Investigating the PROMIS Physical Function and Pain Interference Domains in Elite Athletes.

BACKGROUND: Multiple studies have demonstrated the National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) to be a responsive and efficient measure for patients undergoing orthopaedic surgery. While these studies were rigorous in their protocol and methodology, no efforts in recent literature have been made to identify if these reference scores apply to elite athletes. PURPOSE/HYPOTHESIS: The purpose of this study was to determine whether there is a difference in the baseline scores of elite athletes versus the general population. We hypothesized that athletes' PROMIS upper extremity general function (PROMIS-UE) and general physical function (PROMIS-PF) scores would vary substantially from the mean health state of the general population. We further hypothesized that these scores would be affected by specific sport and level of competition. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Three PROMIS computer adaptive test (CAT) domains were administered to elite athlete (≥18 years) volunteers (either in person or through email). An elite athlete was defined as one participating in sports at the collegiate level or higher. Test domains included PROMIS-PF, PROMIS-UE, and pain interference (PROMIS-PI). PROMIS domain t scores were defined and assessed against NIH reference values to identify significant differences. Distribution analysis was conducted using histograms and normality assessments. Domains were also subject to correlation analysis. Finally, subgroup analysis was conducted for all athlete characteristics to identify any factors associated with variance. RESULTS: In total, 196 elite athletes (mean age, 21.1 years; range, 18.0-36.7 years) completed all 3 PROMIS-CAT forms. Overall, the mean scores were 56.0 ± 6.4, 58.1 ± 7.7, and 47.1 ± 7.3 for PROMIS-UE, PROMIS-PF, and PROMIS-PI, respectively. Distribution analysis showed nonnormal distribution for all 3 PROMIS domains (Kolmogorov-Smirnov test, P < .001). Similarly, in all 3 PROMIS domains the athletes displayed more disparate scores than the NIH-reported reference values (1-way sign test, P < .001). Only the presence of pain and sport played showed association with variance in PROMIS domain scores (P < .001 and P = .003, respectively). CONCLUSION: Elite athletes displayed more disparate reference scores than the NIH-reported average of 50 for PROMIS-UE, PROMIS-PF, and PROMIS-PI. Furthermore, these forms were sensitive to varying levels of sport among collegiate athletes.

Preoperative Patient-Centric Predictors of Postoperative Outcomes in Patients Undergoing Arthroscopic Meniscectomy.

PURPOSE: To determine the minimal clinically important difference (MCID) using Patient-Reported Outcome Measurement Information System (PROMIS) computer-adaptive testing assessments in patients undergoing arthroscopic partial meniscectomy. The secondary purpose was to identify which preoperative patient factors are associated with MCID achievement. METHODS: Three PROMIS computer-adaptive testing assessments (Physical Function [PF], Pain Interference [PI], and Depression [D]) were administered to all patients presenting to 1 of 2 board-certified, sports medicine orthopaedic surgeons. Patients with Current Procedural Terminology codes of 29880 or 29881 were chart reviewed for a host clinical and demographic factors. PROMIS scores were assessed for improvement and patient characteristics were assessed for influence on any improvement. MCID was calculated according to the distribution methodology and receiver operating characteristics were used to assess preoperative scores predictive ability. RESULTS: In total, 166 patients met inclusion criteria (58 exclusions). Postoperative PROMIS-PF (45.6), PROMIS-PI (54.6), and PROMIS-D (44.1) significantly improved at least 3 months after surgery when compared with baseline (P = .002). MCID values for PROMIS-PF, PROMIS-PI, and PROMIS-D were 3.5, 3.3, and 4.4, respectively. Individuals with PROMIS-PF scores below 34.9 yielded an 82% probability of achieving MCID, while PROMIS-PI scores above 67.5 yielded an 86% probability of achieving MCID and a cutoff of 58.9 for PROMIS-D yielded a 60% probability of achieving MCID, with 90% specificity. CONCLUSIONS: PROMIS scores, obtained preoperatively, were shown to be valid predictors of postoperative clinical improvement in patients undergoing meniscectomy. Our findings suggest that patients with physical function scores of 34.9 or less have an increased probability of reaching a minimal clinically important difference. Similarly, patients with pain interference scores of 67.5 and above have increased probability of reaching MCID for pain interference. These cutoffs may be used by physicians to aid in the counseling of patients considering arthroscopic meniscectomy. LEVEL OF EVIDENCE: IV, Case Series.

