Automated quantitative assessment of bone contusions and overlying articular cartilage following anterior cruciate ligament injury.

Quantitative methods to characterize bone contusions and associated cartilage injury remain limited. We combined standardized voxelwise normalization and 3D mapping to automate bone contusion segmentation post-anterior cruciate ligament (ACL) injury and evaluate anomalies in articular cartilage overlying bone contusions. Forty-five patients (54% female, 26.4 ± 11.8 days post-injury) with an ACL tear underwent 3T magnetic resonance imaging of their involved and uninvolved knees. A novel method for voxelwise normalization and 3D anatomical mapping was used to automate segmentation, labeling, and localization of bone contusions in the involved knee. The same mapping system was used to identify the associated articular cartilage overlying bone lesions. Mean regional T1ρ was extracted from articular cartilage regions in both the involved and uninvolved knees for quantitative paired analysis against ipsilateral cartilage within the same compartment outside of the localized bone contusion. At least one bone contusion lesion was detected in the involved knee within the femur and/or tibia following ACL injury in 42 participants. Elevated T1ρ (p = 0.033) signal were documented within the articular cartilage overlying the bone contusions resulting from ACL injury. In contrast, the same cartilaginous regions deprojected onto the uninvolved knees showed no ipsilateral differences (p = 0.795). Automated bone contusion segmentation using standardized voxelwise normalization and 3D mapping deprojection identified altered cartilage overlying bone contusions in the setting of knee ACL injury.

Cell-Based Therapies for Rotator Cuff Injuries: An Updated Review of the Literature.

This review focuses on non-surgical treatment options for rotator cuff injuries and highlights the potential of mesenchymal stem cells (MSCs) as a potential regenerative approach. MSCs, sourced from various tissues like bone marrow and adipose tissue, exhibit promising mechanisms in vitro, influencing tendon-related gene expression and microenvironment modulation. Animal studies support this, showcasing MSCs' ability to reduce inflammation, improve tissue remodeling, and enhance repaired tendon strength. Human trials, while varied and limited, suggest that MSCs might lower retear rates and enhance post-repair outcomes, but randomized controlled trials yield mixed results, emphasizing the necessity for standardized investigations. Ultimately, while cell-based therapies demonstrate an excellent safety profile, more rigorous clinical trials are necessary to determine their efficacy in improving patient outcomes and achieving lasting structural changes in rotator cuff injuries.

Complications and opioid-prescribing patterns following genicular nerve radiofrequency ablation versus intra-articular injection: a matched cohort study.

