Faculty Bibliography

BACKGROUND:Vascularized composite allotransplantation (VCA) holds significant promise for patients with complex structural defects, providing solutions unattainable through traditional methods. Despite technical successes, graft rejection and ischemia-reperfusion injury (IRI) present major challenges, with high rejection rates even under modern immunosuppression protocols. This review synthesizes current literature on immunologic pretreatments (IPTs) designed to mitigate these issues, focusing on interventions applied to donor tissues between procurement and transplantation. METHODS:A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 11 relevant studies, categorizing IPTs into donor tissue modification (DTM), deoxygenated perfusate, and oxygenation methods. RESULTS:DTM, the most common IPT method, shows promise in reducing immunogenicity and prolonging graft survival, primarily through techniques such as recipient bone marrow-derived cell conditioning and MHC-I knockdown using small interfering RNA (siRNA). Deoxygenated perfusate studies highlighted mitomycin C's potential in reducing immune response and extending graft viability. Oxygenation methods, aimed at minimizing IRIs, utilized perfusion techniques to maintain graft viability ex vivo. CONCLUSIONS:Although IPTs for extending graft survival have seen moderate clinical translation, those targeting immunogenicity remain largely experimental. This review underscores the potential of these IPT modalities to improve VCA outcomes by reducing rejection and IRIs. However, it also highlights the need for further research, particularly multi-center clinical trials, to validate these techniques for broader clinical adoption. This comprehensive synthesis aims to guide future studies and enhance clinical strategies for VCA, ultimately improving patient outcomes.

Virtual surgical planning (VSP) has revolutionized orthognathic and craniomaxillofacial surgeries by enabling precise 3-dimensional analysis, detailed osteotomy planning, and custom fabrication of surgical guides and fixation hardware. However, the visualization of registration holes-critical for accurate plate fixation-remains challenging, especially in a blood-filled surgical field. This paper presents a novel technique to enhance the visibility of registration holes using Bonney's blue dye. The technique involves injecting micro-aliquots of Bonney's blue dye (a mixture of crystal violet and brilliant green) into the registration holes before performing osteotomies. This approach ensures that the holes remain clearly marked despite potential visual contamination in the surgical field. The dye helps to identify screw placements and align patient-specific fixation plates more accurately. The proposed method addresses common difficulties in aligning registration holes with patient-specific plates during surgery. Bonney's blue dye provides a clear contrast against the bone, making the registration holes more visible and easier to locate. This improvement is particularly advantageous in a bloody surgical field and benefits less experienced surgeons by offering a straightforward solution to enhance accuracy and efficiency. The technique can also reduce overall operative time by minimizing the time spent locating and aligning the registration holes. Utilizing Bonney's blue dye in virtual surgical planning significantly improves the visibility and alignment of registration holes in orthognathic surgeries. This simple, cost-effective method enhances surgical precision and efficiency and can be applied to other computer-assisted surgical procedures in craniofacial surgery.

Therapeutic, IV.

GENERAL PURPOSE/OBJECTIVE:To review risk factors for the development of medical device-related and immobility-related pressure injuries in hospitalized pediatric patients. TARGET AUDIENCE/BACKGROUND:This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES/OBJECTIVE:After participating in this educational activity, the participant will be better able to:1. Describe trends in pressure injuries (PIs) for hospitalized pediatric patients as summarized in current literature.2. Identify risk factors predictive of medical device-related and immobility-related PIs in hospitalized pediatric patients.3. Summarize the methodology used to understand risk factors for developing PIs in the hospitalized pediatric patient population.

BACKGROUND:The preservation of the alveolar ridge following tooth extraction is crucial to prevent atrophy and maintain structural integrity, facilitating future dental rehabilitations. This study compared the use of two different polymeric, resorbable membranes: polylactic acid (PLA), and 5% polylactic acid + 95% polycaprolactone (PLA/PCL), relative to unassisted socket healing (negative control). MATERIAL AND METHODS/METHODS:A preclinical model involving healthy, skeletally mature beagles (n=7) were used in this study. Surface topography and thermal degradation of the membranes were assessed, followed by in vivo evaluation of socket preservation in extracted maxillary premolars. Histomorphometric analysis was employed to measure bone formation and total socket area. Data was analyzed through linear mixed models with fixed factor of treatment following a post-hoc comparison by the Tukey test. Ranked data of residual membrane presence and inflammatory infiltrate were analyzed through Kruskal-Wallis non-parametric test. All analyses were conducted with statistical significance set at p-value ≤ 0.05. RESULTS:Surface topography depicted a distinctive fibrous network structure for PLA membrane relative to PLA/PCL which exhibited a more porous architecture. Thermal degradation behavior/profile, observed through TGA and DSC, for both membranes was similar. Histomorphometric analysis of bone formation within the induced socket yielded 36.1 ±7.7%, 35.6 ±7.2% and 32.8 ±7.7% for control, PLA and PLA/PCL groups, respectively, with no statistically significant differences between groups (p = 0.796). Analysis of total socket area (mean ± 95% confidence intervals) yielded significantly higher values for experimental groups, PLA (8.95 ± 1.7 mm2) and PLA/PCL (8.8 ± 1.76 mm2), relative to control (6.7 ± 1.8 mm2) (p = 0.041). Residual membrane, along with mild inflammatory infiltrate was observed after the healing period irrespective of membrane type utilized. CONCLUSIONS:Guided bone regeneration (GBR) with PLA and PLA/PCL membranes did not yield higher bone formation within the socket relative to the control group. However, an improvement in the preservation of the socket's architecture was observed.

