Regenerative Medicine

[ampaphb]

How can our field hope to be taken seriously when fringe, unproven therapies like stem cells and PRP are not only accepted by our higher ups, but actually taught at our Annual Assembly by some of the biggest names (Joanne Borg-Stein, MD (Director); Jay Bowen, DO; Ramon Castellanos, MD; Jonathan Finnoff, DO ; Victor Ibrahim, MD; Gerard Malanga, MD; Kenneth Mautner, MD ; Andre Panagos, MD; Luga Podesta, MD; Steven Sampson, DO) in our field?

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[Baritonebass]

Umm have been to lecture cause Borg-Stein quotes and performed research studies and is open about limitations and proper patient selection... Also we're not the only specialty doing these things. I heard a Msk radiologist talking about prp stem cells and treating ailments. Research is pretty decent for tendon related things... OA is a crap shoot

 

[ampaphb]

So what is "proper patient selection" for an unproven modality? And to be clear, the ONLY data that demonstrates minimal efficacy is PRP for epicondylitis.

 

[ampaphb]

Treatment of lateral epicondylitis with platelet-rich plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial.
Krogh TP, Fredberg U, Stengaard-Pedersen K, Christensen R, Jensen P, Ellingsen T.
Am J Sports Med. 2013 Mar;41(3):625-35.

PURPOSE: To examine whether a single injection of platelet-rich plasma (PRP) is more effective than placebo (saline) or glucocorticoid in reducing pain in adults with LE after 3 months.

STUDY DESIGN: Randomized controlled trial; Level of evidence, 1.

METHODS: A total of 60 patients with chronic LE were randomized (1:1:1) to receive either a blinded injection of PRP, saline, or glucocorticoid. The primary end point was a change in pain using the Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaire at 3 months. Secondary outcomes were ultrasonographic changes in tendon thickness and color Doppler activity.

RESULTS: Pain reduction at 3 months (primary end point) was observed in all 3 groups, with no statistically significant difference between the groups; mean differences were the following: glucocorticoid versus saline: -3.8 (95% CI, -9.9 to 2.4); PRP versus saline: -2.7 (95% CI, -8.8 to 3.5); and glucocorticoid versus PRP: -1.1 (95% CI, -7.2 to 5.0). At 1 month, however, glucocorticoid reduced pain more effectively than did both saline and PRP; mean differences were the following: glucocorticoid versus saline: -8.1 (95% CI, -14.3 to -1.9); and glucocorticoid versus PRP: -9.3 (95% CI, -15.4 to -3.2). Among the secondary outcomes, at 3 months, glucocorticoid was more effective than PRP and saline in reducing color Doppler activity and tendon thickness. For color Doppler activity, mean differences were the following: glucocorticoid versus PRP: -2.6 (95% CI, -3.1 to -2.2); and glucocorticoid versus saline: -2.0 (95% CI, -2.5 to -1.6). For tendon thickness, mean differences were the following: glucocorticoid versus PRP: -0.5 (95% CI, -0.8 to -0.2); and glucocorticoid versus saline: -0.8 (95% CI, -1.2 to -0.5).

CONCLUSION: Neither injection of PRP nor glucocorticoid was superior to saline with regard to pain reduction in LE at the primary end point at 3 months. However, injection of glucocorticoid had a short-term pain-reducing effect at 1 month in contrast to the other therapies. Injection of glucocorticoid in LE reduces both color Doppler activity and tendon thickness compared with PRP and saline.

 

[ampaphb]

Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis.
Sheth U, Simunovic N, Klein G, Fu F, Einhorn TA, Schemitsch E, Ayeni OR, Bhandari M.
Source
J Bone Joint Surg Am. 2012 Feb 15;94(4):298-307.

BACKGROUND: The recent emergence of autologous blood concentrates, such as platelet-rich plasma, as a treatment option for patients with orthopaedic injuries has led to an extensive debate about their clinical benefit. We conducted a systematic review and meta-analysis to determine the efficacy of autologous blood concentrates in decreasing pain and improving healing and function in patients with orthopaedic bone and soft-tissue injuries.

METHODS: We searched MEDLINE and Embase for randomized controlled trials or prospective cohort studies that compared autologous blood concentrates with a control therapy in patients with an orthopaedic injury. We identified additional studies by searching through the bibliographies of eligible studies as well as the archives of orthopaedic conferences and meetings.

RESULTS: Twenty-three randomized trials and ten prospective cohort studies were identified. There was a lack of consistency in outcome measures across all studies. In six randomized controlled trials (n = 358) and three prospective cohort studies (n = 88), the authors reported visual analog scale (VAS) scores when comparing platelet-rich plasma with a control therapy across injuries to the acromion, rotator cuff, lateral humeral epicondyle, anterior cruciate ligament, patella, tibia, and spine. The use of platelet-rich plasma provided no significant benefit up to (and including) twenty-four months across the randomized trials (standardized mean difference, -0.34; 95% confidence interval [CI], -0.75 to 0.06) or the prospective cohort studies (standardized mean difference, -0.20; 95% CI, -0.64 to 0.23). Both point estimates suggested a small trend favoring platelet-rich plasma, but the associated wide confidence intervals were consistent with nonsignificant effects.

CONCLUSIONS: The current literature is complicated by a lack of standardization of study protocols, platelet-separation techniques, and outcome measures. As a result, there is uncertainty about the evidence to support the increasing clinical use of platelet-rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft-tissue injuries.

