Iain R. Murray

Open reduction and plate fixation versus nonoperative treatment for displaced midshaft clavicular fractures: a multicenter, randomized, controlled trial.

BACKGROUND There is a growing trend to treat displaced midshaft clavicular fractures with primary open reduction and plate fixation; whether such treatment results in improved patient outcomes is debatable. The aim of this multicenter, single-blinded, randomized controlled trial was to compare union rates, functional outcomes, and economic costs for displaced midshaft clavicular fractures that were treated with either primary open reduction and plate fixation or nonoperative treatment. METHODS In a prospective, multicenter, stratified, randomized controlled trial, 200 patients between sixteen and sixty years of age who had an acute displaced midshaft clavicular fracture were randomized to receive either primary open reduction and plate fixation or nonoperative treatment. Functional assessment was conducted at six weeks, three months, six months, and one year with use of the Disabilities of the Arm, Shoulder and Hand (DASH) and Constant scores. Union was evaluated with use of three-dimensional computed tomography. Complications were recorded, and an economic evaluation was performed. RESULTS The rate of nonunion was significantly reduced after open reduction and plate fixation (one nonunion) as compared with nonoperative treatment (sixteen nonunions) (relative risk = 0.07; p = 0.007). Group allocation to nonoperative treatment was independently predictive of the development of nonunion (p = 0.0001). Overall, DASH and Constant scores were significantly better after open reduction and plate fixation than after nonoperative treatment at the time of the one-year follow-up (DASH score, 3.4 versus 6.1 [p = 0.04]; Constant score, 92.0 versus 87.8 [p = 0.01]). However, when patients with nonunion were excluded from analysis, there were no significant differences in the Constant scores or DASH scores at any time point. Patients were less dissatisfied with symptoms of shoulder droop, local bump at the fracture site, and shoulder asymmetry in the open reduction and plate fixation group (p < 0.0001). The cost of treatment was significantly greater after open reduction and plate fixation (p < 0.0001). CONCLUSIONS Open reduction and plate fixation reduces the rate of nonunion after acute displaced midshaft clavicular fracture compared with nonoperative treatment and is associated with better functional outcomes. However, the improved outcomes appear to result from the prevention of nonunion by open reduction and plate fixation. Open reduction and plate fixation is more expensive and is associated with implant-related complications that are not seen in association with nonoperative treatment. The results of the present study do not support routine primary open reduction and plate fixation for the treatment of displaced midshaft clavicular fractures.

Natural history of mesenchymal stem cells, from vessel walls to culture vessels

Abstract Mesenchymal stem/stromal cells (MSCs) can regenerate tissues by direct differentiation or indirectly by stimulating angiogenesis, limiting inflammation, and recruiting tissue-specific progenitor cells. MSCs emerge and multiply in long-term cultures of total cells from the bone marrow or multiple other organs. Such a derivation in vitro is simple and convenient, hence popular, but has long precluded understanding of the native identity, tissue distribution, frequency, and natural role of MSCs, which have been defined and validated exclusively in terms of surface marker expression and developmental potential in culture into bone, cartilage, and fat. Such simple, widely accepted criteria uniformly typify MSCs, even though some differences in potential exist, depending on tissue sources. Combined immunohistochemistry, flow cytometry, and cell culture have allowed tracking the artifactual cultured mesenchymal stem/stromal cells back to perivascular anatomical regions. Presently, both pericytes enveloping microvessels and adventitial cells surrounding larger arteries and veins have been described as possible MSC forerunners. While such a vascular association would explain why MSCs have been isolated from virtually all tissues tested, the origin of the MSCs grown from umbilical cord blood remains unknown. In fact, most aspects of the biology of perivascular MSCs are still obscure, from the emergence of these cells in the embryo to the molecular control of their activity in adult tissues. Such dark areas have not compromised intents to use these cells in clinical settings though, in which purified perivascular cells already exhibit decisive advantages over conventional MSCs, including purity, thorough characterization and, principally, total independence from in vitro culture. A growing body of experimental data is currently paving the way to the medical usage of autologous sorted perivascular cells for indications in which MSCs have been previously contemplated or actually used, such as bone regeneration and cardiovascular tissue repair.

