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ImportanceAdjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor–positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.ObjectiveTo assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.Design, Setting, and ParticipantsThis prospective-retrospective translational study used all available tumor tissue samples from female patients from the Suppression of Ovarian Function Trial (SOFT). These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. BCI testing was performed blinded to clinical data and outcome. The a priori hypothesis was that BCI HOXB13/IL17BR ratio (BCI[H/I])–high tumors would benefit more from OFS and high BCI portended poorer prognosis in this population. Settings spanned multiple centers internationally. Participants included premenopausal female patients with HR+ early breast cancer with specimens in the International Breast Cancer Study Group tumor repository available for RNA extraction. Data were collected from December 2003 to April 2021 and were analyzed from May 2022 to October 2022.Main Outcomes and MeasuresPrimary end points were breast cancer–free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses.ResultsTumor specimens were available for 1718 of the 3047 female patients in the SOFT intention-to-treat population. The 1687 patients (98.2%) who had specimens that yielded sufficient RNA for BCI testing represented the parent trial population. The median (IQR) follow-up time was 12 (10.5-13.4) years, and 512 patients (30.3%) were younger than 40 years. Tumors were BCI(H/I)-low for 972 patients (57.6%) and BCI(H/I)-high for 715 patients (42.4%). Patients with tumors classified as BCI(H/I)-low exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48 [95% CI, 0.33-0.71]) and an absolute benefit of 7.3% from tamoxifen plus OFS (HR, 0.69 [95% CI, 0.48-0.97]) relative to tamoxifen alone. In contrast, patients with BCI(H/I)-high tumors did not benefit from either exemestane plus OFS (absolute benefit, −0.4%; HR, 1.03 [95% CI, 0.70-1.53]; P for interaction = .006) or tamoxifen plus OFS (absolute benefit, −1.2%; HR, 1.05 [95% CI, 0.72-1.54]; P for interaction = .11) compared with tamoxifen alone. BCI continuous index was significantly prognostic in the N0 subgroup for DRFI (n = 1110; P = .004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk N0 cancers, respectively.Conclusions and RelevanceIn this prospective-retrospective translational study of patients enrolled in SOFT, BCI was confirmed as prognostic in premenopausal women with HR+ breast cancer. The benefit from OFS-containing adjuvant endocrine therapy was greater for patients with BCI(H/I)-low tumors than BCI(H/I)-high tumors. BCI(H/I)-low status may identify premenopausal patients who are likely to benefit from this more intensive endocrine therapy.

Abstract Aims To test whether an index based on the combination of demographics and body volumes obtained with a multisensor 3D body volume (3D-BV) scanner and biplane imaging using a mobile application (myBVI®) will reliably predict the severity and presence of metabolic syndrome (MS). Methods and results We enrolled 1280 consecutive subjects who completed study protocol measurements, including 3D-BV and myBVI®. Body volumes and demographics were screened using the least absolute shrinkage and selection operator to select features associated with an MS severity score and prevalence. We randomly selected 80% of the subjects to train the models, and performance was assessed in 20% of the remaining observations and externally validated on 133 volunteers who prospectively underwent myBVI® measurements. The mean ± SD age was 43.7 ± 12.2 years, 63.7% were women, body mass index (BMI) was 28.2 ± 6.2 kg/m2, and 30.2% had MS and an MS severity z-score of −0.2 ± 0.9. Features β coefficients equal to zero were removed from the model, and 14 were included in the final model and used to calculate the body volume index (BVI), demonstrating an area under the receiving operating curve (AUC) of 0.83 in the validation set. The myBVI® cohort had a mean age of 33 ± 10.3 years, 61% of whom were women, 10.5% MS, an average MS severity z-score of −0.8, and an AUC of 0.88. Conclusion The described BVI model was associated with an increased severity and prevalence of MS compared with BMI and waist-to-hip ratio. Validation of the BVI had excellent performance when using myBVI®. This model could serve as a powerful screening tool for identifying MS.

