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Background Among breast cancers, the triple-negative breast cancer (TNBC) subtype has the worst prognosis with no approved targeted therapies and only standard chemotherapy as the backbone of systemic therapy. Unique metabolic changes in cancer progression provide innovative therapeutic opportunities. The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR), and MET receptor are highly expressed in TNBC, making both promising therapeutic targets. RTK signaling profoundly alters cellular metabolism by increasing glucose consumption and subsequently diverting glucose carbon sources into metabolic pathways necessary to support the tumorigenesis. Therefore, detailed metabolic profiles of TNBC subtypes and their response to tyrosine kinase inhibitors may identify therapeutic sensitivities. Methods We quantified the metabolic profiles of TNBC cell lines representing multiple TNBC subtypes using gas chromatography mass spectrometry. In addition, we subjected MDA-MB-231, MDA-MB-468, Hs578T, and HCC70 cell lines to metabolic flux analysis of basal and maximal glycolytic and mitochondrial oxidative rates. Metabolic pool size and flux measurements were performed in the presence and absence of the MET inhibitor, INC280/capmatinib, and the EGFR inhibitor, erlotinib. Further, the sensitivities of these cells to modulators of core metabolic pathways were determined. In addition, we annotated a rate-limiting metabolic enzymes library and performed a siRNA screen in combination with MET or EGFR inhibitors to validate synergistic effects. Results TNBC cell line models displayed significant metabolic heterogeneity with respect to basal and maximal metabolic rates and responses to RTK and metabolic pathway inhibitors. Comprehensive systems biology analysis of metabolic perturbations, combined siRNA and tyrosine kinase inhibitor screens identified a core set of TCA cycle and fatty acid pathways whose perturbation sensitizes TNBC cells to small molecule targeting of receptor tyrosine kinases. Conclusions Similar to the genomic heterogeneity observed in TNBC, our results reveal metabolic heterogeneity among TNBC subtypes and demonstrate that understanding metabolic profiles and drug responses may prove valuable in targeting TNBC subtypes and identifying therapeutic susceptibilities in TNBC patients. Perturbation of metabolic pathways sensitizes TNBC to inhibition of receptor tyrosine kinases. Such metabolic vulnerabilities offer promise for effective therapeutic targeting for TNBC patients.

Background Social determinants of health (SDOH) encompass social and economic factors that influence healthcare access and outcomes. In orthopaedic surgery, disparities in SDOH contribute to unequal access to care and differences in post-surgical recovery. Prior studies indicate that an increased number of preoperative shoulder dislocations raises the likelihood of recurrent instability following stabilization procedures. However, limited research explores the association between SDOH and preoperative dislocation frequency. This study examines how SDOH factors influence the number of shoulder dislocations before surgical intervention. Methods Patients that underwent shoulder instability surgery at a single center in a large metropolitan area between January 1, 2021, and April 30, 2023, were identified. Patients’ demographic and social determinant variables were extracted using the electronic medical record. Socioeconomic status was assessed using the Social Vulnerability Index (SVI) and the Area Deprivation Index (ADI), based on patient zip codes. Statistical analyses, including univariate and multivariate regression models, evaluated predictors of multiple dislocations before surgery, focusing on factors such as age, body mass index (BMI), and socioeconomic indicators. Results Among 106 patients, 54% identified as White, 29% as Black, and 17% as other. Thirty-eight (35.8%) had a single dislocation before surgery, while 68 (64.2%) experienced multiple instability events. Univariate analysis showed younger age (odds ratio [OR] 0.94, P  = 0.02), lower BMI (OR 0.90, P  = 0.02), higher SVI (OR 1.21, P  = 0.006), and higher ADI (OR 6.04, P  = 0.003) were associated with recurrent instability. Multivariate analysis confirmed lower BMI (OR 1.15, P  = 0.02) and higher ADI (OR 7.46, P  = 0.02) as independent predictors. Conclusions Lower socioeconomic status, as measured by ADI, is an independent predictor of a higher likelihood of recurrent instability before surgery. Recognizing these relationships can motivate surgeons to create pathways to prevent these treatment disparities among shoulder instability patients. Level of evidence III retrospective cohort study.

