carry IDH mutations, and which IDH mutations can be found? (2) Are any specific IDH mutations associated with poorer overall survival, metastasis-free survival, or local recurrence-free survival? METHODS: Between April 2017 and December 2022, we treated 74 patients for atypical cartilaginous tumors or chondrosarcomas in a musculoskeletal tumor referral center. Patients were considered potentially eligible for the present study if the histologic diagnosis was confirmed by two expert soft tissue and bone pathologists following the current WHO classification, complete preoperative imaging and follow-up data were available, surgical excision was performed by sarcoma orthopaedic surgeons directed by a team leader, and the minimum follow-up was 2 years after surgical treatment unless the patient died. Data including sex, age, diagnosis, grade, type of operation, local recurrence, metastasis, and oncologic follow-up were recorded. Forty-one patients (55%) were eligible for the study. For each patient, DNA was extracted and quantified from paraffin-embedded sections of tumor tissue, and the mutational status of IDH1 (codons 105 and 132) and IDH2 (codons 140 and 172) genes was assessed. Of those, 56% (23 of 41) of patients had adequate DNA for analysis of IDH mutations: 10 male and 13 female patients, with a median age of 59 years (range 15 to 98 years). There were 22 conventional chondrosarcomas (8 atypical cartilaginous tumors, 11 Grade 2, and 3 Grade 3) and 1 dedifferentiated chondrosarcoma. Stage was IA in 3 patients, IB in 5, IIA in 1, IIB in 13, and III in 1, according to the Musculoskeletal Tumor Society classification. At a median follow-up of 3.5 years (range 4 months to 5.6 years), 14 patients were disease-free, 2 were alive with disease, and 7 died (3 within 2 years from surgery). Eight patients had metastases, and 7 developed local recurrence. We determined the proportion of patients who carried IDH mutations, and compared patients with and without those mutations in terms of overall survival, metastasis-free survival, and local recurrence-free survival using Kaplan-Meier curves. RESULTS: Six patients showed wild-type IDH genes, and 17 had IDH mutations (12 had IDH1 R132, 3 had IDH1 G105, and 2 had IDH2 R172). Overall survival at 2 years using the Kaplan-Meier estimator was lower in patients with an IDH mutation than in those with the wild-type gene (75% [95% confidence interval 50% to 99%] versus 100% [95% CI 100% to 100%]; p = 0.002). Two-year metastasis-free survival was also lower in patients with an IDH mutation than in those with the wild-type gene (33% [95% CI 7% to 60%] versus 100% [95% CI 100% to 100%]; p = 0.001), as was 2-year local recurrence-free survival (70% [95% CI 42% to 98%] versus 100% [95% CI 100% to 100%]; p = 0.02). CONCLUSION: We found that IDH1 R132 mutations were negatively associated with the prognosis of patients with bone chondrosarcomas. Nevertheless, more extensive studies (such as multicenter international studies) are needed and advisable to confirm our observations in this preliminary small series. Moreover, evaluating mutational status in fresh samples instead of in paraffin-embedded sections could help to increase the number of patients with adequate DNA for analysis. If our findings will be confirmed, the evaluation of IDH mutational status in biopsy samples or resection specimens could be considered when stratifying patients, highlighting those who may benefit from more aggressive treatment (such as adjuvant chemotherapy) or closer follow-up. LEVEL OF EVIDENCE: Level III, prognostic study.

Biomechanics of Chondrocytes and Chondrons in Healthy Conditions and Osteoarthritis: A Review of the Mechanical Characterisations at the Microscale.

Biomechanical studies are expanding across a variety of fields, from biomedicine to biomedical engineering. From the molecular to the system level, mechanical stimuli are crucial regulators of the development of organs and tissues, their growth and related processes such as remodelling, regeneration or disease. When dealing with cell mechanics, various experimental techniques have been developed to analyse the passive response of cells; however, cell variability and the extraction process, complex experimental procedures and different models and assumptions may affect the resulting mechanical properties. For these purposes, this review was aimed at collecting the available literature focused on experimental chondrocyte and chondron biomechanics with direct connection to their biochemical functions and activities, in order to point out important information regarding the planning of an experimental test or a comparison with the available results. In particular, this review highlighted (i) the most common experimental techniques used, (ii) the results and models adopted by different authors, (iii) a critical perspective on features that could affect the results and finally (iv) the quantification of structural and mechanical changes due to a degenerative pathology such as osteoarthritis.