 

[ampaphb]

Platelet-Rich Plasma: The Next Big Thing?: Commentary on an article by Ujash Sheth, BHSc, et al.: "Efficacy of Autologous Platelet-Rich Plasma Use for Orthopaedic Indications: A Meta-Analysis"
Matthew J. Matava, MD
The Journal of Bone & Joint Surgery, Volume 94, Issue 4

Autologous blood concentrates, one of which is platelet-rich plasma, have been becoming more popular as a result of the increasing attention that these products have received in the mainstream media following their use by high-profile athletes. Platelet-rich plasma has been utilized for a number of musculoskeletal conditions despite a relative lack of rigorous supportive data. Thus, there is a growing debate regarding the clinical efficacy of this treatment regimen. Several uncontrolled studies have shown beneficial effects for a variety of indications. However, the results of controlled trials comparing platelet-rich plasma with standard therapies have not been as definitive. Despite this relative lack of robust evidence, the market for platelet-rich plasma is expected to be worth $126 million by 2016.

It is against this backdrop that Sheth et al. provided a timely meta-analysis and systematic review of twenty-three randomized controlled trials and ten prospective cohort studies to assess the clinical results of autologous blood concentrates compared with those of control therapy, such as a placebo, corticosteroid injection, or physical therapy, in the treatment of orthopaedic injuries. Of the 895 eligible studies, thirty-three met the authors' inclusion criteria, with the investigators in those studies using a variety of primary functional and imaging outcome measures.

The authors found significant heterogeneity in these clinical series as the duration of follow-up ranged from as little as five days to up to two years, and the final volume of platelet product used in each study ranged from just 2 mL to 70 mL. The authors found twenty studies to be of high methodological quality and thirteen studies to be of moderate quality. Nevertheless, there was a lack of consistency in outcome measures across the studies. Of the thirty-three trials, nine showed a significant functional benefit for platelet-rich plasma, twenty-one showed no difference between platelet-rich plasma and the control, and two studies actually revealed a significant functional benefit for the control. (Functional outcomes were not evaluated in the remaining study.) Overall, the authors found no significant benefit for platelet-rich plasma, up to and including twenty-four months, across both the randomized trials and the prospective cohort studies. According to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria, a classification scheme based on the strength of clinical recommendations and quality of evidence, the overall quality of evidence was very low because of serious methodological limitations, variability in platelet separation techniques, lack of standardization in outcome measures, and uncertainty surrounding the precision of the results.

In summary, the authors of this well-written, comprehensive study found a significant lack of evidence to support the increasing clinical use of platelet-rich plasma and autologous blood concentrates as a treatment modality for orthopaedic bone and soft-tissue injuries. Strengths of this study include its rigid inclusion and exclusion criteria, application of a comprehensive search strategy, and use of a quantitative analysis designed to assess the methodological quality of the studies. Interestingly, the published data have shown that platelet-rich plasma, when used alone in various case series, is often effective in terms of decreasing symptoms in a variety of musculoskeletal conditions. Yet, the results of platelet-rich plasma therapy have not been as robust when compared with a standard control. This finding supports the implementation of Level-I randomized controlled trials as the "gold standard" for evidence-based clinical research. My own experience with platelet-rich plasma has been mixed at best, with approximately a 50% improvement in symptom relief noted by patients compared with what would be expected from typical treatment regimens for muscle strains and partial tendon tears.

Despite basic-science data that have demonstrated that platelet-rich plasma use in animal and in vitro studies has a positive effect on healing, there are several issues that remain unanswered regarding the use of this treatment in the care of patients. Questions regarding the timing of platelet-rich plasma administration, optimal platelet concentration and platelet separation technique, ideal volume of the platelet concentrate, number of applications, and duration of the treatment benefit should be addressed in future studies because of the heterogeneous nature of the previously published studies. The authors of future clinical trials should also use validated, disease-specific, and patient-relevant outcomes that can be consistently applied for a variety of similar indications. Until these important issues are adequately addressed, clinicians should temper their enthusiasm for the use of autologous blood products for the treatment of musculoskeletal conditions.

 

[ampaphb]

Are platelet-rich products necessary during the arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis.
PLoS One. 2013 Jul 12;8(7) e69731
Zhang Q1, Ge H, Zhou J, Cheng B.

BACKGROUND:
Platelet-rich products (PRP) are widely used for rotator cuff tears. However, whether platelet-rich products produce superior clinical or radiological outcomes is controversial. This study aims to use meta-analysis to compare clinical and radiological outcomes between groups with or without platelet-rich products.

METHODS:
The Pubmed, Embase, and Cochrane library databases were searched for relevant studies published before April 20, 2013. Studies were selected that clearly reported a comparison between the use or not of platelet-rich products. The Constant, ASES, UCLA, and SST scale systems and the rotator cuff retear rate were evaluated. The weighted mean differences and relative risks were calculated using a fixed-effects model.

RESULTS:
Seven studies were enrolled in this meta-analysis. No significant differences were found for the Constant scale (0.73, 95% CI, -1.82 to 3.27, P=0.58), ASES scale (-2.89, 95% CI, -6.31 to 0.53, P=0.1), UCLA scale (-0.79, 95% CI, -2.20 to 0.63, P=0.28), SST scale (0.34, 95% CI, -0.01 to 0.69, P=0.05), and the overall rotator cuff retear rate (0.71, 95% CI, 0.48 to 1.05, P=0.08). Subgroup analysis according to the initial tear size showed a lower retear rate in small- and medium-sized tears (0.33, 95% CI, 0.12 to 0.91, P=0.03) after platelet-rich product application but no difference for large- and massive-sized tears (0.86, 95% CI, 0.60 to 1.23, P=0.42).

CONCLUSION:
In conclusion, the meta-analysis suggests that the platelet-rich products have no benefits on the overall clinical outcomes and retear rate for the arthroscopic repair of full-thickness rotator cuff tears. However, a decrease occurred in the rate of retears among patients treated with PRP for small- and medium-sized rotator cuff tears but not for large- and massive-sized tears.