AbstractBBB dysfunction during aging is characterized by an increase in its permeability and phenotypic alterations of brain endothelial cells (BECs) including dysregulation of tight junction's expression. Here we have investigated the role of BEC senescence in the dysfunction of the BBB. Our results suggest that the transition from young to aged BBB is mediated, at least in part by BEC senescence.

Objectives: The purpose of this study is to use standing anterior cruciate ligament (ACL) stress radiographs to evaluate how posterior tibial slope (PTS) compared to anterior tibial translation (ATT) in an injured knee. A secondary purpose was to determine how posterior tibial slope (PTS) affects ATT side-to-side difference. Our hypothesis was that anterior tibial translation would be higher in the injured knee compared to the contralateral side and posterior tibial slope will have a positive effect on anterior tibial translation. Methods: A retrospective study of ACL stress radiographs was assessed from patients with primary ACL reconstructions with no concomitant ligamentous injury between January 2023 and August 2023. Institutional Review Board approval was obtained. The bilateral radiographs were long-leg lateral “stress views” which was accomplished by monopodal weight-bearing in 20° flexion and are a part of the initial patient workup. Stress radiographs were utilized to measure the anterior tibial translation (ATT) and posterior tibial slope (PTS) for both knees. Differences in ATT between knees and the correlation between PTS and ATT was assessed via paired t-tests and regression analysis. Results: A final cohort of 39 patients were analyzed using preoperative ACL stress radiographs. The results reported a significant regression with positive correlation between posterior tibial slope (PTS) and anterior tibial translation for the injured knee using both anatomic (Figure 1, P<0.001, R 2 =0.302) and mechanical (Figure 2, P=0.038, R 2 =0.111) PTS measurements. Anatomic PTS measurements are better at predicting ATT for the injured knee compared to mechanical PTS measurements. Conclusions: The findings of this study report a significant regression with a positive correlation between posterior tibial slope (PTS) and anterior tibial translation (ATT) of the injured knee, with anatomic PTS measurements being a better predictor of ATT than mechanical PTS measurements. This indicates an important relationship between PTS and ATT with higher PTRS predicting higher ATT.

Objectives: The purpose of this paper was to compare patient reported outcomes (PROMs) between isolated anterior cruciate ligament (ACLR) and ACLR with concomitant medial meniscus ramp and lateral meniscus root repairs and compare PROMs between different medial meniscus ramp and lateral meniscus root repair techniques. Methods: All patients with isolated (ISO) ACL reconstruction or ACL reconstruction with concomitant medial meniscus ramp and lateral meniscus root repairs with a minimum 2 years of follow-up were retrospectively evaluated. Institutional review board approval was obtained for this study. A final total of 42 ISO-ACL patients were matched based upon age, sex, and body mass index to 40 in the “terrible triad” (TT) cohorts. Outcome measures were obtained from 32 patients in the ISO cohort, and 38 patients in the TT cohort. The PROMs used for this study include the International Knee Documentation Committee (IKDC) Subjective Knee, Cincinnati, Tegner, Lysholm, Veterans RAND 12-Item Health Survey (VR-12), and Knee Injury and Osteoarthritis Outcomes Score (KOOS) questionnaire forms. T tests and chi-square goodness of fit tests were used to compare the above PROMs both pre- and postoperatively within each cohort, and between cohorts and rates of revision or reoperation. Results: The preoperative and postoperative PROMs between patients in the isolated cohort and the triad cohort demonstrated no significant differences, except for the Physical category of the VR-12, in which the triad cohort had significantly higher results (p = 0.04) (Figure 1). Both the isolated cohort and the triad cohort reported significant differences between pre- and postoperative PROMs within their own cohorts. When comparing methods of surgery, including all-inside vs. inside-out for the medial meniscus repairs and tunnel versus no-tunnel for the lateral meniscus root repairs, no significant differences were found between postoperative PROMs. Additionally, no significant difference was found in revision or reoperative rates between the triad and isolated cohorts (p = 0.374) (Figure 2), the all-inside versus inside-out medial meniscus cohorts (p = 0.267), or the tunnel vs. no-tunnel lateral meniscus cohorts (p = 0.781). Conclusions: There was no significant difference in PROMs between isolated ACLR versus ACLR with concomitant medial meniscus ramp and lateral meniscus root repairs. While the complexity of the TT ACLR patients was more involved, PROMs and healing rates were similar and performing concurrent medial ramp and lateral root repairs at the time of ACLR should be considered.

