Computed tomography-based structural rigidity analysis can assess tumor- and treatment-induced changes in rat bones with metastatic lesions.

BACKGROUND: Breast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious complications such as pain, fractures, and compromised mobility. Structural rigidity, crucial for bone strength, becomes compromised with osteolytic lesions, highlighting the vulnerability and increased fracture risk in affected areas. Historically, two-dimensional radiographs have been employed to predict these fracture risks; however, their limitations in capturing the three-dimensional structural and material changes in bone have raised concerns. Recent advances in CT-based Structural Rigidity Analysis (CTRA), offer a promising, more accurate non-invasive 3D approach. This study aims to assess the efficacy of CTRA in monitoring osteolytic lesions' progression and response to therapy, suggesting its potential superiority over existing methodologies in guiding treatment strategies. METHODS: Twenty-seven female nude rats underwent femoral intra-medullary inoculation with MDA-MB-231 human breast cancer cells or saline control. They were divided into Control, Cancer Control, Ibandronate, and Paclitaxel groups. Osteolytic progression was monitored weekly using biplanar radiography, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DEXA). CTRA was employed to predict fracture risk, normalized using the contralateral femur. Statistical analyses, including Kruskal-Wallis and ANOVA, assessed differences in outcomes among groups and over time. RESULTS: Biplanar radiographs showed treatment benefits over time; however, only certain time-specific differences between the Control and other treatment groups were discernible. Notably, observer subjectivity in X-ray scoring became evident, with significant inter-operator variations. DEXA measurements for metaphyseal Bone Mineral Content (BMC) did not exhibit notable differences between groups. Although diaphyseal BMC highlighted some variance, it did not reveal significant differences between treatments at specific time points, suggesting a limited ability for DEXA to differentiate between treatment effects. In contrast, the CTRA consistently demonstrated variations across different treatments, effectively capturing bone rigidity changes over time, and the axial- (EA), bending- (EI), and torsional rigidity (GJ) outcomes from the CTRA method successfully distinguished differences among treatments at specific time points. CONCLUSION: Traditional approaches, such as biplanar radiographs and DEXA, have exhibited inherent limitations, notably observer bias and time-specific inefficacies. Our study accentuates the capability of CTRA in capturing real-time, progressive changes in bone structure, with the potential to predict fractures more accurately and provide a more objective analysis. Ultimately, this innovative approach may bridge the existing gap in clinical guidelines, ushering in enhanced Clinical Decision Support Tool (CDST) for both surgical and non-surgical treatments.

The effect of cannabinoids on single-level lumbar arthrodesis outcomes in a rat model.

BACKGROUND CONTEXT: The opioid epidemic is a public health crisis affecting spine care and pain management. Medical marijuana is a potential non-opioid analgesic yet to be studied in the surgical setting since its effects on bone healing are not fully understood. Studies have demonstrated analgesic and potentially osteoinductive properties of cannabinoids with endocannabinoid receptor expression in bone tissue. PURPOSE: We hypothesize that tetrahydrocannabinol (THC) and cannabidiol (CBD) will not decrease bone healing in spinal fusion. STUDY DESIGN: Seventy-eight adult Sprague-Dawley rats were used for this study. Utilizing allogenic bone grafts (6 donor rats), posterolateral inter-transverse lumbar fusion at the L4-L5 level was performed. The animals were equally divided into four treatment groups, each receiving 0.1 ml intraperitoneal injections weekly as follows: placebo (saline), 5 mg/kg THC, 5 mg/kg CBD, and a combination of 5 mg/kg THC and 5mg/kg CBD (Combo). METHODS: Callus tissue was harvested 2- and 8-weeks post-surgery for qPCR assessment to quantify changes in the expression of osteogenic genes. Manual palpation was done to assess the strength of the L4-L5 arthrodesis on all rats. µCT image-based callus analysis and histology were performed. One-way ANOVA followed by post hoc comparisons was performed. RESULTS: µCT demonstrated no significant differences. Treatment groups had slightly increased bone volume and density compared to control. qPCR at two weeks indicated downregulated RANKL/OPG ratios skewing towards osteogenesis in the CBD group, with the THC and CBD+THC groups demonstrating a downward trend (p>.05). ALPL, BMP4, and SOST were significantly higher in the CBD group, with CTNNB1 and RUNX2 also showing an upregulating trend. The CBD group showed elevation in Col1A1 and MMP13. Data at eight weeks showed ALPL, RUNX2, BMP4, and SOST were downregulated for all treatment groups. In the CBD+THC group, RANK, RANKL, and OPG were downregulated. OPG downregulation reached significance for the THC and CBD+THC group compared to saline. Interestingly, the RANKL/OPG ratio showed upregulation in the CBD and CBD+THC groups. RANKL showed upregulation in the CBD group. At 2 and 8 weeks, the CBD treatment group showed superior histological progression, increasing between time points. CONCLUSION: This study demonstrates that CBD and THC have no adverse effect on bone healing and the rate of spinal fusion in rats. Osteogenic factors were upregulated in the CBD-treated groups at two weeks, which indicates a potential for bone regeneration. In this group, compared to control, the RANKL/OPG ratio at the early healing phase demonstrates the inhibition of osteoclast differentiation, enhancing bone formation. Interestingly, it shows promoted osteoclast differentiation at the later healing phase, enhancing bone remodeling. This aligns with the physiological expectation of a lower ratio in the early phases and a higher ratio in the later remodeling phases. CLINICAL SIGNIFICANCE: CBD and THC showed no inhibitory effects on bone healing in a spinal fusion model. Moreover, histologic and gene expression analysis demonstrated that CBD may, in fact, enhance bone healing. Further research is needed to confirm the safe usage of THC and CBD in the post-operative setting following spinal fusions.