 

[ampaphb]

Platelet-rich plasma does not enhance return to play in hamstring injuries: a randomised controlled trial.
Br J Sports Med. 2015 Jul;49(14):943-50
Hamilton B, Tol JL, Almusa E, Boukarroum S, Eirale C, Farooq A, Whiteley R, Chalabi H.

BACKGROUND:
To evaluate the efficacy of a single platelet-rich plasma (PRP) injection in reducing the return to sport duration in male athletes, following an acute hamstring injury.

METHODS:
A randomised, three-arm (double-blind for the injection arms), parallel-group trial, in which 90 professional athletes with MRI positive hamstring injuries were randomised to injection with PRP-intervention, platelet-poor plasma (PPP-control) or no injection. All received an intensive standardised rehabilitation programme. The primary outcome measure was time to return to play, with secondary measures including reinjury rate after 2 and 6 months.

RESULTS:
The adjusted HR for the PRP group compared with the PPP group was 2.29 (95% CI 1.30 to 4.04) p=0.004; for the PRP group compared with the no injection group 1.48 (95% CI 0.869 to 2.520) p=0.15, and for the PPP group compared with the no injection group 1.57 (95% CI 0.88 to -2.80) p=0.13. The adjusted difference for time to return to sports between the PRP and PPP groups was -5.7 days (95% CI -10.1 to -1.4) p=0.01; between the PRP and no injection groups -2.9 days (95% CI -7.2 to 1.4) p=0.189 and between the PPP and no injection groups 2.8 days (95% CI -1.6 to 7.2) p=0.210. There was no significant difference for the secondary outcome measures. No adverse effects were reported.

CONCLUSIONS:
Our findings indicate that there is no benefit of a single PRP injection over intensive rehabilitation in athletes who have sustained acute, MRI positive hamstring injuries. Intensive physiotherapy led rehabilitation remains the primary means of ensuring an optimal return to sport following muscle injury.

 

[ampaphb]

Platelet-rich plasma injections in the treatment of chronic rotator cuff tendinopathy: a randomized controlled trial with 1-year follow-up.
Am J Sports Med. 2013 Nov;41(11):2609-16
Kesikburun S, Tan AK, Yilmaz B, Yaşar E, Yazicioğlu K.

BACKGROUND:
Rotator cuff tendinopathy (RCT) is a significant source of disability and loss of work. Platelet-rich plasma (PRP) has been suggested to be beneficial in the treatment of RCT.

PURPOSE:
To investigate the effect of PRP injections on pain and shoulder functions in patients with chronic RCT.

STUDY DESIGN:
Randomized controlled trial; Level of evidence, 1.

METHODS:
A total of 40 patients, 18 to 70 years of age, with (1) a history of shoulder pain for >3 months during overhead-throwing activities, (2) MRI findings of RCT or partial tendon ruptures, and (3) a minimum 50% reduction in shoulder pain with subacromial injections of an anesthetic were included in this placebo-controlled, double-blind randomized clinical trial. Patients were randomized into a PRP group (n = 20) or placebo group (n = 20). Patients received an ultrasound-guided injection into the subacromial space that contained either 5 mL of PRP prepared from autologous venous blood or 5 mL of saline solution. All patients underwent a 6-week standard exercise program. Outcome measures (Western Ontario Rotator Cuff Index [WORC], Shoulder Pain and Disability Index [SPADI], 100-mm visual analog scale [VAS] of shoulder pain with the Neer test, and shoulder range of motion) were assessed at baseline and at 3, 6, 12, and 24 weeks and 1 year after injection.

RESULTS:
Comparison of the patients revealed no significant difference between the groups in WORC, SPADI, and VAS scores at 1-year follow-up (P = .174, P = .314, and P = .904, respectively). Similar results were found at other assessment points. Within each group, the WORC, SPADI, and VAS scores showed significant improvements compared with baseline at all time points (P < .001). In the range of motion measures, there were no significant group × time interactions.

CONCLUSION:
At 1-year follow-up, a PRP injection was found to be no more effective in improving quality of life, pain, disability, and shoulder range of motion than placebo in patients with chronic RCT who were treated with an exercise program.

 

[Baritonebass]

Not going to get get into a pissing contest about literature was just trying explain why the presentation was useful. We can't improve if we don't discuss it. You can always grab the mike and ask tough questions at the conference but posting a bunch of random studies to prove there is nothing to discuss is pointless... No one is saying any of this stuff is first line therapy... I think discussing the current literature, the limitation of the modalities and when it is appropriate and inappropriate to use prp/stem cells is reasonable considering that a lot of people come to the conference to learn about emerging technology which may or may not be proven. Patient will and do as question and require a non biased answer... That answer may be it not a proven modality and I would like to begin with methods that are proven but for those that fail and don't want the knife or the opioids it could be helpful. Besides outpatient PMR is growing and it's nice to see that they have workshops and lectures reflecting those interests. Also you could propose your on point counter point for next year if you feel the need to share that opinion

 

[ampaphb]

Offering unproven therapeutic options is fine, so long as you are transparent, and explain that there is no clinical evidence that this works any better than a placebo.

 

[lobelsteve]

Offering unproven therapeutic options is fine, so long as you are transparent, and explain that there is no clinical evidence that this works any better than a placebo.

It will be a cheerleader talk with nonsense terms and a call for more research. They do it because the base is reeling from ineffective leadership in lobbying yo not get emg destroyed. We all know it comes down to money. Prp is in its infancy and needs to be noted as fringe medicine until it can be proven useful and standardized. Early adopters might be trying to help or trying just go make a buck. If only were a snake oil salesman. I vould offer intradiscal prp and cure LBP.

