Correlation of systemic metabolic inflammation with knee osteoarthritis.

PURPOSE: The aim of this study was to analyze local and systematic inflammatory status in knee osteoarthritis (KOA), focusing on intra-articular and remote adipose tissue depots, and to explore its potential association with metabolic syndrome (MetS). METHODS: Patients (n = 27) with end-stage KOA were enrolled in the study and samples from infrapatellar fat pad (IFP), synovium, subcutaneous adipose tissue (SAT), synovial fluid (SF), and serum were collected. In homogenates from the tissues, mRNA expression of developmental endothelial locus-1 (DEL-1) was determined. Interleukin 6 (IL-6) and interleukin 8 (IL-8) were measured in tissues and SF and serum samples by enzyme-linked immunosorbent assay. RESULTS: Fifteen patients fulfilled MetS criteria (w-MetS group) and 12 did not (non-MetS). In the entire population, IL-6 levels were significantly higher in IFP compared to synovium (median (interquartile range), 26.05 (26.16) vs. 15.75 (14.8) pg/mg of total protein, p = 0.043), but not to SAT (17.89 (17.9) pg/mg); IL-8 levels were significantly higher in IFP (17.3 (19.3) pg/mg) and SAT (24.2 (26) pg/mg) when compared to synovium (8.45 (6.17) pg/mg) (p = 0.029 and < 0.001, respectively). Significantly higher IL-6 concentrations in SF were detected in w-MetS patients compared to non-MetS (194.8 (299) vs. 64.1 (86.9) pg/ml, p = 0.027). Finally, DEL-1 mRNA expression was higher in IFP compared to synovium (eightfold, p = 0.019). CONCLUSIONS: Our findings support the critical role of IFP in knee joint homeostasis and progression of KOA. Furthermore, in KOA patients w-MetS, SAT is thought to play an important role in intra-knee inflammation via secretion of soluble inflammatory mediators, such as IL-6.

Influence of reaming intramedullary nailing on MSC population after surgical treatment of patients with long bone fracture.

Reamed intramedullary nailing (RIN) is a surgical method of choice for treatment of diaphyseal fractures. This procedure affects the biological environment of bone tissue locally and systemically. This study investigated the influence of RIN on mesenchymal stem cells (MSCs) in patients with long bone fractures. The axis of C-X-C motif chemokine receptor 4 (CXCR4)/stromal cell-derived factor 1 (SDF­1) was selected since it is considered as major pathway for MSC homing and migration. Iliac crest bone marrow (IC­BM) samples and blood samples were collected at two different time points. One sample was collected before the RIN (BN) and the other immediately after RIN (AN). BM­MSCs were cultured and RT­qPCR was performed for CXCR4 mRNA levels and ELISA for the SDF­1 sera levels. The experimental study revealed that there was a correlation between the increase of SDF­1 levels in peripheral blood and a decrease in the levels of CXCR4 in MSCs in the IC­BM following RIN. The levels of SDF­1 showed a significant increase in the sera of patients after RIN. In conclusion, the present study is the first providing evidence of the effects of RIN on MSC population via the CXCR4/SDF­1 axis. The levels of serum SDF­1 factor were elevated after RIN while increased levels of SDF­1 in peripheral blood were inversely correlated with the mRNA levels of CXCR4 on BM­MSCs after RIN. Therefore, this study contributes to enlighten the systematic effects of RIN on the population of MSCs at a cellular level.

Age, Comorbidities and Fear of Fall: mortality predictors associated with fall-related fractures.

Objectives: To determine mortality predictors following fall related fractures in older patients. Materials and methods: Patients aged ≥ 70 years hospitalized for fall related fractures were prospectively evaluated. Mortality was the main outcome. Age, functional-cognitive function, medications, comorbidities, fall history, fear of falls were also assessed. Outcomes: A total of 100 patients were enrolled. Ninety-one out of 100 (91%) suffered a hip fracture; 92 (92%) had surgery. The one-year post-discharge mortality was 20%. Univariate analysis revealed that older age, increased Charlson comorbidity index, low abbreviated mental test on admission, low modified Barthel index (MBI), fear of falls and delirium were significantly correlated with one-year post discharge mortality (p=.03, p=.003, p=.04, p=.005, p=.004, p=.015, respectively). Conclusion: Age, fear of falls and Charlson comorbidity index are predictors of one-year mortality after hospitalization for fracture. It is of utmost importance to identify older patients suffering from fracture at risk of dying that may benefit from patient-centered care.

Current understanding of the structure and function of family B GPCRs to design novel drugs.

