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
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
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
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
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
Angus Hotchkies 11/07 08:41PM
Apologies on my behalf for it not having any more interesting stats!
Bradley Storey 11/07 08:42PM
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
will_rey 11/07 08:42PM
Sarah Michael 11/07 08:42PM
Angus Hotchkies 11/07 08:43PM
Thanks again Daniel, and thank you to everyone who came!
sianjuniper 11/07 08:43PM
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