 

[spme]

I agree with other posters. why would you only quote negative studies here? Peerboomes, Gosens, Say, Mishra?? How about those? Again just like others have said, I won't start back and forth of cut and paste wars but those folks you menitoend are helping us pave the frontiers along with basic scientist for all of us followers / late adapters. We should appreciate their work and be patient. This is especially true if you are just being a consumer of their information and are not actively doing researches to help us move forward. I am sure those guys you mentioned are fine in finding that biologics do not work.

 

[ampaphb]

I posted every study I could find dating back to 2012. The peerboomes and gosens articles precede that.

I missed the Mishra study, and thank u for the reference: http://www.ncbi.nlm.nih.gov/pubmed/23825183

 

[j4pac]

After I have read all of the articles you posted, included many others you have not...here is my impression. PRP and MSC treatment offers a novel approach to CURE patients of previously untreatable disease process. The basic science is there and rapidly progressing each day...though it will likely be another couple decades until we see the benefits realized. Pre-clinical studies for efficacy on a number of conditions have resulted in mixed results. There has been a rush to get into clinical trials, however, it is very presumptuous to perform clinical trials without good pre-clinical trials showing a reproducible and predictive result.

One of the HUGE errors of clinical trials is inconsistent methods. Mautner et al in PMR 2015 made a very convincing argument that there needs to be a standardization of methods. I agree with the authors that the lack of standardized methods could be a huge reason for the mixed clinical outcomes.

Another enormous problem is the assumption that squirting PRP or MSC into an area will result in benefits. I believe that the Sports Med folks have undervalued the importance of quality scaffolds. Dentistry is lightyears ahead of PM&R/Sports Med right now and the biggest reason is that they are lightyears ahead on developing therapeutic scaffolds.

Right now...regenerative med isn't ready to be used on patients. More work needs to be done. With that said...I hope to have the tools necessary in my training in order to one day use these therapies. There is too much to lose by not knowing how to use these therapies.

 

[lobelsteve]

Buckyballs. That is the answer.

 

[Mad Jack]

Everything is fringe science before we get good enough at it. Regenerative medicine is a key to the future of medicine, and if you guys aren't blazing that trail, who will?

 

[ampaphb]

Everything is fringe science before we get good enough at it. Regenerative medicine is a key to the future of medicine ...

Conceptually, you're right. Over time, regenerative medicine is clearly a direction we need to explore.

That being said, We ain't there yet. Efficacy has not been established. As has been stated earlier, dose, method of insertion, and target structures have yet to be standardized.

PRP and stem cells are like intradiscal devices and infusions - nice in theory, but unproven. Kinda like IDET, disctrode, and all the other perc-disc technologies of 5 years ago.

Slipman and Kaparal used to do the studies, Bogduk et al would then knock them down. The difference is, there does not appear to be a voice of reason tempering the enthusiasm at this point with a dose of reality.

 

[drusso]

How can our field hope to be taken seriously when fringe, unproven therapies like stem cells and PRP are not only accepted by our higher ups, but actually taught at our Annual Assembly by some of the biggest names (Joanne Borg-Stein, MD (Director); Jay Bowen, DO; Ramon Castellanos, MD; Jonathan Finnoff, DO ; Victor Ibrahim, MD; Gerard Malanga, MD; Kenneth Mautner, MD ; Andre Panagos, MD; Luga Podesta, MD; Steven Sampson, DO) in our field?

You left out Jay Smith, MD. He's still kind of a "big name" for the field too...

http://www.mayo.edu/research/centers-programs/center-regenerative-medicine

http://www.ncbi.nlm.nih.gov/pubmed/25796605

Gene. 2015 Jun 10;564(1):1-8. doi: 10.1016/j.gene.2015.03.022. Epub 2015 Mar 19.
Efficacy of intervertebral disc regeneration with stem cells - a systematic review and meta-analysis of animal controlled trials.
Wang Z1, Perez-Terzic CM2, Smith J3, Mauck WD4, Shelerud RA5, Maus TP6, Yang TH7, Murad MH1, Gou S8, Terry MJ3, Dauffenbach JP3, Pingree MJ8, Eldrige JS4, Mohammed K1, Benkhadra K1, van Wijnen AJ9, Qu W10.
Author information

• 1Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, USA.
• 2Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN 55905, USA.
• 3Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA.
• 4Department of Anesthesiology Pain Division, Mayo Clinic, Rochester, MN 55905, USA.
• 5Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Spine Center, Mayo Clinic, Rochester, MN 55905, USA.
• 6Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA.
• 7Department of Biomedical Engineering, National Cheng Kung University, Taiwan; Biomechanics Laboratory and Tendon and Soft Tissue Biology Laboratory, Division of Orthopedic Research, Mayo Clinic, Rochester, MN 55905, USA.
• 8Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Department of Anesthesiology Pain Division, Mayo Clinic, Rochester, MN 55905, USA.
• 9Department of Orthopedics, Rochester, MN 55905, USA.
• 10Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Department of Anesthesiology Pain Division, Mayo Clinic, Rochester, MN 55905, USA; Spine Center, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: [email protected].

Abstract
Management of intervertebral disc (IVD) degenerative disease is challenging, as it is accompanied by irreversible loss of IVD cells. Stem cell transplantation to the disc has shown promise in decelerating or arresting the degenerative process. Multiple pre-clinical animal trials have been conducted, but with conflicting outcomes. To assess the effect of stem cell transplantation, a systematic review and meta-analysis was performed. A comprehensive literature search was conducted through Week 3, 2015. Inclusion criteria consisted of controlled animal trials. Two reviewers screened abstracts and full texts. Disagreements were resolved by a third reviewer. Random effects models were constructed to pool standardized mean difference (SMD). Twenty two studies were included; nine of which were randomized. Statistically significant differences were found with the stem cell group exhibiting increased disc height index (SMD=3.64, 95% confidence interval (CI): 2.49, 4.78; p<0.001), increased MRI T2 signal intensity (SMD=2.28, 95% CI: 1.48, 3.08; p<0.001), increased Type II collagen mRNA expression (SMD=3.68, 95% CI: 1.66, 5.70; p<0.001), and decreased histologic disc degeneration grade (SMD=-2.97, 95% CI: -3.97, -1.97; p<0.001). There was statistical heterogeneity between studies that could not be explained with pre-planned subgroup analyses based on animal species, study designs, and transplanted cell types. Stem cells transplanted to the IVD in quadruped animals decelerate or arrest the IVD degenerative process. Further studies in human clinical trials will be needed to understand if such benefit can be translated to bipedal humans.
Copyright © 2015 Elsevier B.V. All rights reserved.

