Surgery with locking plate or hemiarthroplasty versus nonoperative treatment of 3-4-part proximal humerus fractures in older patients (NITEP): An open-label randomized trial.

BACKGROUND: Proximal humerus fractures (PHFs) are common fractures, especially in older female patients. These fractures are commonly treated surgically, but the consensus on the best treatment is still lacking. METHODS AND FINDINGS: The primary aim of this multicenter, randomized 3-arm superiority, open-label trial was to assess the results of nonoperative treatment and operative treatment either with locking plate (LP) or hemiarthroplasty (HA) of 3- and 4-part PHF with the primary outcome of Disabilities of the Arm, Shoulder, and Hand (DASH) at 2-year follow-up. Between February 2011 and December 2019, 160 patients 60 years and older with 3- and 4-part PHFs were randomly assigned in 1:1:1 fashion in block size of 10 to undergo nonoperative treatment (control) or operative intervention with LP or HA. In total, 54 patients were assigned to the nonoperative group, 52 to the LP group, and 54 to the HA group. Five patients assigned to the LP group were reassigned to the HA group perioperatively due to high comminution, and all of these patients had 4-part fractures. In the intention-to-treat analysis, there were 42 patients in the nonoperative group, 44 in the LP group, and 37 in the HA group. The outcome assessors were blinded to the study group. The mean DASH score at 2-year follow-up was 30.4 (standard error (SE) 3.25), 31.4 (SE 3.11), and 26.6 (SE 3.23) points for the nonoperative, LP, and HA groups, respectively. At 2 years, the between-group differences were 1.07 points (95% CI [-9.5,11.7]; p = 0.97) between nonoperative and LP, 3.78 points (95% CI [-7.0,14.6]; p = 0.69) between nonoperative and HA, and 4.84 points (95% CI [-5.7,15.4]; p = 0.53) between LP and HA. No significant differences in primary or secondary outcomes were seen in stratified age groups (60 to 70 years and 71 years and over). At 2 years, we found 30 complications (3/52, 5.8% in nonoperative; 22/49, 45% in LP; and 5/49, 10% in HA group, p = 0.0004) and 16 severe pain-related adverse events. There was a revision rate of 22% in the LP group. The limitation of the trial was that the recruitment period was longer than expected due to a high number of exclusions after the assessment of eligibility and a larger exclusion rate than anticipated toward the end of the trial. Therefore, the trial was ended prematurely. CONCLUSIONS: In this study, no benefit was observed between operative treatment with LP or HA and nonoperative treatment in displaced 3- and 4-part PHFs in patients aged 60 years and older. Further, we observed a high rate of complications related to operative treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT01246167.

In vivo corrosion on retrieved hip endoprostheses and in vitro effects of corrosion products on bone mineralization.