Microbe-Dependent Exacerbated Alveolar Bone Destruction in Heterozygous Cherubism Mice.

Cherubism (OMIM#118400) is a craniofacial disorder characterized by destructive jaw expansion. Gain-of-function mutations in SH3-domain binding protein 2 (SH3BP2) are responsible for this rare disorder. We have previously shown that homozygous knock-in (KI) mice (Sh3bp2 KI/KI ) recapitulate human cherubism by developing inflammatory lesions in the jaw. However, it remains unknown why heterozygous KI mice (Sh3bp2 KI/+ ) do not recapitulate the excessive jawbone destruction in human cherubism, even though all mutations are heterozygous in humans. We hypothesized that Sh3bp2 KI/+ mice need to be challenged for developing exacerbated jawbone destruction and that bacterial stimulation in the oral cavity may be involved in the mechanism. In this study, we applied a ligature-induced periodontitis model to Sh3bp2 KI/+ mice to induce inflammatory alveolar bone destruction. Ligature placement induced alveolar bone resorption with gingival inflammation. Quantification of alveolar bone volume revealed that Sh3bp2 KI/+ mice developed more severe bone loss (male: 43.0% ± 10.6%, female: 42.6% ± 10.4%) compared with Sh3bp2 +/+ mice (male: 25.8% ± 4.0%, female: 30.9% ± 6.5%). Measurement of bone loss by the cement-enamel junction-alveolar bone crest distance showed no difference between Sh3bp2 KI/+ and Sh3bp2 +/+ mice. The number of osteoclasts on the alveolar bone surface was higher in male Sh3bp2 KI/+ mice, but not in females, compared with Sh3bp2 +/+ mice. In contrast, inflammatory cytokine levels in gingiva were comparable between Sh3bp2 KI/+ and Sh3bp2 +/+ mice with ligatures. Genetic deletion of the spleen tyrosine kinase in myeloid cells and antibiotic treatment suppressed alveolar bone loss in Sh3bp2 KI/+ mice, suggesting that increased osteoclast differentiation and function mediated by SYK and accumulation of oral bacteria are responsible for the increased alveolar bone loss in Sh3bp2 KI/+ mice with ligature-induced periodontitis. High amounts of oral bacterial load caused by insufficient oral hygiene could be a trigger for the initiation of jawbone destruction in human cherubism. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Alveolar Bone Protection by Targeting the SH3BP2-SYK Axis in Osteoclasts.

Periodontitis is a bacterially induced chronic inflammatory condition of the oral cavity where tooth-supporting tissues including alveolar bone are destructed. Previously, we have shown that the adaptor protein SH3-domain binding protein 2 (SH3BP2) plays a critical role in inflammatory response and osteoclastogenesis of myeloid lineage cells through spleen tyrosine kinase (SYK). In this study, we show that SH3BP2 is a novel regulator for alveolar bone resorption in periodontitis. Micro-CT analysis of SH3BP2-deficient (Sh3bp2 -/- ) mice challenged with ligature-induced periodontitis revealed that Sh3bp2 -/- mice develop decreased alveolar bone loss (male 14.9% ± 10.2%; female 19.0% ± 6.0%) compared with wild-type control mice (male 25.3% ± 5.8%; female 30.8% ± 5.8%). Lack of SH3BP2 did not change the inflammatory cytokine expression and osteoclast induction. Conditional knockout of SH3BP2 and SYK in myeloid lineage cells with LysM-Cre mice recapitulated the reduced bone loss without affecting both inflammatory cytokine expression and osteoclast induction, suggesting that the SH3BP2-SYK axis plays a key role in regulating alveolar bone loss by mechanisms that regulate the bone-resorbing function of osteoclasts rather than differentiation. Administration of a new SYK inhibitor GS-9973 before or after periodontitis induction reduced bone resorption without affecting inflammatory reaction in gingival tissues. In vitro, GS-9973 treatment of bone marrow-derived M-CSF-dependent macrophages suppressed tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation with decreased mineral resorption capacity even when GS-9973 was added after RANKL stimulation. Thus, the data suggest that SH3BP2-SYK is a novel signaling axis for regulating alveolar bone loss in periodontitis and that SYK can be a potential therapeutic target to suppress alveolar bone resorption in periodontal diseases. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.