 

[Doctodd]

Which conference?

 

[Louisville04]

AAPMR Conference in Boston 10/1 to 10/4
Regenerative Medicine
Stem Cell Treatment in Osteoarthritis: Office-Based Application
IW802. Thursday, October 1: 11:30 am – 2:30 pm
IW804. Thursday, October 1: 3 pm – 6 pm
IW806. Friday, October 2: 10 am – 1 pm
IW808. Friday, October 2: 3 pm – 6 pm

 

[Doctodd]

thanks

 

[GH253]

A better question for the OP is how can anyone take you as an individual seriously when you shun promising new therapies and the best thing you can offer anyone is prescription-strength Advil?

 

[ampaphb]

After I have read all of the articles you posted, included many others you have not...here is my impression. PRP and MSC treatment offers a novel approach to CURE patients of previously untreatable disease process.

I would contend this is an overstatement. It is as yet unproven. It MIGHT cure patients, but it is far too early to say definitively one way or the other.

 

[ampaphb]

A better question for the OP is how can anyone take you as an individual seriously when you shun promising new therapies and the best thing you can offer anyone is prescription-strength Advil?

Would you do it on a family member?

What data can you supply to support your claim that it is "promising"?

When you recommend it to your patients, are you transparent? Do you tell them that the American Academy of Orthopedic Surgeons is not able to support its use at present, and has definitively said so in the JAAOS?

Do you tell them it is controversial at best? That the dose, method of insertion, and target structures have yet to be standardized? That no funding source will pay for it, and it is still considered experimental?

You're right - it MIGHT work. Then again, until you can show me a meta-analysis that demonstrates consistent efficacy, saline might work too. Afterall, we know the placebo effect is responsible for efficacy in 30-35% of cases.

So no, I wouldn't put my mom at risk for an unproven, experimental therapy. Not PRP, not stem cells, and not any other magic pixie dust. Generally, the rule is, do the studies FIRST, then, and only then, employ them on patients.

 

[j4pac]

I would contend this is an overstatement. It is as yet unproven. It MIGHT cure patients, but it is far too early to say definitively one way or the other.

Oh...I agree. It's not curing anyone as of now (except a few mice with MS...see Adam Caplan's work). But that is the reason why regenerative medicine is a big deal right? We have tons of medications that manage medical conditions...but very few that cure. Regenerative medicine theoretically could lead to cures. If it does...which side do you want to be on: the doctor of the future or the doctor of the past? It may be a pipe dream...but it's a pipe dream worth investing. If PM&R doesn't invest itself into the potential of regenerative medicine...other specialities will...and our patients could potentially become patients of Ortho and Neurology.

 

[GH253]

Would you do it on a family member?

What data can you supply to support your claim that it is "promising"?

When you recommend it to your patients, are you transparent? Do you tell them that the American Academy of Orthopedic Surgeons is not able to support its use at present, and has definitively said so in the JAAOS?

Do you tell them it is controversial at best? That the dose, method of insertion, and target structures have yet to be standardized? That no funding source will pay for it, and it is still considered experimental?

You're right - it MIGHT work. Then again, until you can show me a meta-analysis that demonstrates consistent efficacy, saline might work too. Afterall, we know the placebo effect is responsible for efficacy in 30-35% of cases.

So no, I wouldn't put my mom at risk for an unproven, experimental therapy. Not PRP, not stem cells, and not any other magic pixie dust. Generally, the rule is, do the studies FIRST, then, and only then, employ them on patients.

Not only would I use it on a loved one, I have already used it on myself and intend to do so again in the future. I might withhold it from family members I don't like.

Success in double-blind clinical trials is not the standard that every therapy has to meet in order to be worth considering. "Experimental" doesn't mean "quackery." One has to look at the existing evidence and weight it against the current treatment options—which in the case of degenerative joint/disc disease are clearly inadequate—and the price of inaction, which may be the worst course of all, leading only to the certainty of a painful, debilitated future. Given the current conventional treatment options, I've often wondered why PM&R even exists as a specialty. Why should anyone pay you hundreds of dollars to bask in your glory for 10 minutes when you can't give him anything better than what he can get over the counter or on Silk Road without the indignity of being profiled in the course of seeking treatment? The mainstay of conventional treatment, NSAIDs, have well-known dangers and adverse effects, and their use is a leading cause of iatrogenic injury. How can you ignore that?

In the last few years, a substantial body of research has demonstrated that mesenchymal stem cells have the potential to regenerate articular cartilage and intervertebral discs (confirmed objectively by radiographic evidence) and improve patient symptoms and function with little or nothing in the way of adverse effects reported. The evidence that now exists is enough that many doctors want to recommend and many patients want to try it given the alternative of certain suffering and morbidity. It could take decades for data to accumulate to the point that you consider satisfactory. What's the point of erring on the side of caution when much or all of one's remaining lifespan will go up in smoke before that happens?

One thing's for sure, which is that evidence would accumulate a lot faster if the therapy could be used freely, i.e. without the often insurmountable financial burden that regulatory complications impose (realize that the FDA started regulating cultured stem cells—the kind proven to work—as drugs in 2010 and that this has already mostly shut down the stem cell industry).