Family B of G-protein-coupled receptors (GPCRs) and their ligands play a central role in a number of homeostatic mechanisms in the endocrine, gastrointestinal, skeletal, immune, cardiovascular and central nervous systems. Alterations in family B GPCR-regulated homeostatic mechanisms may cause a variety of potentially life-threatening conditions, signifying the necessity to develop novel ligands targeting these receptors. Obtaining structural and functional information on family B GPCRs will accelerate the development of novel drugs to target these receptors. Family B GPCRs are proteins that span the plasma membrane seven times, thus forming seven transmembrane domains (TM1-TM7) which are connected to each other by three extracellular (EL) and three intracellular (IL) loops. In addition, these receptors have a long extracellular N-domain and an intracellular C-tail. The upper parts of the TMs and ELs form the J-domain of receptors. The C-terminal region of peptides first binds to the N-domain of receptors. This 'first-step' interaction orients the N-terminal region of peptides towards the J-domain of receptors, thus resulting in a 'second-step' of ligand-receptor interaction that activates the receptor. Activation-associated structural changes of receptors are transmitted through TMs to their intracellular regions and are responsible for their interaction with the G proteins and activation of the latter, thus resulting in a biological effect. This review summarizes the current information regarding the structure and function of family B GPCRs and their physiological and pathophysiological roles.

Differential expression of cell cycle and WNT pathway-related genes accounts for differences in the growth and differentiation potential of Wharton's jelly and bone marrow-derived mesenchymal stem cells.

BACKGROUND: In view of the current interest in exploring the clinical use of mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side comparison of the biological properties of MSCs isolated from the Wharton's jelly (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs, the most extensively studied MSC population. METHODS: MSCs were isolated and expanded from BM aspirates of hematologically healthy donors (n = 18) and from the WJ of full-term neonates (n = 18). We evaluated, in parallel experiments, the MSC immunophenotypic, survival and senescence characteristics as well as their proliferative potential and cell cycle distribution. We also assessed the expression of genes associated with the WNT- and cell cycle-signaling pathway and we performed karyotypic analysis through passages to evaluate the MSC genomic stability. The hematopoiesis-supporting capacity of MSCs from both sources was investigated by evaluating the clonogenic cells in the non-adherent fraction of MSC co-cultures with BM or umbilical cord blood-derived CD34+ cells and by measuring the hematopoietic cytokines levels in MSC culture supernatants. Finally, we evaluated the ability of MSCs to differentiate into adipocytes and osteocytes and the effect of the WNT-associated molecules WISP-1 and sFRP4 on the differentiation potential of WJ-MSCs. RESULTS: Both ex vivo-expanded MSC populations showed similar morphologic, immunophenotypic, survival and senescence characteristics and acquired genomic alterations at low frequency during passages. WJ-MSCs exhibited higher proliferative potential, possibly due to upregulation of genes that stimulate cell proliferation along with downregulation of genes related to cell cycle inhibition. WJ-MSCs displayed inferior lineage priming and differentiation capacity toward osteocytes and adipocytes, compared to BM-MSCs. This finding was associated with differential expression of molecules related to WNT signaling, including WISP1 and sFRP4, the respective role of which in the differentiation potential of WJ-MSCs was specifically investigated. Interestingly, treatment of WJ-MSCs with recombinant human WISP1 or sFRP4 resulted in induction of osteogenesis and adipogenesis, respectively. WJ-MSCs exhibited inferior hematopoiesis-supporting potential probably due to reduced production of stromal cell-Derived Factor-1α, compared to BM-MSCs. CONCLUSIONS: Overall, these data are anticipated to contribute to the better characterization of WJ-MSCs and BM-MSCs for potential clinical applications.

Complications of Intra-articular Calcaneal Fractures in Adults: Key Points for Diagnosis, Prevention, and Treatment.

Calcaneal fractures are complex injuries with high complication rates and they can lead to serious disability. The proper management remains controversial and complications may occur regardless of the chosen type of treatment (operative or nonoperative). The present article reviews the studies that are related to the complications of calcaneal fractures. The incidence, the diagnosis, the prevention and the treatment of these complications were researched and analyzed, with the use of PubMed database, abstracts and original articles in English than investigate the etiology. The aim of the article is to discuss the most suitable management of the complications of calcaneal fractures and recommend a specific treatment as well as prevention methods. LEVELS OF EVIDENCE: Level IV.

Evaluation of the reliability of a new non-invasive method for assessing the functionality and mobility of the spine.