In vivo corrosion of modular endoprostheses remains a great concern, as the release of heavy metal ions can impair the implant's service life and the wellbeing of the patient. The detailed corrosion mechanisms that occur in vivo are so far not completely understood. In this context, the effects of implant released cobalt (Co) and chromium (Cr) ions on osteoblast mineralization and gene expression have not been investigated extensively. This comprehensive study aimed at furthering the understanding of in vivo implant corrosion from the clinical signs via prosthesis retrievals and histology of the synovial membranes down to the molecular processes instigated by corrosion products and its effects on bone mineralization. A detailed in vivo failure analysis was performed investigating 22 retrieved hip endoprostheses from different manufacturers and taper material combinations. The aim was to find a correlation of taper damage and especially corrosion to susceptible biomedical alloys and its effect on periprosthetic tissue as well as the clinical implant performance with regard to revision diagnosis and presence of radiolucent lines (RLL). A second part investigated the effects of Co and Cr ions on the in vitro mineralization process of osteoblasts. Cell cultures were exposed to relevant concentrations of CoCl2 and CrCl3 (0 µM, 100 µM, 200 µM) with and without addition of phosphate. Mineralization behavior was analyzed with Alizarin Red assay and Von Kossa staining of calcium depots, alkaline phosphatase activity of osteoblasts and gene expression was analyzed with real time quantitative PCR. The retrieval study provides evidence of in vivo fretting and crevice corrosion on all metallic tapers combined with either ceramic or metal femoral heads. Within the modular taper junctions, selective dissolution of the α phase occurred in wrought TiAl6V4 alloys, and etching of the fine-grained wrought CoCr28Mo6 alloy implants was observed in formed crevices. In addition, significant amounts of wear particles and corrosion products were detected in retrieved synovial membranes. An increased risk for the occurrence of a RLL in the proximal zones was determined for patients with a corroded mixed metal taper. Whereas Co ions have hardly any effects on mineralization, Cr ions cause a significant concentration dependent decrease in mineralization rate of osteoblasts. However, this effect is alleviated by addition of a phosphate source. Our data reveal that Cr ions depleted dissolved phosphates by forming an insoluble complex (CrPO4), which inhibits the phosphate dependent mineralization process. No significant effect of the heavy metal ions on osteoblast activity by means of alkaline phosphate activity as well as on gene expression is determined. This study broadens the understanding of in vivo corrosion of metallic modular implants and its clinically relevant effects on mineralization. Based on these findings, in vivo corrosion of CoCr28Mo6 endoprostheses should be limited to avoid inhibitory effects of Cr3+ on bone mineralization which can contribute to premature implant failure.

Synovial Fluid in Knee Osteoarthritis Extends Proinflammatory Niche for Macrophage Polarization.

Macrophage polarization is a steering factor of osteoarthritis (OA) progression. Synovial fluid (SF) obtained from OA patients with different Kellgren-Lawrence grades (KL grades) holds several proinflammatory factors and was hypothesized to induce macrophage differentiation and polarization by providing the needed microenvironment. U937 cells and peripheral-blood-mononuclear-cell-derived monocytes (PBMC-derived CD14+ cells) were induced with SFs of progressive KL grades for 48 h, and the status of the differentiated cells was evaluated by cell surface markers representing M1 and M2 macrophage phenotypes. Functional viability assessment of the differentiated cells was performed by cytokine estimation. The fraction of macrophages and their phenotypes were estimated by immunophenotyping of SF-isolated cells of different KL grades. A grade-wise proteome analysis of SFs was performed in search of the factors which are influential in macrophage differentiation and polarization. In the assay on U937 cells, induction with SF of KL grade III and IV showed a significant increase in M1 type (CD86+). The percentage of M2 phenotype (CD163+) was significantly higher after the induction with SF of KL grade II. A Significantly higher M1/M2 ratio was estimated in the cells induced with KL grade III and IV. The cell differentiation pattern in the assay on PBMC-derived CD14+ cells showed a grade-wise decline in both M1 (CD11C+, CD86+) and M2 phenotype (CD163+). Cytokine estimation specific to M1 (TNF-α, IL-6, IL-1ß, IFN-γ) and M2 (IL-4 and IL-10) macrophages corelated with the differentiation pattern in the U937 cell assay, while it did not reveal any significant changes in the PBMC-derived CD14+ cells assay. SF cells' immunophenotyping showed the highest percentage of CD14+ macrophages in KL grade II; CD86+ and CD163+ cells were minimal in all KL grades' SFs. The proteome analysis revealed significantly expressed MIF, CAPG/MCP, osteopontin, and RAS-related RAB proteins in KL grade III and IV samples, which are linked with macrophages' movement, polarization, and migration-behavior. In conclusion, this study demonstrated that SF in OA joints acts as a niche and facilitates M1 phenotype polarization by providing a proinflammatory microenvironment.

