Introduction

Knee pain effects 25% of individuals over age 55, and is most commonly due to osteoarthritis, although other etiologies can occur [1]. For many of these patients, their arthritis is too advanced for arthroscopy but too premature for arthroplasty. This leaves many patients in a grey zone where no good surgical treatments remain. Furthermore, even well indicated total knee arthroplasty outcomes result in persistent knee pain in 10-34% of cases [2]. Therefore, there is a large unmet need to help understand and treat knee pain outside of the structural abnormalities that is typically the focus for surgeons. Through collaborating with other medical fields and basic scientists, translational research can further our understanding, and eventually our treatment practices, of the knee in the future.

Content

The knee is a unique joint that may be better perceived as an organ due to its complexity and multiple tissue types and should be treated as such. When taking this approach, it becomes reasonable to focus treatments based on the different tissue types including the following: hyaline articular cartilage, bone, synovial fluid, meniscus, ligaments, and the synovial lining. Along with this, the contributions to pain can be significant when considering the bone and synovial lining as the cartilage is aneural. This was demonstrated by Dye et al. when he had an arthroscopy performed on his knee while awake and demonstrated that the most sensitive area was in fact the synovium [3]. Therefore, while treating structural abnormalities in the knee are important, treating the knee environment such as the synovial fluid and synovium itself can be just as relevant. These treatments can result from collaboration with the field of Rheumatology and have included treatments such as injections of steroids for post-traumatic osteoarthritis and IL1-Ra for ACL injury [4-5]. Novel injections are also being investigated, such as ABT-981, an immunoglobin that targets IL-1α and IL-1β and intraarticular injections of Etanercept [6].

Treatment options for patients with knee pathologies, both surgical and non-surgical, continue to evolve. This is largely in part due to a greater volume of basic and translational science literature of the knee, especially our understanding of the role of synovial fluid and the healing potential of cartilage. This understanding has led to a recent interest in the role of biologic treatments. Biologics, including adipose tissue, platelet-rich plasma, hyaluronic acid (HA), bone marrow aspiration (BMAC), and amniotic fluid, have been relatively understudied in the treatment of knee pain [7]. These compounds have the potential to alter the synovial fluid environment and may have a clinical benefit intraoperatively and postoperatively. Early evidence of their efficacy has been shown in some studies. For example, the AMELIA study, which investigated HA in knee arthritis, showed symptom improvement [8]. Other current clinical trials include the investigation of intraarticular BMAC for the treatment of early arthritis. As we continue researching these compounds, basic scientists must collaborate with physicians to understand the mechanism behind these interventions by testing the effects of biologics on an in vitro knee environment and exploring compounds, namely growth factors and cytokines, that likely play a role.

While different structures in the knee can cause pain, the nerves themselves can be the source of pain as well. For example, anesthesiologists have shown that the addition of cooled radiofrequency ablation with corticosteroid injection improves outcomes in patients with symptomatic osteoarthritis [9]. Furthermore, pain management physicians have shown that Botox can be used in the treatment of patellofemoral pain syndrome [10].

The components of the knee, from articular cartilage to synovium, create a unique environment that works as a synergistic unit. However, when parts of this system go awry, pain often ensues. Therefore, physicians from different specialties, researchers, physical therapists, and other healthcare personnel need to collaborate to understand and treat the pain of this complex joint.

References

[1] Peat, G., R. McCarney, and P. Croft. "Knee Pain and Osteoarthritis in Older Adults: A Review of Community Burden and Current Use of Primary Health Care." Ann Rheum Dis 60, no. 2 (Feb 2001): 91-7.

[2] Beswick, A. D., V. Wylde, R. Gooberman-Hill, A. Blom, and P. Dieppe. "What Proportion of Patients Report Long-Term Pain after Total Hip or Knee Replacement for Osteoarthritis? A Systematic Review of Prospective Studies in Unselected Patients." BMJ Open 2, no. 1 (2012): e000435.

[3] Dye, S. F., G. L. Vaupel, and C. C. Dye. "Conscious Neurosensory Mapping of the Internal Structures of the Human Knee without Intraarticular Anesthesia." Am J Sports Med 26, no. 6 (Nov-Dec 1998): 773-7.

[4] Kraus, V. B., J. Birmingham, T. V. Stabler, S. Feng, D. C. Taylor, C. T. Moorman, 3rd, W. E. Garrett, and A. P. Toth. "Effects of Intraarticular Il1-Ra for Acute Anterior Cruciate Ligament Knee Injury: A Randomized Controlled Pilot Trial (Nct00332254)." Osteoarthritis Cartilage 20, no. 4 (Apr 2012): 271-8.

