It used to be that if a doctor told you, “I’m recommending arthroscopic surgery to clean up your knee” or “You need a total knee replacement,” you had just two choices: surgery or painkillers. With the advent of “biomedicine” (blood and stem cell therapies and injections), the choices have changed dramatically. From this point of view, arthroscopic surgery is now seen as the least desirable option, and knee replacement something that should be delayed as long as possible. Stimulating the growth of cartilage and damaged or worn tissue is now seen as the most desirable option. In the last decade, studies on Stem Cell Therapy and knee cartilage began to be published at an amazing rate. The reason for this explosion in research is simple: doctors and patients are seeing poor results from surgery, along with unexpected side effects, and the powerful new tools of biomedicine are thus becoming a major focus.
Before biomedicine, stem cells, and blood platelets, the gold standard of treatment for patients suffering from debilitating joint pain due to a “bone-on-bone” condition was joint replacement. However, as the decades progressed, patients who had received replacement therapy grew older, and their prosthetic joints began to wear out.
Doctors became aware of a new challenge for themselves and their patients, one that did not have an easy solution. In older joint replacements, bone was removed and replaced with metal. When a revision (second) replacement was needed, some patients no longer had enough bone to have this surgery. These patients’ knees, shoulders, and hips became “salvage” jobs, as doctors tried to do what they could with whatever was left of the original joint. During my internship, after a patient’s surgical hip joint replacement failure, I assisted my mentor in carving an entire femur from a cadaver, and placing it into the pelvis and knee to create new joints. The chance for success was minimal, but at least amputation was postponed—for good or bad, I am not sure.
Do people really have bone on bone knees?
Many of my patients present with a diagnosis of “bone-on-bone knee arthritis,” terminology used to describe a knee that has lost all cartilage to cushion the bones. Few actually have true “bone on bone.” If the joint moves, there is typically cartilage present since cartilage is the slippery surface on the end of the bones that allow range of motion. When the doctor says you have bone-on-bone arthritis, it may be used as an umbrella term to describe various levels of knee degeneration. In the knee joint, cartilage covers the tibia, femur, and the back of the kneecap (the patella); in addition to cartilage, there is the meniscus, which is the fibrous padding between the bones. A healthy knee glides efficiently and painlessly on these structures.
Bone-on-bone can mean that some or all of the cartilage and/or the meniscus have worn down or have defects, thereby causing the bones to rub together. Another diagnostic term that may refer to bone-on-bone is “osteochondral defect.” The term “osteochondral” refers to the cartilage and bone as a unit.
Patients often assume that bone-on-bone or an osteochondral defect means extreme and advanced cartilage deterioration, which is not usually the case. Joint space, the space between the bones, is a challenge to surgeons. If there is no space between the bones, i.e, the cartilage has worn down—surgery cannot restore it. The philosophy then is to manage the knee pain as long as possible (often with repeated steroid injections that temporarily reduce pain, but eventually destroy whatever cartilage is left) prior to the knee replacement surgery.
A brief discussion on MRI readings
I often receive emails from prospective patients who have an X-ray or MRI they want to send us. Sometimes they want an opinion to back up a surgical recommendation; sometimes they want an opinion to support their desire to avoid surgery. In either case, when I tell them that the X-ray or MRI may not be telling the truth about their pain source, they become surprised and confused. New findings say that many MRIs are useless. Investigators examined patients who had had an MRI for knee pain to determine whether the MRI was helpful in determining the final outcome of treatment. I ask you to refer to my article How accurate are MRI scans of the knee? For a detailed discussion.
Below I will give a brief summary of the following knee osteoarthritis treatments:
Treatments for Knee osteoarthritis: Total Knee replacement
While knee replacement can sometimes be a viable and effective treatment for patients with knee osteoarthritis, the number of patients asking about knee replacement alternatives continues to grow. Patients need to be aware of the potential downsides of the procedure, particularly in light of the new therapies available.