At least one company is putting a product based on MSC technology through clinical trials. It completed Phase 2 successfully last year:

http://globenewswire.com/news-relea...RESULTS-USING-MESOBLAST-ADULT-STEM-CELLS.html

 

[ampaphb]

Not only would I use it on a loved one, I have already used it on myself and intend to do so again in the future. I might withhold it from family members I don't like.

Success in double-blind clinical trials is not the standard that every therapy has to meet in order to be worth considering. "Experimental" doesn't mean "quackery." One has to look at the existing evidence and weight it against the current treatment options—which in the case of degenerative joint/disc disease are clearly inadequate—and the price of inaction, which may be the worst course of all, leading only to the certainty of a painful, debilitated future. Given the current conventional treatment options, I've often wondered why PM&R even exists as a specialty. Why should anyone pay you hundreds of dollars to bask in your glory for 10 minutes when you can't give him anything better than what he can get over the counter or on Silk Road without the indignity of being profiled in the course of seeking treatment? The mainstay of conventional treatment, NSAIDs, have well-known dangers and adverse effects, and their use is a leading cause of iatrogenic injury. How can you ignore that?

In the last few years, a substantial body of research has demonstrated that mesenchymal stem cells have the potential to regenerate articular cartilage and intervertebral discs (confirmed objectively by radiographic evidence) and improve patient symptoms and function with little or nothing in the way of adverse effects reported. The evidence that now exists is enough that many doctors want to recommend and many patients want to try it given the alternative of certain suffering and morbidity. It could take decades for data to accumulate to the point that you consider satisfactory. What's the point of erring on the side of caution when much or all of one's remaining lifespan will go up in smoke before that happens?

One thing's for sure, which is that evidence would accumulate a lot faster if the therapy could be used freely, i.e. without the often insurmountable financial burden that regulatory complications impose (realize that the FDA started regulating cultured stem cells—the kind proven to work—as drugs in 2010 and that this has already mostly shut down the stem cell industry).

At least one company is putting a product based on MSC technology through clinical trials. It completed Phase 2 successfully last year:

http://globenewswire.com/news-relea...RESULTS-USING-MESOBLAST-ADULT-STEM-CELLS.html

Experimental may not mean quackery, but, in fact, unproven does.

"Quackery is the promotion of an unproven product or service."
http://www.quackwatch.com/01QuackeryRelatedTopics/quackdef2.html

The notion that NSAIDS have side effects ignores the risk of intra-articular injections. Let's not forget, prior to whichever form of magic fairy dust you are infusing into the patients joint, they have undergone multiple IA steroid injections, and at least a few courses of viscosupplenmentation. The risk of iatrogenically induced joint infection is not insignificant.

Yor reference to Silk Road, and thus your advocacy of obtaining narcotics or illicits illegally, is not worthy of response.

The use of stem cells, growth factors, PRP etc in the disc has NOT been shown to be effective, or, in the alternative, has been found to cause more harm than good. As was mentioned by an earlier poster, creating the appropriate scaffold remains the overarching issue, and one that has, as of yet, not been solved.

So if you want to experiment with your own joint, or that of your family, go right ahead. Anyone else? I certainly wouldn't, unless it was part of a study protocol. You may think that makes me a fuddy duddy. I personally don't like the idea of trying unproven, experimental technologies on my patients, based soley on "potential".

I also don't think the best and the brightest in our field ought to be advocating that. I am glad they are looking into bleeding edge cures. Once they can demonstrate that they actually work, then, and only then, will I offer them to my patients.

 

[GH253]

"Quackery is the promotion of an unproven product or service."
http://www.quackwatch.com/01QuackeryRelatedTopics/quackdef2.html

I don't read anything Stephen Barrett writes or consider him a credible source of information on quackery. The issue is not whether it is desirable for a therapy to be proven, but what standard of proof is appropriate in the context of an experimental therapy, and whether doctors and patients should have the freedom to decide for themselves whether it's worthwhile to them to try one.

As was mentioned by an earlier poster, creating the appropriate scaffold remains the overarching issue, and one that has, as of yet, not been solved

Based on this, it's clear that you don't even follow research in the field in question; you read one thing on a forum and took it as definitive because it appeared at first glance to validate your bias against stem cell treatments.

 

[ampaphb]

No, actually that is based on the state of the art updates reported by Michael Depalma, Michael Whitworth, Gwendolyn Sowa, Howard An, etc at recent ISIS and NASS meetings.

You also might want to take a look at what the AAOS has to say: http://www.aaos.org/news/aaosnow/sep14/cover2.asp (then again, you seem to be the world expert on the subject, so you probably know more than everyone else)

 

[drusso]

Ultrasound-Guided Intratendinous Injections With Platelet-Rich Plasma or Autologous Whole Blood for Treatment of Proximal Hamstring Tendinopathy
A Double-Blind Randomized Controlled Trial

Kathleen L. Davenport, MD, Jose Santiago Campos, MD, Joseph Nguyen, MPH, Gregory Saboeiro, MD, Ronald S. Adler, MD, PhD and Peter J. Moley, MD⇑
+ Author Affiliations

Preferred Orthopedics of the Palm Beaches, Boynton Beach, Florida USA (K.L.D.); Carteret Comprehensive Medical Care, PC, Carteret, New Jersey USA (J.S.C.); Departments of Epidemiology and Biostatistics (J.N.), Radiology and Imaging (G.S.), and Physiatry (P.J.M.), Hospital for Special Surgery, New York, New York USA; and Department of Radiology and Imaging, New York University Langone Medical Center, New York, New York USA (R.S.A.).
Address correspondence to Peter J. Moley, MD, Department of Physiatry, Hospital for Special Surgery, 541 E 71st St, New York, NY 10021 USA., E-mail: [email protected]

Objectives—To compare the effects of ultrasound-guided platelet-rich plasma (PRP) and whole blood (WB) injections in patients with chronic hamstring tendinopathy.