Proximal humeral fractures

Most proximal humeral fractures are stable injuries of the ageing population, and can be successfully treated non-operatively. The management of the smaller number of more complex displaced fractures is more controversial and new fixation techniques have greatly increased the range of fractures that may benefit from surgery. This article explores current concepts in the classification and clinical aspects of these injuries, reviewing the indications, innovations and outcomes for the most common methods of treatment.

Proximal humeral fractures: CURRENT CONCEPTS IN CLASSIFICATION, TREATMENT AND OUTCOMES

Most proximal humeral fractures are stable injuries of the ageing population, and can be successfully treated non-operatively. The management of the smaller number of more complex displaced fractures is more controversial and new fixation techniques have greatly increased the range of fractures that may benefit from surgery. This article explores current concepts in the classification and clinical aspects of these injuries, reviewing the indications, innovations and outcomes for the most common methods of treatment.

Injuries associated with traumatic anterior glenohumeral dislocations.

BACKGROUND A number of shoulder girdle injuries are associated with acute anterior glenohumeral dislocations. In the present study we evaluated the prevalence of neurological deficits, greater tuberosity fractures, and rotator cuff injuries in a population of unselected patients who presented with a traumatic anterior glenohumeral dislocation. METHODS A prospective trauma database was used to record the demographic details on 3633 consecutive patients (2250 male patients and 1383 female patients with a mean age of 47.6 years) who had sustained a traumatic anterior glenohumeral dislocation between 1995 and 2009. On the basis of these data, we assessed the prevalence of and risk factors for ultrasound-proven rotator cuff tears, tuberosity fractures, and neurological deficits occurring in association with the dislocation. RESULTS Of the 3633 patients who had a dislocation, 492 patients (13.5%) had a neurological deficit following reduction and 1215 patients (33.4%) had either a rotator cuff tear or a greater tuberosity fracture. A dislocation with a neurological deficit alone was found in 210 patients (5.8%), a dislocation with a rotator cuff tear or a greater tuberosity fracture was found in 933 patients (25.7%), and a combined injury pattern was found in 282 patients (7.8%). Female patients with an age of sixty years or older who were injured in low-energy falls were more likely to have a rotator cuff tear or a greater tuberosity fracture. The likelihood of a neurological deficit after an anterior glenohumeral dislocation was significantly increased for patients who had a rotator cuff tear or a greater tuberosity fracture (relative risk, 1.9 [95% confidence interval, 1.7 to 2.1]; p < 0.001). CONCLUSIONS The prevalence of rotator cuff tear, greater tuberosity fracture, or neurological deficit following primary anterior glenohumeral dislocation is greater than previously appreciated. These associated injuries may occur alone or in combined patterns. Dislocations associated with axillary nerve palsy have similar demographic features to isolated dislocations. Injuries associated with a rotator cuff tear, greater tuberosity fracture, or complex neurological deficit are more common in patients sixty years of age or older. Careful evaluation of rotator cuff function is required for any patient with a dislocation associated with a neurological deficit, and vice versa.

Identification of Perivascular Mesenchymal Stromal/Stem Cells by Flow Cytometry

Mesenchymal stem/stromal cells (MSCs) are adult multipotent progenitors of great promise for cell therapy. MSCs can mediate tissue regeneration, immunomodulation, and hematopoiesis support. Despite the unique properties of MSCs and their broad range of potential clinical applications, the very nature of these cells has been uncertain. Furthermore, MSCs are heterogeneous and only defined subpopulations of these are endowed with the particular abilities to sustain hematopoietic stem cells, regulate immune responses, or differentiate into mesodermal cell lineages. It is becoming evident that current criteria used to define cultured polyclonal MSCs (expression of nonspecific markers and in vitro mesodermal differentiation) are not sufficient to fully understand and exploit the potential of these cells. Here, we describe how flow cytometry has been used to reveal a perivascular origin of MSCs. As a result, the prospective purification of MSCs and specialized subsets thereof is now possible, and the clinical use of purified autologous MSCs is now within reach.

