Histologic grading correlates with inflammatory biomarkers in tibialis posterior tendon dysfunction.

BACKGROUND: It has been theorized that tibialis posterior tendon dysfunction (TPTD) is a degenerative process unrelated to inflammation. The purpose of this study was to determine if inflammatory cytokines, matrix metalloproteases (MMPs), and glutamate were elevated in diseased tibialis posterior tendons (TPTs). METHODS: Matched diseased TPT, TPT insertion, and flexor digitorum longus (FDL) samples were collected from 21 patients. The samples were individually incubated in media, which was analyzed for inflammatory cytokines, MMPs, and glutamate. Histology and statistical analyses were performed. RESULTS: Diseased TPT and TPT insertion were significantly elevated compared to transferred FDL in eight inflammatory markers (p < 0.005). Only the diseased TPT was significantly elevated compared to the transferred FDL tendons for glutamate (p < 0.01). Histologic grading correlated with inflammatory cytokine levels. CONCLUSION: Diseased TPT and TPT insertion demonstrated significantly elevated levels of inflammatory markers compared to the transferred tendons used as controls, suggesting a role for inflammation in the disease process. The amount of inflammation correlated with increased tendon degradation. LEVEL OF EVIDENCE: Level III.

Evaluation and Management of Posterior Wall Acetabulum Fractures.

Posterior wall acetabulum fractures typically result from high-energy mechanisms and can be associated with various orthopaedic and nonorthopaedic injuries. They range from isolated simple patterns to multifragmentary with or without marginal impaction. Determination of hip stability, which can depend on fragment location, size, and displacement, directs management. Although important in the assessment of posterior wall fractures, CT is unreliable when used to determine stability. The dynamic fluoroscopic examination under anesthesia (EUA) is the benchmark in assessment of hip stability, and fractures deemed stable by EUA have good radiographic and functional outcomes. In fractures that meet surgical criteria, accurate joint reduction guides outcomes. Joint débridement, identification and elevation of impaction, and adjunctive fixation of posterosuperior and peripheral rim fragments along with standard buttress plate fixation are critical. Complications of the fracture and surgical fixation include sciatic nerve injury, posttraumatic osteoarthritis, osteonecrosis of the femoral head, and heterotopic ossification. Although accuracy of joint reduction is paramount for successful results, other factors out of the surgeon's control such as comminution, femoral head lesions, and dislocation contribute to poor outcomes. Even with anatomic restoration of the joint surface, good clinical outcomes are not guaranteed and residual functional deficits can be expected.

Anatomic Magnetic Resonance Imaging Measurements in First-Time Patellar Dislocators by Sex and Age.

CONTEXT: Anatomic differences of the knee in first-time patellar dislocators have not been clearly elucidated. OBJECTIVE: To compare structural differences of the knee in those who have sustained an acute first-time patellar dislocation resulting in a medial patellofemoral ligament (MPFL) tear by sex and age (≤17 years old, ≥18 years old). DESIGN: Case series. SETTING: Retrospective magnetic resonance imaging analysis. PATIENTS OR OTHER PARTICIPANTS: Thirty-five acute first-time patellar dislocators with an associated MPFL tear. MAIN OUTCOME MEASURE(S): Patellar height using 3 methods, patellar alignment using congruency angles, and trochlear morphology using the sulcus angle. We compared the means of these variables by sex and age. The intraclass correlation coefficient was then calculated to assess the agreement of the independent reviewers. RESULTS: A total of 21 left and 14 right knees were analyzed. The MPFL tear location did not differ by sex (P = .34) or age (P = .43). Patellar height did not differ as measured by the Caton-Deschamps ratio (P = .29 for sex, P = .49 for age), Insall-Salvati index (P = .15 for sex, P = .33 for age), or patellotrochlear index (P = .67 for sex, P = .49 for age). The congruence angle (P = .81 for sex, P = .06 for age) and trochlear morphology as measured by the sulcus angle (P = .64 for sex, P = .45 for age) were similar between groups. CONCLUSIONS: Patellar height and trochlear morphology did not differ by sex or age among patients whose first-time patellar dislocations resulted in an MPFL tear. In addition, the location of the tear did not appear to vary by sex or age.