Objectives: The vascularity of the human meniscus was first famously described by Arnoczky and Warren, who used histological analysis to map out vessel contributions to the medial and lateral menisci. This study determined that the medial and lateral superior and inferior genicular arteries branches give rise to a perimeniscal capillary plexus within the capsular and synovial tissues of the knee. However, since this study, there have been limited investigations into the macro- and microvascularity of the menisci. This includes anatomical, biomechanical, and imaging studies. Doppler ultrasound is an easily accessible, safe, and non-invasive modality that gives clinicians real-time visualization of vascular anatomy. To date, there have been no ultrasound studies that have highlighted vascular deviations from the popliteal artery to the medical meniscus, including the newly discovered medial meniscal artery (MMA), as described in Part 1 of this study (Figure 1, from Part 1 of this investigation). The purpose of this study was to use find a reproducible ultrasound technique to identify the MMA and provide a detailed characterization of the vessel’s precise anatomy. We hypothesized that the MMA would be consistently identifiable in vivo using ultrasound imaging and that multiple anatomic variants of the MMA would exist. Methods: Fifty-six patients underwent ultrasound examination of the left knee. Patient demographics were collected. The MMA was isolated by one of two techniques. In the first approach, the inferior medial genicular artery (IMGA) was isolated and followed back to the popliteal artery, where the examiner then coursed the artery proximally to find medial-sided vasculature branching to the medial meniscus. In the second approach, the probe was started on the medial meniscus and once an arterial supply was found, it was traced back to the popliteal artery. Once the MMA was isolated by either technique, the following variables were measured: presence or absence of MMA, artery diameter, presence of arterial calcifications or atheromatous plaques, and any vascular variations. Once the MMA was found and isolated in the left knee, its presence was investigated in the right knee. Results: The MMA was identified in 50/56 patients (89.2%). The average vessel diameter was 0.89 mm (SD ± 0.39). All 50 patients with a MMA present on the left knee also had the presence of the artery on the right knee. None of the MMA isolated in this study were noted to have any plaques or calcifications. 45 patients were noted to have a Type 1 MMA, whereas five patients were noted to have a Type 2 MMA where the vessel shares an origin with the IMGA (Figure 2). Conclusions: This is the first study to utilize ultrasound to isolate and characterize the MMA in a in vivo human model. The MMA can be consistently seen on ultrasonography in the majority of patients and ultrasound examination demonstrated that the artery perforates into the meniscal tissue to contribute to the meniscal microplexus. The key methods to ensure reproducible identification of the artery and patient characteristics that produce lesser quality images are discussed in detail. Ultrasound identification in clinic may serve as a point-of-care diagnostic modality to determine the likelihood of success of procedures such as medial meniscal repair, given the artery provides a direct blood supply to the meniscus. The MMA may play a pivotal role in meniscal injury, repair, healing, and preservation. Future studies are necessary to determine the extent to which this vessel contributes to said mechanisms.

