Assessment of Ulnar Carpal Translocation and Carpal Alignment After Volar Plate Fixation With Vascularized Bone Graft for Scaphoid Waist Fracture Nonunions.

PURPOSE: Multiple fixation methods with or without vascularized graft have been described to treat scaphoid nonunions. This study aimed to assess the incidence of carpal malalignment and the degree of ulnar carpal translocation after scaphoid volar plate fixation with pedicled vascularized bone graft in scaphoid waist nonunions with humpback deformity. METHODS: A retrospective cohort study of individuals with recalcitrant scaphoid fracture nonunion treated with volar scaphoid plating and vascularized bone graft was analyzed. All patients had radiographs with the wrist at neutral with clinical follow-up of at least 3 months after surgery. Ulnar subluxation of the carpus was assessed by the change in lunate uncovering and carpal-radial distance before and after surgery. RESULTS: Seventeen patients were included for analysis. Average age was 26 years with an average follow-up interval of 11.0 months. After surgery, 16 patients (94.1%) had fracture union. Between preoperative and initial postoperative imaging, there was an increase in lunate uncovering (mean difference: 8.8%; 95% confidence interval, 4.6% to 13.1%) and carpal-radial distance (mean difference: 3.3% ulnar shift; 95% confidence interval, 1.1% to 5.4%). After surgery, there was minimal change in lunate uncovering and carpal-radial distance from immediately after surgery to final follow-up. CONCLUSIONS: Preoperative lunate uncovering was lower than normal values, suggesting an abnormal radial shift of the carpus with a collapsed scaphoid. Postoperative lunate uncovering was similar to normal values, reflecting an ulnar shift of the carpus after operative intervention. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Probiotics: Can it modulate fracture healing?

OBJECTIVE: Fractures remain a huge burden and their management adversely affects individuals' function and productivity during the lengthy healing period. Gut microbiota exerts a systemic influence on diverse aspects of host physiology, including bone. The primary objective of this study was to evaluate if oral probiotic treatment before or after a fracture in a mouse model could increase cytokines and biomarkers essential for bone healing with subsequent improvement in the biomechanical properties of the healed callus. METHODS: Femoral osteotomy and intramedullary pinning were performed on C57BL/6 mice. Group 1 received either control PBS or probiotic via oral gavage for 5 weeks before fracture (pre-fracture). Group 2 received equivalent treatments for 4 weeks only after fracture (post-fracture). Fracture calluses were harvested on day 3 and 7 for RT-qPCR to quantify osteogenic-related inflammatory cytokines and bone biomarkers. Fractured femurs were evaluated day 28 post-osteotomy via microstructural analysis (µCT) and biomechanical testing (torsion). RESULTS: Mice treated with probiotics pre-fracture (group 1) showed significantly increased gene expression on day 3 of cytokines TGF-ß, IL-6 and IL-17F and a corresponding increase in gene expression on day 7 for Col1 and Runx2. Significant improvement was also seen in bone volume fraction, bone mineral density, tissue mineral density, maximum yield torque, stiffness and strain energy. Mice treated with probiotics post-fracture (group 2), demonstrated no changes in cytokine or bone marker gene expression with no significant changes on microstructural analysis. However, significant increases were seen in twist angle at failure and strain energy, with a corresponding reduction in torsional stiffness. CONCLUSION: Our results suggest that oral probiotic administration, before or after a fracture, may sufficiently alter the gut flora microenvironment leading to improved bone healing biomechanical properties. The use of probiotics may provide a cost-effective and low-risk adjunctive therapy to improve fracture healing.

Distal Biceps Tendon Tears: Diagnosis and Treatment Algorithm.