Objectives: The remnant anterior cruciate ligament (ACL) ligament contains a wealth of vascular blood supply and proprioceptive nerve fibers. Previous literature has suggested that preservation of this remnant may promote graft healing and stability, as well as improved knee proprioception. The ACL-Hybrid Remnant Preservation Reconstruction (HRPR) technique involves preserving and tensioning the tibial remnant in combination with a traditional ACL reconstruction. The purpose of this study was to assess if ACL-HRPR leads to improved patient-reported outcomes and if the technique can be performed safely without increased complications compared to traditional ACLR. Methods: A prospective randomized controlled trial was performed to include patients undergoing primary ACL reconstruction +/- HRPR by a single surgeon from 2022-2023. Exclusion criteria included patients <14 years old, multi-ligamentous knee injury, date of injury >6 months prior to presentation, and revision ACLR. Preoperatively, patients were randomized to receive either ACL-HRPR or traditional ACLR with bone patellar tendon bone (BTB) or hamstring tendon autograft. If randomized for HRPR, the surgeon decided intraoperatively if the tibial remnant was amenable for preservation/repair. The primary outcome was Patient-Reported Outcome Measurement Information System (PROMIS)-Physical Function scores, which requires 50 patients per group to achieve 80% power. Secondary outcomes included range of motion (ROM), knee stability via KT-1000 measurements, timed hop testing, and complications. Patients who have completed 6-month follow-up were included for analysis. Results: Seventy-eight patients were eligible for analysis, with 35 undergoing HRPR and 43 controls. No demographic differences were observed. After 6 months, patients demonstrated equivalent PROMIS-PF, -PI, International Knee Documentation Committee (IKDC), VAS pain scores, and percent achieving Patient Acceptable Symptom State (PASS). The HRPR group reported significantly increased ROM at 6 months compared to controls (138.7± 7.79 vs 134.52 ± 9.8, p=0.04), with no loss of terminal extension. No differences were observed in return to running time (HRPR 20.22 ± 12.25 vs. Control 19.81 ± 10.34 weeks, p-0.09) Complications rates were similar between groups, as well (5.7% HRPR vs 4.7% controls, p=0.83). Conclusions: After 6 months, ACL-HRPR achieves equivalent patient-reported outcomes, knee stability, and return to play testing parameters without increased complications compared to traditional ACL reconstruction.

Objectives: The impact of social determinants of health (SDOH) on postoperative outcomes in orthopaedic surgery continues to grow. For patients undergoing anterior cruciate ligament (ACL) reconstruction, previous studies have demonstrated that socioeconomic variables are associated with differential patient-reported outcomes and complications. However, delays in care have not been fully explored. Therefore, the purpose of this study was to investigate the association between socioeconomic variables and timing to presentation and surgery in ACLR patients. Methods: A retrospective cohort review of patients undergoing ACLR patients at a single healthcare system in a large metropolitan area between January 2020 to December 2023 was conducted. Patients’ demographic variables, mean household income (MHI) and Area of Deprivation Index (ADI) were collected using the electronic medical record and online mapping data tools based on zip codes. Patients with less than 1 year of Patient Reported Outcome Measurment Information System (PROMIS) scores were excluded. The primary outcome was to compare time from injury to orthopaedic presentation and to surgical intervention based on various sociodemographic parameters. The secondary outcome was to compare PROMIS scores at preoperative, 3, 6, and 12 months from surgery based on social determinants of health variables. Results: Three-hundred and ninety-eight ACLR patients were included (median age, 21 years; 54.5% male). Compared with White patients, Black patients were more frequently in the lowest median household income (MHI) quartile (54% vs. 9%, respectively; p < .001). White patients were more frequently in the lowest area deprivation index (ADI) quartile when compared with Black patients (50% vs 9%, respectively; p < .001). Black patients experienced a longer delay to surgery compared to White patients, although only approached significance (5.14 vs. 4.14 weeks respectively; p=0.08). Compared to the least deprived ADI quartile 1, those in the highest ADI quartile 4 experienced a significantly longer delay to surgery (5.57 wks. vs 3.0 wks. respectively, p<0.001). Patients in the lowest income quartile experienced significantly longer delay to surgery than patients in MHI quartile 4, (5.14 wks. vs 3.86 wks. respectively; p=0.016). Additionally, increasing age was correlated with longer times from injury to presentation (rs =0.268, p<0.001) and presentation to surgery (rs =0.210, p<0.001). Increasing BMI was correlated with increased time from injury to presentation (rs =0.132, p=0.009). When examining PROs at one year, patients in the lowest income quartile (MHI Q4) demonstrated worse PROMIS-PI (52 vs. 50 p=0.035) and PROMIS-PF (49 vs. 52, p=0.018) scores compared to MHI Q1. Current smokers also demonstrated significantly worse PROMIS-PF scores compared to never smokers (47 vs. 51, p=0.014 respectively) Conclusions: Patients in the most socioeconomically deprived and lowest incomes quartiles experience significant delays in presentation and time to ACLR . These socioeconomic differences appear to be associated with worse pain and physical function for these patients at 1 year.