Objectives: Radial tears of the meniscus are increasingly treated with repair instead of partial meniscectomy, with satisfactory short-term clinical outcomes. There remains a paucity of mid- and long-term outcomes data for this preservation technique. The purpose of this study was to 1) evaluate the mid- to long-term clinical outcomes and reoperation rate of radial meniscal repair versus bucket-handle meniscal repair and 2) evaluate the outcomes of both surgeries overtime. We hypothesized that radial repair would provide similar outcomes and reoperation rates to that of bucket-handle meniscal repair in this propensity-matched cohort. Methods: A previously identified cohort of radial meniscal tears without concurrent root injuries undergoing surgical repair at a single institution between 2011 and 2015 were reviewed. Inclusion criteria was patients undergoing repair of full-thickness radial tears. Exclusion criteria were patients who had 1) not consented for research follow-up, 2) <2 year of follow-up, 3) high-grade (Outerbridge grade 3 or 4) chondromalacia, 4) knee dislocations or combined anterior cruciate ligament and posterior cruciate ligament injuries, 5) repair of posterior meniscal root tears, and 6) repair of partial radial tears. Propensity matching was performed based on age at surgery, sex, laterality, body mass index (BMI), and concomitant anterior cruciate ligament reconstruction (ACLR) using a comparison pool of 70 bucket-handle meniscal repairs (BHMR). Reoperation-free survival rates, Tegner Activity Score, visual analog scale (VAS) for pain, and International Knee Documentation Committee (IKDC) scores were analyzed. Results: Twenty-four patients (18 males, 6 females, age 22.8 ± 11.9 years, BMI 26.5 ± 5.8) with radial meniscal repair were included in this study. Eighteen of these patients were successfully propensity matched to 18 bucket-handle meniscal tears for an overall mean follow-up of 10.2 ± 1.7 years (range, 7.3-13.5) (Table 1). The 24 radial tear repairs demonstrated significant and durable postoperative improvements at mean 10.2 years across VAS at rest (3.0 ± 2.5 vs 0.5 ± 1.0, p < 0.001), VAS for pain at use (5.8 ± 2.9 vs 1.4 ± 1.9, p < 0.001) Tegner (2.6 ± 1.4 vs 6.8 ± 2.0, p < 0.001) and IKDC (39.8 ± 12.3 vs 84.1 ± 16.5, p < 0.001) (Table 1). Of patients not undergoing reoperation (19), 100% reported being “Satisfied” 4/19 (21%) or “Very Satisfied” 15/19 (79%). When the 18 radial tear repairs were compared to the 18 BHMT repairs, there was no significant difference across VAS for pain at rest (0.6 ± 1.2 vs 0.3 ± 0.7, p = 0.48), VAS for pain at use (1.6 ± 2.1 vs 1.1 ± 1.3, p = 0.48) Tegner (6.9 ± 2.2 vs 6.4 ± 2.1, p = 0.51) and IKDC (83.4 ± 17.4 vs 82.1 ± 14.1, p = 0.83) (Table 2). Importantly, survival without reoperation rates were not statistically different between the 2 groups at 10-year follow-up (14/18 (78%) vs 16/18 (89%), p = 0.37) (Figure 1). There was no significant difference between clinical outcomes (Tegner and IKDC) at final follow-up in the radial repair group as compared to the 4-year mid-term outcomes (p = 0.58 and 0.19 respectively). For the BHMR group, Tegner scores were not significantly different (p = 0.60) compared with their 4-year timepoint; however, IKDC scores at the final timepoint were significantly lower 93.4 ± 3.4 vs 82.1 ± 14.1 (p = 0.01). Notably, both the radial repair and bucket-handle repairs groups reported final follow-up Tegner scores that were not significantly different from their preinjury Tegner scores (p = 0.70 for the radial group and p = 0.62 for the bucket-handle group). Conclusions: At mean 10-year follow-up, significant clinical improvements and high rates of satisfaction were observed for radial meniscal tear repair. When propensity matched, radial and BHMR demonstrated durable improvements in postoperative VAS for pain, IKDC, and Tegner scores, as well as similar, acceptable reoperation rates. [Figure: see text]