An Institutional Standardised Protocol for the Treatment of Acute Displaced Midshaft Clavicle Fractures (ADMCFs): Conservative or Surgical Management for Active Patients?

BACKGROUND AND OBJECTIVES: The treatment of acute displaced midshaft clavicle fractures (ADMCFs) is still under debate. The aim of this study was to verify the effectiveness of our institutional protocol by comparing the clinical and radiographic outcomes of two groups of patients with ADMCFs treated operatively and non-operatively. MATERIALS AND METHODS: active patients with a traumatic, isolated non-pathological ADMCF with at least 1-year clinical and radiographic follow up were included. Surgical treatment was performed in the cases where the residual displacement was higher than 140% after the application of a figure-of-eight bandage (F8-B). All other cases were treated conservatively with a F8-B. A total of 134 patients were enrolled and divided into two groups: surgical and conservative groups, with 59 and 75 patients, respectively. Radiological and clinical parameters were evaluated. RESULTS: Good clinical (Constant-Murley Score, the Quick Disability of the Arm, Shoulder and Hand score, and VAS satisfaction) and radiographic outcomes (initial and residual shortening, initial and residual displacement) were obtained for ADMCFs in both groups. Multivariate analysis showed that patients treated conservatively had better clinical outcomes compared to surgically treated patients (p < 0.001). Return to sports was longer in those treated with surgery. Initial shortening was found to impact clinical outcomes as well as initial displacement. None of the patients showed signs of non-union in both groups. CONCLUSIONS: Very good mid-term clinical results can be obtained in adult patients with ADMCFs, conservatively or operatively managed, by applying our institutional treatment protocol based on objective radiographic parameters evaluated in the ER.

Defective excitation-contraction coupling and mitochondrial respiration precede mitochondrial Ca2+ accumulation in spinobulbar muscular atrophy skeletal muscle.

Polyglutamine expansion in the androgen receptor (AR) causes spinobulbar muscular atrophy (SBMA). Skeletal muscle is a primary site of toxicity; however, the current understanding of the early pathological processes that occur and how they unfold during disease progression remains limited. Using transgenic and knock-in mice and patient-derived muscle biopsies, we show that SBMA mice in the presymptomatic stage develop a respiratory defect matching defective expression of genes involved in excitation-contraction coupling (ECC), altered contraction dynamics, and increased fatigue. These processes are followed by stimulus-dependent accumulation of calcium into mitochondria and structural disorganization of the muscle triads. Deregulation of expression of ECC genes is concomitant with sexual maturity and androgen raise in the serum. Consistent with the androgen-dependent nature of these alterations, surgical castration and AR silencing alleviate the early and late pathological processes. These observations show that ECC deregulation and defective mitochondrial respiration are early but reversible events followed by altered muscle force, calcium dyshomeostasis, and dismantling of triad structure.

Musculoskeletal Diseases: From Molecular Basis to Therapy.

Musculoskeletal diseases (MSDs) comprise a plethora of different disorders (more than 150 conditions) affecting the locomotor system [...].

Mechanical Behaviour of Plantar Adipose Tissue: From Experimental Tests to Constitutive Analysis.

Plantar adipose tissue is a connective tissue whose structural configuration changes according to the foot region (rare or forefoot) and is related to its mechanical role, providing a damping system able to adsorb foot impact and bear the body weight. Considering this, the present work aims at fully describing the plantar adipose tissue's behaviour and developing a proper constitutive formulation. Unconfined compression tests and indentation tests have been performed on samples harvested from human donors and cadavers. Experimental results provided the initial/final elastic modulus for each specimen and assessed the non-linear and time-dependent behaviour of the tissue. The different foot regions were investigated, and the main differences were observed when comparing the elastic moduli, especially the final elastic ones. It resulted in a higher level for the medial region (89 ± 77 MPa) compared to the others (from 51 ± 29 MPa for the heel pad to 11 ± 7 for the metatarsal). Finally, results have been used to define a visco-hyperelastic constitutive model, whose hyperelastic component, which describes tissue non-linear behaviour, was described using an Ogden formulation. The identified and validated tissue constitutive parameters could serve, in the early future, for the computational model of the healthy foot.

Macroscopic Synovial Inflammation Correlates with Symptoms and Cartilage Lesions in Patients Undergoing Arthroscopic Partial Meniscectomy: A Clinical Study.

