Faculty Bibliography

Complex extremity wounds, if not addressed properly, are a leading cause of major limb amputation. Chronic wounds in salvaged extremities contribute to long-term morbidity in the extremity. Orthoplastic surgery treats limb-threatening conditions through the combined application of orthopaedic and plastic surgical principles, applied to clinical problems simultaneously. Key components include early stakeholder evaluation of the limb and patient and open collaborative communication between orthopaedic and plastic surgeons. Meticulous débridement at the time of presentation and careful selection of fixation informed by the overall reconstructive plan should be executed when the patient presents to the emergency department. Implementation of Orthoplastic protocols results in quicker time to skeletal stabilization and soft tissue coverage, reduced risk of infection, improved functional outcomes, and less cost for care. This review presents a protocol-driven guide for establishing an Orthoplastic program and optimizing limb salvage outcomes across diverse practice settings.

BACKGROUND:The authors aimed to evaluate dentists' knowledge of, diagnostic confidence in, perception of, and clinical management for molar incisor hypomineralization (MIH) across countries with varying income levels and identify predictors of MIH familiarity. METHODS:and Mann-Whitney U tests and generalized linear models. RESULTS:A total of 4,056 dentists participated. Familiarity and diagnostic confidence increased with country income level (P < .001) and were highest among pediatric dentists (P < .001). Knowledge scores varied; they were higher among dentists from higher-income countries, women, pediatric dentists, and those aged 31 through 40 years, with 5 or more years of experience, working in public settings, and holding advanced degrees (all, P < .001). Enamel hypoplasia was the common diagnostic challenge, and fewer than one-half reported using established MIH criteria. Preventive and minimally invasive strategies were frequent in high- and upper-middle-income countries, whereas low- and lower-middle-income dentists relied on basic restorative materials and extensive tissue removal. Pulpal therapy followed standard protocols, although conservative vital pulpal therapy was common in upper-middle-income settings. Respondents from high-income countries cited technical failures often, and those from low-income countries reported greater behavioral barriers. Regression analysis confirmed income level, specialty, and experience as predictors of familiarity and confidence. CONCLUSIONS:Substantial global disparities exist in MIH knowledge, diagnostic confidence, and clinical management strategies. Improved training and resource-appropriate guidelines are essential to reduce inequities in MIH care. PRACTICAL IMPLICATIONS/CONCLUSIONS:The authors highlight the need for targeted training and context-specific guidelines to improve MIH diagnosis, confidence, and management, particularly in low-income settings.

BACKGROUND:Smoking has been linked to alterations in cellular inflammatory pathways and adverse outcomes in orthopaedic procedures. It is unclear how patient smoking affects the intra-articular microenvironment in the setting of symptomatic meniscal tears. PURPOSE/OBJECTIVE:To investigate the association between tobacco use and variation in cytokine concentrations in knee synovial fluid in patients undergoing arthroscopic knee surgery for symptomatic meniscal injury. STUDY DESIGN/METHODS:Cohort study; Level of evidence, 3Methods:Patients who underwent knee arthroscopy for meniscal injury were prospectively enrolled between July 2011 and June 2019. Synovial fluid was aspirated and the concentrations of 10 biomarkers were measured by immunoassay. Smoking status, pack-years, and time since smoking cessation were collected. Log-normalized biomarker concentrations and smoking status were analyzed using analysis of variance (ANOVA) and linear regression. RESULTS:= .0084). CONCLUSION/CONCLUSIONS:Smoking status was found to be significantly associated with alterations in synovial fluid biomarker profiles in patients undergoing arthroscopic knee surgery for meniscal injury. RANTES was negatively associated with pack-years in current smokers, and IL-6 was positively associated with time since smoking cessation in former smokers. These findings suggest that smoking may have lasting effects on joint inflammation after injury, and that biomarker profiles can provide insight into local tissue responses influenced by smoking history.

