Nicholas M. Bernthal

Background and Objectives Periprosthetic infection is a devastating complication following endoprosthetic reconstruction. This study utilized a large database of endoprostheses to describe the incidence, risk factors, and microbial profile of such infections to better catalogue and understand these catastrophic events. Methods A retrospective review of endoprosthetic reconstructions for an oncologic indication from January 1, 1981 to December 31, 2020 was performed. Demographic, oncologic, procedural and outcome data was analyzed. Multivariable logistic regression was used to identify potential risk factors for infection with significance defined as p < 0.05. Results Forty four out of 712 (6.2%) reconstructions resulted in infection at a mean time of 39.9 ± 44.5 months. Revision surgery (odds ratio [OR] 6.14, p < 0.001) or having a postoperative wound complication (OR 7.67, p < 0.001) were significantly associated with infection. Staphylococcus aureus and Staphylococcus epidermidis were the most commonly cultured organisms at a rate of 34.1% (15/44) and 22.7% (10/44), respectively. Ten infections resulted in amputation; five due to antimicrobial‐resistant infections and three due to polymicrobial infections. Conclusion Understanding the microbial profile of patients undergoing endoprosthetic reconstruction is paramount. This study demonstrates a relatively high rate of polymicrobial and antibiotic‐resistant infections that portend worse outcomes, thus suggesting that pathogen‐specific infectious practices may be warranted. Level of Evidence Retrospective cohort study, level III.

Tenosynovial giant cell tumor (TGCT) is a rare, benign, locally aggressive synovial based neoplastic process that can result in functional debilitation and end‐stage arthrtitis. Although surgical resection is the primary treatment modality, novel systemic therapies are emerging as part of the multimodal armamentarium for patients with unresectable or complex disease burden. This review discusses the pathogenesis of TGCT, potential druggable targets and therapeutic approaches. It also evaluates the safety and efficacy of different systemic therapies.

Chordomas are rare tumors of notochordal origin, most commonly arising in the sacrum or skull base. Chordomas are considered insensitive to conventional chemotherapy, and their rarity complicates running timely and adequately powered trials to identify effective treatments. Therefore, there is a need for discovery of novel therapeutic approaches. Patient-derived organoids can accelerate drug discovery and development studies and predict patient responses to therapy. In this proof-of-concept study, we successfully established organoids from seven chordoma tumor samples obtained from five patients presenting with tumors in different sites and stages of disease. The organoids recapitulated features of the original parent tumors and inter- as well as intrapatient heterogeneity. High-throughput screenings performed on the organoids highlighted targeted agents such as PI3K/mTOR, EGFR, and JAK2/STAT3 inhibitors among the most effective molecules. Pathway analysis underscored how the NF-κB and IGF-1R pathways are sensitive to perturbations and potential targets to pursue for combination therapy of chordoma.