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.

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.

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.

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.

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.

Treatment and outcomes of pelvic malunions and nonunions: a systematic review.

UNLABELLED: Although acute management of pelvic fractures and their long-term functional outcome have been widely documented, important information regarding malunion and nonunion of these fractures is sparse. Despite their relative rarity, malunions and nonunions cause disabling symptoms and have major socioeconomic implications. We analyzed the factors predisposing a pelvic injury to develop malunion/nonunion, the clinical presentation of these complications, and the efficacy of the reported operative protocols in 437 malunions/nonunions of 25 clinical studies. Treatment of these demanding complications appeared effective in the majority of the cases: overall union rates averaged 86.1%, pain relief as much as 93%, patient satisfaction 79%, and return to a preinjury level of activities 50%. Nevertheless, the patient should be informed about the incidence of perioperative complications, including neurologic injury (5.3%), symptomatic vein thrombosis (5.0%), pulmonary embolism (1.9%), and deep wound infection (1.6%). For a successful outcome, a thorough preoperative plan and methodical operative intervention are essential. In establishing effective evidence-based future clinical practice, the introduction of multicenter networks of pelvic trauma management appears a necessity. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

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.

Varicosities as an etiology of tarsal tunnel syndrome and the significance of tinel's sign: report of two cases in young men and a review of the literature.

Two cases of tarsal tunnel syndrome in two young men with surgical and radiologic details are reported. The role of varicosities as a cause of tarsal tunnel syndrome and the significance of Tinel's sign are discussed through a large review of the literature.

The natural history of a mistreated ipsilateral Galeazzi and Monteggia lesion: report of a case 39 years post-injury.

Galeazzi injury combined with ipsilateral Monteggia lesion is extremely rare. A 45-year-old male patient with a mistreated Galeazzi lesion combined with an ipsilateral Monteggia fracture at the age of 6 is presented. Thirty-nine years post-injury his elbow was asymptomatic and stable and his distal radioulnar and radiocarpal joints were also asymptomatic. The strength of the limb was equal to the unaffected contralateral upper limb and he was able to work manually as a waiter for the last 20 years without any problem. The only obvious defect was a 30 degrees lack of elbow flexion and a 10 degrees lack of forearm pronation in comparison to the normal side.

Intradural tumours of the lumbar spine presenting with low back pain: report of two cases and review of the literature.

Two cases of spinal cord tumours (one schwannoma and one ependymoma) of the lumbar spine are reported. The treatment with radical excision and posterolateral fusion, along with adjuvant radiation therapy in the case with ependymoma was successful, with follow-up of six and seven years respectively. A literature review is presented, and a possible presentation with low back pain is analysed.

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.

Release of the subscapularis tendon and muscle: a limited gain in length.

This study measured in vitro the degree of lateral advancement of the subscapularis tendon achieved by circumferential release. Thirty-eight cadaveric shoulders underwent circumferential subscapularis release with anterior capsulotomy. Release was performed in two phases. The first phase consisted of four stages: 1) cutting the capsule parallel to the superior border of the subscapularis tendon to the level of the glenoid; 2) division of the anterior capsule and blunt dissection along the glenoid neck; 3) safe separation of the capsule and muscle inferiorly; and 4) blunt, with a finger, dissection between the conjoined tendon and the subscapularis to the level of the joint line. The second phase was performed by cutting the coracohumeral ligament and the consistently found fibrous band that connects the superior aspect of the subscapularis tendon to the base of the coracoid. After each phase, 3 kg of traction were applied to the muscle and the lateral advancement of the subscapularis was measured using a millimeter caliper. The lateral advancement of the subscapularis was 5.5 +/- 3.4 mm after the first step and 9.8 +/- 4.5 mm after the second step. The difference was statistically significant (P < .001). These results indicate that, although necessary, anterior soft tissue balancing during shoulder replacement is limited.

Isolated synovial cyst of the acromio-clavicular joint associated with joint degeneration and an intact rotator cuff.

The majority of acromioclavicular joint cysts are the manifestation of underlying pathology of the rotator cuff. A chronic rotator cuff tear should be the first option in differential diagnosis, when facing such a condition, although this is not always the case. A case of a 67-year-old male patient, who abruptly developed a painless lump over his right acromioclavicular joint, is presented. Imaging studies were diagnostic for a cystic lesion, and degeneration of the acromioclavicular joint without communication with the subdeltoid bursa and the glenohumeral joint. The rotator cuff was intact. Surgical treatment, with cyst removal and resection of the distal end of the clavicle, was performed. The lesion was proved to be a synovial cyst. Eighteen months postoperatively, the patient was asymptomatic and no recurrence of the cyst was evident.

