AOA Critical Issues: Perceptions on the State of Diversity, Equity, and Inclusion in Orthopaedic Surgery: A Survey of the AOA Membership.

BACKGROUND: Orthopaedic surgery continues to trail other specialties in increasing diversity among its physician workforce. Various efforts have been and are currently being made to not only increase diversity, but also promote equity and inclusion in the field. The purpose of this study was to survey members of the American Orthopaedic Association (AOA) to determine how leaders in orthopaedics view diversity, equity, and inclusion (DEI) at the present time and to understand their perspective while moving into the future. METHODS: An anonymous 11-question survey was disseminated online to AOA members in May 2022. These individuals were identified by the AOA membership directory and the email ListServe. The survey included free-response and multiple-choice questions. Demographic information was self-identified, and both qualitative and quantitative data were collected. RESULTS: Of the 1,657 AOA members who were provided the survey, 262 (15.8%) responded. Approximately 29.5% (77) and 45.6% (119) of the surveyed population ranked "retention of underrepresented populations in orthopaedic residency (women, URiM)" as "very important" or "absolutely essential," respectively. The answers to the free-response questions identified multiple core themes that responders were passionate about, namely resident and attending physician recruitment and retention, as well as resident selection. CONCLUSIONS: Leaders in the field of orthopaedic surgery desire for action to be taken in the field of DEI. The findings of this survey denote positive attitudes even though many inequalities still pervade the field of orthopaedics. Through mentorship, objective evaluation, transparency, and continued intentional action, orthopaedic surgery is well-positioned to continue to move forward with DEI.

A Case of Periprosthetic Joint Infection Because of Rothia Mucilaginosa.

Periprosthetic joint infection (PJI) is a rare but devastating complication of total joint arthroplasty. Identifying the offending infectious agent is essential to appropriate treatment, and uncommon pathogens often lead to a diagnostic delay. This case describes the first known instance of a total knee arthroplasty (TKA) with Rothia mucilaginosa, a typical respiratory tract organism. This report aims to provide insight into the treatment of this atypical PJI, as there are only six previously published cases of Rothia species PJI septic arthritis. The patient is a 64-year-old diabetic male who underwent a right TKA and left TKA ∼6 months later. Approximately 3 weeks status post-left TKA, he showed evidence of left PJI. One year after treatment and recovery from his left PJI, he presented with several months of right knee pain and fatigue. Subsequent labs and imaging revealed right PJI. No recent history of dental disease or work was observed. He then underwent two-stage revision right knee arthroplasty and microbial cultures yielded Rothia mucilaginosa. After initial empiric treatment, antibiotic therapy was narrowed to 6 weeks of vancomycin. Following negative aspiration cultures the patient underwent reimplantation of right TKA components. One year following treatment, the patient was fully recovered with no evidence of infection. This case emphasizes the possibility of microbial persistence despite various antibiotic treatment regimens for the patient's contralateral knee arthroplasty and PJI. Additionally, this case demonstrates the importance of two-stage revision in patients with PJI, and the viability of treating Rothia species PJIs with vancomycin.

Thermal stability and structure of glyceraldehyde-3-phosphate dehydrogenase from the coral Acropora millepora.

Corals are vulnerable to increasing ocean temperatures. It is known that elevated temperatures lead to the breakdown of an essential mutualistic relationship with photosynthetic algae. The molecular mechanisms of this temperature-dependent loss of symbiosis are less well understood. Here, the thermal stability of a critical metabolic enzyme, glyceraldehyde-3-phosphate dehydrogenase, from the stony coral Acropora millepora was found to increase significantly in the presence of its cofactor NAD+. Determination of the structure of the cofactor-enzyme complex (PDB ID 6PX2) revealed variable NAD+ occupancy across the four monomers of the tetrameric enzyme. The structure of the fully occupied monomers was compared to those with partial cofactor occupancy, identifying regions of difference that may account for the increased thermal stability.

The anthraquinone emodin inhibits the non-exported FIKK kinase from Plasmodium falciparum.

The FIKK family of kinases is unique to parasites of the Apicomplexan order, which includes all malaria parasites. Plasmodium falciparum, the most virulent form of human malaria, has a family of 19 FIKK kinases, most of which are exported into the host red blood cell during malaria infection. Here, we confirm that FIKK 8 is a non-exported member of the FIKK kinase family. Through expression and purification of the recombinant kinase domain, we establish that emodin is a relatively high-affinity (IC50=2µM) inhibitor of PfFk8. Closely related anthraquinones do not inhibit PfFk8, suggesting that the particular substitution pattern of emodin is critical to the inhibitory pharmacophore. This first report of a P. falciparum FIKK kinase inhibitor lays the groundwork for developing specific inhibitors of the various members of the FIKK kinase family in order to probe their physiological function.

FIKK Kinase, a Ser/Thr Kinase Important to Malaria Parasites, Is Inhibited by Tyrosine Kinase Inhibitors.

A relatively high-affinity inhibitor of FIKK kinase from the malaria parasite Plasmodium vivax was identified by in vitro assay of recombinant kinase. The FIKK kinase family is unique to parasitic organisms of the Apicomplexan order and has been shown to be critical in malaria parasites. The recombinant kinase domain was expressed and screened against a small molecule library, revealing a number of tyrosine kinase inhibitors that block FIKK kinase activity. A family of tyrphostins was further investigated, to begin exploring the FIKK kinase pharmacophore. Finally, emodin was identified as a relatively high-affinity FIKK kinase inhibitor, identifying this family of anthraquinones as potential lead compounds for the development of antimalarials targeting the FIKK kinase.