Markers of Inflammation, Oxidative Stress, and Fibrosis in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice. The pathogenesis of AF is linked to inflammatory reaction and oxidative stress, which leads to fibrosis of the atria and progression of the disease. The purpose of this study was to define the role of several biomarkers of inflammation, fibrosis, and oxidative stress (OxS). We included 75 patients with paroxysmal/persistent AF, who were admitted for electrical cardioversion or pulmonary vein isolation (PVI). High-sensitivity C-reactive protein (hsCRP), galectin-3 (Gal-3), myeloperoxidase (MPO), oxidized low-density lipoprotein (oxLDL), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before the procedures. We compared the results with those of 75 healthy age-, sex-, and blood pressure-matched individuals. The patients were followed up for 1 year after the intervention to establish the recurrence of AF and its association with the measured markers. Patients with AF had higher MPO (52.6 vs. 36.2 ng/ml, p < 0.001) and NT-proBNP (209.0 vs. 28.0 pg/ml, p < 0.001) compared to healthy subjects. Also, they showed significantly higher levels of hsCRP (1.5 vs. 1.1 mg/l, p = 0.001) and Gal-3 (11.4 vs. 9.7 mg/l, p = 0.003), while there was no difference found in oxLDL (71.5 vs. 71.7 U/l, p = 0.449). MPO (OR = 1.012, p = 0.014), hsCRP (OR = 1.265, p = 0.026), and weight (OR = 1.029, p = 0.013) were independently associated with AF in a multivariable logistic regression analysis. Patients with successful maintenance of sinus rhythm (SR) for one year had lower baseline MPO (40.5 vs. 84.3 ng/ml, p = 0.005) and NT-proBNP (127.5 vs. 694.0 pg/ml, p < 0.001) compared to patients with recurrent AF episodes, but there was no difference in hsCRP, Gal-3, or oxLDL between them. MPO (OR = 0.985, p = 0.010) was independently associated with AF recurrence during the follow-up period when adjusted for cofounders. Patients with AF had increased markers of inflammation and fibrosis, while there was no increase detected in the OxS marker oxLDL. MPO was independently associated with AF in a multivariate model. Inflammatory and fibrotic mechanisms are important factors in electrical and structural remodelling progress in the atria of patients with AF.

Isolated greater trochanter fracture may impose a comparable risk on older patients' survival as a conventional hip fracture: a population-wide cohort study.

BACKGROUND: Isolated greater trochanter fracture (IGT) and conventional hip fracture (HF) affect the same anatomical area but are usually researched separately. HF is associated with high mortality, and its management is well established. In contrast, IGT's effect on mortality is unknown, and its best management strategies are unclear. This study aims to compare these patient populations, their acute- and post-acute care, physical and occupational therapy use, and up to three-year mortality. METHODS: This retrospective cohort study is based on population-wide data of Estonia, where routine IGT management is non-operative and includes immediate weight-bearing as tolerated. The study included patients aged ≥ 50 years with a validated index HF or IGT diagnosis between 2009-2017. The fracture populations' acute- and post-acute care, one-year physical and occupational therapy use and three-year mortality were compared. RESULTS: A total of 0.4% (50/11,541) of included patients had an IGT. The baseline characteristics of the fracture cohorts showed a close resemblance, but the IGT patients received substantially less care. Adjusted analyses showed that the IGT patients' acute care was 4.5 days [3.4; 5.3] shorter they had 39.2 percentage points [25.5; 52.8] lower probability for receiving post-acute care, and they had 50 percentage points [5.5: 36]] lower probability for receiving physical and occupational therapy. The IGT and HF patients' mortality rates were comparable, being 4% and 9% for one month, 28% and 31% for one year, and 46% and 49% for three years, respectively. Crude and adjusted analyses could not find significant differences in their three-year mortality, showing a p-value of 0.6 and a hazard ratio of 0.9 [0.6; 1.3] for the IGT patients, retrospectively. CONCLUSIONS: Despite IGT being a relatively minor injury, the evidence from this study suggests that it may impose a comparable risk on older patients' survival, as does HF due to the close resemblance of the two fracture populations. Therefore, IGT in older patients may signify an underlying need for broad-based medical attention, ensuring need-based, ongoing, coordinated care. TRIAL REGISTRATION: Retrospectively registered.

Simple Excel and ICD-10 based dataset calculator for the Charlson and Elixhauser comorbidity indices.

