Femoral shaft displacement and Winquist classification provide predictive characteristics for combined femoral neck and femoral shaft fractures.

OBJECTIVES: The goal of this study is to establish radiographic features and characteristics of patient injury in cases of femoral shaft fractures that predict the presence of ipsilateral femoral neck fractures (IFNFs). METHODS: Patient data was retrospectively assessed from a single level I trauma center through the electronic health record using (Current Procedural Terminology) CPT codes for both isolated and combined ipsilateral femoral shaft and neck fractures. Demographic information, injury characteristics, and independently reviewed radiographic features were collected and compared against the same information from a group of isolated femoral shaft fractures. Multivariable logistic regression was performed to identify risk factors for concomitant IFNFs and their respective odds ratios. A probability algorithm for assessing ipsilateral femoral neck fractures based on independent multivariate predictors was constructed and used. RESULTS: A total of 113 patients with either isolated femoral shaft fractures or combined femoral shaft and IFNF (n = 33) met inclusion criteria and were identified for this study. Fracture displacement was most strongly associated with increased risk of combined injury with an aOR of 25.64 (95 %CI = 5.96-110.28) for every 100 % displacement. Motorcycle crash (MCC) was the mechanism associated with the highest risk of combined injury, with an aOR of 9.85 (95 % CI = 1.99-48.74). Combined injury was also correlated with lower Winquist score and presentation with a closed fracture, with aORs of 0.38 (95 %CI = 0.21 - 0.68) and 11.61 (95 %CI = 1.93-69.94), respectively. Presence of at least 3 of the statistically significant variables produced a positive predictive value (PPV) of ≥ 89 % for combined femoral shaft and IFNF. CONCLUSIONS: Identification of combined femoral shaft and IFNF is of critical importance when caring for orthopedic trauma patients. While diagnosis remains a challenging task, MCC mechanism, >100 % fracture displacement, and lower Winquist classification were found to be associated with combined injuries. The combination of these variables might assist in predicting the probability of combined injury and potentially guide decision making on the appropriateness of obtaining single sequence MRI or implementing prophylactic femoral neck fixation. LEVEL OF EVIDENCE: Level III.

Testosterone replacement therapy is associated with increased odds of Achilles tendon injury and subsequent surgery: a matched retrospective analysis.

BACKGROUND: Prescription of testosterone replacement therapy (TRT) has increased in the United States in recent years, and though anabolic steroids have been associated with tendon rupture, there is a paucity of literature evaluating the risk of Achilles tendon injury with TRT. This study aims to evaluate the associative relationship between consistent TRT, Achilles tendon injury, and subsequent surgery. METHODS: This is a one-to-one matched retrospective cohort study utilizing the PearlDiver database. Records were queried for patients aged 35-75 who were prescribed at least 3 consecutive months of TRT between January 1, 2010 and December 31, 2019. Achilles tendon injuries and subsequent surgeries were identified using ICD-9, ICD-10, and CPT billing codes. Multivariable logistic regression was used to compare odds of Achilles tendon injury, Achilles tendon surgery, and revision surgery, with a p-value < 0.05 representing statistical significance. RESULTS: A sample of 423,278 patients who filled a TRT prescription for a minimum of 3 consecutive months was analyzed. The 2-year incidence of Achilles tendon injury was 377.8 (95% CI, 364.8-391.0) per 100,000 person-years in the TRT cohort, compared to 245.8 (95% CI, 235.4-256.6) in the control (p < 0.001). The adjusted analysis demonstrated TRT to be associated with a significantly increased likelihood of being diagnosed with Achilles tendon injury (aOR = 1.24, 95% CI, 1.15-1.33, p < 0.001). Of those diagnosed with Achilles tendon injury, 287/3,198 (9.0%) of the TRT cohort subsequently underwent surgery for their injury, compared to 134/2,081 (6.4%) in the control cohort (aOR = 1.54, 95% CI, 1.19-1.99, p < 0.001). CONCLUSIONS: There is a significant association between Achilles tendon injury and prescription TRT, with a concomitantly increased rate of undergoing surgical management. These results provide insight into the risk profile of TRT and further research into the science of tendon pathology in the setting of TRT is an area of continued interest.

Smart Strategies to Overcome Drug Delivery Challenges in the Musculoskeletal System.