Objectives: Physical therapy (PT) is essential for successful surgical outcomes after anterior cruciate ligament reconstruction (ACLR). Multiple PT regimens and modalities can be utilized with a consensus regarding certain elements of ACLR postoperative rehabilitation, however there is no universal protocol. Hospital affiliated PT may be more closely monitored and more strictly adhere to surgeon protocols, while external PT quality can vary. The purpose of this study is to compare the demographics and clinical outcomes between ACLR patients who undergo postoperative PT at hospital affiliated (internal) or external locations. Methods: A retrospective review was performed of all ACLRs at a single health system from 2020 to 2023. Inclusion criteria consisted of primary ACLR patients with documented physical therapy location and a minimum one year clinical follow up and completed Patient-Reported Outcome Measurement Information System Physical Function (PROMIS-PF) and Pain Interference (PROMIS-PI) scores. Excluded criteria was revision ACLR, history of previous knee surgery, incomplete 1-year PROMIS scores, and no PT location documentation. Demographic data including age, sex, body mass index (BMI), race, ethnicity, smoking history, employment, and insurance type was collected. Area Deprivation Index (ADI) was calculated using the patient’s home address. PROMIS-PF and PI were collected at preoperative, 3 months 6 months, and 1 year postoperative timepoints. Patient PT location was recorded as a health system affiliated (internal) or outside facility (external) location. Statistical analysis was performed with a significance level of p<0.05. A sub-analysis was performed utilizing propensity matching between cohorts via age, ADI, and body mass index (BMI). Results: A total of 382 patients were included with 228 undergoing internal PT and 154 undergoing external PT. Internal PT patients were significantly older (23.0 [18.0, 34.0] vs. 18.0 [16.0, 25.0] years; P<.0001), higher BMI (26.1 [23.0, 30.1] vs. 23.8 [21.6, 27.0] kg/m2; P <.0001; P<.0001), lived in higher ADI areas (53.0 [30.0, 81.0] vs. 39.0 [21.5, 65.0]; P= 0.0004), more likely to be Black (24.6% vs. 17.5%; P=0.0308), Hispanic or Latino (6.6% vs. 3.9%; P=0.0323), current smokers (9.3% vs. 2.0%), and have public/government insurance (22.4% vs. 10.4%; P=0.0114). Internal PT patients had significantly higher preoperative PROMIS-PI scores (63.0 [57.0, 68.0] vs. 61.0 [56.0, 67.0]; P=0.0427) and lower 1-year PROMIS-PF scores (51.0 [47.0, 54.0] vs. 52.0 [50.0, 64.0]; P=0.0019). No significant differences were found between preoperative, 3-month, and 6-month PROMIS-PF and 3-month, 6-month, and 1-year postoperative PROMIS-PI scores. After propensity match, no significant differences were found between cohort demographics and PROMIS PI and PF scores at all time points. Conclusions: ACLR patients who underwent PT at a health system affiliated location were significantly older, had higher BMIs, lived in areas with worse social deprivation, and were more likely to be Black, current smokers, and have government insurance compared to patients who underwent PT at an external location. This suggests that socioeconomic factors influence choice of physical therapy location amongst our patient population. There were no differences in patient outcomes postoperatively indicating the choice of physical therapy setting does not impact postoperative outcomes.