Over the years I have seen many patients who still had knee pain following knee replacement surgery. What I see in my practice agrees with what medical research states—that knee replacement surgery offers hope to some patients, and these patients have high expectations of what the new knee will offer them, but that in many cases those expectations are not met.
English doctors wrote in a June 2022 study (1) that up to 20% of people who undergo total knee replacement surgery have ongoing pain and discomfort. The researchers write:
- Patients describing chronic postsurgical pain also “described sensations of discomfort, including heaviness, numbness, pressure, and tightness associated with the prosthesis.
- Participants reported “a lack of felt connection with and agency over their replaced knee, often describing it as alien or other, and lacked confidence in the knee.”
Research: Realistically 9 to 30% of patients do not return to work after knee replacement
In my article: How fast can you get back to work or sport following knee replacement? I refer to studies which suggest that some patients have an over-expectation of what their knee replacement will do for them. Their doctors are concerned that people have a limited understanding of the realistic variables that determine the ability to return to work. In other words – they think they can get back to work sooner than they will actually be able to. As the research of this article shows 9 – 30% of people who have knee replacement, do not return to work.
Weight and Knee Replacement Failure
There are many studies connecting weight and knee replacement failure. Many total knee replacement patients are overweight or obese. There is a thinking among many that after the knee replacement, their physical activity levels and weight will improve. This does not appear to be true for some as research points out. In many knee replacement patients, weight loss does not occur. In my article Research: Knee replacements do not help you lose weight, I discuss many of these studies patients suffered from knee pain, loss of knee function, swelling, and an inability to walk or stand for any length of time, but thought that knee replacement would help restore their activities and thereby they could lose weight. For many people, this is not what happens, research cited in my article shows “the majority of total knee replacement patients are overweight or obese and physical activity levels and weight do not appear to change in a high proportion of patients after knee replacement.”
In my article Do Women Have More Knee Replacement Complications? I discuss research which suggests that in the postoperative period, women, happy that they had the knee replacement lost motivation and confidence in the post-surgery recover. This may help explain, as I cite in the research why women appear to have worse outcomes, more pain, and poorer functional outcomes following total knee replacement than men and what may have caused these outcomes. The research suggests that women had significantly worse pre-surgery pain, limited function, depression, were more likely to be obese, and had pain in more than four joints.
Other factors discussed were knee replacement complications from weak bones in postmenopausal women. The connection of osteoporosis and osteoarthritis commonly coexist in postmenopausal females can be sometimes lost.
Treatments for Knee osteoarthritis: Anti-inflammatories and painkillers
A study from 2022 (5) gives a review of the standard conservative care for knee osteoarthritis patients: “Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee osteoarthritis has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, none of them has articular cartilage regenerating potential. . .”
Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences.
A study from 2022 (13) writes about the need for new knee pain treatments: “Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee osteoarthritis has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, none of them has articular cartilage regenerating potential. . .(in this paper the researchers) focus on emerging osteoarthritis knee treatments, relieving symptoms, and regenerating damaged articular cartilage that includes intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), metformin, lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC),” and other treatments. We will be discussing some of these treatments in this article and the research published by other investigators.
Irenka and Cymbalta
A May 2022 paper (16) Irenka and Cymbalta
Assessed the effectiveness of duloxetine (Irenka and Cymbalta) in addition to usual care in patients with chronic osteoarthritis pain. Patients with chronic hip or knee osteoarthritis pain who had an insufficient response to acetaminophen and nonsteroidal antiinflammatory drugs were included. Patients received duloxetine (60 mg/day) in addition to usual care or usual care alone.
- A total of 66 patients were randomized to receive duloxetine in addition to usual care, and 66 patients were randomized to receive usual care alone.
- No difference in pain scores between the groups at 3 months or at 12 months.
- Conclusion: Researchers found no effect of duloxetine added to usual care compared to usual care alone in patients with chronic knee or hip osteoarthritis pain.