Risk factors for nonunion after nonoperative treatment of displaced midshaft fractures of the clavicle.

BACKGROUND Identification of patients at higher risk of nonunion after diaphyseal clavicular fractures is desirable to improve patient counseling and enable targeted surgical treatment. METHODS Seventy-nine percent (941 of 1196) of diaphyseal clavicular fractures were followed to union or nonunion. Demographic, injury, and radiographic characteristics associated with nonunion were determined with use of bivariate and multivariate statistical analyses. RESULTS In patients who were eighteen years of age or older, 125 (13.3%) of the fractures had clinical and radiographic evidence of nonunion. Factors significantly associated with nonunion on bivariate analysis were sex, smoking status, overall fracture displacement, overlap, translation, and comminution. The factors that maintained significance on multivariate analysis were smoking (odds ratio, 3.76), comminution (odds ratio, 1.75), and fracture displacement (odds ratio, 1.17). If all displaced midshaft fractures were managed operatively, 7.5 procedures would need to be undertaken to prevent a single nonunion. If only fractures with a predicted probability of ≥40% were managed operatively, the number of patients managed operatively to prevent a single nonunion would fall to 1.7. CONCLUSIONS Thirteen percent of displaced diaphyseal fractures in patients who were at least eighteen years of age did not heal. Smoking was the strongest risk factor, and smoking cessation should be an integral part of treatment. The probability of nonunion in a particular individual can be estimated with use of a statistical model based on known risk factors. This information can be useful when counseling the patient even though nonunion remains difficult to predict accurately in that individual. The number who would need to be treated to prevent a single nonunion can be reduced by identifying those at higher risk.

Revision anterior cruciate ligament reconstruction: TIMING OF SURGERY AND THE INCIDENCE OF MENISCAL TEARS AND DEGENERATIVE CHANGE

We reviewed 87 patients who underwent revision reconstruction of the anterior cruciate ligament. The incidence of meniscal tears and degenerative change was assessed and related to the interval between failure of the primary graft and revision reconstruction. Patients were divided into two groups: early revision surgery within six months of graft failure, and delayed revision. Degenerative change was scored using the French Society of Arthroscopy system. There was a significantly higher incidence of articular cartilage degeneration in the delayed group (Mann-Whitney U-test, 53.2% vs 24%, p < 0.01). No patient in the early group had advanced degenerative change, compared to 9.2% of patients in the delayed group. There was no significant difference (Mann-Whitney U-test, p = 0.3) in the incidence of meniscal tears between the two groups. We conclude that revision reconstruction should be carried out within six months of primary graft failure, in order to minimise the risk of degenerative change.

Recent insights into the identity of mesenchymal stem cells

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses. Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure. In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Biologic Treatments for Sports Injuries II Think Tank—Current Concepts, Future Research, and Barriers to Advancement, Part 1 Biologics Overview, Ligament Injury, Tendinopathy

Biologic therapies, including stem cells, platelet-rich plasma, growth factors, and other biologically active adjuncts, have recently received increased attention in the basic science and clinical literature. At the 2015 AOSSM Biologics II Think Tank held in Colorado Springs, Colorado, a group of orthopaedic surgeons, basic scientists, veterinarians, and other investigators gathered to review the state of the science for biologics and barriers to implementation of biologics for the treatment of sports medicine injuries. This series of current concepts reviews reports the summary of the scientific presentations, roundtable discussions, and recommendations from this think tank.