Objectives: While uncommon, acute traumatic patellar dislocations can lead to recurrent symptoms of patellar instability in 15% to 45% of patients. Patellar stability is an interplay of bony and soft tissue restraints as well as anatomic factors, however, a mainstay of treatment remains reconstruction of the medial patellofemoral ligament (MPFL). Instability events can lead to intra-articular derangements of the knee, both in the acute and chronic patellar instability setting. These findings may not always be appropriately identified on magnetic resonance imaging (MRI). The incidence of these “surprise” injuries have not been previously reported. The purpose of this study is to determine the rates of coexisting intra-articular pathology in patients with patellar instability requiring MPFL reconstruction and elucidate any discordance between preoperative MRI findings and diagnostic arthroscopy findings. Methods: All patients undergoing MPFL reconstruction at a single institution between 2010 and 2023 were identified and preoperative MRI reports, defined as the most recent MRI report to the date of surgery with no interval traumatic events, were queried. Records without full MRI reports as read by a radiologist or cases in which a diagnostic arthroscopy was not conducted were excluded. MRI findings were discordant from arthroscopic findings if a lesion identified on diagnostic arthroscopy was not present in the full MRI report. Procedures that were undertaken because of these missed pathologies on MRI were recorded. Results: A total of 640 patients were identified during the study period, and 507 complete records were ultimately included. Preoperative MRI identified patellar osteochondral lesions or cartilage fissures in 333 patients (66%), loose bodies in 119 patients (24%), lateral femoral condyle osteochondral lesions or fissures in 97 patients (19%) and meniscus tears in 47 patients (9%). Among these patients, 172 (34%) had a diagnosis at the time of arthroscopy which was not identified on the preoperative MRI. These arthroscopic findings resulted in 75 loose body removals, 74 patellar shaving chondroplasties, 16 partial meniscectomies, 3 microfractures, 3 osteochondral lesion open reduction internal fixation, and 2 meniscal repairs which would have been missed without diagnostic arthroscopy due to discordant MRI findings. Conclusions: Over one-third of patients at a single institution who underwent diagnostic arthroscopy in the setting of patellar instability surgery had pathology identified which required surgical intervention that was not reported on a preoperative MRI. A comparison of MRI and diagnostic arthroscopy has been extensively reported on for other knee pathologies including ACL tear and lateral meniscal tear; however, there has been no similar investigation of the reliability of MRI for identification of concomitant pathology in the setting of patellar instability to date. The findings of this study highlight the importance of diagnostic arthroscopy in the treatment of patellar instability, the frequency with which this altered treatment, and the high preponderance of discordant MRI findings.

Objectives: Medial meniscus posterior root tears (MMPRTs) render the meniscus essentially non-functional, resulting in increased peak contact pressures, reduced forced dissipation, and increased risk of early osteoarthritis. Transtibial root repair has shown promise at restoring meniscus function and improving clinical outcomes; however, a paucity of literature exists evaluating the prognostic clinical and radiographic factors for poor outcomes following isolated meniscus root repair. The purpose of this study was to 1) describe the patient reported clinical outcomes after isolated MMPRT repair at minimum 2-year follow-up, 2) determine the retear and conversion to arthroplasty rates, and 3) identify prognostic factors for clinical outcomes and International Knee Documentation Committee (IKDC) Patient Acceptable Symptom State (PASS) achievement. Methods: Isolated MMPRT repairs from 2010-2020 at three institutions in Rochester, MN; Jacksonville, FL; and Phoenix, AZ were followed prospectively for postoperative Tegner Activity Scale, Visual Analog Scale (VAS) for pain, IKDC, Forgotten Joint Score (FJS), subjective improvement and knee preference, and subsequent surgeries at minimum 2-year follow up. PASS for IKDC was set at 69. Demographics, injury characteristics, and surgical details were collected. Results: Eighty-four patients were included in this study (age: 49.7 ± 11.0 years [range: 13-76]; sex: 75.0% female; BMI: 31.6 ± 6.9 kg/m 2 [MH1] ). Forty-five