The musculoskeletal system (MSKS) is composed of specialized connective tissues including bone, muscle, cartilage, tendon, ligament, and their subtypes. The primary function of the MSKS is to provide protection, structure, mobility, and mechanical properties to the body. In the process of fulfilling these functions, the MSKS is subject to wear and tear during aging and after injury and requires subsequent repair. MSKS diseases are a growing burden due to the increasing population age. The World Health Organization estimates that 1.71 billon people suffer from MSKS diseases worldwide. MSKS diseases usually involve various dysfunctions in bones, muscles, and joints, which often result in pain, disability, and a decrease in quality of life. The most common MSKS diseases are osteoporosis (loss of bone), osteoarthritis (loss of cartilage), and sarcopenia (loss of skeletal muscle). Because of the disease burden and the need for treatment, regenerative drug therapies for MSKS disorders are increasingly in demand. However, the difficulty of effective drug delivery in the MSKS has become a bottleneck for developing MSKS therapeutics. The abundance of extracellular matrix and its small pore size in the MSKS present a formidable barrier to drug delivery. Differences of vascularity among various MSKS tissues pose complications for drug delivery. Novel strategies are necessary to achieve successful drug delivery in different tissues composing the MSKS. Those considerations include the route of administration, mechanics of surrounding fluids, and biomolecular interactions, such as the size and charge of the particles and targeting motifs. This review focuses on recent advances in challenges to deliver drugs to each tissue of the MSKS, current strategies of drug delivery, and future ideas of how to overcome drug delivery challenges in the MSKS.

Matrilin-2 within a three-dimensional lysine-modified chitosan porous scaffold enhances Schwann cell migration and axonal outgrowth for peripheral nerve regeneration.

Background: Matrilin-2 is a key extracellular matrix protein involved in peripheral nerve regeneration. We sought to develop a biomimetic scaffold to enhance peripheral nerve regeneration by incorporating matrilin-2 within a chitosan-derived porous scaffold. We hypothesized that the use of such a novel biomaterial delivers microenvironmental cues to facilitate Schwann cell (SC) migration and enhance axonal outgrowth during peripheral nerve regeneration. Materials and Methods: The effect of matrilin-2 on SC migration was evaluated with agarose drop migration assay on matrilin-2 coated dishes. SC adhesion was determined with SCs cultured atop tissue culture dishes coated with matrilin-2. Various formulations of chitosan vs matrilin-2 in scaffold constructs were examined with scanning electron microscopy. The effect of the matrilin-2/chitosan scaffold on SC migration in the collagen conduits was determined by capillary migration assays. Neuronal adhesion and axonal outgrowth were evaluated with three-dimensional (3D) organotypic assay of dorsal root ganglions (DRG). DRG axonal outgrowth within the scaffolds was determined by immunofluorescence staining of neurofilaments. Results: Matrilin-2 induced SC migration and enhanced its adhesion. A formulation of 2% chitosan with matrilin-2 demonstrated an optimal 3D porous architecture for SC interaction. Matrilin-2/chitosan scaffold enabled SCs to migrate against gravity within conduits. Chemical modification of chitosan with lysine (K-chitosan) further improved DRG adhesion and axonal outgrowth than the matrilin-2/chitosan scaffold without lysine modification. Conclusion: We developed a matrilin-2/K-chitosan scaffold to mimic extracellular matrix cues and provide a porous matrix to enhance peripheral nerve regeneration. Taking advantage of matrilin-2's capability to stimulate SC migration and adhesion, we formulated a porous matrilin-2/chitosan scaffold to support axongal outgrowth. Chemical modification of chitosan with lysine further improved matrilin-2 bioactivity in the 3D scaffold. The 3D porous matrilin-2/K-chitosan scaffolds have high potential for enhancing nerve repair by stimulating SC migration, neuronal adhesion, and axonal outgrowth.

COBRE for Skeletal Health and Repair: The Impact of Aging on the Capacity for Peripheral Nerve Regeneration.

Peripheral nerves are crucial to the motor and sensory function provided by our upper and lower extremities to our brain and spinal cord. Following trauma or illness, these nerves may be injured, leading to a loss of function that can be significantly debilitating. Fortunately, given the type of injury and under the right conditions, peripheral nerves can regenerate through well-coordinated biochemical processes. However, as individuals age, the ability for nerves to regenerate becomes less efficient, reducing nerve's potential for the nerve to return to its prior level of function. In this article, we review the research that has been conducted to illustrate the reasons for such a decline in regenerative capacity. In doing so, we explore the concept of inflammaging alongside aging-related impairments of the macrophage and Schwann cell during nerve regeneration.