While the Incidence of Venous Thromboembolism After Shoulder Arthroscopy Is Low, the Risk Factors Are a Body Mass Index Greater than 30 and Hypertension.

Purpose: This study aims to determine the overall incidence of venous thromboembolism (VTE) following shoulder arthroscopy and to define potential risk factors associated with its development that may help define guidelines for the use of thromboprophylaxis. Methods: A systematic review was performed using PubMed, Embase, Web of Science, CINAHL, and Cochrane databases per PRISMA guidelines. The search terms consisted of variations of "Venous Thromboembolism" and "Shoulder Arthroscopy." Information regarding arthroscopy indication, risk factors, outcomes, and patient demographics was recorded and analyzed, and pooled odds ratios were reported for each variable. Results: Six hundred eighty-five articles were identified in the initial search, and 35 articles reported DVT, PE, or VTE incidence following shoulder arthroscopy. Seventeen nonoverlapping articles with a unique patient population incidence rates. Four articles were then used for subgroup meta-analysis. The incidence rate of VTE was 0.24%, ranging from 0.01% to 5.7%. BMI >30 (OR = 1.46; 95% CI = [1.22, 1.74]; I2 = 0%) and hypertension (OR = 1.64; 95% CI = [1.03, 2.6]; I2 = 75%) were significant risk factors (P < .05) for developing VTE following shoulder arthroscopy. Diabetes (OR = 1.2; 95% CI = [0.97, 1.48]; I2 = 0%), insulin-dependent diabetes (OR = 5.58; 95% CI = [0.12, 260.19]; I2 = 85%), smoking (OR = 1.04; 95% CI = [0.79, 1.37]; I2 = 12%), male sex (OR = 0.95; 95% CI = [0.49, 1.85]; I2 = 86%) and age over 65 (OR = 4.3; 95% CI = [0.25, 72.83]; I2 = 85%) were not associated with higher VTE risk. Conclusion: The VTE incidence following shoulder arthroscopy is low at 0.24%. Patients with BMI >30 and hypertension are at a higher risk for VTE after shoulder arthroscopy. Level of Evidence: Level IV, systematic review and meta-analysis of Level I-IV studies.

Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis.

Substantial advances in biotherapeutics are distinctly lacking for musculoskeletal diseases. Musculoskeletal diseases are biomechanically complex and localized, highlighting the need for novel therapies capable of addressing these issues. All frontline treatment options for arthrofibrosis, a debilitating musculoskeletal disease, fail to treat the disease etiology-the accumulation of fibrotic tissue within the joint space. For millions of patients each year, the lack of modern and effective treatment options necessitates surgery in an attempt to regain joint range of motion (ROM) and escape prolonged pain. Human relaxin-2 (RLX), an endogenous peptide hormone with antifibrotic and antifibrogenic activity, is a promising biotherapeutic candidate for musculoskeletal fibrosis. However, RLX has previously faltered through multiple clinical programs because of pharmacokinetic barriers. Here, we describe the design and in vitro characterization of a tailored drug delivery system for the sustained release of RLX. Drug-loaded, polymeric microparticles released RLX over a multiweek time frame without altering peptide structure or bioactivity. In vivo, intraarticular administration of microparticles in rats resulted in prolonged, localized concentrations of RLX with reduced systemic drug exposure. Furthermore, a single injection of RLX-loaded microparticles restored joint ROM and architecture in an atraumatic rat model of arthrofibrosis with clinically derived end points. Finally, confirmation of RLX receptor expression, RXFP1, in multiple human tissues relevant to arthrofibrosis suggests the clinical translational potential of RLX when administered in a sustained and targeted manner.

Contamination of the Mini C-Arm During Foot and Ankle Surgery.

BACKGROUND: Many orthopedic surgeries utilize intraoperative fluoroscopy. The mini C-arm is an advantageous device as it can be easily used without the need for a dedicated radiology technician. However, there are concerns that the mini C-arm may represent a potential source of contamination and subsequent postoperative infection. Previous investigations of standard C-arm drapes have shown high rates of contamination. Similar contamination rates would be even more concerning for the mini C-arm as it requires physically maneuvering the machine. This study aimed to determine the rate of mini C-arm drape contamination and identify high-risk areas. METHODS: Fifty foot and ankle surgeries requiring the use of mini C-arm fluoroscopy were included. Eight locations on the mini C-arm drape were sampled at the conclusion of each procedure. Culture Q-swabs were used for sampling defined locations. Swab samples were then assessed for bacterial growth on a 5% blood agar plate using a semiquantitative technique. RESULTS: In 70% of surgical cases, contamination was observed in at least 1 location. Six of the 8 evaluated locations were found to have significantly higher contamination in comparison with their corresponding negative controls (Mann-Whitney U test, P < .05). The "outer portion of the upper arm" (location 1) exhibited bacteria growth in 26% (P < .0001) of cases. The "superior portion of the x-ray source" (location 2) exhibited growth in 30% (P < .0001) of cases. These were the highest-risk areas for contamination and were both significantly more likely to be involved than the "inferior portion of the x-ray source" and "superior portion of the beam receiver," locations 4 and 5, respectively. Fourteen percent (7/50) C-arm cases and 1.72% (1/58) Achilles tendon surgery control cases developed surgical site infection (P = .0234; OR, 9.27). CONCLUSION: Bacterial contamination of the mini C-arm drape was found to be common after foot and ankle procedures. Contamination was more prevalent on the outer ring areas of the C-arm, both at the emitter and receiver. LEVEL OF EVIDENCE: Level III, prospective cohort study.