Progression and recurrence of breast cancer, as well as reduced survival of patients with breast cancer, are associated with chronic stress, a condition known to impact the hypothalamic-pituitary axis and the autonomic nervous system. Preclinical and clinical evidence support the involvement of the sympathetic nervous system in the control of bone remodeling and in pathologies of the skeleton, including bone metastasis. In experimental mouse models of skeletal metastasis, administration of the βAR agonist isoproterenol (ISO), used as a surrogate of norepinephrine, the main neurotransmitter of sympathetic neurons, was shown to favor bone colonization of metastatic breast cancer cells via an increase bone marrow vascularity. However, successful extravasation of cancer cells into a distant organ is known to be favored by an activated endothelium, itself stimulated by inflammatory signals. Based on the known association between high sympathetic outflow, the expression of inflammatory cytokines and bone metastasis, we thus asked whether βAR stimulation in osteoblasts may alter the vascular endothelium to favor cancer cell engraftment within the skeleton. To address this question, we used conditioned medium (CM) from PBS or ISO-treated bone marrow stromal cells (BMSCs) in adhesion assays with bone marrow endothelial cells (BMECs) or the endothelial cell line C166. We found that ISO treatment in differentiated BMSCs led to a robust induction of the pro-inflammatory cytokines interleukin-1 beta (IL-1β) and interleukin-6 (IL-6). The CM from ISO-treated BMSCs increased the expression of E- and P-selectin in BMECs and the adhesion of human MDA-MB-231 breast cancer cells to these cells in short-term static and dynamic adhesion assays, and a blocking antibody against IL-1β, but not IL-6, reduced this effect. Direct IL-1β treatment of BMECs had a similar effect, whereas the impact of IL-6 treatment on the expression of adhesion molecules by BMECs and on the adhesion of cancer cells to BMECs was negligible. Collectively, these in vitro results suggest that in the context of the multicellular and dynamic bone marrow environment, sympathetic activation and subsequent βAR stimulation in osteoblasts may profoundly remodel the density but also the activation status of bone marrow vessels to favor the skeletal engraftment of circulating breast cancer cells.

Physical rehabilitation is essential for enhancing recovery in individuals with spinal cord injury (SCI); however, aside from early surgical intervention and hemodynamic management, there are no proven interventions for promoting recovery in the acute phase. In general, early rehabilitation is considered beneficial, but optimal parameters and potential contraindications for implementing rehabilitation at very early time points are unclear. Moreover, clinical trials to date are limited to studies initiating rehabilitation 2 weeks after injury and later. To address these gaps, this article reviews the preclinical literature on physical interventions initiated within the first 8 days postinjury. Effects of early rehabilitation on molecular and structural nervous system changes, behavioral function, and body systems are considered. Most studies utilized treadmill or cycle training as the primary intervention. Treadmill training initiated within the first 3 days and terminated by 1 week after injury worsened autonomic function, inflammation, and locomotor outcomes, while swim training during this period increased microvascular dysfunction. In contrast, lower-intensity rehabilitation such as reach training, ladder training, or voluntary wheel or ball training showed benefits when implemented during the first 3 days. Rehabilitation initiated at 4 days postinjury was also associated with enhanced motor recovery. Cycling appears to have the greatest risk-benefit ratio; however, the effects of cycle training in the first 3 days were not investigated. Overall, research suggests that lower intensity or voluntary rehabilitation during the hyperacute phase is more appropriate until at least 4 days postinjury, at which point higher-intensity activity becomes safer and more beneficial for recovery.