BACKGROUND AND OBJECTIVES: Genicular nerve radiofrequency ablation (GNRFA) is an emerging procedure used to relieve pain from severe knee osteoarthritis. While there have been rare reports of significant complications, their incidence has not been well established. The objective of this study was to examine complication rates at 30 and 90 days post treatment as well as characterize opioid-prescribing patterns before and after treatment. METHODS: A large national database was queried to identify patients undergoing GNRFA from 2015 to 2022 and matched to control cohorts composed of patients receiving either intra-articular corticosteroid (CSI) or hyaluronic acid injection (HAI) of the knee. Complication rates at 30 and 90 days were analyzed. Opioid utilization was assessed in the 6 months before and after treatment. RESULTS: Rates of infection (0.1%, CI 0.02% to 0.5% vs 0.2%, CI 0.05% to 0.6%), septic arthritis (<0.1%, CI 0.003% to 0.4% vs 0.1%, CI 0.02% to 0.5%), deep vein thrombosis (2.0%, CI 1.3% to 2.7% vs 1.6%, CI 1.0% to 2.2%), pulmonary embolism (1.2%, CI 0.6% to 1.7% vs 1.3%, CI 1.1% to 2.5%), bleeding (<0.1%, CI 0.003% to 0.4% vs 0%, CI 0% to 0.3%), seroma (<0.1%, CI 0.003% to 0.4% vs 0.2%, CI 0.05% to 0.6%), nerve injury (0%, CI 0% to 0.3% vs 0%, CI 0% to 0.3%) and thermal injury (0%, CI 0% to 0.3% vs 0%, CI 0% to 0.3%) were not different between CSI and GNRFA cohorts at 30 days. Rate of swelling was significantly greater in the GNRFA cohort (9.4%, CI 7.6% to 10.4% vs 6.4%, CI 4.8% to 7.2%, p=0.003) at 30 days. At 90 days, rates of septic arthritis (0.1%, CI 0.02% to 0.5% vs 0.3%, CI 0.08% to 0.7%), deep vein thrombosis (3.1%, CI 2.1% to 3.8% vs 3.1%, CI 2.2% to 3.9%), pulmonary embolism (1.5%, CI 0.9% to 2.1% vs 1.8%, CI 1.2% to 2.5%), and nerve injury (0%, CI 0% to 0.3% vs <0.1%, CI 0.003% to 0.4%) were not significantly different.Between HAI versus GNRFA cohorts, no significant differences were seen in rates of infection (0.3%, CI 0.08% to 0.07% vs 0.7%, CI 0.3% to 1.2%), septic arthritis (0.2%, CI 0.05% to 0.6% vs 0.4%, CI 0.2% to 0.9%), deep vein thrombosis (2.0%, CI 1.3% to 2.7% vs 1.9%, CI 1.2% to 2.7%), pulmonary embolism (1.5%, CI 0.9% to 2.2% vs 1.7%, CI 1.1% to 2.5%), bleeding (0.1%, CI 0.02% to 0.5% vs 0.2%, CI 0.05% to 0.6%), seroma (<0.1%, CI 0.03% to 0.4% vs 0%, CI 0% to 0.3%), nerve injury (0%, CI 0% to 0.3% vs 0%, CI 0% to 0.3%), swelling (14.0%, CI 11.6% to 15.1% vs 12.0%, CI 10.3% to 13.6%), and thermal injury (<0.1%, CI 0.03% to 0.4% vs <0.01%, CI 0.3% to 0.4%) at 30 days. Rates of infection (0.7%, CI 0.3% to 1.2% vs 1.4%, CI 0.9% to 2.1%), septic arthritis (0.3%, CI 0.1% to 0.8% vs 0.5%, CI 0.2% to 1.1%), deep vein thrombosis (3.6%, CI 2.6% to 4.4% vs 3.1%, CI 2.2% to 4.0%), pulmonary embolism (2.3%, CI 1.5% to 3.0% vs 2.1%, CI 1.4% to 3.0%) and nerve injury (0%, CI 0% to 0.3% vs 0.1%, CI 0.02% to 0.5%) were not significantly different at 90 days.There were no significant differences in level of pretreatment opioid utilization although overall consumption in mean daily morphine equivalents was greater in the GNRFA cohort. Opioid utilization significantly increased in the first 30 days after ablation in patients with no prior opioid use compared to controls. In patients with some and chronic prior opioid use, opioid requirements were generally decreased in all treatment groups at 6 months with no clearly superior treatment in reducing opioid consumption. CONCLUSION: Our study demonstrated that GNRFA possesses a safety profile similar to that of intra-articular injections although significant adverse events such as venous thromboembolism and septic arthritis may occur rarely. Although opioid utilization generally increased in the 30 days after ablation compared with intra-articular injection, similar reduction in opioid consumption at 6 months was seen in patients with prior opioid use in the ablation and control cohorts.

Leukocyte-Rich Platelet-Rich Plasma Is Predominantly Anti-inflammatory Compared With Leukocyte-Poor Platelet-Rich Plasma in Patients With Mild-Moderate Knee Osteoarthritis: A Prospective, Descriptive Laboratory Study.

BACKGROUND: Platelet-rich plasma (PRP) has been used extensively in clinical practice to treat patients with symptomatic knee osteoarthritis (OA). Leukocyte-poor PRP (LP-PRP) has been clinically preferred over leukocyte-rich PRP (LR-PRP); however, it is unclear which cytokine mediators of pain and inflammation are present in LR-PRP and LP-PRP from patients with mild to moderate knee OA in order to rationalize a specific formulation. HYPOTHESIS: LP-PRP would be predominantly anti-inflammatory and have reduced nociceptive pain mediators compared with LR-PRP from the same individual with mild to moderate knee OA. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 24 unique samples of PRP were prepared in order to assess 48 samples of LR-PRP and LP-PRP taken from 12 patients (6 male and 6 female) with symptomatic knee OA of Kellgren-Lawrence grade 2 to 3. Patients underwent blood collection for LR-PRP and LP-PRP preparation through a double-spin protocol to obtain baseline whole blood, platelet concentration, and white blood cell subtypes. LR-PRP and LP-PRP from the same patient were produced at the same time and underwent a comprehensive panel through Luminex (multicytokine profiling) to assess key mediators of inflammation: interleukin 1 receptor antagonist (IL-1Ra), interleukin 4, 6, 8, and 10 (IL-4, IL-6, IL-8, and IL-10), IL-1ß, tissue necrosis factor α (TNF-α), and matrix metalloproteinase 9 (MMP-9). To assess mediators of nociceptive pain, nerve growth factor (NGF) and tartrate resistant acid phosphatase 5 (TRAP5) were also assessed. RESULTS: LR-PRP from patients with mild to moderate knee OA expressed significantly more IL-1Ra, IL-4, IL-8, and MMP-9 compared with LP-PRP formulations from the same patients. No significant differences were found between LR-PRP and LP-PRP in mediators of nociceptive pain-namely, NGF and TRAP5. Other mediators including TNF-α, IL-1ß, IL-6, and IL-10 were also found to have no significant expression differences between LR-PRP and LP-PRP. CONCLUSION: LR-PRP expressed significantly more IL-1Ra, IL-4, and IL-8, suggesting that LR-PRP may be more anti-inflammatory than LP-PRP. MMP-9 was expressed in higher concentrations in LR-PRP, suggesting that LR-PRP may be more chondrotoxic than LP-PRP. CLINICAL RELEVANCE: LR-PRP was found to have a robust expression of anti-inflammatory mediators compared with LP-PRP and may be beneficial to patients with long-term knee OA where chronic low-grade inflammation is present. Mechanistic clinical trials are needed to elucidate the key mediators in both LR-PRP and LP-PRP to assess their effect on long-term progression of knee OA.

