Faculty Bibliography

BACKGROUND:Arthrofibrosis is a debilitating complication of total knee arthroplasty (TKA) and may benefit from arthroscopic lysis of adhesions (LOA) to improve range of motion and decrease pain. However, the rates of periprosthetic joint infection (PJI) and of the need for future revision TKA (rTKA) have only been studied in a limited capacity in the literature. In this study, we aimed to compare PJI and revision outcomes in patients who had undergone TKA between those who subsequently underwent arthroscopic LOA and those who did not undergo arthroscopic LOA. METHODS:The PearlDiver database was utilized to identify patients who had undergone primary TKA between 2016 and 2021. ICD-10 (International Classification of Diseases, Tenth Revision) and CPT (Current Procedural Terminology) codes were then used to identify patients who underwent LOA for arthrofibrosis. The rates of PJI and rTKA were compared between patients who did and did not undergo LOA. Multivariable logistic and Cox regressions, controlling for age, sex, Charlson Comorbidity Index, tobacco use, and a body mass index of >30 kg/m2, were performed to compare the rates of PJI and revision between the LOA and no-LOA groups. RESULTS:A total of 383,143 patients were identified, of whom 703 had undergone arthroscopic LOA. Patients who underwent LOA had higher overall rates of PJI (2.7% versus 1.3%; p = 0.001) and all-cause revision (9.8% versus 1.8%; p < 0.001) than those who did not. Patients who underwent LOA had significantly higher odds of PJI (odds ratio [OR], 2.00; p < 0.014), aseptic loosening-related revision (OR, 3.31; p = 0.002), and all-cause revision (OR, 5.32; p < 0.001) within 1 year after the initial TKA. There was no significant difference in 1-year PJI-related revisions between the groups (OR, 1.71; p = 0.193). In a time-to-event analysis, patients undergoing LOA had significantly higher risks of PJI (p = 0.003) and all-cause revision (p = 0.001) but not PJI-related revision (p = 0.322) or aseptic loosening-related revision (p = 0.111). CONCLUSIONS:Arthroscopic LOA after primary TKA was associated with higher rates of PJI and subsequent revision surgery. Surgeons should consider the results of these studies when counseling patients on the importance of early rehabilitation and improving modifiable risk factors after TKA. LEVEL OF EVIDENCE/METHODS:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

BACKGROUND/UNASSIGNED:Hospital websites play a key role when patients seek specialist care. Patients may become overwhelmed with the number of search results generated by hospital websites when looking for facial aesthetics procedures. This study characterizes plastic surgeons' representation on major hospital system websites in the United States for facial aesthetic procedures. METHODS/UNASSIGNED:The "find a doctor" tool on the top 20 US hospitals, as described in the US News and World Report's Hospital Rankings 2020-2021, was queried for 6 facial aesthetic procedures: rhinoplasty, facial rejuvenation, face lift, neck lift, blepharoplasty, and brow lift. Physician information such as their sex, medical specialty, medical school location, and residency program was recorded. RESULTS/UNASSIGNED:Our study revealed 1189 healthcare professionals, with 1077 being physicians. Plastic surgeons were consistently underrepresented in the results for each of the six search terms. The search term "blepharoplasty" produced the greatest number of plastic surgeons (44%), whereas the term "facial rejuvenation" produced the lowest number of plastic surgeons (32%). Nonsurgeons represented 6% of queries. CONCLUSIONS/UNASSIGNED:This study highlights the underrepresentation of plastic surgeons on hospital websites when searching for common facial aesthetic procedures. Factors such as the prevalence of procedures performed outside of hospitals, overlapping procedural privileges, and search engine inaccuracies may contribute to this issue. Patients may face challenges locating a plastic surgeon and could benefit from more streamlined guidance when using hospital websites.

BACKGROUND:Glioblastoma (GBM) represents a complex ecosystem characterized by numerous interactions between tumor cells and the surrounding tumor microenvironment (TME). Here, we show that WNT10A, a member of the WNT family, plays an important role in GBM growth where its influence is mediated via both autocrine and paracrine pathways thereby stimulating not only the tumor cells but also normal cell types within the tumor microenvironment (TME). METHODS:In silico analysis was performed to identify high-expressing WNT family members in GBM. Knockdown and overexpression methods were used to examine the function of WNT10A in GBM cells and in orthotopic GBM xenografts in vivo. Co-immunoprecipitation (Co-IP) was used to confirm receptor binding and chromatin immunoprecipitation (ChIP) was performed to analyze transcriptional activation of downstream genes. RESULTS:WNT10A was found to be highly expressed in GBMs and its knockdown significantly suppressed GBM malignant behavior in vitro and in vivo. Co-IP assays confirmed an interaction between WNT10A and FZD1, which activated the JNK/c-Jun/FOSB signaling pathway and enhanced the transcription of FOSB. Importantly, GBM cells secreted WNT10A into the tumor microenvironment, leading to an activation of the PI3K-AKT pathway in tumor-associated macrophages (TAMs) and the JNK pathway in tumor-associated astrocytes. The latter caused a secretion of tumor-promoting cytokines IL-6, MCP-1, and angiogenin. LGK974, a PORCN inhibitor, inhibited the secretion of WNT10A to suppress the malignant GBM phenotype. CONCLUSION/CONCLUSIONS:Our findings revealed that WNT10A is a critical factor promoting GBM progression through both autocrine and paracrine mechanisms. Thus, our findings provide the foundation for WNT-targeted clinical GBM treatment.