Treatments for Knee osteoarthritis: Weight loss
In my article Weight loss can be a knee replacement alternative treatment, I write that “People who are overweight understand that their arthritis related knee problems can be made worse because of their weight.” Research cited in the article describes how small reductions in body weight can decrease osteoarthritic knee pain and thus should provide a strong incentive for weight-loss. Highlights of that research is a Wake Forrest study which found for every 1 pound of weight loss, there is a 4-pound reduction in knee-joint load per step. Numerous studies have suggested that the magnitude of 10 pounds of weight loss would be a significant reduction in osteoarthritis risk and knee pain.
A July 2022 study (17) examined the recommended non-surgical interventions for osteoarthritis.
- Nine knee osteoarthritis studies, evaluating diet plus exercise, exercise, unloading shoes, high-expectation communication during acupuncture and telephone-based weight loss plus exercise were identified.
- In knee osteoarthritis, some evidence suggests that the benefits of i) diet and exercise are mediated through changes in body weight, systemic inflammation and self-efficacy; ii) exercise is mediated through changes in knee muscle strength and self-efficacy; and iii) high-expectation communication style is mediated through changes in self-efficacy.
Weight loss saves a meniscus
A recent study concluded that overweight and obese people who lost a substantial amount of weight over a 48-month period showed significantly lower degeneration of their knee cartilage.
A July 2022 study (6) examined the recommended non-surgical interventions for osteoarthritis including weight loss plus exercise.
- Nine knee osteoarthritis studies, evaluating diet plus exercise, exercise, unloading shoes, high-expectation communication during acupuncture and telephone-based weight loss plus exercise were identified.
- In knee osteoarthritis, some evidence suggests that the benefits of:
- diet and exercise are mediated through changes in body weight, systemic inflammation and self-efficacy;
- exercise is mediated through changes in knee muscle strength and self-efficacy; and
- high-expectation communication style is mediated through changes in self-efficacy.
- Treatments for Knee osteoarthritis: Knee braces
- Treatments for Knee osteoarthritis: Chiropractic care
Treatments for Knee osteoarthritis: Acupuncture
When going through the medical research one can find many positive studies regarding pain alleviation in patients treated with acupuncture. Other research however points out that much of these positive outcomes should be understood in the terms of bias. While many studies cite the benefits of treatment a January 2022 paper however (3) did not. The researcher here wrote: “At short-term, there was low to very low evidence and there were statistically significant differences in pain intensity and knee function in favor of acupuncture versus control interventions in patients with knee osteoarthritis. A July 2019 study (4) demonstrated this by saying: “According to the high-quality evidence, we concluded that acupuncture may have some advantages in treating knee osteoarthritis. However, there are some risk of bias and reporting deficiencies still needed to be improved.” In other words, the evidence was not reliable.”
Please refer to my article Does acupuncture help knee osteoarthritis?
Treatments for Knee osteoarthritis: Cortisone injections
We see many patients who have concerns about prolonged cortisone injections. Most recently we have been seeing many patients concerned about frequent recommendations to cortisone while they wait for knee surgery. Initially their doctors advised them that cortisone injections can be effective and safe if used in moderation or as a one time treatment. But as this knee replacement recommended patient continued to wait for a surgery during and after the pandemic and surgical cases significantly back-logged, decisions had to be made as to how cortisone could be used to provide comfort until the surgical date. This was a difficult question for doctors to answer. A number of new research studies began to appear to try to offer medical professionals some basis for continued cortisone use.
A September 2021 paper (9) found: “There are growing concerns with the widely used glucocorticoids during the Coronavirus disease-19 (COVID-19) pandemic due to the associated immunosuppressive effects, which may increase the risk of COVID-19 infection and worsen COVID-19 patient outcome. Heavily affecting orthopedics (elective joint and spine surgeries), the pandemic led to delay and cancellation of almost all surgical cases, and procedures including perioperative intra-articular corticosteroid injections saw similar decreases. However, the benefits of intra-articular corticosteroid injections treatments during the pandemic may outweigh these potential risks, and their continued use may be warranted.”