BACKGROUND: The aim of the study was to examine the relationship among patients' characteristics, intraoperative pathology and pre/post-operative symptoms in a cohort of patients undergoing arthroscopic partial meniscectomy for symptomatic meniscal tears. METHODS: Clinical data were collected (age, sex, body mass index, time to surgery, trauma). Intraoperative cartilage pathology was assessed with Outerbridge score. Meniscal tears were graded with the ISAKOS classification. Synovial inflammation was scored using the Macro-score. Patient symptoms were assessed pre/post-operatively using the KOOS instrument. RESULTS: In the series of 109 patients (median age 47 years), 50% of the meniscal tears were traumatic; 85% of patients showed mild to moderate synovitis; 52 (47.7%) patients had multiple cartilage defects and 31 (28.4%) exhibited a single focal chondral lesion. Outerbridge scores significantly correlated with patient age, BMI and synovial inflammation. There was a correlation between severity of chondral pathology and high-grade synovial hyperplasia. Pre-operative KOOS correlated with BMI, meniscal degenerative changes and symptom duration. Obesity, time to surgery, presence of high-grade synovial hyperplasia and high-grade cartilage lesions were independent predictors of worse post-operative pain and function. CONCLUSION: We demonstrated that pre-operative symptoms and post-operative outcomes correlate with synovitis severity and cartilage pathology, particularly in old and obese patients that underwent arthroscopic partial meniscectomy. Importantly, patients with a degenerative meniscal pattern and with longer time to surgery experienced more severe cartilage damage and, consequentially, pain and dysfunction. These findings are fundamental to identify patients suitable for earlier interventions.

Exploring Anatomo-Morphometric Characteristics of Infrapatellar, Suprapatellar Fat Pad, and Knee Ligaments in Osteoarthritis Compared to Post-Traumatic Lesions.

Several studies have investigated cartilage degeneration and inflammatory subchondral bone and synovial membrane changes using magnetic resonance (MR) in osteoarthritis (OA) patients. Conversely, there is a paucity of data exploring the role of knee ligaments, infrapatellar fat pad (IFP), and suprapatellar fat pad (SFP) in knee OA compared to post-traumatic cohorts of patients. Therefore, the aim of this study was to analyze the volumetric and morphometric characteristics of the following joint tissues: IFP (volume, surface, depth, femoral and tibial arch lengths), SFP (volume, surface, oblique, antero−posterior, and cranio−caudal lengths), anterior (ACL) and posterior cruciate ligament (PCL) (volume, surface, and length), and patellar ligament (PL) (volume, surface, arc, depth, and length). Eighty-nine MR images were collected in the following three groups: (a) 32 patients with meniscal tears, (b) 29 patients with ACL rupture (ACLR), and (c) 28 patients affected by end-stage OA. Volume, surface, and length of both ACL and PCL were determined in groups a and c. A statistical decrease of IFP volume, surface, depth, femoral and tibial arch lengths was found in end-stage OA compared to patients with meniscal tear (p = 0.002, p = 0.008, p < 0.0001, p = 0.028 and p < 0.001, respectively) and patients with ACLR (p < 0.0001, p < 0.0001, p = 0.008 and p = 0.011, respectively). An increment of volume and surface SFP was observed in group b compared to both groups a and c, while no differences were found in oblique, antero−posterior, and cranio−caudal lengths of SFP among the groups. No statistical differences were highlighted comparing volume, surface, arc, and length of PL between the groups, while PL depth was observed to be decreased in end-OA patients compared with meniscal tear patients (p = 0.023). No statistical differences were observed comparing ACL and PCL lengths between patients undergoing meniscectomy and TKR. Our study confirms that IFP MR morphometric characteristics are different between controls and OA, supporting an important role of IFP in OA pathology and progression in accordance with previously published studies. In addition, PL depth changes seem to be associated with OA pathology. Multivariate analysis confirmed that OA patients had a smaller IFP compared to patients with meniscal tears, confirming its involvement in OA.

Management of Displaced Midshaft Clavicle Fractures with Figure-of-Eight Bandage: The Impact of Residual Shortening on Shoulder Function.