BACKGROUND: The Charlson and Elixhauser Comorbidity Indices are the most widely used comorbidity assessment methods in medical research. Both methods are adapted for use with the International Classification of Diseases, which 10th revision (ICD-10) is used by over a hundred countries in the world. Available Charlson and Elixhauser Comorbidity Index calculating methods are limited to a few applications with command-line user interfaces, all requiring specific programming language skills. This study aims to use Microsoft Excel to develop a non-programming and ICD-10 based dataset calculator for Charlson and Elixhauser Comorbidity Index and to validate its results with R- and SAS-based methods. METHODS: The Excel-based dataset calculator was developed using the program's formulae, ICD-10 coding algorithms, and different weights of the Charlson and Elixhauser Comorbidity Index. Real, population-wide, nine-year spanning, index hip fracture data from the Estonian Health Insurance Fund was used for validating the calculator. The Excel-based calculator's output values and processing speed were compared to R- and SAS-based methods. RESULTS: A total of 11,491 hip fracture patients' comorbidities were used for validating the Excel-based calculator. The Excel-based calculator's results were consistent, revealing no discrepancies, with R- and SAS-based methods while comparing 192,690 and 353,265 output values of Charlson and Elixhauser Comorbidity Index, respectively. The Excel-based calculator's processing speed was slower but differing only from a few seconds up to four minutes with datasets including 6250-200,000 patients. CONCLUSIONS: This study proposes a novel, validated, and non-programming-based method for calculating Charlson and Elixhauser Comorbidity Index scores. As the comorbidity calculations can be conducted in Microsoft Excel's simple graphical point-and-click interface, the new method lowers the threshold for calculating these two widely used indices. TRIAL REGISTRATION: retrospectively registered.

The use of antibiotic-loaded bone cement does not increase antibiotic resistance after primary total joint arthroplasty.

PURPOSE: One of the preventive strategies for periprosthetic joint infection (PJI) is the use of antibiotic-loaded bone cement (ALBC) in primary total joint arthroplasty (TJA). Even though it is widely used, there are concerns about the development of antibacterial resistance. The aim of the study was to investigate whether using ALBC in primary TJA increases the antibiotic-resistant PJI. The hypothesis was that the regular use of ALBC does not increase the rate of resistant PJI. METHODS: Patients with confirmed PJI who had revision surgery from year 2010 to 2019 were included in this international multicenter study. The ALBC group was compared to the non-ALBC TJA group from the same time period. Medical records were used to collect clinical (age, gender, body mass index, comorbidities), TJA-related (type of operation, implant type and survival) and PJI-related (cultured microorganism, antibiogram) data. Resistance to gentamicin, clindamycin and vancomycin were recorded from the antibiograms. Multiple logistic regression model was used to identify risk factors and account for the potential confounders. RESULTS: 218 patients with PJI were included in the study: 142 with gentamicin-loaded bone cement and 76 in the non-ALBC group. The average age in the ALBC group was 71 ± 10 years and 62 ± 12 years in the comparison group (p < 0.001). Coagulase negative Staphylococci (CONS) were the most common (49%) isolated pathogens. The use of ALBC did not increase the rate of any resistant bacteria significantly (OR = 0.79 (0.42-1.48), p = 0.469). The presence of CONS was associated with higher risk of antibiotic resistance. CONCLUSIONS: The current study demonstrates no increase in antibiotic resistance due to ALBC after primary TJA. Thus, the use of ALBC during primary TJA should not be feared in the context of antimicrobial resistance. LEVEL OF EVIDENCE: III.

