Naproxen treatment inhibits articular cartilage loss in a rat model of osteoarthritis.

The effects of naproxen, a nonsteroidal anti-inflammatory drug (NSAID), on articular cartilage degeneration in female Sprague-Dawley rats was examined. Osteoarthritis (OA) was induced by destabilization of the medial meniscus (DMM) in each knee. Rats were treated with acetaminophen (60 mg/kg), naproxen (8 mg/kg), or 1% carboxymethylcellulose (placebo) by oral gavage twice daily for 3 weeks, beginning 2 weeks after surgery. OA severity was assessed by histological Osteoarthritis Research Society International (OARSI) scoring and by measuring proximal tibia cartilage depth using contrast enhanced µCT (n = 6 per group) in specimens collected at 2, 5, and 7 weeks after surgery as well as on pristine knees. Medial cartilage OARSI scores from the DMM knees of naproxen-treated rats were statistically lower (i.e., better) than the medial cartilage OARSI scores from the DMM knees of placebo-treated rats at 5-weeks (8.7 ± 3.6 vs. 13.2 ± 2.4, p = 0.025) and 7-weeks (9.5 ± 1.2 vs. 12.5 ± 2.5, p = 0.024) after surgery. At 5 weeks after DMM surgery, medial articular cartilage depth in the proximal tibia specimens was significantly greater in the naproxen (1.78 ± 0.26 mm, p = 0.005) and acetaminophen (1.94 ± 0.12 mm, p < 0.001) treated rats as compared with placebo-treated rats (1.34 ± 0.24 mm). However, at 7 weeks (2 weeks after drug withdrawal), medial articular cartilage depth for acetaminophen-treated rats (1.36 ± 0.29 mm) was significantly reduced compared with specimens from the naproxen-treated rats (1.88 ± 0.14 mm; p = 0.004). The results indicate that naproxen treatment reduced articular cartilage degradation in the rat DMM model during and after naproxen treatment.

Intracompartmental Versus Extracompartmental Transposition of the Extensor Pollicis Longus for Treating Thumb-in-Palm Deformity: A Biomechanical Comparison.

PURPOSE: Transecting the extensor pollicis longus (EPL) tendon and rerouting it through the first extensor compartment is an established technique for treating thumb-in-palm deformity (TIPD). An alternative technique that approximates the trajectory of the first extensor compartment without violating the compartment or transecting the EPL tendon can be accomplished by creating an artificial sheath from the extensor retinaculum to radialize the tendon glide path. This study compares this extracompartmental (EC) EPL transposition to the established, intracompartmental (IC) transposition by evaluating, in a cadaver model, the extent of thumb extension in both techniques. METHODS: Eighteen fresh-frozen cadaveric hands were each tested under 3 different conditions: EPL in situ (baseline); EPL rerouted above the first extensor compartment (EC); and EPL rerouted through the first extensor compartment (IC). A controlled traction of 10 N was applied to the EPL under each condition. The range of thumb extension with respect to the fixed index finger was recorded utilizing infrared reflective markers and digital video capture. RESULTS: The mean extension of the thumb with the EPL tendon in situ was 16.7°. The mean extension of the thumb was 22.0° with the EC transposition versus 25.0° with the IC technique. The measured thumb extension in both the EC and the IC techniques were found to be similar because both EPL transpositions yielded a significant difference in thumb extension when compared with baseline. CONCLUSIONS: This biomechanical model demonstrates that radial transposition of the EPL tendon enhances extension of the thumb regardless of whether the tendon is routed through, or superficial to, the first extensor compartment. CLINICAL RELEVANCE: A novel technique, the EC EPL transposition, offers a similar enhancement in measured thumb extension as the already-described IC EPL transposition.

The Role of BMI in Hip Fracture Surgery.

INTRODUCTION: Obesity is an oft-cited cause of surgical morbidity and many institutions require extensive supplementary screening for obese patients prior to surgical intervention. However, in the elderly patients, obesity has been described as a protective factor. This article set out to examine the effect of body mass index (BMI) on outcomes and morbidity after hip fracture surgery. METHODS: The National Surgical Quality Improvement Program database was queried for all patients undergoing 1 of 4 surgical procedures to manage hip fracture between 2008 and 2012. Patient demographics, BMI, and known factors that lead to poor surgical outcomes were included as putative predictors for complications that included infectious, cardiac, pulmonary, renal, and neurovascular events. Using χ2 tests, 30-day postoperative complication rates were compared between 4 patient groups stratified by BMI as low weight (BMI < 20), normal (BMI = 20-30), obese (BMI = 30-40), and morbidly obese (BMI > 40). RESULTS: A total of 15 108 patients underwent surgery for hip fracture over the examined 5-year period. Of these, 18% were low weight (BMI < 20), 67% were normal weight (BMI = 20-30), 13% were obese (BMI = 30-40), and 2% were morbidly obese (BMI > 40). The low-weight and morbidly obese patients had both the highest mortality rates and the lowest superficial infection rates. There was a significant increase in blood transfusion rates that decreased linearly with increasing BMI. Deep surgical site infection and renal failure increased linearly with increasing BMI, however, these outcomes were confounded by comorbidities. CONCLUSION: This study demonstrates that patients at either extreme of the BMI spectrum, rather than solely the obese, are at greatest risk of major adverse events following hip fracture surgery. This runs contrary to the notion that obese hip fracture patients automatically require additional preoperative screening and perioperative services, as currently implemented in many institutions.