The treatment of displaced midshaft clavicle fractures (MCFs) is still controversial. The aims of our study were to evaluate clinical and radiological outcomes and complications of patients with displaced MCFs managed nonoperatively and to identify potential predictive factors of worse clinical outcomes. Seventy-five patients with displaced MCFs were enrolled and treated nonoperatively with a figure-of-eight bandage (F8-B). Initial shortening (IS) and displacement (ID) of fragments were radiographically evaluated at the time of diagnosis and immediately after F8-B application by residual shortening (RS) and displacement (RD). The clavicle shortening ratio was evaluated clinically at last follow-up. Functional outcomes were assessed using Constant (CS), q-DASH, DASH work and DASH sport scores. Cosmetic outcomes and rate of complications were evaluated. Good to very good mid-term clinical results were achieved by using the institutional treatment protocol. Multiple regression identified RS as an independent predictor of shoulder function, while RD affects fracture healing. These findings support the efficacy of our institutional protocol and thus could be useful for orthopedic surgeons during the decision-making process.

Do Synovial Inflammation and Meniscal Degeneration Impact Clinical Outcomes of Patients Undergoing Arthroscopic Partial Meniscectomy? A Histological Study.

The menisci exert a prominent role in joint stabilization and in the distribution of mechanical loading. Meniscal damage is associated with increased risk of knee OA. The aim of this study was to characterize the synovial membrane and meniscal tissues in patients undergoing arthroscopic partial meniscectomy for meniscal tear and to evaluate association with clinical outcomes. A total of 109 patients were recruited. Demographic and clinical data were collected. Visual Analogic Scale (VAS) measuring pain and Knee injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and at 2-years follow-up. Histological and immunohistochemical characterizations were performed on synovial membranes and meniscal tissues. More than half of the patients demonstrated synovial mononuclear cell infiltration and hyperplasia. Synovial fibrosis was present in most of the patients; marked vascularity and CD68 positivity were observed. Inflammation had an impact on both pain and knee symptoms. Patients with synovial inflammation had higher values of pre-operative VAS and inflammation. Higher pre-operative pain was observed in patients with meniscal MMP-13 production. In conclusion, multivariate analysis showed that synovial inflammation was associated with pre-operative total KOOS scores, knee symptoms, and pain. Moreover, meniscal MMP-13 expression was found to be associated with pre-operative pain in multivariate analysis. Thus, targeting inflammation of the synovial membrane and meniscus might reduce clinical symptoms and dysfunction at the time of surgery.

Mechanical behavior of infrapatellar fat pad of patients affected by osteoarthritis.

The infrapatellar fat pad (IFP) is an adipose tissue present in the knee that lies between the patella, femur, meniscus and tibia, filling the space between these structures. IFP facilitates the distribution of the synovial fluid and may act to absorb impulsive actions generated through the joint. IFP in osteoarthritis (OA) pathology undergoes structural changes characterized by inflammation, hypertrophy and fibrosis. The aim of the present study is to analyze the mechanical behavior of the IFP in patients affected by end-stage OA. A specific test fixture was designed and indentation tests were performed on IFP specimens harvested from OA patients who underwent total knee arthroplasty. Experiments allowed to assess the typical features of mechanical response, such as non-linear stress-strain behavior and time-dependent effects. Results from mechanical experimentations were implemented within the framework of a visco-hyperelastic constitutive theory, with the aim to provide data for computational modelling of OA IFP role in knee mechanics. Initial and final indentation stiffness were calculated for all subjects and statistical results reveled that OA IFP mechanics was not significantly influenced by gender, BMI and sample preparation. OA IFP mechanical behavior was also compared to that of other adipose tissues. OA IFP appeared to be a stiffer adipose tissue compared to subcutaneous, visceral adipose tissues and heel fat pads. It is reasonable that fibrosis induces a modification of the tissue destabilizing the normal distribution of forces in the joint during movement, causing a worsening of the disease.

Mid-Term Outcomes after Arthroscopic "Tear Completion Repair" of Partial Thickness Rotator Cuff Tears.

Background and Objectives: Different arthroscopic procedures are used for partial-thickness rotator cuff tears (PT-RCTs), but there is still no evidence on the superiority of one procedure over the other. The aim of this study was to evaluate the clinical outcomes and the rate of complications of a tear completion repair (TCR) technique. Materials and Methods: Patients who had undergone arthroscopic TCR technique for PT-RCTs with a follow-up of at least 2-years after surgery were included. The TCR technique involved the removal of the "critical zone" and creating microfractures to biologically support tendon healing. Functional outcomes were assessed prospectively by the Constant score (CS) and active and passive range of movement (ROM). Pain and patient satisfaction were measured using a visual analog scale (VAS). Complication rates were recorded, and tendon integrity was assessed with magnetic resonance imaging (MRI) or ultrasound performed at least 2-years after surgery. Results: Eighty-seven patients with a median age of 57 years were followed-up for a median of 5 years. The CS score improved from 53.5 preoperatively to 94.0 postoperatively (p < 0.001). Median VAS score decreased from 8.6 to 1.0 (p < 0.0001). Median patient satisfaction was 9.3. The overall complication rate was 14.9%. Conclusions: Patients with PT-RCTs of the supraspinatus tendon treated by the TCR technique with "critical zone" removal and biological stimulation by microfractures showed good functional results with excellent strength recovery, a high degree of patient satisfaction, and resolution of painful symptoms at mid-term follow-up.