Atrial fibrillation is associated with increased central blood pressure and arterial stiffness.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and beta blockers (BBs) are the drugs of choice for rate or rhythm control in these patients. The purpose of this study was to describe differences in arterial stiffness (AS), central blood pressure (cBP), and the role of BBs on cBP in patients with AF compared to healthy individuals. The authors included 76 patients with paroxysmal/persistent AF. Carotid-femoral pulse wave velocity (PWV) and cBP were measured and compared with data from 75 healthy individuals. Patients with AF had higher PWV (8.0 m/s vs. 7.2 m/s, p < .001), central systolic blood pressure (cSBP) (118 mm Hg vs. 114 mm Hg, p = .033), central pulse pressure (cPP) (39 mm Hg vs. 37 mm Hg, p = .035) and lower pulse pressure amplification (PPA) (1.24 vs. 1.30, p = .015), without differences in peripheral blood pressure (pBP) and heart rate (HR). AF patients had significantly increased PWV (ß= 0.500, p = .010, adjusted R² = 0.37) after adjustment for confounding factors. The use of BBs significantly reduced PPA (ß = -0.059, p = .017, adjusted R² = 0.30). AF patients have higher PWV, cSBP, cPP, and lower PPA, compared to healthy patients. These findings support the role of AS in the development of AF. Use of BBs is related to a potential adverse effect on cBP.

Nonoperative hip fracture management practices and patient survival compared to surgical care: an analysis of Estonian population-wide data.

A notable proportion of hip fracture patients receive nonoperative management, but such practice is seldom analysed. Although highly variable reasons underpin hip fracture nonoperative management, none of these practices conclusively outweigh the superiority of operative management. Nonoperative management should be only considered when surgery is not an option. PURPOSE: Reasons underpinning hip fracture (HF) nonoperative management (NOM) are seldom analysed. This study aims to identify the reasons behind NOM and assess the accuracy of these decisions using these patients' survival compared with those treated with operative management (OM). METHODS: This is a retrospective cohort study based on population-wide administrative health data, including patients aged ≥ 50 with an index HF diagnosis between January 2009 and September 2017. NOM patients were subgrouped according to their expected prognoses, and their survival up to 36 months was compared with those treated surgically. RESULTS: From a total of 11,210 included patients, 6.8% (766) received NOM. Varying reasons lead to NOM, dividing them further into five distinct subgroups: (I) 46% NOM decision due to poor expected prognosis with OM; (II) 29% NOM decision due to poor expected prognosis for mixed reasons; (III) 15% NOM decision due to good expected prognosis with NOM; (IV) 8.0% NOM decision due to patient's refusal of OM; and (V) 1.3% NOM decision due to occult HF. Only poor prognosis and patients who refused OM (I, II, IV) had worse survival than OM patients. However, a relatively high proportion of the poor prognosis patients survived 1 year (29%). CONCLUSION: Although there was high variability in reasons underpinning HF NOM, none of these practices conclusively outweigh OM's superiority. NOM should be considered with utmost care and only for patients for whom OM is out of the question - well-defined medical unfitness or carefully considered refusal by understanding the increased mortality risk.

Metabolomic Signature of Amino Acids, Biogenic Amines and Lipids in Blood Serum of Patients with Severe Osteoarthritis.

Metabolomic analysis is an emerging new diagnostic tool, which holds great potential for improving the understanding of osteoarthritis (OA)-caused metabolomic shifts associated with systemic inflammation and oxidative stress. The main aim of the study was to map the changes of amino acid, biogenic amine and complex lipid profiles in severe OA, where the shifts should be more eminent compared with early stages. The fasting serum of 70 knee and hip OA patients and 82 controls was assessed via a targeted approach using the AbsoluteIDQ™ p180 kit. Changes in the serum levels of amino acids, sphingomyelins, phoshatidylcholines and lysophosphatidylcholines of the OA patients compared with controls suggest systemic inflammation in severe OA patients. Furthermore, the decreased spermine to spermidine ratio indicates excessive oxidative stress to be associated with OA. Serum arginine level was positively correlated with radiographic severity of OA, potentially linking inflammation through NO synthesis to OA. Further, the level of glycine was negatively associated with the severity of OA, which might refer to glycine deficiency in severe OA. The current study demonstrates significant changes in the amino acid, biogenic amine and low-molecular weight lipid profiles of severe OA and provides new insights into the complex interplay between chronic inflammation, oxidative stress and OA.