[5] Lattermann, C., C. A. Jacobs, M. Proffitt Bunnell, L. J. Huston, L. G. Gammon, D. L. Johnson, E. K. Reinke, et al. "A Multicenter Study of Early Anti-Inflammatory Treatment in Patients with Acute Anterior Cruciate Ligament Tear." Am J Sports Med 45, no. 2 (Feb 2017): 325-33.

[6] Wang, S. X., S. B. Abramson, M. Attur, M. A. Karsdal, R. A. Preston, C. J. Lozada, M. P. Kosloski, et al. "Safety, Tolerability, and Pharmacodynamics of an Anti-Interleukin-1alpha/Beta Dual Variable Domain Immunoglobulin in Patients with Osteoarthritis of the Knee: A Randomized Phase 1 Study." Osteoarthritis Cartilage 25, no. 12 (Dec 2017): 1952-61.

[7] Devitt, B. M., S. W. Bell, K. E. Webster, J. A. Feller, and T. S. Whitehead. "Surgical Treatments of Cartilage Defects of the Knee: Systematic Review of Randomised Controlled Trials." Knee 24, no. 3 (Jun 2017): 508-17.

[8] Navarro-Sarabia, F., P. Coronel, E. Collantes, F. J. Navarro, A. R. de la Serna, A. Naranjo, M. Gimeno, G. Herrero-Beaumont, and Amelia study group. "A 40-Month Multicentre, Randomised Placebo-Controlled Study to Assess the Efficacy and Carry-over Effect of Repeated Intra-Articular Injections of Hyaluronic Acid in Knee Osteoarthritis: The Amelia Project." Ann Rheum Dis 70, no. 11 (Nov 2011): 1957-62.

[9] Davis, T., E. Loudermilk, M. DePalma, C. Hunter, D. Lindley, N. Patel, D. Choi, et al. "Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation with Corticosteroid Injection in the Management of Knee Pain from Osteoarthritis." Reg Anesth Pain Med 43, no. 1 (Jan 2018): 84-91.

[10] Chen, J. T., A. C. Tang, S. C. Lin, and S. F. Tang. "Anterior Knee Pain Caused by Patellofemoral Pain Syndrome Can Be Relieved by Botulinum Toxin Type a Injection." Clin Neurol Neurosurg 129 Suppl 1 (Feb 2015): S27-9.

Purpose

Prior to undergoing a cartilage restoration procedure of the knee, such as osteochondral allograft (OCA), osteochondral autograft (OAT), or autologous chondrocyte implantation (ACI), a diagnostic scope is often performed to evaluate the knee joint and characterize the cartilage damage. After diagnostic arthroscopy, a subset of patients experiences substantial relief and elects not to undergo a cartilage procedure. This study aims to identify factors which may be associated with successful outcomes after diagnostic arthroscopy.

Methods and Materials

99 patients scheduled to undergo diagnostic arthroscopy for cartilage evaluation, OCA, or ACI between May 2017 and March 2019 and were prospectively enrolled and age, BMI, procedure, size and location of lesion were collected. KOOS, IKDC and Marx were also collected pre-operatively as well as at 6-weeks, 6-months, and 1-year post-operatively. Patient demographics and lesion characteristics were compared between those who underwent only a diagnostic arthroscopy and those who underwent a cartilage restoration procedure.

Results

52 patients underwent only diagnostic arthroscopy (average age 32.48±9.55 years, BMI 28.21±5.72, 53.4% male). Average total lesion area was 4.29±3.22cm². Average number of lesions was 1.4±0.71. 47 patients underwent cartilage restoration procedure (average age 34.04±8.17 years, BMI 28.08±4.95, 49.0% male). Average total lesion area was 4.98±2.37cm². Average number of lesions was 1.40±0.64. No significant difference in total lesion area (p=0.22), number of lesions (p=0.97), sex (p=0.88), age (p=0.39) or BMI (0.92) was found between the two groups. In the diagnostic arthroscopy group, 28 (53.8%) had isolated patellofemoral cartilage damage, significantly more than the 15 (31.9%) in the cartilage procedure group that had isolated patellofemoral cartilage damage (p=0.02) .

