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7th November 2017 - Meniscus repair using mesenchymal stem cells – a c ... (Thread closed)

7th November 2017 - "Meniscus repair using mesenchymal stem cells – a comprehensive review"

Link to paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415251/

Angus Hotchkies 11/07 07:32PM

Welcome to SCALPEL's fifth online journal club of the year! Thanks for coming along, hopefully it will be a useful discussion! We are joined by Daniel Lewis, a neurosurgical registrar who has kindly agreed to facilitate the discussion. I’m Angus Hotchkies, a 4th year based at Salford. Firstly if everyone wants to introduce themselves and include an email (so we can send certificates out later) that would be great!

We will make a start in a few minutes (just in case anyone is running a bit late!)

Sarah Michael 11/07 07:33PM

Sarah Michael, 3rd year at UHSM

Sianjuniper 11/07 07:33PM

Siân Juniper - 4th Year UHSM

Danni Wilkinson 11/07 07:34PM

Danni Wilkinson, 4th year at Salford

will_rey 11/07 07:34PM

Will Reynolds, 3rd year at Salford

Daniel Lewis 11/07 07:34PM

Hi Everyone

Mark Woodward 11/07 07:34PM

Mark Woodward 5th Year Preston

Bradley Storey 11/07 07:34PM

Bradley, final year SRFT

Americos 11/07 07:34PM

Amerikos Argyriou, 2nd Year

Angus Hotchkies 11/07 07:37PM

Great thanks guys - that looks like everyone. Shall we make a start? 

Sianjuniper 11/07 07:37PM

go for it

Daniel Lewis 11/07 07:38PM

What did you all think of the paper? 

sianjuniper 11/07 07:39PM

I liked it but it was very wordy. But I like orthopaedics and want to do this kind of thing one day so thought it was interesting

Angus Hotchkies 11/07 07:40PM

I enjoyed it! I thought it was interesting and highlighted the need for further research in tissue engineering

sianjuniper 11/07 07:40PM

kind of made me want to intercalate in that haha

Mark Woodward 11/07 07:40PM

Interesting. A lot of the data is from animal studies

will_rey 11/07 07:40PM

I feel that it was interesting as it showed that there is obvious potential but also it was also very aware of the short comings of its investigation

Daniel Lewis 11/07 07:41PM

ca

Can anyway summarise what question the review was trying to address? 

Angus Hotchkies 11/07 07:43PM

Whether TE / mesenchymal cells are a viable option to treat meniscal damage in the future?

Bradley Storey 11/07 07:43PM

based on current existing literature

Daniel Lewis 11/07 07:44PM

Yes I think so. The review was very much a descriptive overview of the field so far, and not a systematic review per se where a specific question is asked

sianjuniper 11/07 07:45PM

yeah i found it quite difficult to get through the description myself i found it really wordy

Americos 11/07 07:45PM

I thought as a general review of the current field in TE for meniscus repair it did a good job... it was a mouthful to read!

Sianjuniper 11/07 07:45PM

it also seemed to compare the benefit of different cell types as well

Daniel Lewis 11/07 07:46PM

What do you think of the included tables? Did they help your understanding of the field at all?

Bradley Storey 11/07 07:47PM

No

will_rey 11/07 07:48PM

I feel it was more just a way of sorting the references but gave you no real further understanding unless you went into the references themselves

Sarah Michael 11/07 07:48PM

no i found them confusing

sianjuniper 11/07 07:48PM

not really

Daniel Lewis 11/07 07:48PM

I'm inclined to agree, I thought they were pretty poor. What would have been nice is if they had put i not only references but also advantages/shortcomings of different techniques/ cell types

will_rey 11/07 07:50PM

It doesnt really show what the specific references actually added to their own paper

Americos 11/07 07:50PM

Would have been nice to have had a table/graph with the different types based on their advances and how close they all are to higher animal trials/human trials...