Intraoperative complications in total hip arthroplasty using a new cementless femoral implant (SP-CL®).

BACKGROUND: Considering the excellent results already achieved in total hip arthroplasty (THA), new implants must be at least as safe as currently used implants and lead to longer survival. A new cementless femoral stem, SP-CL®, has been introduced. The aim of this study is to evaluate intraoperative complications and assess the risk factors of THA with the SP-CL® implant. MATERIALS AND METHODS: All THA patients who were operated on using the SP-CL® (LINK, Hamburg, Germany) implant between 2015 and 2018 were included in the analysis. Data were collected from medical records from national and hospital electronic databases. Radiological measurements were made from standard pre- and postoperative radiographs. RESULTS: A total of 222 THA were performed using the SP-CL® implant. The average age of the patients was 56 years (14-77 years). There were 1 transient sciatic nerve injury, 1 acetabular fracture, and 11 (5.0%) intraoperative femoral fractures (IFF), of which 7 were treated with cerclage wire or titanium band during the operation while the other fractures were treated conservatively. None of the IFF patients were revised due to fracture during the follow-up period (one revision due to infection). The radiographic morphology of proximal femur was associated with increased risk of IFF (p = 0.02). CONCLUSIONS: The results of the current study demonstrate a 5% incidence of IFF when using the LINK SP-CL® femoral stem in THA. The radiographic morphology of the proximal femur was an important predictor of IFF and should be assessed when using SP-CL®. LEVEL OF EVIDENCE: Level 4.

Isolated Mediastinal Lymphadenopathy Caused by Rhodococcus equi Infection.

Mediastinal lymphadenopathy is common finding in thoracic surgery, and it often requires morphologic confirmation to establish the definitive diagnosis. The most frequent diagnoses are metastatic lung cancer, sarcoidosis, lymphoma, tuberculosis, and other causes of granulomatous infections. Rhodococcus equi is a rare pathogen in humans that mostly affects immunocompromised patients. This report presents a case with isolated mediastinal lymphadenopathy caused by Rhodococcus equi infection in a 71-year-old immunocompetent patient.

Medium- and long-chain acylcarnitines are associated with osteoarthritis severity and arterial stiffness in end-stage osteoarthritis patients: a case-control study.

AIM: Arterial pathology has been suggested to be involved in osteoarthritis (OA). Metabolic profiling enables the determination of low-molecular-weight molecules, which might further explain the pathogenesis of OA and its relationship with cardiovascular diseases (CVD). The aim of this study was to compare the metabolic profile of lipid metabolism-related compounds and arterial stiffness in OA patients and in controls. METHOD: The serum of 70 end-stage OA patients prior to joint replacement surgery and 82 age-matched controls were analyzed by the AbsoluteIDQ™ p180 kit (BIOCRATES Life Sciences AG, Innsbruck, Austria) using the targeted metabolomic approach. Arterial stiffness was assessed by measuring carotid-femoral and carotid-radial pulse wave velocity. Aortic-brachial pulse wave velocity ratio (PWV-ratio) was used as the measure of arterial stiffness gradient. Principal component analysis was performed to analyze the large number of metabolites. RESULTS: The OA patients had decreased levels of C10:1, C10:2, C12, C12:1, C14, C14:2, C14:1-OH, carnitine palmitoyltransferase 1 (CPT1) ratio and total AC/C0 compared with age-matched controls. There was independent association between acylcarnitines and PWV-ratio in the OA patients. Furthermore, acylcarnitines were associated with OA radiographic severity. The component that resembles acylcarnitines was an independent predictor of the PWV-ratio for OA patients. CONCLUSION: We found decreased levels of acylcarnitines in OA patients. Furthermore, medium-and long-chain acylcarnitines associated independently with arterial stiffness and were related to radiographic severity of OA. Thus, acylcarnities might play an important role in the association between OA and CVD.

Metabolic factors and oxidative stress in osteoarthritis: a case-control study.

