Blog category: Papers

 

The effect of intra-articular autologous protein solution on knee osteoarthritis symptoms
Ross et al.
The Bone and Joint Journal. 2024; 106-B 9; 907-915. https://pubmed.ncbi.nlm.nih.gov/39216848/

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There is a plethora of ‘stuff’ that some people seem happy to inject into patient’s knees. This is partly driven, no doubt, by clinicians’ desire to try and help patients, even in situations where ‘no specific intervention’ (or just activity modification / rest) might actually be the best option. The more cynical (awake!) amongst you might question the potential influence of The Pharmaceutical Industry (‘Big Pharma’!) and the undue influence they exert through marketing, through financial incentives and through the adverse influence that they so often seem to exert on the published research (much of which they fund!). Very sadly, on top of all this, there are undoubtedly some clinicians out there who simply see joint injections as a very lucrative business, and who seem more than happy to inject ‘any old stuff’ into anyone’s knee, just to make an easy fast buck!).

Of the long list of potions and ‘magic pixie dust’ that some people seem prepared to tout to the unsuspecting public (and, in particular, to uninformed, desperate and hence vulnerable patients), one type of product is PRP (platelet-rich plasma). There are several different versions of PRP in clinical use, but fundamentally, they are all similar, in that they involve taking blood from a patient’s arm, spinning the blood to remove various things, such as the red blood cells +/- the white cells, and then injecting the solution back into the knee, on the premise that the couple of millilitres of fluid that is produced somehow contains ‘magic growth factors’ that supposedly somehow ‘slow down the arthritis and reduce patients’ pain’.

Importantly, there is very poor evidence to support the use of PRP injections into knees for the treatment of early arthritis. Undoubtedly, injecting anything into a knee can have a positive effect simply due to the placebo effect (if you simply inject just saline into people’s knees, about 40% of people report a (temporary) improvement in their knee symptoms!). However, there is no decent evidence that PRP injections make any significant difference to the long-term prognosis of an arthritic knee, either in terms of symptoms or the likelihood of the patient ending up needing a knee replacement.

This is why PRP injections are not recommended by NICE for the treatment of knee arthritis (not without ‘special arrangements’ being place).

(And this is also why some people believe that the true meaning of ‘PRP’ is actually ‘Pointless Rich Physicians’!!?!)

One ‘special version’ of PRP is something called nSTRIDE – which is referred to as an ‘APS’: an ‘Autologous Protein Solution’. With this, 60ml of venous blood is taken from the patient’s arm. The blood is then spun in a centrifuge. This is then said to leave 3ml of ‘protein-rich fluid’ (quite how this leaves behind the ‘good proteins’ I have genuinely no idea!!?! – and I’ve scoured the internet for a decent logical scientific explanation of just how this might actually work… but so far, have found none!)… and the 3ml of fluid (AKA blood, but without the cells) is then injected into the knee.

The company that sell nSTRIDE state that it is:

“a cell concentration system that is designed to concentrate anti-inflammatory cytokines and anabolic growth factors… to significantly decrease pain and promote cartilage health”.

Some clinicians market these injections with statements such as:

“The nSTRIDE APS injection treatment is designed to alleviate pain and bring balance back to your inflamed knee joint by introducing high levels of “good” proteins concentrated from your own blood. These good proteins can block the “bad” proteins responsible for the inflammatory condition in your joint. At the same time, nSTRIDE APS also concentrates growth factors which are beneficial for cartilage health.”

with claims that:

“nSTRIDE is the only single-injection therapy where the benefits are sustained for up to 3 years.”

So, what does this latest study from Ross et al actually show?….

Well, in this high-quality prospective randomised study, the authors took 40 patients with unilateral moderate osteoarthritis on the knee. They randomised 21 to having an nSTRIDE injection in their knee versus 19 whose knees were simply injected with saline (placebo). The patients were followed up for 12 months, and the authors found the following:

1. no significant differences were found between nSTRIDE and placebo for any of the standard knee scores used (the WOMAC knee score and the KOOS knee score), but
2. The pain scores were actually lower in the placebo group!