I have numerous articles on this website on cortisone injections. I invited you to review the material and the research presented here.
- How much cortisone can I get in my knee? Are there alternatives to cortisone?
Systemic effects of cortisone injections including cartilage damage
Ultrasound-guided genicular nerve blocks
July 2022 study: (14) “Ultrasound-guided genicular nerve blocks using pharmacological agents for pain control in chronic knee osteoarthritis are gaining in popularity. There is fair evidence to at least target the superior medial genicular nerve, inferior medial genicular nerve, and Inferior medial genicular nerve using local anesthetics, corticosteroids, or alcohol to reduce pain and to improve knee function in patients with chronic knee osteoarthritis under ultrasound guidance. The procedure is safe but more research is needed to determine the optimal interventional approach.”
A September 2022 (20) paper describes Genicular nerve ablation (GNA)as a percutaneous, needle-based therapy option designed to palliatively treat knee pain. Analogous to an intra-articular injection with corticosteroid, GNA is not intended to remedy the root cause of pain or structurally alter the joint in any way; rather, the goal is to block/interrupt the transmission of pain signals from the knee, itself, thus eliminating the perception of pain by the brain.
Treatments for Knee osteoarthritis: Hyaluronic acid injections
I have seen patients require incision and drainage with antibiotic treatment after experiencing allergic reactions to hyaluronic acid injections. When the injections are mistakenly placed into the soft tissue instead of the joint, severe reactions can occur. Studies have confirmed that when knee injections are made blindly—that is, without ultrasound guidance—one-third of the injections do not enter the joint. Unfortunately, most doctors do not inject under ultrasound guidance.
- Treatments for Knee osteoarthritis: Botox injections
- Treatments for Knee osteoarthritis: Holistic Care Exercise Yoga
- Treatments for Knee osteoarthritis: Holistic Care Nutritional Guidelines
Placebos can improve symptoms in various medical conditions including knee pain
May 2022 study (15) Recent studies indicate that the administration of open-label placebos can improve symptoms in various medical conditions. The primary aim of this 3-week randomized controlled trial was to examine the effects of open-label placebos treatments on pain, functional disability, and mobility in patients with arthritic knee pain. Evaluation of daily pain ratings indicated significant pain decrease in the open-label placebos groups compared to no treatment group. open-label placebos treatment improved knee pain in elderly patients with symptomatic knee osteoarthritis (OA), while functional disability and mobility of the knee did not change. The content of the verbal suggestion was of minor importance. open-label placebos administration may be considered as supportive analgesic treatment in elderly patients with symptomatic knee osteoarthritis.
Virtual reality as a clinical treatment for older adults with chronic osteoarthritis knee pain
A June 2022 study (19) “There is an urgent need for safe and effective nonpharmacologic approaches to treat chronic knee pain in older adults. Although virtual reality (VR) has shown some effectiveness for acute pain, there is limited evidence on the effects of virtual reality on chronic pain particularly with older adult populations. This study evaluated the feasibility and effectiveness of virtual reality as a clinical treatment for older adults with chronic osteoarthritis knee pain.
- Nineteen participants aged 60+ years old participated in a 10-min virtual reality meditation program. Results suggest that virtual reality meditation had significant moderate to large analgesic effects on knee pain intensity, primarily during virtual reality and post virtual reality, with some lasting effects into next day. The findings also suggest virtual reality meditation intervention had a positive effect on affect, with a significant large decrease in negative affect scores pre- to post-virtual reality. The significant moderate to large decreases in pain interference for normal work, mood, sleep, and enjoyment of life suggest that older adults may have a higher ability to participate in meaningful daily activities up to 24-48 hours after virtual reality meditation. VR appears to be a feasible and effective nonpharmacological tool for older adults to treat chronic overall and knee-specific pain.