Methods—In a prospective double-blind randomized controlled trial, PRP or WB was injected under ultrasound guidance into the proximal hamstring tendon in a cohort of patients with clinically suspected hamstring tendinosis. Questionnaires were administered before injection and 2, 6, and 12 weeks and 6 months after injection. Pain and function outcomes were measured via the Modified Harris Hip Score (MHHS), Hip Outcome Scores for activities of daily living (ADL) and sport-specific function, and International Hip Outcome Tool 33 (IHOT-33). Diagnostic ultrasound was used to compare preinjection and 6-month postinjection tendon appearances.

Results—The WB group showed greater improvements in pain and function over the PRP group before 12 weeks, whereas the PRP group showed improved outcomes over WB at 6 months. None of these between-group outcome measures, except 6-week IHOT-33, showed statistical significance. Comparing preinjection and 6-month scores, the PRP group showed significant improvements in ADL (P = .018) and IHOT-33 (P = .28) scores, whereas the WB group showed no significant improvements from baseline. The WB group showed significantly decreased pain with 15-minute sitting (P= .008) at 6 months. Ultrasound imaging showed no significant differences between PRP and WB group tendon appearances.

Conclusions—Both PRP and WB groups showed improvements in all outcome measures at 6 months. The PRP group showed significant improvements in 6-month ADL and IHOT-33 scores. The WB group reached significance in 15-minute sitting pain. No significant between-group differences were observed at any time point.

**Can we agree that PRP (or whole blood) is a reasonable alternative for patients, with some conditions, who have a preference to avoid steroids?**

 

[lobelsteve]

Ultrasound-Guided Intratendinous Injections With Platelet-Rich Plasma or Autologous Whole Blood for Treatment of Proximal Hamstring Tendinopathy
A Double-Blind Randomized Controlled Trial

Kathleen L. Davenport, MD, Jose Santiago Campos, MD, Joseph Nguyen, MPH, Gregory Saboeiro, MD, Ronald S. Adler, MD, PhD and Peter J. Moley, MD⇑
+ Author Affiliations

Preferred Orthopedics of the Palm Beaches, Boynton Beach, Florida USA (K.L.D.); Carteret Comprehensive Medical Care, PC, Carteret, New Jersey USA (J.S.C.); Departments of Epidemiology and Biostatistics (J.N.), Radiology and Imaging (G.S.), and Physiatry (P.J.M.), Hospital for Special Surgery, New York, New York USA; and Department of Radiology and Imaging, New York University Langone Medical Center, New York, New York USA (R.S.A.).
Address correspondence to Peter J. Moley, MD, Department of Physiatry, Hospital for Special Surgery, 541 E 71st St, New York, NY 10021 USA., E-mail: [email protected]

Objectives—To compare the effects of ultrasound-guided platelet-rich plasma (PRP) and whole blood (WB) injections in patients with chronic hamstring tendinopathy.

Methods—In a prospective double-blind randomized controlled trial, PRP or WB was injected under ultrasound guidance into the proximal hamstring tendon in a cohort of patients with clinically suspected hamstring tendinosis. Questionnaires were administered before injection and 2, 6, and 12 weeks and 6 months after injection. Pain and function outcomes were measured via the Modified Harris Hip Score (MHHS), Hip Outcome Scores for activities of daily living (ADL) and sport-specific function, and International Hip Outcome Tool 33 (IHOT-33). Diagnostic ultrasound was used to compare preinjection and 6-month postinjection tendon appearances.

Results—The WB group showed greater improvements in pain and function over the PRP group before 12 weeks, whereas the PRP group showed improved outcomes over WB at 6 months. None of these between-group outcome measures, except 6-week IHOT-33, showed statistical significance. Comparing preinjection and 6-month scores, the PRP group showed significant improvements in ADL (P = .018) and IHOT-33 (P = .28) scores, whereas the WB group showed no significant improvements from baseline. The WB group showed significantly decreased pain with 15-minute sitting (P= .008) at 6 months. Ultrasound imaging showed no significant differences between PRP and WB group tendon appearances.

Conclusions—Both PRP and WB groups showed improvements in all outcome measures at 6 months. The PRP group showed significant improvements in 6-month ADL and IHOT-33 scores. The WB group reached significance in 15-minute sitting pain. No significant between-group differences were observed at any time point.

**Can we agree that PRP (or whole blood) is a reasonable alternative for patients, with some conditions, who have a preference to avoid steroids?**

Did you give a p value of 0.28 and then conclude it was a significant difference?

 

[drusso]

Did you give a p value of 0.28 and then conclude it was a significant difference?

If you read the whole article you'll see that the PRP group had more sustained improvement. It's a small study; I'm not overstating its findings---but this is real science--not MOO-SHU PORK.

http://acupuncturetoday.com/mpacms/at/article.php?id=27914

"In either case, acupuncture can play an important part in the overall treatment scheme. The choice of local points along with points such as UB40, GB34 and UB36 is easy, and the general "ropiness" of the hamstrings makes it easy to indentify a-shi points and areas of disruption of qi flow. The key to using acupuncture in treating the hamstrings lies in selecting proper distal points that adequately affect the region involved. I would suggest five distal points (or sets of points) that, through a variety of channel relationships, may prove to be key to affecting the hamstring area, whether used with needles, moxa, or both.

UB67: The jing-well point of the UB channel, it also affects the entire tendinomuscular channel.
UB65: The shu-stream point of the channel, it is also the "wood" point channel, and thus also affects the tendinomuscular structure.
SI1: The jing-well point of the SI channel, it can have a systemic effect on the whole tai yang complex.
LU6: While this xi-cleft is now commonly used for some types of back pain, it may also affect the hamstrings.
KI4: The luo point of the kidney channel, this point may be manipulated to remove excess qi from the UB channel complex and "channel" it into more constructive uses."