UNLABELLED: For the evaluation of the functionality and mobility of the spine, several methods have been developed. The purpose of this study was to estimate the test-retest reliability of the Spinal Mouse, a new, non-invasive, computer-assisted wireless telemetry device for the assessment of the curvatures, the mobility and the functionality of the spine. MATERIALS AND METHODS: the test-retest reliability was evaluated in 50 adults with back or low back pain. Twenty four parameters were studied in the sagittal and frontal plane. For the characterization of the precision, the intraclass correlation coefficient and the standard error of measurement were used. RESULTS: in the sagittal plane, 22 of the 24 parameters showed high and good reliability, while only two fair and poor. In the frontal plane, 17 parameters showed high and good reliability, five fair and two poor. DISCUSSION: the Spinal Mouse showed excellent test-retest reliability in the sagittal plane, while a slightly inferior performance in the frontal plane, for the evaluation of curvatures, deformation and mobility of the spine.

Evidence of sympathetic innervation and α1-adrenergic receptors of the long head of the biceps brachii tendon.

BACKGROUND: The primary purpose of this study was to investigate the sympathetic innervation of the long head of the biceps brachii tendon LHB via immunohistochemical staining for protein S-100 and neuropeptide Y (NPY) in patients with complex proximal humerus fractures, in individuals with chronic biceps tendinosis in the setting of large rotator cuff tears (RC), and in cadaveric samples with no previously reported shoulder pathology. METHODS: We investigated the presence of sympathetic innervation and α1-adrenergic receptors of the long head of the biceps brachii tendon (LHB) in patients with complex proximal humerus fractures and individuals with chronic biceps tendinosis in the setting of large rotator cuff tears (RC). The correlation of morphological features with immunohistochemical evidence of neural element presence was also investigated. Forty-one LHB tendon specimens were examined. Seventeen were harvested from patients who underwent hemiarthroplasty for proximal humerus fractures, 14 were from individuals with biceps tendinosis in the context of a large RC tear, and ten were from cadaveric controls with no previous shoulder pathology. Histologic examination was performed using hematoxylin and eosin. Immunohistochemistry was used to detect the expression of the protein S-100, neuropeptide Y, and α1-adrenergic receptors, as well as to characterize the potential neural differentiation of tendon cells. RESULTS: A strong correlation between the expression of NPY/S-100, α1-adrenergic/S-100, and α1-adrenergic/NPY was found. The LHB tendon has sympathetic innervation and α1-adrenergic receptors in acute and chronic pathological conditions. CONCLUSION: Our results provide useful guidance on the management of tendinosis and the handling of the LHB in hemiarthroplasties for fractures.

Fractures of the ulnar coronoid process.

The ulnar coronoid process plays a central role in elbow stability due to its unique anatomic characteristics. A fracture of the coronoid, although uncommon, represents a serious injury that can adversely affect functional outcome if not treated appropriately. Several surgical interventions addressing different fracture patterns are being increasingly recognised as effective treatment options even for smaller fragments. A review of the literature was performed in order to evaluate different treatment strategies applied to clearly defined fracture configurations. 14 articles reporting data for the management of 236 coronoid fractures met our inclusion criteria and were subjected to critical analysis. The data suggest that recognition of specific coronoid fracture patterns, use of appropriate classification systems and application of staged surgical protocols can stabilise the elbow effectively and lead to favourable outcomes.

The effect of antibiotics on bone healing: current evidence.

INTRODUCTION: Bone healing is a complex cascade of events that involves the proliferation and differentiation of osteoblastic cells under the influence of signals from growth factors, cytokines and mechanical loading. Several medications have been found to interact negatively with this process including cytostatics, NSAIDs and corticosteroids; however, the effect of antibiotics on bone repair processes remains obscure. AREAS COVERED: The authors offer a comprehensive review of the existing literature on the in vivo and in vitro effect of antibiotics on bone, bone cells and fracture healing. The authors describe the pharmacokinetic characteristics of antibiotics after parenteral administration as well as their levels when applied locally together with a delivery vehicle. EXPERT OPINION: The available experimental data and clinical evidence are rather limited to allow safe conclusions. In vitro studies indicate that high doses administered after systemic administration have little or no direct effect on bone cells. Further studies are desirable to define the effect of higher or prolonged concentrations on bone biology and especially that of high concentrations released by locally implanted antibiotic-delivery systems, that is, bone cement, spacers and beads.

Use of femoral shaft fracture classification for predicting the risk of associated injuries.

