Nikhil R. Oak

Inhibition of 5-LOX, COX-1, and COX-2 Increases Tendon Healing and Reduces Muscle Fibrosis and Lipid Accumulation After Rotator Cuff Repair

Background: The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)–1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration. Hypothesis: After the repair of a chronic rotator cuff tear in rats, licofelone would increase the load to failure of repaired tendons and increase the force production of muscle fibers. Study Design: Controlled laboratory study. Methods: Rats underwent supraspinatus release followed by repair 28 days later. After repair, rats began a treatment regimen of either licofelone or a vehicle for 14 days, at which time animals were euthanized. Supraspinatus muscles and tendons were then subjected to contractile, mechanical, histological, and biochemical analyses. Results: Compared with controls, licofelone-treated rats had a grossly apparent decrease in inflammation and increased fibrocartilage formation at the enthesis, along with a 62% increase in the maximum load to failure and a 51% increase in peak stress to failure. Licofelone resulted in a marked reduction in fibrosis and lipid content in supraspinatus muscles as well as reduced expression of several genes involved in fatty infiltration. Despite the decline in fibrosis and fat accumulation, muscle fiber specific force production was reduced by 23%. Conclusion: The postoperative treatment of cuff repair with licofelone may reduce fatty degeneration and enhance the development of a stable bone-tendon interface, although decreases in muscle fiber specific force production were observed, and force production in fact declined. Clinical Relevance: This study demonstrates that the inhibition of 5-LOX, COX-1, and COX-2 modulates the healing process of repaired rotator cuff tendons. Although further studies are necessary, the treatment of patients with licofelone after cuff repair may improve the development of a stable enthesis and enhance postoperative outcomes.

Phosphorylation of CCAAT/Enhancer-binding Protein α Regulates GLUT4 Expression and Glucose Transport in Adipocytes

The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is required during adipogenesis for development of insulin-stimulated glucose uptake. Modes for regulating this function of C/EBPα have yet to be determined. Phosphorylation of C/EBPα on Ser-21 has been implicated in the regulation of granulopoiesis and hepatic gene expression. To explore the role of Ser-21 phosphorylation on C/EBPα function during adipogenesis, we developed constructs in which Ser-21 was mutated to alanine (S21A) to model dephosphorylation. In two cell culture models deficient in endogenous C/EBPα, enforced expression of S21A-C/EBPα resulted in normal lipid accumulation and expression of many adipogenic markers. However, S21A-C/EBPα had impaired ability to activate the Glut4 promoter specifically, and S21A-C/EBPα expression resulted in diminished GLUT4 and adiponectin expression, as well as reduced insulin-stimulated glucose uptake. No defects in insulin signaling or GLUT4 vesicle trafficking were identified with S21A-C/EBPα expression, and when exogenous GLUT4 expression was enforced to normalize expression in S21A-C/EBPα cells, insulin-responsive glucose transport was reconstituted, suggesting that the primary defect was a deficit in GLUT4 levels. Mice in which endogenous C/EBPα was replaced with S21A-C/EBPα displayed reduced GLUT4 and adiponectin protein expression in epididymal adipose tissue and increased blood glucose compared with wild-type littermates. These results suggest that phosphorylation of C/EBPα on Ser-21 may regulate adipocyte gene expression and whole body glucose homeostasis.

Complications in hip arthroscopy.

Over the past several years, hip arthroscopy has become an effective treatment option for a variety of intra-articular and extra-articular pathologies. With the rapid growth in the technical capabilities of hip arthroscopy, there has been much interest in the indications, limitations, and complications associated with the procedure. The procedure remains technically demanding and carries with it a steep surgical learning curve that may lead to heterogeneity in individual surgeon complication rates. Furthermore, with expanding indications and treatment of pathology in the peripheral compartment, peritrochanteric, and subgluteal space, it is vital to remain cognizant of all potential pitfalls that may occur throughout the entire procedure. This article reviews the complications associated with hip arthroscopy, from preoperative planning through postoperative care.

Intra-Articular Fractures of the Hand

Fractures of the hand are common injuries and in particular, fractures involving the articular surfaces can present difficulties to the orthopedic surgeon in practice. Although the treatment of these fractures needs to be individualized based on fracture pattern and location, the goals for these fractures are to restore the alignment, stability, and congruity and to allow for early motion to prevent stiffness and traumatic arthritis. This article classifies the various types of intra-articular hand fractures as well as the workup and management of these injuries.