 

[ampaphb]

Study was powered to demonstrate that prp was able to yield greater efficacy that whole blood. No statistically significant difference was able to be demonstrated.

 

[drusso]

Study was powered to demonstrate that prp was able to yield greater efficacy that whole blood. No statistically significant difference was able to be demonstrated.

...so its non-inferior...

 

[lobelsteve]

...so its non-inferior...

Or both are ineffective compared to no treatment?

 

[drusso]

Or both are ineffective compared to no treatment?

That would have required a no treatment group. I've already suggested to authors "acupuncture."

 

[ampaphb]

...so its non-inferior...

There is no evidence that whole blood works. PRP is no better than a method that is at best unproven, and at worst ineffective.

 

[j4pac]

Lack of efficacy is an issue but that is not as big of an issue is the lack of safety of use studies. That is the biggest value of FDA testing...and it's a big thing missing from regenerative medicine. If, like OMT and acupuncture, PRP/MSC lacks to consistently demonstrate efficacy people will still line up around the block for the chance of it helping. I don't think that is unethical...however, I'm not sure that it is ethical giving these treatments to people without a safety profile. Just as there is theoretical benefit of treatment there is theoretical side effects. Sure, people are willing to be a test dummy with the hope of getting better, but these people are often desperate and willing to try anything.

These studies shouldn't be carried out expect with the expectation of being apart of an enormous standardized study to demonstrate efficacy and safety.

 

[RUOkie]

Cost is a very important issue in this as well. We are very limited in our total health care dollars. If regenerative techniques are going to be used, we need to prove effectiveness, or let them go away.
Who (meaning insurers) is going to pay hundreds or thousands of dollars for something that "Might help"?

 

[drusso]

Cost is a very important issue in this as well. We are very limited in our total health care dollars. If regenerative techniques are going to be used, we need to prove effectiveness, or let them go away. Who (meaning insurers) is going to pay hundreds or thousands of dollars for something that "Might help"?

No one should advocate for insurance to pay for regenerative medicine. Third-party payors should **NOT** pay for regenerative medicine. It's better kept outside the third-party system. IF, it proves useful, third-party payors may start to pick it up.

 

[GH253]

lSure, people are willing to be a test dummy with the hope of getting better, but these people are often desperate and willing to try anything.

Why should desperation preclude someone from trying something? A patient is desperate, so let's turn some hope into none...for his own good?

 

[RUOkie]

Why should desperation preclude someone from trying something? A patient is desperate, so let's turn some hope into none...for his own benefit?

Because that is not how medicine works, or worse yet how silly treatments become the "standard of care". There was a time not too long ago when people had multilevel fusions for "Black disk disease" (otherwise known as degenerative disk disease)

 

[drusso]

Because that is not how medicine works, or worse yet how silly treatments become the "standard of care". There was a time not too long ago when people had multilevel fusions for "Black disk disease" (otherwise known as degenerative disk disease)

Here is how it works : research changes policy, policy changes payment, payment changes practice.

 

[ampaphb]

But Dave. All these altruistic PM&R docs don't need to get paid. I'm sure the fact that this unproven technology is paid in cash isn't at all a reason why they are so enthusiastic.

 

[RUOkie]

But Dave. All these altruistic PM&R docs don't need to get paid. I'm sure the fact that this unproven technology is paid in cash isn't at all a reason why they are so enthusiastic.

They must be doing it for all the right reasons, they are the leaders in the field! (where's that purple font when I need it)

 

[drusso]

But Dave. All these altruistic PM&R docs don't need to get paid. I'm sure the fact that this unproven technology is paid in cash isn't at all a reason why they are so enthusiastic.

I wonder how third-party payors influence provider enthusiasm for **ANY** treatment?

 

[j4pac]

The enthusiasm for PRP and MSC is going to die quickly if third-party payers get involved. I've heard stories of docs getting $600+ cash per injection. In the right geographic location...a provider can work a day a week on that type of cash flow.

It appears to me that docs are trying to tight rope this situation. They want to demonstrate enough efficacy to use the treatments without liability...but not enough to make it standard of care. It's a dangerous game. What happens when the random patient that ends up developing cancer decides to sue? PRP and MSC is a theoretical wonder drug....but it is also a theoretical producer of malignancy...not to mention the other plethora of joint injection related side effects. I think that the doc is going to be fried. He/she won't be able to fall back on the handful of small pre-clinical trials that have shown safety for use.

 

[Doctodd]

The enthusiasm for PRP and MSC is going to die quickly if third-party payers get involved. I've heard stories of docs getting $600+ cash per injection. In the right geographic location...a provider can work a day a week on that type of cash flow.

It appears to me that docs are trying to tight rope this situation. They want to demonstrate enough efficacy to use the treatments without liability...but not enough to make it standard of care. It's a dangerous game. What happens when the random patient that ends up developing cancer decides to sue? PRP and MSC is a theoretical wonder drug....but it is also a theoretical producer of malignancy...not to mention the other plethora of joint injection related side effects. I think that the doc is going to be fried. He/she won't be able to fall back on the handful of small pre-clinical trials that have shown safety for use.

Please cite the literature that states that mesenchymal stem cells develops or produces cancer?

 

[drusso]

It's a dangerous game. What happens when the random patient that ends up developing cancer decides to sue? PRP and MSC is a theoretical wonder drug....but it is also a theoretical producer of malignancy...not to mention the other plethora of joint injection related side effects. I think that the doc is going to be fried. He/she won't be able to fall back on the handful of small pre-clinical trials that have shown safety for use.

Maybe PRP is the next lumbar provocation discography...