In a June 2022 study (21) Doctors investigated the incidence and risk of knee and hip replacement in patients with osteoarthritis treated with different medications. Compared to non-users, bisphosphonate users had a reduced risk of knee replacement.
Regenerative medicine treatments for degenerative knee disease
An August 2021 paper (18) described the various regenerative medicine treatments for degenerative knee disease. “Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the knee, including symptomatic osteoarthritis and chondral injuries, as well as injuries to tendon, meniscus, and ligament, including the anterior cruciate ligament. Promising and established treatment modalities include hyaluronic acid in liquid or scaffold form; platelet-rich plasma (PRP); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs), hematopoietic stem cells, endothelial progenitor cells, and growth factors; connective tissue progenitor cells (CTPs) including adipose-derived mesenchymal stem cells (AD-MSCs) and tendon-derived stem cells (TDSCs); matrix cell-based therapy including autologous chondrocytes or allograft; vitamin D; and fibrin clot.”
Non-surgical knee osteoarthritis treatments: Stem cell therapy
It became clear to many researchers that joint replacement had to be redefined and disputed as the gold standard of treatment. Others, however, had already decided to abandon joint replacement and explore growing tissue as the new standard of care. The thinking was simple—why remove bone and tissue when these could be repaired and rejuvenated?
What was found in the initial research was startling. Doctors discovered that one type of stem cell (mesenchymal stem cells found in bone marrow and body fat) could morph into bone cells and cartilage cells when injected into a joint. The ramifications for the treatment of osteoarthritis or “bone-on-bone” joints were enormous. Stem cell injections showed that cartilage could be regrown, something that doctors had previously thought impossible because of the cartilage’s limited blood supply within the joint.
An October 2022 paper (8) writes: “In knee osteoarthritis, most of the evidence for mesenchymal stem cells comes from case series and small, randomized trials. Overall, there were improvements in pain and functional outcomes when patients were treated with mesenchymal stem cells, and the results suggest that mesenchymal stem cells found in bone marrow can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions.”
- Non-surgical knee osteoarthritis treatments: Donated cell therapy
- Non-surgical knee osteoarthritis treatments: Cell tissue therapy
Non-surgical knee osteoarthritis treatments: Platelet Rich Plasma therapy
- PRP treatments involve collecting a small amount of your blood and spinning it in a centrifuge to separate the platelets from the red cells. The collected platelets are then injected back into the injured area to stimulate healing and regeneration.
- The platelets contain healing agents, or “growth factors.” including Platelet-derived growth factor (PDGF), Transforming growth factor beta (or TGF-β, Insulin-like growth factors, Vascular endothelial growth factor (VEGF) and Epidermal growth factors.
- The number of treatments needed can vary from patient to patient depending on the level of knee degeneration and the level of activity the patient wishes to return to.
PRP injections are considered controversial by some, mostly because of the lack of standardization in the preparation and administering of this treatment. I address these studies and commentaries in my article Platelet Rich Plasma injections for knee osteoarthritis. A January 2023 paper (7) also addressed these issues by writing: “The use of platelet-rich plasma (PRP) has been supported by encouraging data from in vitro and preclinical in vivo studies, both in terms of safety and efficacy. This led to the wide use of PRP injections in the clinical practice, with promising results especially as a minimally invasive treatment for cartilage degeneration and osteoarthritis. While many controversies remain on the best PRP formulation, the overall available clinical studies support the benefits of PRP, with functional improvement and reduction of pain-related symptoms up to 12 months, especially in young patients and early osteoarthritis stages.”
Non-surgical knee osteoarthritis treatments: Prolotherapy
Prolotherapy is the injection, often dextrose (a simple sugar), into the knee. Prolotherapy, which is short for “proliferation therapy” (the proliferation of new cells following the injection of a substance that will stimulate new tissue growth). Prolotherapy is injected into the knee or other area, it causes the body’s immune system to stimulate the inflammatory process. This new inflammatory response attracts fibroblasts (immature cells present in connective tissue) and chondrocytes (cells that produce cartilage) and brings them to the area of degeneration or injury. These cells rebuild the collagen (more specifically, what is called the “collagen matrix” of the tissue) and enable it to strengthen and restore the body part in many cases to pre-injury status.