So, this high-quality study shows that not only does nSTRIDE not work… but that simply injecting saline as placebo gave better pain reduction than nSTRIDE!!!

In conclusion

There are an awful lot of companies and clinicians making a lot of bold and unsubstantiated claims when it comes to joint injections, and it is clear that ‘the joint injection market’ is a highly-lucrative money earner for some less-scrupulous individuals.

If you want to STAY SAFE…. then STAY SCEPTICAL! … Do your reading and do your own research… and if a suave medical salesman tries to sell you a magic cure that sounds too good to be true… then guess what: it’s not true!

I just hope that one day the medical profession will drain the swamp of some of the individuals out there who are clearly doing things for their own benefit (for the benefit of their bank accounts) rather than acting in the best interests of their patients!

 

 

Gulbrandsen MT et al. Spin in the Abstracts of Meta-analyses and Systematic Reviews: Quadriceps Tendon Graft for Anterior Cruciate Ligament Reconstruction. The American Journal of Sports Medicine. 2023; 51(8): 2079-2084. doi:10.1177/03635465231169042

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Far too often in the ‘trusted’ medical literature, the headlines can be deceiving, and this should be a major concern to all.

The volume of readily-available information that people have access to nowadays is vastly greater than was routinely accessible in the past. This is a good thing, in terms of putting people in the driving seat when it comes to taking ownership for one’s own decision-making, and there are few areas where this is more important than healthcare, and one’s own heath.

Unfortunately, however, nowadays people’s attention spans seem to have shortened significantly, and far too many people are now addicted to just short punchy headlines, and brief social media posts with limited character counts. The danger comes in believing these sound bites without one actually doing the background reading necessary to validate (or refute!) what the person posting the info / opinion might be saying. In healthcare, this can be particularly dangerous, as patients and doctors alike can be misled by false information that may unduly and inappropriately influence their decision-making.

In a very interesting paper published last year in The American Journal of Sports Medicine, authors from the Loma Linda University in California analysed a collection of papers looking at the issue of the use of distal quads tendons for ACL reconstruction. The authors scrutinised a total of 13 published meta-analyses and systematic reviews, specifically looking for the presence of “spin” within the abstracts; meaning, the presence of reporting bias that misrepresents the actual research.

Shockingly, and worryingly, the authors that in over 50% of the papers there was clear evidence of spin, with the most common kind of spin observed being “selective reporting of or overemphasis on efficacy of outcomes”.

What does this mean?

It means that in over half of published meta-analyses or systematic reviews studied, there was clear evidence that the abstract of the paper ‘over-egged’ the potential positive results of the outcomes that can be anticipated from the use of quads tendons grafts for ACL reconstruction.

What’s the solution?

Simple: beware and be wary of what you read, particularly when it comes to just headlines or when it comes to abstracts. Abstracts, on their own, simply cannot be trusted, and if you want a proper understanding of a paper, then you simply have to read the whole paper!!

 

 

Risk Factors for Graft Failure After Meniscal Allograft Transplantation: A Systematic Review and Meta-analysis.
Kunze et al
Orthopaedic Journal of Sports Medicine 2023, 11(6). doi:10.1177/23259671231160296

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There’s nothing new about meniscal transplantation – indeed, the first case series of meniscal transplants reported in the English-speaking scientific literature was from Klaus Milachowski, from München, in the way back in 1989! The problem is that most people simply don’t seem to know about it or realise that it’s a potential option for their knee.