¼: Distal biceps tendon (DBT) tears occur most commonly in middle-aged men after a sudden, forced eccentric contraction of the flexed elbow. ¼: An understanding of the multiple risk factors, mechanisms, and pathophysiological causes is essential for proper and timely diagnosis. ¼: High clinical suspicion and routine physical examination with appropriate special examination tests, including the hook test, the passive forearm pronation test, the biceps crease interval test, and the bicipital aponeurosis flex test, can help with rapid and accurate diagnosis and guide appropriate and timely management. ¼: Treatment for DBT tears depends on the extent (complete versus incomplete) and timing (acute versus chronic) of the injury, and options include nonoperative management, repair, and reconstruction with or without repair of the bicipital aponeurosis.

Hyaluronic acid/carboxymethyl cellulose directly applied to transected nerve decreases axonal outgrowth.

Neuroma management is an unresolved problem. Biomaterials to limit unwanted axonal growth could be a tool to manage neuroma. Hyaluronic acid/carboxymethyl cellulose (HA/CMC) is an antiadhesive, biodegradable material that is nontoxic to nerve. The purpose of this study was to evaluate the efficacy of this biomaterial to limit axonal growth. Rats received a sciatic nerve transection and repair with a short conduit (5 mm) containing HA/CMC, fibrin, or nothing (empty conduit). In another study, nerve was transected and either left undisturbed or wrapped with HA/CMC around the proximal and distal ends. In a final study, nerve was transected and repaired with an HA/CMC wrap. Four weeks following the procedures, nerves were harvested and assessed using histomorphometry to measure axonal regeneration. Axonal regeneration following transection was significantly inhibited by direct axonal contact with HA/CMC, whether within a conduit or wrapped around the transected proximal nerve end. Axonal regeneration following epineurial repair was not affected by HA/CMC wrapped around nerve, demonstrating axonal growth inhibition due to direct contact of regenerating axons with HA/CMC. These studies demonstrate the efficacy of HA/CMC to limit axonal outgrowth by contact with regenerating axons. HA/CMC barriers may prove to be a tool to prevent neuroma formation by inhibiting axonal growth. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 568-574, 2017.

A cellular response linking eIF4AI activity to eIF4AII transcription.

The recruitment of ribosomes to eukaryotic cellular mRNAs requires the activity of two prototypic RNA helicases, eukaryotic initiation factor (eIF) 4AI and eIF4AII. The eIF4A isoforms are highly conserved, are thought to be functionally interchangeable, and are directed to the 5' m(7)GpppN cap structure of mRNAs during translation initiation by virtue of their assembly into eIF4F, a heterotrimeric complex that also harbors the eIF4E cap binding protein and eIF4G scaffolding unit. During the course of RNA interference experiments aimed at investigating the respective roles of eIF4AI and eIF4AII in translation, we uncovered a cellular response pathway whereby suppression of eIF4AI increases transcription of the eIF4AII gene, leading to elevated eIF4AII mRNA and protein levels. Inhibition of eIF4AI suppresses protein synthesis, and although eIF4AII protein levels increase above and beyond what should be sufficient to compensate for the decrease in eIF4AI levels, there is no corresponding rescue of translation or of the block on cellular proliferation that occurs upon eIF4AI suppression. These results were phenocopied using the small molecule eIF4A inhibitor hippuristanol. Taken together, our results indicate that eIF4AI and eIF4AII expression appear linked and that the two protein isoforms exhibit functional differences.

Targeting protein synthesis in a Myc/mTOR-driven model of anorexia-cachexia syndrome delays its onset and prolongs survival.

Anorexia-cachexia syndrome (ACS) is a major determinant of cancer-related death that causes progressive body weight loss due to depletion of skeletal muscle mass and body fat. Here, we report the development of a novel preclinical murine model of ACS in which lymphomas harbor elevated Myc and activated mTOR signaling. The ACS phenotype in this model correlated with deregulated expression of a number of cytokines, including elevated levels of interleukin-10 which was under the direct translational control of mTOR. Notably, pharmacologic intervention to impair protein synthesis restored cytokine production to near-normal levels, delayed ACS progression, and extended host survival. Together, our findings suggest a new paradigm to treat ACS by strategies which target protein synthesis to block the production of procachexic factors.