Bioabsorbable materials in orthopaedics.

The applications of bioabsorbable implants in orthopaedic surgery have mainly been mandated from the need to eliminate implant removal operations. Although they have not gained widespread popularity among orthopaedic surgeons, they still represent an area of evolution. Considerable effort has been put into developing new bioabsorbable materials with fewer adverse effects. In this article an extensive review of the literature is presented emphasising on basic science and clinical applications of these materials. A review of the types of implants, the materials used, their biochemical properties, their adverse effects and some of the potential future applications is presented.

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.

Stabilisation of a posteriorly unstable glenohumeral joint during total shoulder arthroplasty: A novel capsulorrhaphy technique.

Restoration of the soft tissue balance is of great importance during shoulder arthroplasty. We report a novel technique of posterior capsulorrhaphy through an anterior approach for the management of intraoperative posterior instability during implantation of the prosthesis. After the operation, the patients were able to follow a rehabilitation program with some minor restrictions, avoiding the necessity of a shoulder spica or other constrictive measures. This technique is simple, safe and sufficient to address instability due to abundance of the posterior shoulder capsule.

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.

The effect of surgical weight reduction on functional status in morbidly obese patients with low back pain.

BACKGROUND: Although low back (LBP) pain is not a life-threatening disease, it is a source of significant discomfort and disability and accounts for work absences. It has been shown previously that morbid obesity is associated with increased frequency of LBP and that surgical weight loss improves the symptomatology. However, there are no studies to quantitatively assess the exact degree of functional disability caused by severe obesity and the degree of improvement of LBP that follows weight loss from bariatric surgery. METHODS: 29 morbidly obese candidates for bariatric surgery with LBP, weight 132.5+/-27 (mean+/-SD) kg and BMI 47.2+/-8.8 kg/m2 were examined for their functional status using psychometric instruments specifically designed to objectively assess the patients' complaints. The preoperative scores were measured by a) visual analogue scales (VAS1, VAS2, VAS3), b) Roland-Morris disability questionnaire, c) Oswestry LBP disability questionnaire, and d) Waddell disability index, and were compared with the scores obtained by the same instruments 2 years after vertical banded gastroplasty. RESULTS: The postoperative weight (92.3+/-19 kg) and BMI (32.9+/-6.3 kg/m2) of the 29 patients were significantly reduced (P<0.001). The improved functional disability scores were statistically significant: a) VAS1 1.59+/-1.86 (mean+/-SD) vs 0.32+/-0.64, P<0.001; b) VAS2 5.5+/-1.97 vs 2.14+/-1.88, P<0.001; c) VAS3 0.77+/-1.11 vs 0.09+/-0.29, P=0.006, d) Roland-Morris 7.89+/-5.11 vs 1.89+/-2.13, P<0.001; e) Oswestry 21.22+/-15.63 vs 5.61+/-7.51, P<0.001; f) Waddell 2.81+/-1.37 vs 0.56+/-0.72, P<0.001. CONCLUSIONS: Surgical weight loss significantly improves the degree of functional disability of morbidly obese patients suffering from LBP.

Sympathetic and sensory neural elements in the tendon of the long head of the biceps.

BACKGROUND: Although the tendon of the long head of the biceps is a well-known source of shoulder pain, the pathophysiological basis of this pain has yet to be explained. The aim of this study was to detect and characterize any nervous element of the tendon and to determine a possible explanation for pain originating from this structure. METHODS: The nature of the neuronal innervation of the tendon of the long head of the biceps was studied immunohistochemically, in four tendons from different human cadavers, with use of neurofilament antibody 2H3, neurofilament-like antibody 3A10, calcitonin gene-related peptide, substance P, and tyrosine hydroxylase. RESULTS: A large neuronal network, asymmetrically distributed along the length of the tendon with a higher degree of innervation at the tendon origin, was identified by the neurofilament and neurofilament-like antibodies 2H3 and 3A10. This innervation was found to be positive for calcitonin gene-related peptide and substance P, suggesting the presence of thinly myelinated or unmyelinated sensory neurons. It was also positive for tyrosine hydroxylase, suggesting a post-ganglionic sympathetic origin. CONCLUSIONS AND CLINICAL RELEVANCE: These findings demonstrate that the tendon of the long head of the biceps is innervated by a network of sensory sympathetic fibers, which may play a role in the pathogenesis of shoulder pain.