Meniscus absent from knee	Meniscal allograft implanted

Kunze and a team from The Hospital For Special Surgery in New York recently performed a systematic review and meta-analysis of the published outcomes after meniscal transplantation surgery, particularly looking at what factors might potentially affect success. They analysed a total of 17 studies including 2184 patients, and found the following:

5-year outcomes	~10% failure (~90% success)
10-year outcomes	~20% failure (~80% success)

Sex or laterality (medial vs lateral) did not seem to affect outcome; however, poorer results were seen in those patients with more-advanced articular cartilage damage in their knee.

These conclusions fit in exactly with our own findings, from where we analysed the outcomes of our patients undergoing meniscal transplantation surgery:

The results of meniscal allograft transplantation surgery: what is success?
Searle, Asopa, Coleman & McDermott
BMC Musculoskelet Disord 2020 Mar 12;21(1):159. doi: 10.1186/s12891-020-3165-0.

Conclusions

So, one can expect a roughly 80% success rate for patients undergoing meniscal transplantation surgery; however, the longer you leave a knee with no meniscus and the worse the articular cartilage damage in the affected compartment becomes, the lower the probability will be that the patient will achieve a good outcome.

This strongly emphasises how meniscal transplantation is a very good option for those patients suffering pain in the knee from early wear and tear secondary, specifically, to the previous loss of some or all of their meniscus from that side of their knee previously, and how if this surgery is going to be needed, then it is better done sooner rather than later.

(Please note, however, that meniscal transplantation is not a viable option for people who have already developed fully-blown arthritis in their knee.)

Find out more about meniscal transplantation: CLICK HERE

 

 

 

 

 

Never judge a book by its cover, let alone just the title…

and, some of what doesn’t glitter might actually be gold!

The importance of reading articles in full, with a critical eye,

rather than relying purely on just the abstract or, even, just the title!

 

“No difference in patient‐reported satisfaction after 12 months between customised individually made and off‐the‐shelf total knee arthroplasty”
Wendelspiess S, Kaelin R, Vogel N, Rychen T, Arnold MP
Knee Surgery, Sports Traumatology, Arthroscopy (2022) 30:2948–2957 https://doi.org/10.1007/s00167-022-06900-z

This paper should be read, carefully, in full. When one does, then the following important issues become very apparent:

ISSUES

1. The patients were not randomised, and although it is not very clear from the wording in the paper, it would appear that it was the patients themselves that chose whether to have a CIM rather than a standard OTS knee:

“CIM TKA patients chose their surgeon (MPA) accordingly because of their interest in the new technology.”

Importantly, patients who are more proactively engaged in their healthcare decision-making processes tend to have higher expectations, and it is harder to achieve a good result (high patient satisfaction post-op) in patients with higher pre-operative expectations.¹ Therefore, immediately, one can see that there is selection bias in this study (which is always a drawback of non-randomised studies).

2. There is further, and important, selection bias in that some patients specifically had CIM knees on the recommendation of their surgeon if they had marked joint line obliquity:

“In rare cases, the patient was made aware of the possibility of a CIM TKA because of a marked joint line obliquity (tibial mechanical angle of ≤84° on long-leg radiographs) with an obvious anatomical difference in shape between the medial and lateral femoral condyles or hypoplasia of the lateral femoral condyle.”

Unfortunately, the authors fail to specify what their definition of “rare” might be, and exactly how many of the CIM patients actually fell into this category. Again, however, this is an example of selection bias, in that it is harder to achieve a good outcome in patients with more ‘difficult’ knees, and yet these ‘more difficult’ cases were specifically allocated to the CIM group.

3. Patellar resurfacing was only performed selectively. However, information is given about what percentage of the CIM knees had patellar resurfacing performed compared to the OTS group. This is another potential confounding factor.

4. The two groups (CIM vs OTS) were not comparable in their demographics, either, and importantly, the CIM patients were slightly younger and there were also more males in the CIM group.

Younger patients tend to have higher functional demands and higher expectations, and it therefore tends to be harder to match expectations and achieve satisfaction in these patients. This is another important confounding factor within the study.