Cystic degeneration of thymoma can occur, although rarely to the extent that the lesion appears entirely cystic. We present a case of a 26-year-old man with a large anterior mediastinal cyst that was resected with histopathologic examination revealing a cystic thymoma.

BACKGROUND:Federal laws require healthcare organizations (HCOs) to provide patients' disability accommodations when requested. However, patients' accommodations needs are often unmet, contributing to inequities in healthcare access and outcomes. Little is known about the systems and processes HCOs use to provide accommodations in varied settings. OBJECTIVE:To understand HCOs' systems and processes to provide disability accommodations. METHODS:We conducted qualitative interviews with HCO representatives responsible for disability-related initiatives within their organizations. The interviews elicited participants' current processes for providing disability-related accommodations at their HCOs. We used a team-based approach to thematic analysis, reviewing and summarizing quotations to identify themes and categorize text that exemplified themes. RESULTS:We interviewed 17 participants representing 15 HCOs, and identified four themes related to HCOs providing disability accommodations: 1) Providing accommodations proactively begins with identifying a need, though is often disconnected from the rest of the process; 2) Clinical areas had varied and duplicative processes; 3) Different workflows were created ad hoc for different types of accommodations; and 4) Critical need to educate staff on disability accommodations. Participants drew parallels between disability accommodations and language interpreter services, and also emphasized the importance of providing disability accommodations in a proactive rather than reactive manner. CONCLUSIONS:Health systems struggle with a lack of standardized processes to provide disability accommodations in an efficient, systematic way. While processes should be adapted to local contexts, standardized guidelines for providing accommodations could improve consistency in their delivery, ultimately helping to mitigate health-related disparities in the healthcare setting.

Minoritized groups experience interpersonal, structural, and systemic marginalization that is also perpetuated within academic institutions. This marginalization produces barriers that exclude racial/ethnic minoritized groups within academic medicine from career opportunities and advancement. Racial/ethnic minoritized faculty are often expected to take on additional labor to serve the diversity needs of the program and/or institution that are often unrecognized or undervalued in the tenure or promotion process or detract from additional responsibilities. The unique needs resulting from multiple intersecting identities must be considered when planning initiatives to support minoritized groups in academia. This is detrimental to medicine as it limits innovation, perpetuates health disparities, and prevents the recruitment of scholars/physicians that are representative of the diversity within the U.S. population. Cluster hiring is a newer initiative adopted by many institutions; recently supported by funding from the National Institutes of Health (NIH) to improve diversity and inclusion of racial/ethnic minoritized groups. Here we discuss the elements of the cluster hire process and how they might be particularly relevant to intersectional inclusion and structural change of academic institutions, while also highlighting potential limitations to broad adoption. We conclude with recommendations for the potential need for integration of more culturally informed cluster hiring practices that can be made at the departmental, institutional and national level to positively impact the hiring, retention and advancement of faculty from marginalized populations.

This paper presents a Bayesian regression model relating scalar outcomes to brain functional connectivity represented as symmetric positive definite (SPD) matrices. Unlike many proposals that simply vectorize the matrix-valued connectivity predictors, thereby ignoring their geometric structure, the method presented here respects the Riemannian geometry of SPD matrices by using a tangent space modeling. Dimension reduction is performed in the tangent space, relating the resulting low-dimensional representations to the responses. The dimension reduction matrix is learned in a supervised manner with a sparsity-inducing prior imposed on a Stiefel manifold to prevent overfitting. Our method yields a parsimonious regression model that allows uncertainty quantification of all model parameters and identification of key brain regions that predict the outcomes. We demonstrate the performance of our approach in simulation settings and through a case study to predict Picture Vocabulary scores using data from the Human Connectome Project.

In May 2023 the World Health Organization (WHO) declared the end of COVID-19 as a public health emergency. Seroprevalence studies performed in African countries, such as Cameroon, depicted a much higher COVID-19 burden than reported by the WHO. To better understand humoral responses kinetics following infection, we enrolled 333 participants from Yaoundé, Cameroon between March 2020 and January 2022. We measured the levels of antibodies targeting the SARS-CoV-2 receptor-binding-domain (RBD) and the Spike glycoproteins of Delta, Omicron BA.1 and BA.4/5 and the common cold coronavirus HCoV-OC43. We also evaluated plasma capacity to neutralize authentic SARS-CoV-2 virus and to mediate Antibody-Dependent Cellular Cytotoxicity (ADCC). Most individuals mounted a strong antibody response against SARS-CoV-2 Spike. Plasma neutralization waned faster than anti-Spike binding and ADCC. We observed differences in humoral responses by age and circulating variants. Altogether, we show a global overview of antibody dynamics and functionality against SARS-CoV-2 in Cameroon.

Individuals with heritable thoracic aortic disease (HTAD) face a high risk of deadly aortic dissections, but genetic testing identifies causative variants in only a minority of cases. We explored the contribution of non-canonical splice variants (NCVAS) to thoracic aortic disease (TAD) using SpliceAI and sequencing data from diverse cohorts, including 551 early-onset sporadic dissection cases and 437 HTAD probands with exome sequencing, 57 HTAD pedigrees with whole genome sequencing, and select sporadic cases with clinical panel testing. NCVAS were identified in syndromic HTAD genes such as FBN1, SMAD3, and COL3A1, including intronic variants in FBN1 in two Marfan syndrome (MFS) families. Validation in the Penn Medicine BioBank and UK Biobank showed enrichment of NCVAS in HTAD-associated genes among dissections. These findings suggest NCVAS are an underrecognized contributor to TAD, particularly in sporadic dissection and unsolved MFS cases, highlighting the potential of advanced splice prediction tools in genetic diagnostics.