There is a long history of medical studies on the effectiveness of Prolotherapy for knee pain.
Prolotherapy compared to Hyaluronic injections
In a September 2022 study researchers compared the effectiveness of dextrose Prolotherapy injections to hyaluronic acid injections in knee osteoarthritis patients. The researchers reported that initially there was no statistically significant differences recorded in short-term effectiveness found between prolotherapy and hyaluronic acid treatments in pain control, however, in the subanalysis that included only the studies that used intra-articular injections, prolotherapy was found to be more effective a treatment.
Prolotherapy, Platelet Rich Plasma Injections and exercise therapy
In a September 2022 study researchers demonstrated the effectiveness of Platelet Rich Plasma and dextrose Prolotherapy treatments in knee osteoarthritis. The study suggested: “Pain and disability were significantly improved with prolotherapy and PRP compared with exercise therapy.
Non-surgical knee osteoarthritis treatments: Alpha-2-macroglobulin (A2M)
Alpha-2-macroglobulin (A2M), is a a naturally occurring macromolecule, a protein, that exhibits anti-inflammatory properties. A 2020 study (12) compared one injection of A2M, cortisone and PRP for effectiveness in knee osteoarthritis. At 12 weeks after the injection the study doctors found Alpha 2 Macroglobulin injections showed similar effectiveness to corticosteroids in the treatment of knee osteoarthritis. Both A2M and corticosteroids appear to show marginally better effectiveness than PRP injection, however the differences are small and did not reach statistical significance in most outcome measures.
A January 2023 study (11) examined the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with knee osteoarthritis.
This “randomized, single-blinded, clinical trial” was carried out for 6 weeks of treatment and 6-month follow-up.
- A group of 98 patients were randomly divided into two groups.
- Group 1 received dry needling at latent and active myofascial trigger point and stretching exercises
- Group 2 received oral diclofenac with stretching.
- Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up
Results: A total of 42 patients in the dry needling group and 35 patients in the diclofenac group completed the study, “there was no significant difference in the general data between the two groups.” The researchers added: “After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the dry needling group showed a significantly better result than the diclofenac group. Especially in the results of the 6-month follow-up, the dry needling group showed much better results than the the diclofenac group.”
The researchers conclusion: “Dry needling on latent and active myofascial trigger points combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by knee osteoarthritis. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months.”
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2 Knapik DM, Evuarherhe Jr A, Frank RM, Steinwachs M, Rodeo S, Mumme M, Cole BJ. Nonoperative and operative soft-tissue and cartilage regeneration and Orthopaedic biologics of the knee: an Orthoregeneration network (ON) foundation review. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2021 Aug 1;37(8):2704-21.
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16 van den Driest JJ, Schiphof D, Koffeman AR, Koopmanschap MA, Bindels PJ, Bierma‐Zeinstra SM. No Added Value of Duloxetine in Patients With Chronic Pain due to Hip or Knee Osteoarthritis: A Cluster‐Randomized Trial. Arthritis & Rheumatology. 2022 May;74(5):818-28.
17 Lima YL, Lee H, Klyne DM, Dobson FL, Hinman RS, Bennell KL, Hall M. How do non-surgical interventions improve pain and physical function in people with osteoarthritis? A scoping review of mediation analysis studies. Arthritis Care Res (Hoboken). 2022 Jul 22. doi: 10.1002/acr.24983. Epub ahead of print. PMID: 35866717.
18 Knapik DM, Evuarherhe Jr A, Frank RM, Steinwachs M, Rodeo S, Mumme M, Cole BJ. Nonoperative and operative soft-tissue and cartilage regeneration and orthopaedic biologics of the knee: An orthoregeneration network (ON) foundation review. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2021 Aug 1;37(8):2704-21.
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