IMPORTANCE/UNASSIGNED:As transcatheter aortic valve replacement (TAVR) is considered for younger and lower-risk populations, the durability of bioprosthetic valves is increasingly important. Limited data exist on long-term (7 years and beyond) valve durability. OBJECTIVE/UNASSIGNED:To report 7-year valve durability outcomes for low-risk patients with symptomatic severe aortic stenosis treated with TAVR vs surgery. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Between March 2016 and October 2017, a total of 1000 patients were enrolled at 71 centers in the US and Canada and randomized to undergo TAVR vs surgery. The patient population for the present analysis consisted of all patients who underwent valve implantation (495 with TAVR and 453 with surgery). The last 7-year follow-up occurred in March 2025. INTERVENTIONS/UNASSIGNED:Patients were randomized to balloon-expandable TAVR with the SAPIEN 3 valve or surgery with any commercially available valve. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The main outcomes of this analysis were stage 2 or 3 bioprosthetic valve dysfunction (BVD) related to structural valve deterioration (SVD), thrombosis, or endocarditis; all-cause bioprosthetic valve failure (BVF); BVF related to SVD; and aortic valve reintervention at 7 years. Analyses are presented as cumulative incidence rates with death as a competing risk. RESULTS/UNASSIGNED:The mean (SD) age of the study population was 73.5 (6.0) years, and 657 participants (69.3%) were male. Of 671 patients who were still alive and enrolled in the study at 7-year follow-up, 537 (80.0%) were available for echocardiographic analysis. Cumulative incidence rates of stage 2 or 3 SVD-related BVD (7.3% vs 7.6%; hazard ratio [HR], 0.96; 95% CI, 0.59-1.57; P = .88), all-cause BVF (6.9% vs 7.5%; HR, 0.91; 95% CI, 0.55-1.49; P = .69), SVD-related BVF (3.9% vs 5.3%; HR, 0.72; 95% CI, 0.39-1.36; P = .31), and valve reintervention (6.0% vs 5.5%; HR, 1.09; 95% CI, 0.62-1.90; P = .77) were low and similar for TAVR and surgery, respectively. Stage 2 or 3 thrombosis-related BVD (subclinical and clinical) occurred more frequently with TAVR (5.2% vs 0.9%; HR, 5.52; 95% CI, 1.92-15.85; P < .001), although most events occurred within 3 years and few progressed to BVF. Rates of stage 2 or 3 endocarditis-related BVD were also low and similar (0.4% in the TAVR group vs 0.5% in the surgery group; HR, 0.85; 95% CI, 0.12-6.07; P = .87). The proportion of patients alive and free of all-cause BVF was 73.4% (331/451) with TAVR vs 74.8% (288/385) with surgery (P = .69). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this ad hoc analysis of a randomized clinical trial among low-risk patients with symptomatic severe aortic stenosis randomized to TAVR or surgery, both TAVR and surgery demonstrated comparable and sustained valve durability, with low and similar rates of SVD, all-cause BVF, and reintervention through 7 years. These findings may inform discussions of valve replacement strategies. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02675114.

Growth/differentiation factor-15 (GDF15) is a secreted cytokine strongly associated with dementia risk. However, the extent to which GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15- to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular, compared to Alzheimer's disease (AD), dementia. Two-sample Mendelian randomization supported plasma GDF15's mechanistic role in AD and related dementias, while cohort studies linked it to cerebral small vessel disease, neurodegeneration, phosphorylated tau, and a cerebrospinal fluid proteomic signature indicative of neuroimmune activation. Exposure of cultured myeloid cells to recombinant GDF15 altered biological pathways that we subsequently demonstrated are predictive of dementia risk, including interferon/antiviral responses. These findings support circulating GDF15's role as an early biomarker-particularly for vascular dementia and neuroinflammation-and identify the mechanisms by which it may drive dementia risk.

Melanoma is a highly aggressive and invasive form of skin cancer that arises from the uncontrolled growth of melanocytes. It is characterized by early spread through the lymphatic system and metastasis. The success of metastasis is linked to the ability of melanoma and other cancer cells to resist anoikis, a type of cell death that occurs when cells lose their adhesion to the extracellular matrix. Redox signaling plays an essential role in anoikis resistance. The balance between intracellular levels of nitric oxide (NO) and the reactive oxygen species (ROS) O₂

We propose Open Immune Oncology (OpenIO), a framework integrating generative AI and omics to advance precision oncology. By leveraging biological scaling laws and foundation models, we aim to transition immunotherapy from empirical screening to rational, AI-native engineering of therapeutic interventions.