Faculty Bibliography

OBJECTIVE:The purpose of this study was to perform a network meta-analysis of level I and II evidence comparing different management techniques to define the optimum treatment method for humeral shaft fractures (HSFs). DATA SOURCES/METHODS:A systematic review of the literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of MEDLINE, Embase, and Cochrane Library was screened from 2010 to 2023. STUDY SELECTION/METHODS:Inclusion criteria were evidence level I or II studies comparing nonoperative and/or operative repair techniques including open reduction internal fixation plate osteosynthesis (ORIF-Plate), minimally invasive percutaneous plating (MIPO), and intramedullary nail (IMN) fixation for the management of HSFs (OTA/AO 12A, B, C). DATA EXTRACTION/METHODS:The risk of bias and methodologic quality of evidence were assessed according to the guidelines designed by the Cochrane Statistical Methods Group and Cochrane Methods Bias Group. DATA SYNTHESIS/RESULTS:Network meta-analysis was conducted with a frequentist approach with a random-effects model using the netmeta package version 0.9-6 in R. RESULTS:A total of 25 studies (1908 patients) were included. MIPO resulted in the lowest complication rate (2.1%) when compared with ORIF-Plate (16.1%) [odds ratio (OR), 0.13; 95% confidence interval (CI), 0.04-0.49]. MIPO resulted in the lowest nonunion rate (0.65%) compared with all management techniques (OR, 0.28; 95% CI, 0.08-0.98), whereas Non-Op resulted in the highest (15.87%) (OR, 3.48; 95% CI, 1.98-6.11). MIPO demonstrated the lowest rate of postoperative radial nerve palsy overall (2.2%) and demonstrated a significantly lower rate compared with ORIF-Plate (OR, 0.22; 95% CI, 0.07-0.71, P = 0.02). IMN resulted in the lowest rate of deep infection (1.1%) when compared with ORIF-Plate (8.6%; P = 0.013). MIPO resulted in a significantly lower Disabilities of the Arm, Shoulder, and Hand score (3.86 ± 5.2) and higher American Shoulder and Elbow Surgeons score (98.2 ± 1.4) than ORIF-Plate (19.5 ± 9.0 and 60.0 ± 5.4, P < 0.05). CONCLUSION/CONCLUSIONS:The results from this study support that surgical management results in better postoperative functional outcomes, leads to higher union rates, reduces fracture healing time, reduces revision rate, and decreases malunion rates in patients with HSFs. In addition, MIPO resulted in statistically higher union rates, lowest complication rate, lowest rate of postoperative radial nerve palsy, and lower intraoperative time while resulting in better postoperative Disabilities of the Arm, Shoulder, and Hand and American Shoulder and Elbow Surgeons scores when compared with nonoperative and operative (ORIF and IMN) treatment modalities. LEVEL OF EVIDENCE/METHODS:Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic aorta (ATA) compared to distal segments of the aorta and that collagen content increases in both the medial and adventitial compartments of the ATA during aging. The single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T lymphocyte clusters accumulate in the adventitia, while the activation of mechanosensitive Piezo-1 enhances vasoconstriction and contributes to the overall functional decline of ATA tissues. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

PURPOSE/OBJECTIVE:The primary goal of this study was to determine the anatomic relationship between the clavicle and the apical lung segment. The secondary goal was to determine the incidence of pneumothorax (PTX) in patients who underwent clavicle ORIF to analyze the utility of postoperative chest radiographs. METHODS:Six hundred thirty-one patients with a midshaft clavicle fracture who underwent superior plating at a single institution were identified. Forty-two patients had a CT scan of the chest. Three points on the uninjured clavicle were defined: 2 cm from the medial end of the clavicle, the mid-point of the clavicle, and 2 cm from the lateral end of the clavicle. At each point, the distance from both the inferior cortex and the superior cortex of the clavicle to the apical lung segment was measured. All 631 patients who underwent Open Reduction and Internal Fixation had a postoperative chest radiograph to evaluate implant placement, restoration of clavicular length, and presence of PTX. RESULTS:From the lateral end of the clavicle, the mean distance of the lung was 60.0 ± 14.9 mm (20.1 to 96.1 mm) from the inferior cortex of the clavicle. At the mid-point, the mean distance of the lung was 32.3 ± 7.2 mm (20.4 to 45.5 mm) from the inferior cortex of the clavicle. At the medial end, the mean distance of the lung was 18.0 ± 5.5 mm (8.1 to 28.9 mm) from the inferior cortex of the clavicle. A review of postoperative radiographs for all 631 patients revealed none (0%) with a postoperative iatrogenic PTX. CONCLUSION/CONCLUSIONS:The risk of injury is minimal in all three zones. Postoperative chest radiographs after clavicle fracture repair to rule out PTX are unnecessary.

Bone regeneration remains a significant clinical challenge, often necessitating surgical approaches when healing bone defects and fracture nonunions. Within this context, the modulation of adenosine signaling pathways has emerged as a promising therapeutic option, encouraging osteoblast activation and tempering osteoclast differentiation. A literature review of the PubMed database with relevant keywords was conducted. The search criteria involved in vitro or in vivo models, with clear methodological descriptions. Only studies that included the use of indirect adenosine agonists, looking at the effects of bone regeneration, were considered relevant according to the eligibility criteria. A total of 29 articles were identified which met the inclusion and exclusion criteria, and they were reviewed to highlight the preclinical translation of adenosine agonists. While preclinical studies demonstrate the therapeutic potential of adenosine signaling in bone regeneration, its clinical application remains unrealized, underscoring the need for further clinical trials. To date, only large, preclinical animal models using indirect adenosine agonists have been successful in stimulating bone regeneration. The adenosine receptors (A₁, A_2A, A_2B, and A₃) stimulate various pathways, inducing different cellular responses. Specifically, indirect adenosine agonists act to increase the extracellular concentration of adenosine, subsequently agonizing the respective adenosine receptors. The agonism of each receptor is dependent on its expression on the cell surface, the extracellular concentration of adenosine, and its affinity for adenosine. This comprehensive review analyzed the multitude of indirect agonists currently being studied preclinically for bone regeneration, discussing the mechanisms of each agonist, their cellular responses in vitro, and their effects on bone formation in vivo.