Daniel Lewis 11/07 07:51PM

Most of this review discusses the different results from different animal studies. Do you think they could have presented the different results from these different studies differently? 

Danni Wilkinson 11/07 07:51PM

Yeah I agree, I think the use of tables could have really helped the extensive results

Mark Woodward 11/07 07:53PM

A figure/ table summarising the results, categorising them into the different cell types and studies would be useful

Angus Hotchkies 11/07 07:53PM

Possibly, but it seems hard to display the different studies in a table as they all seem to have different outcome measures

Daniel Lewis 11/07 07:56PM

A better summarative table would be an option, but as you say some of the studies have different endpoints. A common theme though is the extent of regenerated tissue. Does anyone think they could have attempted a more quantitative comparison between different studies?

As in actually undertake a systematic review of whether stem cell implantation increases regenerated meniscal tissue in vivo animal models

sianjuniper 11/07 07:57PM

how would you go about doing a quantitive comparison?

oh i see 

will_rey 11/07 07:58PM

In some ways once again it might be difficult to compare as we are dealing with different animals who might have very different physiology in regard to their regeneration so would be difficult to compare. Is there the potential to chose something like a percentage change

Angus Hotchkies 11/07 07:59PM

If all the studies quantified, for example, the percentage of regenerated meniscal tissue then yes it would be good to compare. Is that the sort of thing they would include in all papers? I wouldn't know enough around the subject to be honest.

sianjuniper 11/07 07:59PM

I suppose you would have to take the results from studies that used the same animals or the same outcome measures

if that wasn't possible

Danni Wilkinson 11/07 07:59PM

Yeah grouping same animals makes sense

Daniel Lewis 11/07 08:00PM

As you've all hinted at, there are multiple problems here: different animals, different experimental setups, different cell numbers injected, different ways of measuring meniscal regeneration

sianjuniper 11/07 08:00PM

different cells used as well

so no i don't think i could do a systematic review!

will_rey 11/07 08:01PM

But when it comes to choosing a suitable animal it'd have to be something which is relatively suitable to humans for it to actually be of use

Daniel Lewis 11/07 08:01PM

One way round it is to group the studies based on similar animals/ similar experiment setup and then do a systematic review. there is another bigger problem here when trying to answer a question like that with animal data?

Sianjuniper 11/07 08:02PM

we don't know if it is possible in humans?

Bradley Storey 11/07 08:02PM

yeah surely its how relevant/similar it is

Daniel Lewis 11/07 08:03PM

True a lot of very promising animal data doesn't translate which is in part due to biological differences. Another issue though is that some animal studies are poorly/ not at all blinded and the negative results dont get published

There is a very strong literature bias especially ehen you look at older in vivo studies, people only publish positive results

Angus Hotchkies 11/07 08:06PM

Must be very hard to compare the studies then

Daniel Lewis 11/07 08:07PM

It is possible but be especially critical of animal data - is the investigator blinded, were the animals randomly allocated, how biologically relevant is the model?

The authors of this review have not done that. they have accepted everything at face value

What do we think of the human data presented?

Angus Hotchkies 11/07 08:11PM

So the one large study that's been done seems fairly promising? But I'm not really sure how relevant "meniscal volume gain" is when it comes to reporting good outcome measures

Danni Wilkinson 11/07 08:12PM

And the other studies seem to have really small numbers so unsure how reliable they are

Angus Hotchkies 11/07 08:12PM

The decrease in pain in OA patients with MSC injections also seems good but it's just a statement, no significance etc. presumably due to low numbers

Daniel Lewis 11/07 08:13PM

Good points. The use of single case reports in a review is justified if there is a paucity of human studies which is the case, but need to be interpreted with caution. The main evidence is the RCT

Did anyone read the RCT cited?