Comparison of 2-Dimensional and 3-Dimensional Metacarpal Fracture Plating Constructs Under Cyclic Loading

PURPOSE Metacarpal fractures are commonly treated by a variety of means including casting or open reduction internal fixation when unacceptable alignment is present following attempted closed reduction. Dorsal plating with either single-row 2-dimensional or double-row 3-dimensional plates has been proposed. This studys purpose was to determine if there are any differences in fixation construct stability under cyclic loading and subsequent load to failure between the lower profile 3-dimensional and the larger 2-dimensional plates in a metacarpal fracture gap sawbone model. METHODS Thirty metacarpal cortico-cancellous synthetic bones were cut with a 1.75-mm gap between the 2 fragments simulating mid-diaphyseal fracture comminution. Half of the metacarpals were plated with 2.0-mm locking 2-dimensional plates and half with 1.5-mm locking 3-dimensional plates. The plated metacarpals were mounted into a materials testing apparatus and cyclically loaded under cantilever bending for 2,000 cycles at 70 N, then 2,000 cycles at 120 N, and finally monotonically loaded to failure. Throughout testing, fracture gap sizes were measured, failure modes were recorded, and construct strength and stiffness values were calculated. RESULTS All 3-dimensional constructs survived both cyclic loading conditions. Ten (67%) 2-dimensional constructs survived both loading conditions, whereas 5 (33%) failed the 120-N loading at 1377 ± 363 cycles. When loaded to failure, the 3-dimensional constructs failed at 265 N ± 21 N, whereas the 2-dimensional constructs surviving cyclic loading failed at 190 N ± 17 N. CONCLUSIONS The shorter, thinner 3-dimensional metacarpal plates demonstrated increased resistance to failure in a cyclic loading model and increased load to failure compared with the relatively longer, thicker 2-dimensional metacarpal plates. CLINICAL RELEVANCE The lower-profile 3-dimensional metacarpal plate fixation demonstrated greater stability for early postoperative resistance than the thicker 2-dimensional fixation, whereas the smaller size and lower profile of the 3-dimensional plates potentially reduces soft tissue stripping, implant prominence, and risk of extensor tendon irritation.

Distal radius fracture complicated by carpal tunnel syndrome

Carpal tunnel syndrome is a well-described complication following distal radius fractures. Onset of symptoms can vary from hours to years after injury. It is important to identify the risks of median nerve compression such as local anesthetic hematoma-block injection, immobilization in a Cotton-Loder position, or malunion. Delayed carpal tunnel syndrome can be treated similar to chronic carpal tunnel in the general population. Although prophylactic carpal tunnel release at the time of distal radius fixation has not been recommended by the AAOS, it is important to recognize and treat acute carpal tunnel syndrome when symptoms occur. Lack of early recognition can lead to a delay in diagnosis and treatment, which can cause permanent nerve dysfunction.

Ulnar Styloid Fracture with Distal Radioulnar Joint Instability

A distal radius fracture with associated ulnar styloid fracture may place the patient at higher risk for distal radioulnar joint (DRUJ) instability. With anatomical reduction and volar plate fixation of the distal radius fracture, the ulnar styloid fracture is often indirectly reduced and the DRUJ remains stable. It has been shown that ulnar styloid fractures or its nonunion does not affect the outcome with adequate reduction and fixation of the distal radius fracture. However, large ulnar styloid base fractures or displacement over 2 mm may require open reduction and fixation of the ulnar styloid fracture to achieve DRUJ stability due to proximity of major DRUJ stabilizing ligaments. DRUJ instability may lead to chronic pain, decreased range of motion, and need for further salvage procedures for relief. The most important guiding principle is to evaluate DRUJ stability following distal radius fixation routinely to determine whether or not to address concomitant ulnar styloid fracture. If the DRUJ remains stable after anatomical fixation of the distal radius, ulnar styloid fixation is rarely required. If the DRUJ remains unstable, we would recommend open reduction and internal fixation of ulnar styloid fracture to achieve stability and reduce the risk of long-term problems.