Suture Fixation of Subacute Pediatric Seymour Fractures.

Seymour fractures are common injuries in the pediatric population. High rates of deep infection have been reported due to delayed presentation and subsequent treatment. This report describes the case of a 13-year-old male wrestler who presented 1 month after a finger injury that was later diagnosed as a subacute Seymour fracture with osteomyelitis. The patient underwent irrigation and debridement and fracture reduction stabilized with nonabsorbable suture fixation. After 6 weeks of intravenous antibiotics, the patient was recovering well, with radiographic evidence of fracture healing and clearance of infection. This case highlights the use of a single suture as a treatment option for fixation of unstable Seymour fractures with delayed presentation. The management of acute open distal phalangeal physeal fractures is well described in the literature; however, further investigations are warranted into the optimal management of chronically infected digits with unstable Seymour fractures.

Characterizing the host response to rhPDGF-BB in a rat spinal arthrodesis model.

BACKGROUND: Due to the constraints surrounding autograft bone, surgeons have turned to osteoinductive agents to augment spinal fusion. Reports of complications and questionable efficacy slowed the adoption of these alternatives. Recombinant human platelet-derived growth factor B homodimer (rhPDGF-BB) has been Food and Drug Administration (FDA)-approved (Augment) to promote fusion in other areas of orthopedics, but its characterization in spine fusion has not yet been tested. The purpose of this study is to characterize the host response to PDGF-BB in vivo. METHODS: Eighty female Fischer rats underwent L4-5 posterolateral fusion using one of four implant types: (a) iliac crest syngeneic allograft harvested from syngeneic donors, (b) ß-TCP/bovine collagen matrix (ß-TCP/Col) with sodium acetate buffer, (c) ß-TCP/Col with 0.3 mg/mL "low dose," or (d) ß-TCP/Col with 3.0 mg/mL "high dose" of rhPDGF-BB. Animals underwent magnetic resonance imaging (MRI) and serum cytokine quantification at 4, 7, 10, and 21 days, postoperatively. Tissues were processed for immunofluorescence staining for Ki67 and von Willebrand factor (vWF) to assess neovascularization. RESULTS: MRI demonstrated no differences in fluid accumulation among the four treatment groups at any of the time points. Serum cytokine analysis showed no clinically significant differences between treatment groups in 20 of the 27 cytokines. Inflammatory cytokines IFN-γ, IL-1ß, IL-18, MCP-1, MIP-1α, TNF-α were not induced by rhPDGF-BB. Histology showed no differences in cell infiltration, and Ki67 and vWF immunofluorescence staining was similar among groups. CONCLUSIONS: rhPDGF-BB delivered with a ß-TCP/Col matrix exerts no exaggerated systemic or local host inflammatory response when compared to iliac crest syngeneic allograft bone or the control carrier. rhPDGF-BB mixed with a ß-TCP/Col matrix could be a viable and safe biologic alternative to syngeneic allograft in spine fusion. Further studies need to be performed to evaluate efficacy in this setting.

Iron Uptake via DMT1 Integrates Cell Cycle with JAK-STAT3 Signaling to Promote Colorectal Tumorigenesis.

Dietary iron intake and systemic iron balance are implicated in colorectal cancer (CRC) development, but the means by which iron contributes to CRC are unclear. Gene expression and functional studies demonstrated that the cellular iron importer, divalent metal transporter 1 (DMT1), is highly expressed in CRC through hypoxia-inducible factor 2α-dependent transcription. Colon-specific Dmt1 disruption resulted in a tumor-selective inhibitory effect of proliferation in mouse colon tumor models. Proteomic and genomic analyses identified an iron-regulated signaling axis mediated by cyclin-dependent kinase 1 (CDK1), JAK1, and STAT3 in CRC progression. A pharmacological inhibitor of DMT1 antagonized the ability of iron to promote tumor growth in a CRC mouse model and a patient-derived CRC enteroid orthotopic model. Our studies implicate a growth-promoting signaling network instigated by elevated intracellular iron levels in tumorigenesis, offering molecular insights into how a key dietary component may contribute to CRC.

HIF2α Is an Essential Molecular Brake for Postprandial Hepatic Glucagon Response Independent of Insulin Signaling.

Glucagon drives hepatic gluconeogenesis and maintains blood glucose levels during fasting. The mechanism that attenuates glucagon action following refeeding is not understood. The present study demonstrates an increase in perivenous liver hypoxia immediately after feeding, which stabilizes hypoxia-inducible factor 2α (HIF2α) in liver. The transient postprandial increase in hepatic HIF2α attenuates glucagon signaling. Hepatocyte-specific disruption of HIF2α increases postprandial blood glucose and potentiates the glucagon response. Independent of insulin/AKT signaling, activation of hepatic HIF2α resulted in lower blood glucose, improved glucose tolerance, and decreased gluconeogenesis due to blunted hepatic glucagon action. Mechanistically, HIF2α abrogated glucagon-PKA signaling by activating cAMP-phosphodiesterases in a MEK/ERK-dependent manner. Repression of glucagon signaling by HIF2α ameliorated hyperglycemia in streptozotocin-induced diabetes and acute insulin-resistant animal models. This study reveals that HIF2α is essential for the acute postprandial regulation of hepatic glucagon signaling and suggests HIF2α as a potential therapeutic target in the treatment of diabetes.