Previous studies suggest that metabolic disturbances might be involved in the development of osteoarthritis (OA). Associations have been found between the individual components of metabolic syndrome (MetS) and OA. MetS has been associated with increased oxidative stress (OxS). The study aimed to clarify the role of MetS components in OA and to evaluate the levels of OxS in OA patients and in age-matched controls. Fifty-five patients with end-stage OA (age 63 ± 7 years) prior to hip or knee joint replacement surgery and 55 age-, gender- and body mass index matched controls (61 ± 8 years) were enrolled in the study. Serum levels of glucose, insulin, c-peptide, cholesterols and OxS markers were recorded. Homeostasis model assessment for insulin resistance was used as the proxy measure of insulin resistance. Radiographic severity was assessed using the Kellgren-Lawrence score. The OA patients had higher total peroxide concentration and oxidative stress index [488 (250-612) µmol/L vs. 326 (168-442) µmol/L, p = .011 and 34 (17-51) vs. 20 (11-28), p = .002, respectively] and decreased total antioxidant capacity (1.49 ± 0.27 vs. 1.66 ± 0.27 mmol trolox equivalent/L, p= .008) compared with the controls. In addition, OA group had significantly higher level of C-peptide compared with the controls [1.8 (0.94-2.47) vs. 1.3 (0.46-1.42) ng/mL, p < .001, respectively]. Furthermore, OA radiographic severity was independently associated with LDL-cholesterol (p = .007) and oxidized LDL (p = .022). This study demonstrates that end-stage OA patients have increased levels of OxS and decreased antioxidant capacity. OA is associated with impaired lipid metabolism and dysglycemia. Our results underline the importance OxS and metabolic disturbances in the pathogenesis of OA.

Severity of Osteoarthritis Is Associated with Increased Arterial Stiffness.

Objective. Osteoarthritis (OA) is associated with increased cardiovascular comorbidity and mortality. Evidence is lacking about whether arterial stiffness is involved in OA. The objective of our study was to find out associations between OA, arterial stiffness, and adipokines. Design. Seventy end-stage knee and hip OA patients (age 62 ± 7 years) and 70 asymptomatic controls (age 60 ± 7 years) were investigated using the applanation tonometry to determine their parameters of arterial stiffness. Serum adiponectin, leptin, and matrix metalloproteinase 3 (MMP-3) levels were determined using the ELISA method. Correlation between variables was determined using Spearman's rho. Multiple regression analysis with a stepwise selection procedure was employed. Results. Radiographic OA grade was positively associated with increased carotid-femoral pulse wave velocity (cf-PWV) (r = 0.272, p = 0.023). We found that OA grade was also associated with leptin and MMP-3 levels (rho = -0.246, p = 0.040 and rho = 0.235, p = 0.050, resp.). In addition, serum adiponectin level was positively associated with augmentation index and inversely with large artery elasticity index (rho = 0.293, p = 0.006 and rho = -0.249, p = 0.003, resp.). Conclusions. Our results suggest that OA severity is independently associated with increased arterial stiffness and is correlated with expression of adipokines. Thus, increased arterial stiffness and adipokines might play an important role in elevated cardiovascular risk in end-stage OA.

Increased arterial stiffness in patients with end-stage osteoarthritis: a case-control study.