OBJECTIVES: To investigate the hypothesis that specific fracture patterns in patients with femoral shaft fractures can predict the likelihood of associated injuries. DESIGN: Retrospective cohort study. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Consecutive patients treated because of a traumatic diaphyseal femoral fracture. MAIN OUTCOME MEASUREMENT: We studied the association between the Orthopaedic Trauma Association (OTA) fracture classification (derived from initial radiographs) and concomitant injuries of the head, spine, chest, abdomen, and pelvis with a severity of two or more points according to the Abbreviated Injury Scale by logistic regression analysis. RESULTS: One hundred forty-three of 203 patients (80 men, 63 women; mean age 54 ± 26 years) met the inclusion criteria. All patients had unilateral diaphyseal fractures, 64 OTA 32.A (45%), 46 OTA 32.B (32%), and 33 OTA 32.C (23%). In addition, 134 associated injuries were identified in 52 patients. Increasing fracture severity, as expressed by the OTA classification (ie, A, B, C), was significantly associated with a higher likelihood of thoracic (odds ratio [OR], 5.89; 95% confidence interval [CI], 2.59-13.40), pelvic (OR, 4.55; 95% CI, 2.01-10.28), upper (OR, 2.38; 95% CI, 1.27-4.48), and lower extremity injuries (OR, 3.12; 95% CI, 1.78-5.46). Fracture severity explained between 70% and 86% of the probability of having accompanying injuries. CONCLUSION: Radiographic grading of the severity of a femoral shaft fracture may signal the presence of accompanying injuries and should contribute to the clinical decision-making process in severe trauma.

Safety and efficacy of rivaroxaban for thromboprophylaxis following lower limb surgery: an update.

INTRODUCTION: Thromboprophylaxis in orthopedic surgery remains a controversial issue despite recent changes to NICE guidelines, particularly with the addition of oral factor Xa inhibitors. The healthcare burden of venous thromboembolism is substantial and needs frequent academic and clinical appraisal. AREAS COVERED: The authors review the available relevant literature on the use of rivaroxaban in orthopedic surgery, identified using an EMBASE (1980 - 2010) and Ovid MEDLINE (1950 - 2010) search of published articles up to August 2010. This includes clinical studies, case reports and experimental studies where applicable. Search terms include: 'rivaroxaban', 'safety', 'efficacy', 'bleeding', 'toxicity', 'tolerability' and 'complication'. EXPERT OPINION: Rivaroxaban is a safe and effective choice of thromboprophylactic agent following lower limb arthroplasty surgery. More research is required to expand the application of this novel agent to other areas of orthopedic surgery.

Prognostic significance of stability in slipped upper femoral epiphysis: a systematic review and meta-analysis.

OBJECTIVE: To examine associations of major complications after surgical treatment of slipped upper femoral epiphysis (SUFE) with condition- and treatment-related risk factors. STUDY DESIGN: This systematic review and meta-analysis of observational studies used an electronic literature search of Embase and Medline supplemented by a manual search of bibliographies. The studies enrolled children and adolescents with SUFE, defined stable and unstable disease, and reported at least 3 primary endpoints: avascular necrosis (AVN), chondrolysis, and reoperation. Random-effects meta-regression analysis was performed when possible. RESULTS: The weighted risk for AVN, derived from intercept-only meta-regression, was estimated as 5.3% (95% confidence interval [CI], 3.4%-7.2%). Patients with unstable slips had a 9.4-fold greater risk of developing AVN. Instability proved to be an independent predictor for AVN. The weighted risk of chondrolysis was 0.8% (95% CI, 0.2%-1.4%), associated with unstable slips and osteotomies. The risk of reoperation was estimated at 5.5% (95% CI, 1.7%-9.3%). Loss of fixation was the primary reason for reoperation. CONCLUSIONS: Current evidence indicates that unstable slips are at a significantly higher risk for AVN than stable slips, regardless of the attempted surgical approach. Little clinical information is available regarding chondrolysis and reoperation in relation to the stability of the physis.

Elderly tibial shaft fractures: Open fractures are not associated with increased mortality rates.

OBJECTIVES: This study aims to assess whether elderly patients (>65 years) with open tibial shaft fractures (OFs) have increased mortality rates than those with closed fractures (CFs). PATIENTS AND METHODS: Patients admitted during 2003-2005 with open/closed diaphyseal (AO 42) fractures of the tibia were eligible to participate. EXCLUSION CRITERIA: Pathological and peri-prosthetic fractures. RESULTS: A total of 54 patients (38 females) met the inclusion criteria. Twenty-six patients had sustained CF and 28 OF (Gustilo grade I (11), grade II (five), grade IIIa (two) and grade IIIb (10)). The OF group was statistically significantly different with higher injury severity score, secondary procedures and length of hospital stay (p<0.05). A higher rate of admission/length of stay to intensive care unit and complication rate was noted in the OF group. Mortality rate between the two groups was comparable (CF=2/26, OF=3/28). CONCLUSIONS: Elderly patients with OFs of the tibial shaft have similar mortality rate to those with CFs.