The results of this study echo other previous studies, and report slightly higher post-operative patient satisfaction in females. However, there were more proportionally more males in the CIM group. Another confounding factor.

5. The “primary” outcome measure used in this study was simply a 5-point Likert scale. This is extremely basic, and it is hard to understand why the authors chose to use such a simplistic and, inevitably, insensitive outcome measure as their primary outcome measure. Using such a basic tool significantly decreases the likelihood of any genuine differences between the two patient groups ended up being visible and apparent in the results.

6. In terms of the results, no differences were seen on the 5-point Likert scale, but the KSS score was higher for the CIM group at both 4 months and 12 months post-op. (p<0.001).

7. Anatomical alignment was better in the CIM group. This is important, but it is barely mentioned by the authors.

One of the specific advantages of CIM implants is that they use 3D-printed patient-specific cutting blocks, and these have been shown to give accuracy of implant placement equivalent to computer navigated / robot-assisted surgery, but without the additional invasiveness, time or costs that these involve.² Accurate implant placement (within 3^o of ideal) has been demonstrated to affect longer-term outcomes.

8. Stability was better for the CIM group.

9. Adverse events were more frequent in the OTS group.

10. Revision was less frequent in the CIM group (4 patients needed revision surgery in the OTS group, compared to none in the CIM group).

11. And finally…

The normal accepted patient satisfaction rate for OTS TKR = about 80%…

• Patient Satisfaction after Total Knee Arthroplasty: Who is Satisfied and Who is Not? Clin Orthop Relat Res2010; 468(1): 57 – 63. doi: 10.1007/s11999-009-1119-9.

“Our data confirmed that approximately one in five (19%) primary TKA patients were not satisfied with the outcome. Satisfaction with pain relief varied from 72–86% and with function from 70–84% for specific activities of daily living.”

However, the authors of the recent KSSTA paper quote a patient satisfaction rate of 89% for their OTS knees. This is way better than average… and it represents a patient dissatisfaction rate that is about 50% lower than the published norm. So, the authors really should be congratulated on that!

If patient satisfaction is reported to be about 90% with a CIM knee (as reported in the published studies on CIM knees to-date)… and if the KSSTA paper’s authors are getting an 89% satisfaction rate already with OTS knees… then there’s absolutely no way that they could ever actually demonstrate any significantly significant difference in outcomes between CIM and OTS – not if their OTS results are so abnormally good already!!

CONCLUSIONS

So, we have a paper here whose title states:

“No difference in patient‐reported satisfaction after 12 months between customised individually made and off‐the‐shelf total knee arthroplasty”

with an abstract where just one single line hints at a possible difference of potential interest:

“The postoperative KSS, notably regarding knee stability, was higher for CIM TKA (p<0.001)”

However, if you read and critically appraise the actual full paper itself then the actual conclusions that should be drawn are:

1. the study is non-randomised, and there is obvious selection bias,
2. there are significant potentially confounding factors between the two study groups,
3. the main outcome measure was simply just a basic 5-point satisfaction scale,
4. the KSS scores were significantly better in the CIM group,
5. the post-operative alignment was better in the CIM group,
6. the post-operative stability was better in the CIM group,
7. adverse events were less frequent in the CIM group,
8. revision was less frequent in the CIM group, and
9. the authors’ results for their patient satisfaction scores for their OTS knees are significantly superior to the usual published expected norm for OTS knees: therefore making it extremely unlikely that any significant difference in ‘satisfaction’ could ever be observed.

A very different-looking set of conclusions compared to the study title, which is clearly deeply simplistic and actually really quite misleading.

The discrepancies between the actual stated results and what the authors chose to write as their study title and abstract is so stark as to make one wonder whether undue outside influence or bias might have been at play? (Or maybe the reviewers were simply half-asleep?!)