Infection and chronic post-traumatic osteomyelitis of the tibia after open fracture are complex problems that cause significant morbidity and threaten the viability of a limb. Therefore, it is of utmost importance for the orthopaedic surgeon to understand both patient and treatment factors that modify the risk of developing these disastrous complications. Infection risk is largely based on severity of open injury in addition to inherent patient factors. Orthopaedic surgeons can work to mitigate this risk with prompt antibiotic administration, thorough and complete debridement, expedient fracture stabilization, and early wound closure. In the case osteomyelitis does occur, the surgeon should use a systematic multidisciplinary approach for eradication.

Hair follicle neogenesis (HFN) occurs following large skin excisions in mice, serving as a rare regenerative model in mammalian wound healing. Wound healing typically results in fibrosis in mice and humans. We previously showed small skin excisions in mice result in scarring devoid of HFN, displaying features of non-regenerative healing, and Hedgehog (Hh) activation in the dermis of such wounds can induce HFN. In this study, we sought to verify the role of dermal Wnt/β-catenin signaling in HFN, as this pathway is essential for HF development, but is also paradoxically well-characterized in fibrosis of adult wounds. By deletion of β-catenin in large wound myofibroblasts, we show Wnt/β-catenin signaling is required for endogenous mechanisms of HFN. Through utilizing a combined mouse model that simultaneously induces deletion of β-catenin and constitutive activation of Smoothened (Smo) in myofibroblasts, we also found β-catenin is required for Hh-driven DP formation. Transcriptome analysis confirms Wnt/β-catenin and Hh pathways are activated in dermal papilla (DP) cells. Our results indicate that Wnt-active fibrotic status may also create a permissive state for the regenerative function of Hh, suggesting that activation of both Wnt and Hh pathways in skin wound fibroblasts must be ensured in future strategies to promote HFN.

The hair follicle and nail unit develop and regenerate through epithelial-mesenchymal interactions. Here, we review some of the key signals and molecular interactions that regulate mammalian hair follicle and nail formation during embryonic development and how these interactions are reutilized to promote their regeneration during adult homeostasis and in response to skin wounding. Finally, we highlight the role of some of these signals in mediating human hair follicle and nail conditions.

With an aging population, and an anticipated increase in overall fracture incidence, a sound understanding of bone healing and how technology can optimize this process is crucial. Concentrated bone marrow aspirate (cBMA) is a technology that capitalizes on skeletal stem and progenitor cells (SSPCs) to enhance the regenerative capacity of bone. This overview highlights the science behind cBMA, discusses the role of SSPCs in bone homeostasis and fracture repair, and briefly details the clinical evidence supporting the use of cBMA in fracture healing. Despite promising early clinical results, a lack of standardization in harvest and processing techniques, coupled with patient variability, presents challenges in optimizing the use of cBMA. However, cBMA remains an emerging technology that may certainly play a crucial role in the future of fracture healing augmentation.

Inflammatory epithelial diseases are spurred by the concomitant dysregulation of immune and epithelial cells. How these two dysregulated cellular compartments simultaneously sustain their heightened metabolic demands is unclear. Single-cell and spatial transcriptomics (ST), along with immunofluorescence, revealed that hypoxia-inducible factor 1α (HIF1α), downstream of IL-17 signaling, drove psoriatic epithelial remodeling. Blocking HIF1α in human psoriatic lesions ex vivo impaired glycolysis and phenocopied anti-IL-17 therapy. In a murine model of skin inflammation, epidermal-specific loss of HIF1α or its target gene, glucose transporter 1, ameliorated epidermal, immune, vascular, and neuronal pathology. Mechanistically, glycolysis autonomously fueled epithelial pathology and enhanced lactate production, which augmented the γδ T17 cell response. RORγt-driven genetic deletion or pharmacological inhibition of either lactate-producing enzymes or lactate transporters attenuated epithelial pathology and IL-17A expression in vivo. Our findings identify a metabolic hierarchy between epithelial and immune compartments and the consequent coordination of metabolic processes that sustain inflammatory disease.

This manuscript reviews the transformative impact of 3-dimensional (3D) printing technologies in the treatment and management of cleft lip and palate (CLP), highlighting its application across presurgical planning, surgical training, implantable scaffolds, and postoperative care. By integrating patient-specific data through computer-aided design and manufacturing, 3D printing offers tailored solutions that improve surgical outcomes, reduce operation times, and enhance patient care. The review synthesizes current research findings, technical advancements, and clinical applications, illustrating the potential of 3D printing to revolutionize CLP treatment. Further, it discusses the future directions of combining 3D printing with other innovative technologies like artificial intelligence, 4D printing, and in situ bioprinting for more comprehensive care strategies. This paper underscores the necessity for multidisciplinary collaboration and further research to overcome existing challenges and fully utilize the capabilities of 3D printing in CLP repair.