RATIONALE & OBJECTIVE/OBJECTIVE:Despite substantial growth in the population of older adults with kidney disease, there remains a lack of evidence to guide clinical care for this group. The Kidney Disease and Aging Research Collaborative (KDARC) conducted a Delphi study to build consensus on research priorities for clinical geriatric nephrology. STUDY DESIGN/METHODS:Asynchronous modified Delphi study. SETTING & PARTICIPANTS/METHODS:Clinicians and researchers in the US and Canada with clinical experience and/or research expertise in geriatric nephrology. OUTCOME/RESULTS:Research priorities in geriatric nephrology. ANALYTICAL APPROACH/METHODS:In the first Delphi round, participants submitted free-text descriptions of research priorities considered important for improving the clinical care of older adults with kidney disease. Delphi moderators used inductive content analysis to group concepts into categories. In the second and third rounds, participants iteratively reviewed topics, selected their top 5 priorities, and offered comments used to revise categories. RESULTS:Among 121 who were invited, 57 participants (47%) completed the first Delphi round and 48 (84% of enrolled participants) completed all rounds. After 3 rounds, the 5 priorities with the highest proportion of agreement were: 1) Communication and Decision-Making about Treatment Options for Older Adults with Kidney Failure (69% agreement), 2) Quality of Life, Symptom Management, and Palliative Care (67%), 3) Frailty and Physical Function (54%), 4) Tailoring Therapies for Kidney Disease to Specific Needs of Older Adults (42%), and 5) Caregiver and Social Support (35%). Health equity and person-centricity were identified as cross-cutting features that informed all topics. LIMITATIONS/CONCLUSIONS:Relatively low response rate and limited participation by private practitioners and older clinicians and researchers. CONCLUSIONS:Experts in geriatric nephrology identified clinical research priorities with the greatest potential to improve care for older adults with kidney disease. These findings provide a roadmap for the geriatric nephrology community to harmonize and maximize the impact of research efforts.

BACKGROUND/UNASSIGNED:In vascularized composite allotransplantation, face transplantation stands as a transformative intervention for patients with severe facial disfigurement. Monitoring of graft rejection, however, remains a critical challenge. This study aimed to investigate the role of lymphocyte subsets in the early detection and monitoring of graft rejection in face transplantation. METHODS/UNASSIGNED:We conducted a retrospective chart review of 3 face transplant recipients who underwent face transplantation at our institution. Peripheral blood samples were analyzed for lymphocyte subsets at multiple time points posttransplantation. A linear mixed-effects model was used, aiming to identify any upregulation associated with episodes of graft rejection. RESULTS/UNASSIGNED:= 0.0015, respectively). CONCLUSIONS/UNASSIGNED:Our study demonstrates that monitoring specific lymphocyte subsets offers a promising adjunct for graft surveillance that is less invasive when compared with traditionally used punch biopsies. This approach not only enhances the precision of rejection monitoring but also improves patient comfort and compliance, thereby contributing to better long-term graft outcomes.