patients (53.6%) had BMI >30 kg/m 2 , and 14 patients (16.7%) reported a history of active smoking (Table 1). Mean medial compartment Outerbridge grade was 2.0 ± 1.1, with 73.8% of patients having grade ≥2 changes. Mean preinjury Tegner score, preoperative VAS at rest, and preoperative VAS with use were 4.6 ± 2.4, 3.6 ± 2.7, and 6.5 ± 2.5, respectively. At final follow-up (mean 3.9 ± 2.0 years), mean Tegner score was 4.3 ± 1.8, mean VAS at rest was 1.2 ± 2.0, and mean VAS with use was 2.3 ± 2.2. There was no significant difference in preinjury vs. postoperative Tegner scores (p = 0.208), and preinjury Tegner was significantly positively correlated with postoperative Tegner (p < 0.001). Significant (p < 0.001) postoperative improvements in both VAS at rest and with use were observed. Mean postoperative IKDC score was 73.3 ± 17.0, and mean FJS was 59.6 ± 27.9 at final follow-up. When asked to rate their knee at final follow-up compared to before surgery on a scale from 0-5 (0 = “significantly worse”, 1 = “mildly worse”, 3 = “unchanged”, 4 = “mildly improved”, 5 = “significantly improved”), the mean score 4.6 ± 0.8. Forty-one patients (74.5%) reported significant improvement, 8 (14.5%) reported mild improvement, 3 (5.5%) reported no change, and 3 (5.5%) reported mild worsening. No patients reported significant worsening. When asked which knee they preferred, 13 patients (26.0%) reported preferring their operated knee, compared to 18 (36.0%) who preferred their nonoperated knee. The remaining 19 patients (38.0%) had no preference for one knee over the other. A summary of all patient reported outcomes is reported in Table 2. At the time of final follow-up, 16 (19.0%) of patients had reached a clinical endpoint. Twenty-nine patients (34.5%) underwent postoperative MRIs at an average of 1.5 ± 1.7 years (range: 0.3-5.9 years) after surgery[MH1] . Twelve of the MRIs (41.4%) were ordered for evaluation of continued pain, while 7 (24.1%) were ordered for new pain or injury, and 10 (34.5%) were ordered for research purposes. Five patients (6.0%) had MRI-confirmed retears of the MMPRT repair at an average of 1.1 ± 1.3 years (range: 0.3-3.4) after surgery[HMMP2] , one of which was in an asymptomatic patient who received a follow-up MRI for research purposes. No patients underwent revision MMPRT repair surgery, and 7 patients (8.3%) progressed to arthroplasty (6 TKA, 1 UKA) at an average of 3.4 ± 4.3 years (range 0.6-12.6), one of whom also sustained a root retear. Therefore, the surgical failure was noted in 11 patients, corresponding to a surgical failure rate of 13.1% in this cohort. Of note, three of the five patients with MRI-confirmed retears had not received any further surgical intervention[MH3] [BA(M4] at the time of final follow-up 2.7, 3.8, and 8.5 years after surgery. Additionally, there were six non-MMPRT revision, non-arthroplasty subsequent surgeries in five patients, and there were three patients (3.6%) who sustained new medial meniscus tears 2.8-, 3.6-, and 5.9-years postoperatively, respectively. A concise summary of clinical endpoints can be found in Table 3 and Table 4. Significantly more females experienced surgical failures than males (17.5% vs. 0%, p = 0.040), and significantly more patients with medial compartment Outerbridge grades ≥2 experienced surgical failure than those with grades <2 (17.7% vs. 0%, p = 0.034). Additionally, patients who failed did have significantly higher mean KL grades than those who did not (1.4 ± 0.9 vs. 0.7 ± 0.7, p = 0.012). There were no other significant differences in the demographic or pathologic characteristics of patients who experienced surgical failure and those who did not. Of note, 37% of patients failed to achieve IKDC PASS, with smoking status associated with a 15-point reduction in IKDC (p=0.010) Conclusions: Patients undergoing transtibial root repair demonstrate restoration of pre-injury activity levels, significant clinical improvements in pain and function, and low surgical failure rates at minimum 2-year follow-up, with 89% of patients reporting subjective improvement after surgery. However, only 63% of patients were able to achieve PASS thresholds, suggesting that while effective, additional research on root repair technical and clinical optimization is warranted.