The Viability and Anti-Inflammatory Effects of Hyaluronic Acid-Chitlac-Tracimolone Acetonide- ß-Cyclodextrin Complex on Human Chondrocytes.

OBJECTIVE: To compare the effects of the complex triamcinolone acetonide-hydroxypropyl-ß-cyclodextrin (TA-CD) on in vitro inflamed primary human articular chondrocytes in the presence or absence of the mixture hyaluronic acid-Chitlac, a lactose-modified chitosan (HA-CTL). DESIGN: Changes in cell viability and pro-inflammatory cytokines gene expression were analyzed in human chondrocytes using an in vitro model of macrophage-mediated inflammation. Human monocytes U937 were differentiated to macrophages by phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharides (LPS). The anti-inflammatory effects of the complex TA-CD and HA-CTL mixture were assessed on chondrocytes exposed for 24 hours to U937 conditioned medium (CM), by quantitative polymerase chain reaction analysis. RESULTS: The TA-CD viability was enhanced by the presence of the HA-CTL mixture in chondrocyte cultures. The exposure of cells to CM significantly increased interleukin-1ß and interleukin-6 gene expression, and when the complex TA-CD was added to the inflamed cells, gene transcription of cytokines was restored to near baseline values, both in the presence or in the absence of HA-CTL mixture. CONCLUSION: The addition of HA-CTL mixture significantly attenuated cytotoxicity induced by TA and preserved the anti-inflammatory effects, thus confirming the chondroprotective role of the HA-CTL mixture.

Correction to: Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors.

An amendment to this paper has been published and can be accessed via the original article.

Metal Ion Release, Clinical and Radiological Outcomes in Large Diameter Metal-on-Metal Total Hip Arthroplasty at Long-Term Follow-Up.

Total hip arthroplasty (THA) with metal-on-metal (MoM) bearings have shown problems of biocompatibility linked to metal ion release at the local level causing an adverse reaction to metal debris (ARMD) and at a systemic level. The aim of this study was to evaluate clinical and radiological outcomes, and metal ion concentrations in the blood and urine of patients who underwent THA with the LIMA Met-Met hip system. Patients with ceramic-on-ceramic (CoC) bearings were included as a control group. In this study, 68 patients were enrolled: 34 with MoM THAs and 34 with CoC THAs. Patients were evaluated clinically (Harris Hip Score, SF-36) and radiologically at a median of 7.4 years after surgery. Whole blood and urinary cobalt and chromium levels were also assessed. Both types of implants were comparable in terms of clinical and functional results. Ion levels were significantly higher in the MoM group compared with CoC group 7 years after surgery. No correlations were found between metal ion levels and patient demographics, functional and radiological outcomes, and prosthesis features. Patient monitoring is thus advised to establish if prosthesis revision is necessary, especially in the case of MoM THA.

Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis.

Infrapatellar Fat Pad Gene Expression and Protein Production in Patients with and without Osteoarthritis.

Osteoarthritis (OA) is one of the most common joint disorders. Evidence suggests that the infrapatellar fat pad (IFP) is directly involved in OA pathology. However, a comparison between OA versus non-OA IFP is still missing. Thus, the aim of this study was to compare IFP molecular, adipocytes and extracellular matrix characteristics of patients affected by OA, and patients undergoing anterior cruciate ligament (ACL) reconstruction. We hypothesized that not only inflammation but also changes in adipocytes and extracellular matrix (ECM) composition might be involved in OA pathogenesis. Fifty-three patients were enrolled. IFP biopsies were obtained, evaluating: (a) lymphocytic infiltration and vascularization; (b) adipocytes area and number; (c) adipo-cytokines and extracellular matrix gene expression levels; (d) IL-6 and VEGF protein production; (e) collagen fibers distribution. OA IFP was more inflamed and vascularized compared to ACL IFP. OA IFP adipocytes were larger and numerically lower (1.3-fold) than ACL IFP adipocytes. An increase of gene expression of typical white adipose tissue genes was observed in OA compared to ACL IFP. Collagen-types distribution was different in the OA IFP group compared to controls, possibly explaining the change of the biomechanical characteristics found in OA IFP. Statistical linear models revealed that the adipocyte area correlated with BMI in the OA group. In conclusion, inflammation and fibrotic changes of OA IFP could represent novel therapeutic targets to counteract OA.