Background: Recent studies have suggested increased rates of lower extremity (LE) musculoskeletal injury after a diagnosed concussion, although significant heterogeneity exists. Purpose: To examine the current body of research and determine whether there is an increased risk for LE musculoskeletal injury after a concussion and to identify populations at an increased risk. Study Design: Systematic review; Level of evidence, 3. Methods: A systematic review of current literature using MEDLINE and PubMed databases was performed. Keywords included concussion, athlete, lower extremity injury, and return to sport. Inclusion criteria required original research articles written in the English language examining the rate of LE injuries after a diagnosed concussion. Results: A total of 13 studies involving 4349 athletes (88.1% male and 11.9% female; mean age, 19.8 years) met inclusion criteria. Athletes were classified as high school (46.1%), collegiate (17.0%), or professional (36.9%). Of the 13 studies, 4 demonstrated an increased risk of LE injury within 90 days of a diagnosed concussion (odds ratio [OR], 3.44; 95% CI, 2.99-4.42), and 6 revealed an elevated risk of injury within 1 year of concussion (OR, 1.85; 95% CI, 1.73-2.84). Increased risk was seen in professional (OR, 2.49; 95% CI, 2.40-2.72) and collegiate (OR, 2.00; 95% CI, 1.96-2.16) athletes compared with high school athletes (OR, 0.97; 95% CI, 0.89-1.05). A stepwise increase in risk of sustaining an LE injury was observed with multiple concussions, with increasing risk observed from ≥2 (OR, 2.29; 95% CI, 1.85-2.83) to ≥3 (OR, 2.86; 95% CI, 2.36-3.48) career concussions. Conclusion: An increased incidence of LE injuries was observed at 90 days and 1 year after the diagnosis of a concussion. Higher levels of competition, such as at the collegiate and professional levels, resulted in an increased risk of sustaining a subsequent LE injury after a diagnosed concussion. These results suggest an at-risk population who may benefit from injury prevention methods after a concussion. Future studies should focus on identifying which injuries are most common, during what time period athletes are most vulnerable, and methods to prevent injury after return to sports.

Study Design General population utility valuation study. Objective To develop a technique for calculating utilities from the Neck Disability Index (NDI) score. Methods We recruited a sample of 1200 adults from a market research panel. Using an online discrete choice experiment (DCE), participants rated 10 choice sets based on NDI health states. A multi-attribute utility function was estimated using a mixed multinomial-logit regression model (MIXL). The sample was partitioned into a training set used for model fitting and validation set used for model evaluation. Results The regression model demonstrated good predictive performance on the validation set with an AUC of .77 (95% CI: .76-.78). The regression model was used to develop a utility scoring rubric for the NDI. Regression results also revealed that participants did not regard all NDI items as equally important. The rank order of importance was (in decreasing order): pain intensity = work; personal care = headache; concentration = sleeping; driving; recreation; lifting; and lastly reading. Conclusions This study provides a simple technique for converting the NDI score to utilities and quantify the relative importance of individual NDI items. The ability to evaluate quality-adjusted life-years using these utilities for cervical spine pain and disability could facilitate economic analysis and aid in allocation of healthcare resources.

Background: The term “social determinants of health” (SDOH) refers to social and economic factors that influence a patient’s health status. The effect of SDOH on the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive test (CAT) scores and postoperative resource utilization in patients with anterior cruciate ligament reconstruction (ACLR) have yet to be thoroughly studied. Purpose: To investigate the impact SDOH have on PROMIS CAT outcomes and postoperative resource utilization in patients with ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: The electronic medical record was used to identify the SDOH for patients who underwent ACLR by 1 of 3 sports medicine fellowship–trained orthopaedic surgeons between July 2017 and April 2020. PROMIS CAT measures of Physical Function (PROMIS-PF), Pain Interference (PROMIS-PI), and Depression (PROMIS-D) were completed at the preoperative, 6-month postoperative, and 12-month postoperative time points. Postoperative health care utilization was recorded as well. Independent 2-group t tests and Wilcoxon rank-sum tests were used to analyze mean differences between patient groups based on SDOH. Results: Two-hundred and thirty patients who underwent ACLR were included (mean age, 27 years; 59% male). Compared with White patients, Black patients were represented more frequently in the lowest median household income (MHI) quartile (63% vs 23%, respectively; P < .001). White patients were represented more frequently in the highest area deprivation index (ADI) quartile when compared with Black patients (67% vs 12%, respectively; P = .006). Significantly worse PROMIS-PF, PROMIS-PI, and PROMIS-D scores at all 3 time points were found among patients who were Black, female, smokers, and in the lower MHI quartiles, with higher ADI and public health care coverage. In terms of resource utilization, Black patients attended significantly fewer postoperative physical therapy visits when compared with their respective counterparts. Those in the lower MHI quartiles attended significantly fewer postoperative imaging encounters, and female patients attended significantly more postoperative virtual encounters than male patients. Conclusion: Specific SDOH variables, particularly those that reflect racial and socioeconomic disparities, were associated with differences in postoperative health care utilization and ACLR outcomes as measured by PROMIS CAT domains.