Conservative Management of Metatarsalgia and Lesser Toe Deformities.

There are several forefoot conditions that can result in metatarsal head pain. Various points of the gait cycle can predispose the metatarsal heads to pain based on intrinsic and extrinsic imbalances. Metatarsalgia can further be classified according to primary, secondary, or iatrogenic etiologies. Within these groups, conservative management is the first line of treatment and can often obviate surgical intervention. Depending on the cause of pain, proper shoewear, orthoses, and inserts coupled with targeted physical therapy can alleviate most symptoms of metatarsalgia and lesser toe deformities.

Synthesis and characterization of silk fibroin microparticles for intra-articular drug delivery.

OBJECTIVE: To determine the utility of silk fibroin (SF) microparticles as sustained release vehicles for intra-articular delivery. DESIGN: SF formulations were varied to generate microparticle drug carriers that were characterized in vitro for their physical properties, release kinetics for a conjugated fluorophore (Cy7), and in vivo for intra-articular retention time using live-animal, fluorescence in vivo imaging. RESULTS: SF microparticle carriers were spherical in shape and ranged from 598 nm to 21.5 µm in diameter. SF microparticles provided for sustained release of Cy7 in vitro, with only 10% of the initial load released over 7 days. Upon intra-articular injection in rat knee joints, the SF microparticles were associated with an intra-articular fluorescence decay half-life of 43.3h, greatly increasing the joint residence over that for an equivalent concentration of SF-Cy7 in solution form. The SF microparticles also increase the localization of dye within the joint cavity as determined by image analysis of fluorescent gradients, significantly reducing distribution of the Cy7 to neighboring tissue as compared to SF-Cy7 in free solution. CONCLUSION: Silk microparticles act to provide for localized and sustained delivery of loaded small molecules following intra-articular injection, and may be an attractive strategy for delivering small molecule drugs for the treatment of arthritis.

Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.

Cell delivery to the pathological intervertebral disc (IVD) has significant therapeutic potential for enhancing IVD regeneration. The development of injectable biomaterials that retain delivered cells, promote cell survival, and maintain or promote an NP cell phenotype in vivo remains a significant challenge. Previous studies have demonstrated NP cell - laminin interactions in the nucleus pulposus (NP) region of the IVD that promote cell attachment and biosynthesis. These findings suggest that incorporating laminin ligands into carriers for cell delivery may be beneficial for promoting NP cell survival and phenotype. Here, an injectable, laminin-111 functionalized poly(ethylene glycol) (PEG-LM111) hydrogel was developed as a biomaterial carrier for cell delivery to the IVD. We evaluated the mechanical properties of the PEG-LM111 hydrogel, and its ability to retain delivered cells in the IVD space. Gelation occurred in approximately 20 min without an initiator, with dynamic shear moduli in the range of 0.9-1.4 kPa. Primary NP cell retention in cultured IVD explants was significantly higher over 14 days when cells were delivered within a PEG-LM111 carrier, as compared to cells in liquid suspension. Together, these results suggest this injectable laminin-functionalized biomaterial may be an easy to use carrier for delivering cells to the IVD.

An ATM/Chk2-mediated DNA damage-responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells.

Epstein-Barr virus (EBV), an oncogenic herpesvirus that causes human malignancies, infects and immortalizes primary human B cells in vitro into indefinitely proliferating lymphoblastoid cell lines, which represent a model for EBV-induced tumorigenesis. The immortalization efficiency is very low, suggesting that an innate tumor suppressor mechanism is operative. We identify the DNA damage response (DDR) as a major component of the underlying tumor suppressor mechanism. EBV-induced DDR activation was not due to lytic viral replication, nor did the DDR marks colocalize with latent episomes. Rather, a transient period of EBV-induced hyperproliferation correlated with DDR activation. Inhibition of the DDR kinases ATM and Chk2 markedly increased transformation efficiency of primary B cells. Further, the viral latent oncoprotein EBNA3C was required to attenuate the EBV-induced DDR. We propose that heightened oncogenic activity in early cell divisions activates a growth-suppressive DDR that is attenuated by viral latency products to induce cell immortalization.