Medical Concerns in Orthobiologics Procedures.

Orthobiologics have shown immense treatment potential in many medical fields including sports medicine, musculoskeletal disorders, and pain management. As with the case of any medical procedures and treatments, there are potential side effects or caveats that physicians and patients should be cognizant of. Nevertheless, the use of orthobiologics does not seem to have consistent severe side effects and do not have increased risks with transmissible disease, immune-modulated reactions, or oncologic processes.

Mesenchymal stem cells for subchondral bone marrow lesions: From bench to bedside.

Subchondral bone marrow lesions (BMLs) are areas of disease within subchondral bone that appear as T1 hypointense and T2 hyperintense ill-defined areas of bone marrow on magnetic resonance imaging. The most common bone marrow lesions include subchondral lesions related to osteoarthritis, osteochondral defects, and avascular necrosis. Emerging therapies include autologous biologic therapeutics, in particular mesenchymal stem cells (MSCs), to maintain and improve cartilage health; MSCs have become a potential treatment option for BMLs given the unmet need for disease modification. Active areas in the preclinical research of bone marrow lesions include the paracrine function of MSCs in pathways of angiogenesis and inflammation, and the use of bioactive scaffolds to optimize the environment for implanted MSCs by facilitating chondrogenesis and higher bone volumes. A review of the clinical data demonstrates improvements in pain and functional outcomes when patients with knee osteoarthritis were treated with MSCs, suggesting that BM-MSCs can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions. Preliminary data examining MSCs in osteochondral defects suggest they can be beneficial as a subchondral injection alone, or as a surgical augmentation. In patients with hip avascular necrosis, those with earlier stage disease have improved outcomes when core decompression is augmented with MSCs, whereas patients in later stages post-collapse have equivalent outcomes with or without MSC treatment. While the evidence for the use of MSCs in conditions with associated bone marrow lesions seems promising, there remains a need for continued investigation into this treatment as a viable treatment option.

Double-Spin Leukocyte-Rich Platelet-Rich Plasma Is Predominantly Lymphocyte Rich With Notable Concentrations of Other White Blood Cell Subtypes.

Purpose: To comprehensively characterize a double-spin leukocyte-rich platelet-rich plasma (LR-PRP) formulation and to compare it with whole blood (WB) by quantitatively assessing platelet and WB cell subtype concentrations in each. Methods: Prospective human ex vivo analysis with 12 healthy adult men with ages ranging from 25 to 31 was performed in a controlled laboratory setting. The main outcome measure was the leukocyte profile of human LR-PRP. Results: In LR-PRP, lymphocytes were the predominant WB cell type (11.94 ± 2.97 × 103 cells/µL) followed by neutrophils (3.72 ± 1.28 × 103 cells/µL). The mean cumulative percentage of granulocytes was 23% ± 8% and agranulocytes was 77% ± 18%. There was a significant difference observed between granulocyte and agranulocyte percentage within both WB (P = .004, [95% CI: (7%,31%)]) and LR-PRP (P < .0001, [95% CI: (42%,66%)]) groups. In addition, there was a significant difference observed between the WB and LR-PRP granulocyte percentages (P < .0001, [95% CI: (29%,43%)]) and between the WB and LR-PRP agranulocyte percentages (P < .0001, [95% CI: (30%,42%)]). Conclusions: Our study found that LR-PRP is predominantly lymphocyte rich with notable concentrations of other WB cell subtypes, including neutrophils, monocytes, eosinophils, basophils, and large unstained cells. While these subtypes are not routinely reported, they may play a role in modulating the local inflammatory environment. We also found significant differences in WB cell subtype concentrations between WB and LR-PRP. Clinical Relevance: PRP has been routinely used in many clinical practices without clear indications for its use and lacks standardization in its formulation. This study provides a comprehensive characterization of a broadly used PRP, LR-PRP, and further characterizes subtypes of WBC cells present in LR-PRP that have not been previously reported. Comprehensively reporting these subtypes in clinical trials of PRP is crucial to understanding how these cells participate in PRP's therapeutic potential. This type of data can help standardize future PRP formulations and improve patient outcomes.