Readability of the Most Commonly Accessed Online Patient Education Materials Pertaining to Pathology of the Hand.

BACKGROUND: The American Medical Association (AMA) and National Institutes of Health (NIH) recommend that patient education materials be written at no higher than a sixth-grade reading level. METHODS: We examined 100 online educational materials for the 10 hand conditions most commonly treated by hand surgeons, as reported by the American Society for Surgery of the Hand. The listed conditions were carpal tunnel syndrome, basal joint arthritis of the thumb, de Quervain syndrome, Dupuytren's contracture, ganglion cysts, hand fractures, trigger finger, extensor tendon injuries, flexor tendon injuries, and mallet finger. Following a Google search for each condition, we analyzed the 10 most visited websites for each disorder utilizing the Flesch-Kincaid formula. RESULTS: The average grade reading level of the 100 websites studied was 9.49 with a reading ease of 53.03 ("fairly difficult high school"). Only 29% of the websites were at or below the national average of an eighth-grade reading level. Carpal tunnel syndrome had the highest average grade reading level at 10.32 (standard deviation: 1.52), whereas hand fractures had the lowest at 8.14 (2.03). Every hand condition in this study had an average readability at or above the ninth-grade reading level. CONCLUSIONS: The most frequently accessed materials for common maladies of the hand exceed both the readability limits recommended by the AMA and NIH, and the average reading ability of most US adults. Therefore, the most commonly accessed websites pertaining to hand pathology may not be comprehended by the audience for which it is intended.

Readability of the Most Commonly Accessed Arthroscopy-Related Online Patient Education Materials.

PURPOSE: To assess the readability and comprehension of written text by the most commonly visited websites containing patient education materials on common conditions that can be treated arthroscopically. METHODS: We examined 50 websites, assessed independently by 2 orthopaedic surgery residents (S.A. and G.G.), with educational materials on 5 common conditions treated by arthroscopic surgeons: anterior cruciate ligament (ACL) tear, meniscus tear, hip labral tear, shoulder labral tear, and rotator cuff tear. Following a Google search for each condition, we analyzed the 10 most visited websites for each disorder using a widely used and validated tool for assessing the reading levels of written materials (Flesch-Kincaid formula). RESULTS: The average grade reading level of the 50 websites studied was 9.90 with a reading ease of 52.14 ("fairly difficult, high school"). Only 26% of the websites were at or below the national average of an eighth-grade reading level. Of the 5 conditions treated by arthroscopic surgery, ACL tear had the highest average grade reading level at 10.73 ± 1.54, whereas meniscus tear had the lowest at 9.31 ± 1.81. Every condition in this study had an average readability at or above the ninth-grade reading level. CONCLUSIONS: The most frequently accessed materials for patients with injuries requiring arthroscopic surgery exceeds the readability recommendations of the American Medical Association and National Institutes of Health, as well as the average reading ability of US adults. Given the fact that these are the most commonly visited websites by the lay public, there needs to be a greater emphasis on tailoring written information to the literacy levels of the patient population. CLINICAL RELEVANCE: This study emphasizes the discrepancy between the recommended versus the measured reading levels of online patient education materials related to conditions treated by arthroscopic surgeons. The subject matter of these conditions is inherently complex; thus, relying solely on text to inform patients increases the likelihood that the reading level of the material exceeds that of the majority of the lay public.

Importance of the posterior bundle of the medial ulnar collateral ligament.

BACKGROUND: There has been a renewed interest in the pathomechanics of elbow dislocation, with recent literature having suggested that the medial ulnar collateral ligament is more often disrupted in dislocations than the lateral ligamentous complex. The purpose of this serial sectioning study was to determine the influence of the posterior bundle of the medial ulnar collateral ligament (pMUCL) as a stabilizer against elbow dislocation. METHODS: An elbow dislocation was simulated in 5 cadaveric elbows by mechanically applying an external rotation moment and valgus force. Medial ulnohumeral joint gapping was measured at 30°, 60°, and 90° of flexion in an intact elbow after sectioning of the medial collateral ligament's anterior bundle (aMUCL) and then after sectioning of the pMUCL as well. RESULTS: After sectioning of the aMUCL, the pMUCL was able to stabilize the joint against dislocation. After aMUCL sectioning, the proximal joint space significantly increased by 4.2 ± 0.6 mm at 30° of flexion and 2.6 ± 0.3 mm at 60° of flexion, although it did not dislocate. The gapping increase of 0.9 ± 0.6 at 90° of flexion did not reach significance. After sectioning of the pMUCL (after having already sectioned the aMUCL), all of the specimens frankly dislocated at all flexion angles. CONCLUSIONS: An intact pMUCL can prevent elbow dislocation and limited joint subluxation to within 6.6 mm. Our findings indicate that repair or reconstruction may be warranted in certain circumstances (ie, residual instability after operative management of a terrible triad injury or after aMUCL reconstruction).