In recognizing the critical role of vitamin D in bone metabolism and osseointegration, research aims to identify whether preoperative vitamin D deficiency serves as a risk factor for early implant failure. By analyzing patient outcomes and their serum vitamin D levels, studies seek to establish evidence-based recommendations for vitamin D assessment and management in the preoperative period, with the ultimate goal of enhancing implant success rates and patient outcomes in dental implantology. Given these insights, it is important for clinicians to incorporate the preoperative evaluation of vitamin D serum levels into their standard protocol for patients undergoing dental implant procedures. The objective of this study is to review and investigate the correlation between early dental implant failure (EDIF) and reduced serum levels of vitamin D, and to evaluate the potential benefits of preoperative screening and supplementation of vitamin D in patients undergoing dental implant surgery. A literature review was performed using a selected database-PubMed, Google Scholar, Cochrane, and SCOPUS-to assess the effect of vitamin D3 level on EDIF and biological factors (i.e., peri-implant bone level). Studies were limited to peer-reviewed, indexed journals. Subsequently, a hypothesis was proposed that vitamin D3 supplementation would mitigate the negative effect of vitamin D3 deficiency. The potential benefit of vitamin D3 supplementation-systemic and topical-was assessed in terms of bone-to-implant contact (BIC) and peri-implant bone level. The deleterious effects of low vitamin D serum levels on osseointegration of dental implants and immune system modulation are increasingly accepted. Evidence has displayed that deficiency of this vitamin can result in impaired peri-implant bone formation. Vitamin D deficiency resulted in nearly a fourfold increase in overall EDIF incidence. Presurgical supplementation of vitamin D3 demonstrated increased levels of implant osseointegration, increased bone-implant contact, enhanced bone level maintenance, and decreased EDIF even in at-risk demographics (i.e., diabetic subjects). The findings of this study reinforce the role of vitamin D in dental implant osseointegration. Our study, particularly, emphasizes the necessity of vitamin D supplementation for individuals with sub-physiologic vitamin D serum levels (≤ 30 ng/mL) and those within specific risk categories: smokers, diabetics, obese individuals, and those with compromised immune systems. Adopting a proactive management plan, including screening and supplementation in these patients, may substantially enhance the clinical outcomes in dental implant surgery.

Preclinical testing of tissue engineering modalities are commonly performed in a healthy wound bed. These conditions do not represent clinically relevant compromised oral wound environments due to radiation treatments seen clinically. This study aimed to characterize the bone regeneration outcomes in critical-sized mandibular defects using particulate grafting in an irradiated preclinical model of compromised wound healing. Sixteen New Zealand white rabbits were divided into two groups (n = 8/group), namely (i) irradiated (experimental) and (ii) non-irradiated (control). The rabbits in the experimental group received a total of 36 Gy radiation, followed by surgical intervention to create critical-sized (10 mm), full-thickness mandibular defects. The control group was subjected to the same surgical intervention. All defects were filled with bovine bone grafting material (Bio-Oss, Geistlich, Princeton, NJ, USA) and allowed to heal for 8 weeks. At the study endpoint, rabbits were euthanized, and their mandibles were harvested for micro-computed tomographic, histological, and histomorphometric processing and analysis. Qualitative histological analysis revealed increased levels of bone formation and bridging in the control group relative to the experimental group. This was accompanied by increased levels of soft tissue presence in the experimental group. Volumetric reconstruction showed a significantly higher degree of bone in the control group (27.59% ± 2.71), relative to the experimental group (22.02% ± 2.71) (p = 0.001). The irradiated rabbit model exhibited decreased bone regeneration capacity relative to the healthy subjects, highlighting its suitability as a robust compromised wound healing environment for further preclinical testing involving growth factors or customized, high-fidelity 3D printed tissue engineering scaffolds.

Sodium-glucose transporter-2 inhibitor (SGLT2i) drugs are widely used for lowering blood glucose levels independent of insulin. Beyond this, these drugs induce various metabolic changes, including weight loss and impaired bone integrity. There is a significant gap in understanding SGLT2i-induced skeletal changes, as SGLT2 is not expressed in osteoblasts or osteocytes, which use glucose to remodel the bone matrix. We studied the impact of 1, 3, or 6 months of canagliflozin (CANA), an SGLT2i treatment, on the skeleton of 6-month-old genetically heterogeneous UM-HET3 mice. Significant metabolic adaptations to CANA were evident as early as 1.5 months post-treatment, specifically in male mice. CANA-treated male mice exhibited notable reductions in body weight and decreased proinflammatory and bone remodeling markers associated with reduced cortical bone remodeling indices. Bone tissue metabolome indicated enrichment in metabolites related to amino acid transport and tryptophan catabolism in CANA-treated male mice. In contrast, CANA-treated female mice showed increases in nucleic acid metabolism. An integrOmics approach of source-matched bone tissue metabolome and bone marrow RNAseq indicated a positive correlation between the two omics data sets in male mice. Three clusters of transcripts and metabolites involved in energy metabolism, oxidative stress response, and cellular proliferation and differentiation were reduced in CANA-treated male mice. In conclusion, CANA affects bone metabolism mainly via the 'glucose restriction state' it induces and impacts bone cell proliferation and differentiation. These findings underline the effects of SGLT2i on bone health and highlight the need to consider sex-specific responses when developing clinical treatments that alter substrate availability.