Background: Fatty accumulation in the rotator cuff is associated with shoulder dysfunction and a risk of failure of rotator cuff repair. The aims of this study were to (1) describe cellular findings in rotator cuff muscles in patients presenting with varying degrees of rotator cuff tendon pathology by examining fat content and myofiber cross-sectional area of rotator cuff muscles and (2) correlate histologic features to magnetic resonance imaging (MRI) grades derived with the Goutallier classification.Methods: Rotator cuff muscle biopsies were performed in a consecutive series of patients undergoing arthroscopic shoulder surgery. Rotator cuffs were graded according to the Goutallier classification and labeled as either partial-thickness or fullthickness. Patients without a rotator cuff tear undergoing arthroscopic surgery served as controls. The biopsy specimens were examined using LipidTOX to visualize lipid accumulation. Laminin was used to quantify myofiber cross-sectional area.Results: Twenty-seven patients with a rotator cuff tear and 12 without a tear (controls) were included. There were 24 males (62%). The mean age was 55 years. Patients in the control cohort were younger (mean, 46 years) than those in the treatment group (mean, 60 years, p < 0.01). Within the treatment group, 12 and 15 patients were recorded as having partial and full-thickness rotator cuff tears, respectively. Lipid accumulation visualized at the cellular level was fairly-tomoderately correlated with the Goutallier classification on MRI (R s = 0.705, 95% confidence interval [CI] = 0.513, 0.829). Muscle biopsy specimens with a Goutallier grade of 21 had significantly more lipid accumulation than those with grade-0 (p < 0.01) or grade-1 (p < 0.01) fatty accumulation. Muscle biopsies at the sites of full-thickness tears showed significantly greater lipid accumulation than those associated with either partial (p < 0.01) or no (p < 0.01) tears. Partialthickness rotator cuff tears had no difference in lipid accumulation in comparison to the control group. Muscle biopsy specimens from full-thickness tears had significantly smaller myofiber cross-sectional area when compared with partialthickness tears (p = 0.02) and controls (p < 0.01).Conclusions: Cellular lipid accumulation correlates with the MRI Goutallier grade of fatty accumulation, thus verifying the Goutallier classification at the cellular level. Muscle biopsy specimens from partial-thickness tears are more similar to controls than to those from full-thickness tears, whereas full-thickness tears of all sizes showed significantly greater lipid content and smaller myofiber cross-sectional area compared with partial-thickness tears and controls.Clinical Relevance: Our research confirms the utility of using the Goutallier classification to predict rotator cuff muscle quality and shows that tendon attachment, even if partially torn, protects the muscle from fatty accumulation. Rotator cuff repairs are among the most commonly performed orthopaedic procedures in the United States 1 . Intact r...

Background: Social media platforms, like TikTok, have become popular options for the distribution of health care information. Because of the lack of scientific oversight, the quality of health care–related videos has become a focus of the current literature. However, orthopaedic surgery has lagged behind other fields in acknowledging the widespread utilization of TikTok videos for medical information consumption. This study aims to assess the quality and educational benefits of ankle sprain–related TikTok videos. Methods: TikTok was queried using the hashtag “#anklesprainexercises.” One hundred videos were included after applying the exclusion criteria. The number of views, likes, shares, comments, and favorites was recorded. The content was graded using DISCERN (a well-validated informational analysis tool) and ASEES (a self-designed tool for exercise evaluation). We hypothesized that information on TikTok related to ankle sprain exercises would be poor in quality. Results: The total number of views of the 100 videos was 6 483 412, with a median of 5377.5 (IQR = 1074-20 275). The videos collectively received 385 847 likes, 3642 comments, 55 574 favorites, and 14 918 shares with a median of 267.5 (IQR = 41.5-1678.0), 4.0 (IQR = 0.0-23.0), 42.0 (IQR = 4.8-264.5), and 13.0 (IQR = 1.8-67.8), respectively. General users had a higher percentage of their videos graded as “very poor” (61.8%) in comparison to the number of videos uploaded by health care professionals deemed “very poor” (34.4%). Neither general user nor health care professionals had videos graded as “good” or “excellent.” There were significant differences between the 2 groups for DISCERN 1, 3, and ASSES scores. Conclusion: Although TikTok is a powerful tool for information distribution, the educational value of the videos related to ankle sprain injury exercises was poor. With only 2% of videos receiving a grade of “fair,” and no videos reaching a score of “good” or “excellent,” health care professionals should be aware of the low-quality content easily accessible on TikTok. Level of Evidence: Level III, cross-sectional study.

BACKGROUND: For percutaneous lumbar fusion (percLIF), magnetic resonance imaging and computed tomography are critical to defining surgical corridors. Currently, these scans are performed separately, and surgeons then use fluoroscopy or neuromonitoring to guide instruments through Kambin's triangle. However, anatomic variations and intraoperative positional changes are possible, meaning that safely accessing Kambin's triangle remains a challenge because nerveroot visualization without endoscopes has not been thoroughly described. OBJECTIVE: To overcome the known challenges of percLIF and reduce the likelihood of iatrogenic injuries by showing real-time locations of neural and bony anatomy. METHODS: The authors demonstrate an intraoperative navigational platform that applies nerve root segmentation and image fusion to assist with percLIF. Five patients from a single institution were included. RESULTS: Of the 5 patients, the mean age was 71 ± 8 years and 3 patients (60%) were female. One patient had general anesthesia while the remaining 4 patients underwent awake surgery with spinal anesthesia. The mean area for the L4-L5 Kambin's triangle was 76.1 ± 14.5 mm 2 . A case example is shown where the side of approach was based on the fact that Kambin's triangle was larger on one side compared with the other. The mean operative time was 170 ± 17 minutes, the mean blood loss was 32 ± 16 mL, and the mean hospital length of stay was 19.6 ± 8.3 hours. No patients developed postoperative complications. CONCLUSION: This case series demonstrates the successful and safe application of nerve segmentation using magnetic resonance imaging/computed tomography fusion to perform percLIF and provide positive patient outcomes.