Atypical Tumoral Presentation of Calcium Pyrophosphate Deposition Disease: A Case Report.

CASE: A 55-year-old man presented with a history of forefoot pain and swelling. Radiographs revealed a mass with internal calcifications and osseous erosion of the fifth metatarsophalangeal bone. The mass was isointense to muscle on T1-weighted magnetic resonance imaging (MRI) and hyperintense on T2-weighted MRI. A biopsy was performed, and intraoperatively, the lesion appeared as chalky white material, which under polarized light microscopy was composed of weakly positively birefringent rhomboid crystals, leading to a diagnosis of tophaceous pseudogout. CONCLUSION: Tophaceus pseudogout should be included in the differential diagnosis of neoplastic-appearing lesions in the foot, and polarized light microscopy should be used when examining biopsy specimens.

Kremen1 restricts Dkk activity during posterior lateral line development in zebrafish.

Canonical Wnt signaling plays crucial roles during development and disease. How Wnt signaling is modulated in different in vivo contexts is currently not well understood. Here, we investigate the modulation of Wnt signaling in the posterior lateral line primordium (pLLP), a cohort of ~100 cells that collectively migrate along the trunk of the zebrafish embryo. The pLLP comprises proliferative progenitor cells and organized epithelial cells that will form the mechanosensory organs of the posterior lateral line. Wnt signaling is active in the leading progenitor zone of the pLLP and restricted from the trailing zone through expression of the secreted Wnt inhibitors dkk1b and dkk2. We have identified a zebrafish strain, krm1(nl10), which carries a mutation in the kremen1 gene, a non-obligate co-receptor for the Dkk family of proteins. Previous studies have shown that Kremen1 inhibits Wnt signaling by facilitating internalization of the Kremen1-Dkk-Lrp5/6 complex. Surprisingly, we found that disruption of Kremen1 in the pLLP exhibited molecular and cellular phenotypes associated with a decrease rather than overactivation of Wnt signaling. Transplantation of wild-type cells into the mutant primordia failed to rescue the krm1(nl10) phenotype, thus revealing that the effects of Kremen1 loss are non-cell-autonomous. Finally, ectopic expression of Dkk1b-mTangerine protein revealed larger spread of the fusion protein in the mutant primordia compared with the wild type. Based on our data, we propose a novel mechanism in which Kremen1 modulates Wnt activity by restricting the range of secreted Dkk proteins during collective cell migration in the pLLP.

Lef1 is required for progenitor cell identity in the zebrafish lateral line primordium.

The zebrafish posterior lateral line (pLL) is a sensory system that comprises clusters of mechanosensory organs called neuromasts (NMs) that are stereotypically positioned along the surface of the trunk. The NMs are deposited by a migrating pLL primordium, which is organized into polarized rosettes (proto-NMs). During migration, mature proto-NMs are deposited from the trailing part of the primordium, while progenitor cells in the leading part give rise to new proto-NMs. Wnt signaling is active in the leading zone of the primordium and global Wnt inactivation leads to dramatic disorganization of the primordium and a loss of proto-NM formation. However, the exact cellular events that are regulated by the Wnt pathway are not known. We identified a mutant strain, lef1(nl2), that contains a lesion in the Wnt effector gene lef1. lef1(nl2) mutants lack posterior NMs and live imaging reveals that rosette renewal fails during later stages of migration. Surprisingly, the overall primordium patterning, as assayed by the expression of various markers, appears unaltered in lef1(nl2) mutants. Lineage tracing and mosaic analyses revealed that the leading cells (presumptive progenitors) move out of the primordium and are incorporated into NMs; this results in a decrease in the number of proliferating progenitor cells and eventual primordium disorganization. We concluded that Lef1 function is not required for initial primordium organization or migration, but is necessary for proto-NM renewal during later stages of pLL formation. These findings revealed a novel role for the Wnt signaling pathway during mechanosensory organ formation in zebrafish.

Netrin-1 is a novel myelin-associated inhibitor to axon growth.

We investigated the influence of the bifunctional guidance molecule netrin-1 on axonal growth in the injured adult spinal cord. In the adult, netrin-1 is expressed on mature oligodendrocytes, cells of the central canal, and the meninges. Netrin-1 protein in white matter is selectively enriched adjacent to paranodal loops of myelin in nodes of Ranvier. The repulsion-mediating netrin-1 uncoordinated-5 (UNC5) receptors are expressed by neurons of the corticospinal and rubrospinal projections, and by intrinsic neurons of the spinal cord, both before and after spinal cord injury. Neutralization of netrin-1 in myelin prepared from adult rat spinal cord using UNC5 receptor bodies increases neurite outgrowth from UNC5-expressing spinal motor neurons in vitro. Furthermore, axon regeneration is inhibited in a netrin-1-enriched zone, devoid of other myelin-associated inhibitors, within spinal cord lesion sites in vivo. We conclude that netrin-1 is a novel oligodendrocyte-associated inhibitor that can contribute to axonal growth failure after adult spinal cord injury.