BACKGROUND: Both osteoarthritis (OA) and cardiovascular diseases (CVD) are prevalent conditions which often co-exist. Vascular involvement in the pathogenesis of these diseases, as well as increased cardiovascular risk in OA patients give occasion to investigate arterial stiffness in OA. The aim of this study was to establish associations between OA and arterial stiffness. METHODS: The characteristics of arterial stiffness were measured with Sphygmocor and HDI devices in 48 patients (age 63 ± 7 years (mean ± SD)) with end-stage OA awaiting knee and hip replacement and in 49 age and gender matched controls (61 ± 7 years). Independent Student's t-test or the Mann-Whitney U test was used to compare means between the groups. Correlation between variables was determined using Pearson's or Spearman's correlation analysis and stepwise multiple regression analysis. RESULTS: Carotid-femoral pulse wave velocity (car-fem PWV) was increased in the patients with OA compared to the controls (9.6 ± 2.4 and 8.4 ± 1.9 m/s, p = 0.015 respectively). High-sensitivity C-reactive protein and white blood cells count were significantly higher in the OA patients compared with the controls (1.80 ± 1.10 and 1.48 ± 1.32 mg/l, p = 0.042; 6.5 ± 1.5 and 5.6 ± 1.9 10(9)/l, p = 0.001 respectively). In multiple regression analysis age (p < 0.001), mean arterial blood pressure (p = <0.001) and OA status (p = 0.029) were found to be independent predictors of car-fem PWV. CONCLUSIONS: This study showed that patients with OA had increased aortic stiffness compared to non-OA controls. The potential link between arterial stiffening and OA suggests that vascular alterations are involved in OA pathogenesis and could be responsible for increased cardiovascular risk in end-stage OA patients.

Early Biomarkers of Renal Damage in Relation to Arterial Stiffness and Inflammation in Male Coronary Artery Disease Patients.

BACKGROUND/AIMS: Plasma neutrophil gelatinase-associated lipocalin (NGAL), urinary liver-type fatty acid-binding protein (L-FABP) and urinary kidney injury molecule-1 (KIM-1) have emerged as promising biomarkers for both acute and chronic kidney injury that also provide prognostic value for cardiovascular morbidity and mortality. Our aim was to evaluate their relationships with arterial stiffness and inflammation in coronary artery disease (CAD) patients and in clinically healthy controls. METHODS: We studied 52 patients with CAD (age 63.2 ± 9.2 years) and 41 healthy controls (age 60.1 ± 7.2 years). Urinary L-FABP and KIM-1 as well as serum NGAL, adiponectin and resistin levels were measured using the enzyme-linked immunosorbent assay method. The technique of applanation tonometry was used for non-invasive pulse wave analysis and pulse wave velocity assessments. RESULTS: Urinary L-FABP and KIM-1 were independent determinants of cf-PWV for the CAD patients (R2=0.584, P<0.001) but not for the controls. Adiponectin correlated with log-KIM-1 (r=0.31, P=0.028) only for the patients, while NGAL correlated with WBC count (rho=0.29, P=0.038; r=0.35, P=0.029) and resistin (rho=0.60, P<0.001; r=0.57, P<0.001) for both the CAD and control groups, respectively. CONCLUSION: Our findings suggest that urinary L-FABP and KIM-1 may be independently associated with aortic stiffness in individuals with CAD.

The patellar shift index: a reliable and valid measure for patellofemoral congruence following total knee arthroplasty with unresurfaced patella.

OBJECTIVE: The aim of this study was to develop a new radiographic measure, the patellar shift index (PSI), for the precise estimation of patellar position relative to the trochlea after a total knee replacement with an unresurfaced patella. METHODS: This study included radiographs of 51 patients suffering from anterior knee pain following total knee arthroplasty. Patellofemoral axial radiographs were analyzed to compare the reliability of the PSI to the classical measures of patellofemoral congruence, the lateral patellar tilt (LPT) and patellar displacement (PD). Intra-rater reliability of the PSI, LPT and PD was estimated using the intraclass correlation coefficient (ICC) and the inter-rater reliability using Krippendorff's alpha (Kα). Agreement proportion of was calculated for the PD. Face validity of the PSI was also tested. RESULTS: The PSI had excellent intra (mean ICC=0.91) and inter-rater (Kα=0.92) reliability, as did LPT (mean ICC=0.96; Kα=0.89). The calculation of PD caused a low level of agreement (47.1%) between evaluators in terms of which images could be measured. The exclusion of these radiographs resulted in a high PD intra (ICC=0.96) and inter-rater (Kα=0.97) reliability. CONCLUSION: The PSI appears to be a reliable and valid measure for patellofemoral congruence in a replaced knee joint with an unresurfaced patella. The superiority of the PSI is the result of its consideration of the geometry and size of the replaced knee joint and independence from radiographic magnification.