Conclusion

While basic patient demographics and lesion size are not significantly different between those undergoing diagnostic arthroscopy alone and those electing to undergo cartilage restoration procedure, those with isolated patellofemoral cartilage damage are less likely to continue to a cartilage restoration procedure.

Purpose

While multiple studies have shown the effectiveness of osteochondral allograft transplantation (OCA) in the treatment of symptomatic chondral defects, outcomes in obese patients (BMI >30) have not been well defined. This study aims to determine outcomes in patients undergoing OCA based on BMI.

Methods and Materials

Between 2014 and 2017, 235 patients underwent OCA at our institution and completed pre-operative patient-reported outcomes. IKDC, KOOS, and Marx were collected pre-operatively and at 6-months, 1-year, and 2-years post-operatively. Patients were stratified into groups based on common obesity classification- BMI: <20, 20-<25, 25-<30, 30-<35, >35. One-way ANOVA and Student T-tests were performed to analyze differences in outcome scores between groups.

Results

A total of 235 patients (30.0±9.42 years, 53.6% female) with average BMI 26.6±4.40 and mean lesion size 3.2±1.17cm² completed 2-year follow-up and were included in this study. Patients with BMI <35 demonstrated significant improvement in PROs at 1-year post-operatively for IKDC, KOOS Symptoms, KOOS Pain, KOOS ADL, and KOOS Sport (all p<0.05). Patients with BMI <30 also showed significant improvement in KOOS QoL. Those with BMI >35 only showed significant improvement in KOOS Pain at 1 year (Table 1). Patients with BMI >25 showed significant decrease in Marx at 1 year. Patients with BMI’s >30 demonstrated significantly lower baseline, 6-month, and 1-year PRO scores relative to those with BMIs <25 (Figure 1) and significantly less improvement in KOOS PS and KOOS JR at 6 months.

Conclusion

Those with BMI >30 have significantly lower preoperative baseline PROs as well as significantly lower 1-year scores when compared to those with BMIs <30. However, significant improvements are still observed across PROMs in patients with BMI <35, suggesting those with BMI <35 experience clinically significant benefits after OCA. Further research should consider defining outcomes in those with greater BMIs based on clinically significant thresholds (MCID, SCB, PASS).

Purpose

In theory, PROMIS instruments allow for improved comparability of outcomes between heterogenous procedures, with decreased question burden and high instrument responsiveness. There is limited information on how PROMIS performs across knee surgical procedures. The purpose of this study was to assess the psychometric properties of PROMIS instruments relative to legacy instruments in anterior cruciate ligament reconstruction (ACLR) and cartilage procedures.

Methods and Materials

PROMIS PF, PI, and Depression CATs were administered alongside legacy instruments in ACLR and cartilage patients. Spearman rank correlations determined correlative strength: >0.8 equated to excellent; 0.71-0.8, very good; 0.61-0.7, good; 0.41-0.6 to fair; 0.21-0.4, poor; <0.20, very poor. Floor and ceiling effects were also evaluated.

Results

PROMIS PF CAT exhibited very poor-good correlations(r=0.01-0.68) in the ACLR cohort and very poor-very good correlations(r=0.14-0.72) in the cartilage cohort relative to function legacies. Legacy HRQoL instruments exhibited fair correlations(r=0.45-0.56) relative to PROMIS PF and PI CAT in ACLR patients, while exhibiting good-very good correlations(r=0.64-0.71) in cartilage patients. The PROMIS Depression CAT performed worse relative to legacy instruments in ACLR patients(r=0.27-0.46) than cartilage patients(r=0.42-0.59). Significant floor effects were demonstrated by the Brief Resilience Scale(15.1%), KOOS Sport(20.5%) and Marx(33.3%). Significant ceiling effects were exhibited by Marx(25.2%), KOOS ADL(25.9%) and all WOMAC scores(22.3%-39.3%).

Conclusion

PROMIS PF and PI CAT correlated well with legacy instruments assessing function and pain in both ACLR and cartilage patients; however, correlation between PF and PI CAT was not as strong for legacy HRQoLs PROMs. Additionally, PROMIS Depression CAT had poor to fair correlations with legacy mental health measures. Significant floor and/or ceiling effects were demonstrated on the Brief Resilience Scale, KOOS Sport, KOOS ADL, Marx and all WOMAC subsets. Neither PROMIS PF, PI, or Depression CAT exhibited any significant floor or ceiling effects. PROMIS PF and PI CATs may allow for comparability of knee surgery procedures while maintaining low questionnaire burden.