Novel assessment of leukocyte-rich platelet-rich plasma on functional and patient-reported outcomes in knee osteoarthritis: a pilot study.

Background: Leukocyte-rich platelet-rich plasma (LR-PRP) has demonstrated to be beneficial for patients with knee osteoarthritis (KOA); however, reliable objective end points to accurately assess its therapeutic effects is lacking. Aim: To investigate the efficacy of LR-PRP as assessed by functional and patient-reported outcomes at early time points (6 weeks). Materials & methods: We conducted a prospective cohort study in 12 patients with diagnosed KOA (Kellgren Lawrence score of II-III), who underwent a single ultrasound-guided LR-PRP injection. Results: There was significant improvement in timed up and go, pain and quality of life scales and balance parameters. There were nonsignificant improvements in range of motion and gait parameters. Conclusion: LR-PRP demonstrates efficacy in meaningful end points for functional and patient-reported outcomes at early time points in patients with KOA.

Therapeutic efficacy of low-dose steroid combined with hyaluronidase in ultrasonography-guided intra-articular injections into the shoulder for adhesive capsulitis.

PURPOSE: The purpose of this study was to compare the efficacy of low-dose steroid, highdose steroid, and low-dose steroid combined with hyaluronidase with respect to intra-articular injection therapy for adhesive capsulitis (AC) of the shoulder. METHODS: Thirty patients with primary AC in the initial stage were randomly assigned into three groups to receive ultrasound-guided intra-articular injections with 20 mg of triamcinolone acetonide (group A, n=10), 40 mg of triamcinolone acetonide (group B, n=10) and 20 mg of triamcinolone acetonide combined with hyaluronidase (group C, n=10). The outcome measures included a visual analogue scale (VAS), the Shoulder Disability Questionnaire (SDQ), abduction and external rotation range of motion, and intra-sheath fluid (ISF) before treatment and at 2, 4, 8, and 16 weeks after treatment. RESULTS: Among the 30 patients, one participant in group B dropped out; therefore, a total of 29 patients completed this study and were successfully injected. After the injection, the VAS, SDQ, range of flexion and external rotation, and ISF improved in all groups compared with the preinjection status, regardless of treatment or time point. In the comparison between groups, the SDQ and ISF showed significantly greater improvements in groups B and C than in group A. CONCLUSION: The therapeutic efficacy of combined low-dose corticosteroid and hyaluronidase is superior to that of low-dose corticosteroid and equivalent to that of high-dose corticosteroid in early AC.

Microfragmented Adipose Tissue With Adjuvant Platelet-Rich Plasma Combination Therapy for Partial-Thickness Supraspinatus Tear.

A 50-year-old male presented with acute, sharp, right shoulder pain. Ultrasound of the right shoulder revealed a partial thickness tear of the supraspinatus. After conservative management failed to provide any relief, he was treated with microfragmented adipose tissue (MFAT) injection followed by platelet-rich plasma (PRP) at 14 weeks. At the 28-week follow-up, he showed significant improvement in pain and mobility with a resolution of the tear on ultrasound. While PRP has been shown to confer some protection against retears, very few studies have investigated the efficacy of MFAT use in rotator cuff pathology. In this case, we used a combination of MFAT and PRP to successfully treat a partial thickness supraspinatus tear. These agents may function in a synergistic manner, with MFAT providing a cell scaffold and PRP modulating the cellular environment to optimize healing. Further studies are needed to better understand the mechanism of this treatment modality in treating similar conditions.

Epidemiology of NCAA Bone Stress Injuries: A Comparison of Athletes in Divisions I, II, and III.