Bradley Storey 11/07 08:14PM

did we go to the paper itself to read it do you mean? I personally didn’t

Angus Hotchkies 11/07 08:15PM

I didn't look through it either

will_rey 11/07 08:15PM

It seems there are short term gains but not necessarily long term ones

Daniel Lewis 11/07 08:16PM

The difference between the control and treatment group pain scores is not significant at any timepoint (P>0.05)

Bradley Storey 11/07 08:17PM

yet they don't mention that in this paper

Daniel Lewis 11/07 08:17PM

They claim the difference is clinically significant but this is poorly justified, and there are potentially confounders such as 7 different surgeons at different institutions

Angus Hotchkies 11/07 08:18PM

so again I guess it's just indicating the need for more unified, specific studies to be carried out

Daniel Lewis 11/07 08:19PM

One of the authors of the RCT is also from the company that makes the tested stem cells

will_rey 11/07 08:20PM

Feels as if the paper is trying to push its own agenda a bit

sianjuniper 11/07 08:21PM

what type of bias is that dan?

Danni Wilkinson 11/07 08:21PM

Oh dear haha

Daniel Lewis 11/07 08:22PM

It would have been declared as a conflict of interest but these things are always worth looking at especially when other authors (this reviewer) start citing the results of key RCTs

Mark Woodward 11/07 08:23PM

In reality a systematic review is only as good as the studies it includes then?

Daniel Lewis 11/07 08:24PM

If there are multiple RCTs is is justified not to discuss the limitations of each in a review but in the case where there is one big study the limitations should have been highlighted

Exactly Mark, a systematic review is less vulnerable to poor studies than the descriptive review here but the best way to appraise the literature and remove the effects of poor studies is a meta analysis. Unfortunately to do that you need lots of RCTs, large human studies

Angus Hotchkies 11/07 08:26PM

So not a very useful paper in some ways - I know it might be out of their scope slightly but it might have been interesting see what other newer techniques are being used/developed to treat meniscal injury

Daniel Lewis 11/07 08:29PM

I think as a descriptive overview it is useful but there is a lack of critical appraisal of the literature in some areas. My overall impression was it had the feeling of someone's PhD literature review that has been condensed into a review paper

Mark Woodward 11/07 08:30PM

Yes or just a literature review presented like a systematic review

Daniel Lewis 11/07 08:34PM

You will often find that the last author on review papers is established in the field, and they're main purpose is to not only summarise but also highlight future research questions and directions. The key thing is to follow up on cited big papers, and appraise them yourself

Angus Hotchkies 11/07 08:34PM

Yeah overall it was really interesting to read for me anyway but looking in to it a bit harder it doesn't really have any useful conclusions other than "further research required"

Bradley Storey 11/07 08:35PM

agreed and as has been concluded doesn't feel like theres much relevance from it

Angus Hotchkies 11/07 08:41PM

Probably all I can say about the paper from my perspective!

Daniel Lewis 11/07 08:41PM

Here's a nice link on how to write a good review if anyone is interested https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715443/#__ffn_sectitle

Angus Hotchkies 11/07 08:41PM

Apologies on my behalf for it not having any more interesting stats!

Bradley Storey 11/07 08:42PM

Thank you

Daniel Lewis 11/07 08:42PM

I think it was very useful nonetheless, review papers are often the first thing you look at when you start researching a field

Mark Woodward 11/07 08:42PM

Thanks Daniel

will_rey 11/07 08:42PM

Thanks!

Sarah Michael 11/07 08:42PM

Thank you!

Angus Hotchkies 11/07 08:43PM

Thanks again Daniel, and thank you to everyone who came!

sianjuniper 11/07 08:43PM

thank you!

Americos 11/07 08:43PM

Thank you everyone

Daniel Lewis 11/07 08:44PM

Thank you all for your contributions , I will have to go but see you at the next one

Angus Hotchkies 11/07 08:44PM

I will email out certificates on Friday as I'm in Wigan at the moment so sorry about the delay!

sianjuniper 11/07 08:44PM

not good enough sorry

Angus Hotchkies 11/07 08:49PM

thanks everyone