The tendon of the long head of the biceps in complex proximal humerus fractures: a histological perspective.

We have studied the histologic and immunohistochemical changes of the long head of the biceps brachii tendon (LHB) in low-energy complex proximal humerus fractures. Our objective was to detect histological features, which may be correlated to pain generation. Biopsy samples were obtained during hemiarthroplasty procedures from 11 patients who suffered a complex proximal humerus fracture. The control group consisted of 10 samples harvested from human cadavers with no history of premortem shoulder problems and no gross shoulder pathology. Histologic investigation included quantitative measurement of tendon degeneration, cellularity, neoangiogenesis, inflammation and metaplasia, as well as immunohistochemical detection of cells with neural differentiation within the tendon tissue proper with S-100 protein and neuropeptide Y (N-Y). The found lesions were significantly more in the group of tendons from fractures compared to the control group (p<0.001). These lesions were also statistically correlated to each other, indicating a possible neural differentiation of tendon stromal cells. The LHB is a potential source of pain and the routine use of tenotomy/tenodesis of this tendon in hemiarthroplasty procedures for fracture may be reinforced by the results of this study.

Efficacy of minimally invasive techniques for enhancement of fracture healing: evidence today.

The successful treatment of nonunions represents a major challenge for orthopaedic surgeons. Lately, ongoing advances made in the field of molecular medicine and molecular biology have increased our understanding of the pathways and involvement of mediators surrounding the bone healing process. As a result, the surgeon's armamentarium has been increased in terms of options for intervention. This article aims to provide an overview of minimally invasive techniques applicable in the treatment of nonunions of fractures.

Treatment of proximal humerus fractures with locking plates: a systematic review.

HYPOTHESIS: Locking plates with special configuration for the anatomic region of the proximal humerus have been introduced recently to address the difficulties of stabilizing proximal humeral fractures. The purpose of this study was to carry out a systematic review of the literature on the efficacy and early to medium term functional results of locking plates for stabilization of proximal humeral fractures. METHODS: Using the PubMed database, a systematic review of the English and German literature was carried out in order to assess the efficacy and complications related to the use of these plates and the patients' functional outcome, using the key words "locking plates proximal humeral fractures," "angular stability plates proximal humeral fractures," "PHILOS plate," and "LPHP plate." Our criteria for eligibility were clinical studies with more than ten cases followed-up, adult patients, and adequate data provided at least in terms of implant related complications. Articles written in English and German language were included. Exclusion criteria were: studies dealing exclusively with 2-part fractures (since this category has a more favorable outcome); experimental studies; case reports; and, literature other than English or German. Each one of the articles was evaluated for quality of the study using the Structured Effectiveness Quality Evaluation Scale (SEQES). RESULTS: Twelve studies including 791 patients met the inclusion criteria. Patients in these studies continued to improve up to one year, achieving a mean Constant score of 74.3. The incidence of the reported complications was: avascular necrosis 7.9%, screw cut-out 11.6% and re-operation rate 13.7%. DISCUSSION: The high incidence of cut-out may be secondary to the rigidity of the implant in combination with medial inadequate support, in cases compromised by severe underlying osteoporotic bone. Definition of indications for the use of locking plates and attention on technical aspects of applying them would help optimization of the results. LEVEL OF EVIDENCE: Systematic Review.

Management of pelvic instability secondary to chronic pyogenic sacroiliitis: case report.

BACKGROUND: Pyogenic sacroiliitis is a rare musculoskeletal infection that is difficult to diagnose and treat. The consequences of delayed diagnosis or inadequate treatment are often the formation of abscesses and sinuses, destructive osteomyelitis, and sequestration. METHODS: Case report and literature review. RESULTS: A 26-year-old woman developed chronic destructive pyogenic sacroiliitis and gross pelvic instability. Over a two-month hospitalization, she required six extensive surgical debridements with application of cement spacer, negative-pressure closure, intravenous antibiotics, and complex definitive fixation of the pelvic ring with autografting and application of bone morphogenetic protein-7. Radiologic union of her symphysis pubis fusion was verified during the fifth postoperative month. Thirteen months postoperatively, the patient was walking freely without aids and reported pain-free function for most of her daily activities. CONCLUSION: Chronic destructive pyogenic sacroiliitis is one of the most demanding infections of the musculoskeletal system. A successful outcome depends on prompt referral, appropriate antibiotic treatment, correct timing of surgical intervention, surgical expertise, and multidisciplinary follow up.