BACKGROUND: Bone stress injuries (BSIs) are a major source of functional impairment in athletes of all sports, with many risk factors, including athlete characteristics and type of sport. In National Collegiate Athletic Association (NCAA) athletics, the stratification of programs into divisions with different characteristics and makeup has been identified as increasing the risk for certain kinds of injuries, but there have been no studies on the difference of BSI rates and characteristics between athletes in Division I (DI) and those in Divisions II and III (DII and DIII). PURPOSE/HYPOTHESIS: To characterize the BSI rates in each division and compare the incidence and characteristics of BSIs within divisions. Our hypothesis was that BSI rates would be higher in DII and DIII athletes as compared with DI athletes. STUDY DESIGN: Descriptive epidemiology study. METHODS: Five years of recorded BSI data in collegiate athletes via the NCAA Injury Surveillance Program were examined for the academic years 2009-2010 to 2013-2014. BSI rates per 100,000 athlete-exposures (AEs) were compared for DI versus DII and DIII athletes using risk ratios and 95% CIs. Time lost to injury, time of season of injury, and class composition of injured athletes were also compared between divisions. RESULTS: Over the 5 years studied, DII and DIII programs reported 252 BSIs more than 1,793,777 AEs (14.05 per 100,000 AEs), and DI programs reported 235 BSIs over 2,022,592 AEs (11.62 per 100,000 AEs). The risk ratio was significant for D1 versus DII and DIII (1.21; 95% CI, 1.01-1.44). There was a significant difference in time lost to injury in DI versus DII and DIII, χ2(5, n = 449) = 16.54; P = .006. When data were stratified by individual sport, there were no significant divisional differences in high-risk sports. CONCLUSION: In the current study, NCAA DII and DIII athletes had higher rates of BSI than their DI counterparts. As compared with DII and DIII athletes, the DI athletes had a significantly greater proportion of BSIs that did not result in absence from participation in sport.

Pain and functional outcomes of the sacroiliac joint after platelet-rich plasma injection: a descriptive review.

The purpose of this manuscript is to highlight and review the status of literature regarding efficacy of platelet-rich plasma (PRP) in the treatment of sacroiliac joint (SIJ) dysfunction. A review of the literature on PRP interventions on the SIJ or ligaments was performed. Seven studies had improvements in their respective primary end point and demonstrated a strong safety profile without any serious adverse events. Only five articles demonstrated clinical efficacy of >50% in their primary outcome measures. There appears to be inconsistent and insufficient evidence for a conclusive recommendation for or against SIJ PRP. There is a need for adequately powered well-designed, standardized, double-blinded randomized clinical trials to determine the effectiveness of PRP in SIJ-mediated pain.

Efficacy of Botulinum Toxin in Treating Lateral Epicondylitis-Does Injection Location Matter?: A Systematic Review.

OBJECTIVE: Clinical trials assessing the efficacy of botulinum toxin in treating recalcitrant lateral epicondylitis have demonstrated varied results and differed greatly in methodology. The objective of this systematic review was to demonstrate injection location as a significant contributor to outcome heterogeneity. DESIGN: Two reviewers independently conducted a systematic review using Scopus, Embase, and PubMed for randomized controlled trials assessing botulinum toxin in the treatment of lateral epicondylitis. After applying inclusion/exclusion criteria to abstracts and reviewing the full-text articles, seven studies were found representing six separate injection locations. Reduction in visual analog scale pain and change in grip strength were the principal outcomes of interest. RESULTS: The largest reduction in pain was seen in injection at 1/3 of the length of the forearm from the lateral epicondyle at 16-wk follow-up, whereas the smallest reduction was seen at 12-wk follow-up after injection at the 0-cm mark. Differences were also identified in grip strength, although all studies reported return to baseline strength by weeks 12-18. CONCLUSIONS: This study demonstrates injection location as a potential source of heterogeneity. This clinical question warrants further evaluation with direct comparison of outcomes at different injection locations while controlling for dosage, toxin type, and ultrasound/electromyographic guidance.

Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020.

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects, and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

Leukocyte-rich platelet-rich plasma application in post-traumatic osteoarthritis with popliteal cyst: a case report.

Aim: To describe the successful treatment of a Baker's cyst in the setting of post-traumatic osteoarthritis using ultrasound-guided injection of platelet-rich plasma. Setting: Outpatient sports clinic. Patient: 29-year old male basketball player. Case description: The patient presented with 2-months history of right knee pain, 17 months after undergoing right knee anterior cruciate ligament reconstruction surgery. Exam revealed medial joint line and medial collateral ligament tenderness with posterior knee swelling. After aspiration, a corticosteroid injection was administered with temporary symptom relief. Diagnostic ultrasound examination confirmed the Baker's cyst. The patient then underwent two serial leukocyte-rich platelet-rich plasma injections into his right knee. Results: The patient reported complete resolution of pain and cyst size. Conclusion: Leukocyte-rich platelet-rich plasma may be considered as a treatment option for patients with Baker's cysts in the setting of post-traumatic osteoarthritis.