Biological Monitoring of Metal Ions Released from Hip Prostheses.

The aim of this study was to evaluate the levels of As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, and Zn, by inductively coupled plasma-mass spectrometry (ICP-MS) in the urine of two groups of patients with two different types of metal-on-metal (MoM) total hip prostheses (ASR DePuy®, group A, 25 patients; total Met-Met System Lima®, group B, 28 patients). The determination of metals reflected a steady-state release (group A: 9 years after surgery and group B: 6 years after surgery). The results obtained confirmed the increase of Co and Cr urinary levels in both group when compared with the reference values for the general population adopted by the Italian Society of Reference Values (SIVR). In particular, Co and Cr levels exceeded the threshold values in urine, respectively, of 30 µg and 21 µg, adjusted to creatinine based on the threshold in whole blood of 7 µg/L proposed by the Medicines and Healthcare Products Regulatory Agency (MHRA). Regarding the other investigated metals, significantly higher values were found in Group A than in Group B. These differences could be due to the type of hip prosthesis implanted, the longer period of time since the implantation, as well as many other factors such as diet, age, drug consumption, physical activity, or presence of dental fillings. The continuous monitoring over the years of metal concentrations in patients carrying a prosthesis could be useful to better identify the sources of these metals.

Challenging Surgical Treatment of Displaced Articular Tibial Plateau Fractures: Do Early Knee Radiographic Features Have a Predictive Value of the Mid-Term Clinical Functional Outcomes?

OBJECTIVE: To evaluate mid-term radiographic and functional outcomes of tibial plateau fracture (TPF) patients treated with the open reduction internal fixation (ORIF) technique and to find predictive factors of clinical outcomes. METHODS: A retrospective, single-center study was performed enrolling a consecutive series of patients with diagnosis of TPF. All subjects were treated by ORIF between January 2010 and December 2015 at our level-1 healthcare trauma center. The inclusion criteria were: age between 18 and 75 years; ORIF technique used for articular TPF, type 41-B and 41-C, isolated or with associated injuries. The patients were divided in two groups, according to fracture patterns and compared. Their characteristics, radiographic and clinical outcomes were recorded. Radiographs 12 months after surgery were evaluated for reduction and alignment, and radiographs at 24 months to describe post-traumatic osteoarthritis (PTOA). Functional outcomes were assessed using the visual analog scale (VAS), the Short Form 36 (SF-36), the knee injury and osteoarthritis outcome score (KOOS), and the American Knee Society score (AKSS) questionnaires. Return to work and sport activities were also investigated. Univariate and multivariate analysis were performed, and the statistical significance was defined as two-tailed P < 0.05. RESULTS: Forty-five patients were included, 29 males and 16 females; the mean age was 54.5 years. The mean follow-up was 57.18 months (range, 26-94). There were AO 41-B fractures (partial articular fractures) in more than half of the patients (66.67%), while the remaining 15 had AO 41-C fractures (complete articular fractures). The sub-type AO 41-B3 was the most common, reported in 62.22% of patients. The mean KOOS score was 69.0. Mean AKSS and SF-36 PCS scores were 79.0 and 41.4, respectively. There were significant relationships between age and functional results (KOOS ADL, Sport, QoL, and SF-36 PCS) and between BMI and KOOS Pain, ADL, Sport, and QoL. No differences were found between the two types of fractures regarding quality of reduction and alignment. AO 41-C TPF tend to develop PTOA more frequently with respect to 41-B fractures, while type AO 41-C TPF had the worst clinical outcomes. We found that the presence of an articular step-off and the malalignment of the tibial axis after surgery were predictive of daily pain felt by patients. PTOA was predictive of a worse AKSS. The overall complication rate was 13.33%: 1 superficial wound infection, 1 deep vein thrombosis, and 4 cases of transitory deficit of the common peroneal nerve. CONCLUSION: The present study demonstrates that early radiographic features may be predictive for pain perceived by patients at mid-term follow-up.