Finally, any paper should never be read or considered purely in isolation, and one should only form an opinion on a subject after a full analysis of the wider evidence available across a broad range of publications and studies. So, if you want to learn more about the potential benefits of custom-made knee replacement surgery, then these papers are useful, for starters:

• “A Comparison of Clinical Outcomes and Implant Preference of Patients with Bilateral TKA. One Knee with a Patient-Specific and One Knee with an Off-the-Shelf Implant.”³

“… patients in this study cohort who underwent staged bilateral TKA with a C-TKA implant in 1 knee and an OTS prosthesis in the other knee reported better for their patient-specific knee replacement, with higher FJS and KOOS, JR values, and overall, preferred the C-TKA knee more often compared with the OTS knee replacement.”

https://journals.lww.com/jbjsreviews/Abstract/2022/02000/A_Comparison_of_Clinical_Outcomes_and_Implant.3.aspx

• “Accurate implant fit and leg alignment after cruciate-retaining patient-specific total knee arthroplasty.”⁴

“The patient-specific iTotal™ CR G2 total knee replacement system facilitated a proper fitting and positioning of the implant components. Moreover, a good restoration of the leg axis towards neutral alignment was achieved as planned.”

https://journals.lww.com/jbjsreviews/Abstract/2020/07000/Patient_Satisfaction,_Functional_Outcomes,_and.7.aspx

• “Patient Satisfaction, Functional Outcomes, and Survivorship in Patients with a Customized Posterior-Stabilized Total Knee Replacement”⁵

“The satisfaction rate was found to be high, with 90% of patients being satisfied or very satisfied and 88% of patients reporting a “natural” perception of their knee either some or all of the time.”

https://journals.lww.com/jbjsreviews/Abstract/2020/07000/Patient_Satisfaction,_Functional_Outcomes,_and.7.aspx

• “Patient Satisfaction, Functional Outcomes, and Implant Survivorship in Patients Undergoing Customized Cruciate-Retaining TKA”⁶

“Patient satisfaction was high, with 89% of C-TKA patients being either satisfied or very satisfied.”

https://journals.lww.com/jbjsreviews/subjects/Knee/Abstract/2021/09000/Patient_Satisfaction,_Functional_Outcomes,_and.8.aspx

 (But remember… you need to actually read these papers in full, not just the abstracts, and certainly not just the titles! Otherwise, I’m afraid you’ve really just not ‘got it’ w.r.t. the fundamental underlying message of this entire blog! Happy reading!)

 

READ THE SCIENCE.

EVALUATE THE SCIENCE.

FOLLOW THE CURRENT SCIENCE.

SCIENCE IS NEVER SET.

 

REFERENCES

1. Patient expectations and satisfaction 6 and 12 months following total hip and knee replacement. Qual Life Res 2020 Mar; 29(3): 705-719 doi: 10.1007/s11136-019-02359-7
2. Comparison of postoperative coronal leg alignment in customized individually made and conventional total Knee arthroplasty. J Pers Med 2021; 11: 549
3. A Comparison of Clinical Outcomes and Implant Preference of Patients with Bilateral TKA. One Knee with a Patient-Specific and One Knee with an Off-the-Shelf Implant. JBJS Reviews 2022; 10(2) – e20.00182. doi: 10.2106/JBJS.RVW.20.00182
4. Accurate implant fit and leg alignment after cruciate-retaining patient-specific total knee arthroplasty.BMC Musculoskelet Disord 2020;21(1): 699 doi: 10.1186/s12891-020-03707-2
5. Patient Satisfaction, Functional Outcomes, and Survivorship in Patients with a Customized Posterior-Stabilized Total Knee Replacement. JBJS Reviews e 8 – Issue 7 – p e19.00104. doi: 10.2106/JBJS.RVW.19.00104
6. Patient Satisfaction, Functional Outcomes, and Implant Survivorship in Patients Undergoing Customized Cruciate-Retaining TKA. JBJS Reviews 2021; Volume 9(Issue 9): e20.00074. doi: 10.2106/JBJS.RVW.20.00074

 

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