Background: Many patients use the internet to learn about their orthopaedic conditions and find answers to their common questions. However, the sources and quality of information available to patients regarding meniscal surgery have not been fully evaluated. Purpose: To determine the most frequently searched questions associated with meniscal surgery based on question type and topic, as well as to assess the website source type and quality. Study Design: Cross-sectional study. Methods: The following search terms were entered into a web search (www.google.com) using a clean-install browser: “meniscal tear,”“meniscus repair,”“meniscectomy,”“knee scope,”“meniscus surgery,” and “knee arthroscopy.” The Rothwell classification system was used to categorize questions and sort them into 1 of 13 topics relevant to meniscal surgery. Websites were also categorized by source into groups. The Journal of the American Medical Association (JAMA) benchmark criteria (medians and interquartile ranges [IQRs]) were used to measure website quality. Results: A total of 337 unique questions associated with 234 websites were extracted and categorized. The most popular questions were “What is the fastest way to recover from meniscus surgery?” and “What happens if a meniscus tear is left untreated?” Academic websites were associated more commonly with diagnosis questions (41.9%, P < .01). Commercial websites were associated more commonly with cost (71.4%, P = .03) and management (47.6%, P = .02). Government websites addressed a higher proportion of questions regarding timeline of recovery (22.2%, P < .01). Websites associated with medical practices were associated more commonly with risks/complications (43.8%, P = .01) while websites associated with single surgeons were associated more commonly with pain (19.4%, P = .03). Commercial and academic websites had the highest median JAMA benchmark scores (4 [IQR, 3-4] and 3 [IQR, 2-4], respectively) while websites associated with a single surgeon or categorized as “other” had the lowest scores (1 [IQR 1-2] and 1 [IQR 1-1.5], respectively). Conclusion: Our study found that the most common questions regarding meniscal surgery were associated with diagnosis of meniscal injury, followed by activities and restrictions after meniscal surgery. Academic websites were associated significantly with diagnosis questions. The highest quality websites were commercial and academic websites.

Background: An updated National Hockey League (NHL) concussion protocol (NHLCP) was established in the 2016-2017 season to mitigate the negative outcomes of sport-related concussions. However, few studies on the effects of implementing the NHLCP have been performed. Purpose: To define concussion incidence and investigate differences in NHL player performance after a concussion during periods before and after NHLCP implementation and assess the financial impact on NHL teams associated with NHLCP implementation. Study Design: Cohort study; Level of evidence, 3 Methods: This was a retrospective review of NHL players who sustained a concussion before (2000-2001 to 2015-2016 seasons) and after (2016-2017 to 2020-2021 seasons) implementing the NHLCP (pre-NHLCP and post-NHLCP groups). For each group, multiple performance metrics—including 30 days, 1 season, and 3 seasons before and after concussion—were compared for both groups. Return to play, total concussion cost, and association of return to play with cost were investigated using regression analysis. Results: A total of 452 players (423 skaters, 29 goalies) sustained concussions during the study period, including 331 players (315 skaters, 16 goalies) in the pre-NHLCP group and 121 players (108 skaters, 13 goalies) in the post-NHLCP group. For both groups, no significant differences in standard performance were observed during the 30-day and 1-season periods before and after concussion. The mean return to play was significantly higher in the pre-NHLCP group than in the post-NHLCP group (20.1 vs 15.7 days; P = .022). The mean adjusted player salary was not different between groups; nonetheless, the mean adjusted replacement player salary was significantly higher in the post-NHLCP group ($744,505 vs $896,942; P = .032). The mean cost of time missed did not differ between groups. The mean return to play time significantly decreased over the entire study period (R2 = 0.33; P = .005), and the mean return to play time was positively associated with cost R2 = 0.215; P = .030). Conclusion: Concussion incidence did not change after implementation of the updated NHLCP; nonetheless, players had significantly less missed time from injury after protocol implementation. Changes in player performance 30 days and 1 year before and after concussion injury were not different before and after NHLCP implementation. No differences were found in the financial cost of concussions between the pre- and post-NHLCP groups, and missed time was significantly correlated with mean cost from missed time.