Is delayed time to surgery associated with increased postoperative complications in patients with pathologic humerus fractures?

INTRODUCTION: Delayed time to surgery, in the case of orthopedic trauma, is well known to be associated with higher morbidity and mortality, an extended duration of hospitalization, and an associated rise in overall cost. Delayed time to surgery of at least 3 days following hospital admission is associated with elevated risk of complications following surgery for a standard, non-pathologic, humeral shaft fracture. To our knowledge, it is unknown whether the same association is present for pathologic humerus fractures. The primary objective of this study was to identify risk factors, including patient characteristics, comorbidities, and postoperative complications, that are associated with delayed time to surgery following pathologic humeral fracture. METHODS: All patients undergoing surgical management of pathologic humerus fractures across a 6-year period from 2015 to 2021 were queried using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Postoperative complications were reported within 30 days of procedure. Delayed time to surgery was defined by ≥ 2 days from hospital admission to surgery. We identified a total of 248 patients, and 39.9% (n = 99) of patients had delayed time to surgery. Multivariate logistic regression adjusted for all significantly associated variables was employed to identify predictors of delayed time to surgery for pathologic humerus fractures. RESULTS: The characteristics of patients significantly associated with delayed time to surgery were ASA classification ≥ 3 (p = 0.016), dependent functional status (p = 0.041), and congestive heart failure (p = 0.008). After adjusting for all significantly associated patient variables, the characteristics of patients independently associated with delayed time to surgery were non-home discharge (OR: 2.93, 95% CI 1.53-5.63; p = 0.001) and extended length of stay (OR: 2.00, 95% CI 1.06-3.77; p = 0.033). CONCLUSION: Delayed time to surgery of at least 2 days was independently associated with non-home discharge and extended postoperative length of stay. After controlling for baseline patient characteristics and comorbidities, delayed time to surgery was not independently associated with increased 30-day complications after surgical treatment of pathologic humeral fractures. This is in contrast to standard, non-pathologic humerus fractures in which delayed time to surgery is associated with an increased risk of postoperative complications. LEVEL OF EVIDENCE III: Retrospective Cohort Comparison; Prognosis Study.

Novel bisphosphonate-based cathepsin K-triggered compound targets the enthesis without impairing soft tissue-to-bone healing.

Background: Osteoadsorptive fluorogenic sentinel 3 (OFS-3) is a recently described compound that contains a bone-targeting bisphosphonate (BP) and cathepsin K (Ctsk)-triggered fluorescence signal. A prior study in a murine Achilles repair model demonstrated its effectiveness at targeting the site of tendon-to-bone repair, but the intrinsic effect of this novel bisphosphonate chaperone on tendon-to-bone healing has not been previously explored. We hypothesized that application of this bisphosphonate-fluorophore cargo conjugate would not affect the biomechanical properties or histologic appearance of tendon-bone repairs. Materials and Methods: Right hindlimb Achilles tendon-to-bone repair was performed on 12-week old male mice. Animals were divided into 2 groups of 18 each: 1) Achilles repair with OFS-3 applied directly to the repair site prior to closure, and 2) Achilles repair with saline applied prior to closure. Repaired hindlimbs from 12 animals per group were harvested at 6 weeks for biomechanical analysis with a custom 3D-printed jig. At 4 and 6 weeks, repaired hindlimbs from the remaining animals were assessed histologically using H&E, immunohistochemistry (IHC) staining for the presence of Ctsk, and second harmonic generation (SHG) imaging to evaluate collagen fibers. Results: At 6 weeks, there was no significant difference in failure load, stiffness, toughness, or displacement to failure between repaired hindlimbs that received OFS-3 versus saline. There was no difference in tissue healing on H&E or Ctsk staining on immunohistochemistry between animals that received OFS-3 versus saline. Finally, second harmonic generation imaging demonstrated no difference in collagen fiber parameters between the two groups. Conclusion: OFS-3 did not significantly affect the biomechanical properties or histologic appearance of murine Achilles tendon-to-bone repairs. This study demonstrates that OFS-3 can target the site of tendon-to-bone repair without causing intrinsic negative effects on healing. Further development of this drug delivery platform to target growth factors to the site of tendon-bone repair is warranted.

Changes in the incidence of stress reactions and fractures among intercollegiate athletes after the COVID-19 pandemic.

PURPOSE: The purpose of this study was to characterize the impact of detraining due to the COVID-19 pandemic on incidence of bony injuries and stress fractures in collegiate athletes. METHODS: A comprehensive collegiate athletic conference injury database was queried for all in-season, sport-related bony injuries (defined as all stress reactions and fractures) that occurred across all sports from January 2016 to June 2021. The bony injury rate per 1000 athlete exposure hours (AEH) was calculated and compared between the immediate post-hiatus season and historic rates from pre-hiatus seasons (2016-2019). Injury characteristics were also compared between the pre- and post-hiatus time periods. RESULTS: A total of 868 bony injuries across 23 sports were identified. The sports with highest overall baseline bony injury rates in historic seasons were women's cross country (0.57 injuries per 1000 AEH) and men's cross country (0.32). Compared to historic pre-hiatus rates, female cross-country runners demonstrated a significantly lower bony injury incidence rate in the post-hiatus season (0.24 vs. 0.57, p = 0.016) while male swimming athletes demonstrated a statistically significant increase in bony injury rate (0.09 vs. 0.01, p = 0.015). The proportion of bony injuries attributed to repetitive trauma increased; while, the proportion of injuries attributed to running decreased between the pre- and post-hiatus seasons. CONCLUSION: Across all sports, there was no consistent trend toward increased rates of bony injury in the immediate post-hiatus season. However, female cross-country runners demonstrated lower rates of bony injury in the post-hiatus season while male swimmers demonstrated higher rates. Furthermore, bony injuries in the post-hiatus season were more likely to be the result of repetitive trauma and less likely to be from running. LEVEL OF EVIDENCE: Level III, retrospective, cross sectional study.

Biologically-coupled bisphosphonate chaperones effectively deliver molecules to the site of soft tissue-bone healing.

Tendon injuries are common and often treated surgically, however, current tendon repair healing results in poorly organized fibrotic tissue. While certain growth factors have been reported to improve both the strength and organization of the repaired enthesis, their clinical applicability is severely limited due to a lack of appropriate delivery strategies. In this study, we evaluated a recently developed fluorescent probe, Osteoadsorptive Fluorogenic Sentinel-3 that is composed of a bone-targeting bisphosphonate (BP) moiety linked to fluorochrome and quencher molecules joined via a cathepsin K-sensitive peptide sequence. Using a murine Achilles tendon-to-bone repair model, BP-based and/or Ctsk-coupled imaging probes were applied either locally or systemically. Fluorescence imaging was used to quantify the resultant signal in vivo. After tendon-bone repair, animals that received either local or systemic administration of imaging probes demonstrated significantly higher fluorescence signal at the repair site compared to the sham surgery group at all time points (p < 0.001), with signal peaking at 7-10 days after surgery. Our findings demonstrate the feasibility of using a novel BP-based targeting and Ctsk-activated delivery of molecules to the site of tendon-to-bone repair and creates a foundation for further development of this platform as an effective strategy to deliver bioactive molecules to sites of musculoskeletal injury.