Episode Transcript
[00:00:02] Speaker A: Welcome to your Cases on Hold, the JVGS podcast hosted by Andrew Schoenfeld and Aisha Adkeen.
[00:00:08] Speaker B: Here we discuss the best of what each issue of JBJS has to offer with the usual dose of entertainment and pop culture.
[00:00:16] Speaker A: Take us with you in the gym, on the commute, and as ever, whenever your case is on hold.
[00:00:25] Speaker B: Welcome back to another episode of youf Case Is on hold, episode number 104. If you're listening, on the day we drop, this is April 14th for the April 15th issue.
My name is Aisha Abdeen. I'm Chief of the Division of Hip and Knee Arthroplasty at Boston Medical center and Associate professor of Orthopedic Surgery at Boston University. And I have with me my co
[00:00:47] Speaker A: host hello Andrew Schoenfeld, professor of Orthopedic Surgery at Harvard Medical School and Vice Chair for Education at Mass General Brigham.
[00:00:58] Speaker B: As a reminder, the opinions expressed here are exclusively our own and do not represent those of jbjs, the Editorial Board and the Board of Directors, nor the affiliate journals of jbjs.
In this episode of youf Cases on Hold is brought to you by the Miller Review Course, an unmatched ABOS Exam prep experience led by dedicated faculty with mock exam and one on one session prep for the ABOS Oral Exam Part two coming up in May through July and in a couple of months. So get ready to get prepped and crush part two of your boards.
So without any further delay, I'm going to get to the top of the pile.
We have what's New in Biologics by Chu. This is Permanently Free Surgical Robotic System for Precision Femoral Fracture Reduction by Rezipur and Shafi.
Learning from Surgical Failures by Menendez. And this is a highlight at Two Tables by Noland. Permanently free.
You can be reminded of the profound humanity in our specialty in this piece by Anand entitled Where the Scalpel Can't Reach. This is by Anand and it's permanently free.
Then we have a legacy piece on the Vancouver Classification for periprosthetic fractures written by the original authors of the classification entitled Fractures of the Femur after Hip Joint Replacement. The Vancouver classification after 30 years by Duncan. It's the lead article. There is a commentary and it's permanently free.
We have the association between Perioperative Denosumab and Local Recurrence after Surgical Management of Giant Cell Tumors, A meta analysis by Daher. This is a highlight and there's 30 days free.
In this issue of JBJS we pay tribute to a giant in orthopedics in memorandum to Dr. Kenneth Krakow, 1944-2026, whose legacy will endure. Dr. Krakow is known worldwide for his tremendous contributions and numerous publications that have influenced how we think about surgical technique and arthropl.
Dr. Krakow has become a household name in orthopedics, in orthopedic training and practice. I challenge you to go more than a day or a week without using one of his eponyms, be it the Krakow suture or the Krakow Hungerford classification of the valgus knee or the lesser known but oft used Krakow maneuver for placing a tourniquet on a patient with obesity. Look it up. Published in core circa 1982. It's a technique that I continue to use to this day. We thank Dr. Krakow for his incredible, wide reaching contributions to our field.
This is an obituary and it's permanently free.
Now we'll get to our headlines, starting with the first paper which will be presented by Dr. Schoenfeld entitled Sustained improvement in Pain with Taylor Osteoperiostic Grafting from the Iliac Crest, also known as topic for Medial Osteochondral Lesions of the talus. A concise 5 year follow up of a previous report by Hollander. There is a commentary and infographic and it is permanently free.
[00:03:49] Speaker A: Yes. So this is a, as it says, five year follow up of a series of patients by the team at University of Amsterdam and Dr. Kirchhoffs is the senior author.
He did come and speak as a grand round speaker recently and I had the opportunity to, you know, hear a retrospective of his holistic, the holistic work that he's been doing over time in this area.
So this is, as I mentioned, a five year follow up of a previous series of patients. It's always nice to get these. I think you have to appreciate these for what they are.
And a lot of times when you're getting these follow ups, they're either an extended follow up on a randomized controlled trial or a sustained follow up, as in this case, for a prospective series of patients.
And these are very difficult to do, as any of us who are in practice are. It's very easy to lose track of patients after a surgery or some other treatment that you might administer to them. They get better, they don't come back.
There's a significant amount of effort exerted by these teams to keep these patients engaged, to have them come in or to be in touch with them by whatever means to complete assessments and patient reported outcome measures, et cetera.
So for those who may not be familiar with the initial paper, the talar osteoperiostatic grafting from the iliac crest is a technique that they first described that uses osteoperiosteal autograph from the ipsilateral iliac crest, including the overlying periosteal layer. And the authors maintain that the curvature of the iliac crest matches the curvature of the talar surface to address defects. And then the periosteum might further provide additional benefit as the cambium layer they postulate, has chondrogenic potential.
Fun fact. I actually have a publication in the foot and ankle literature. Actually, I have two publications, one in JBJS on certain grafting for osteochondral lesions. But the one that I was thinking of that reminded me of this was use of fresh frozen cadaveric osteochondral graft for the treatment of giant cell tumor of the talus.
And that was. That was, like, published 20 years ago, which is crazy, because I don't feel that old. But guess what?
[00:06:20] Speaker B: You decided to go into spine surgery.
[00:06:22] Speaker A: I'm that old. No, I think I had already. I was just. I was just, you know, an academic person at heart who is like, this is a fascinating thing. And I was still a resident. And I was like, we should write this up. And they were like, if you want to write it up, go for it.
You don't have to tell me twice.
[00:06:38] Speaker B: Very cool.
[00:06:39] Speaker A: Yeah, so. So I, you know, I felt like this. This was a personally meaningful study for me. I could relate to this, to this project.
And so, again, you know, within the parameters of what this is, it's a relatively small series of patients. It's essentially, at this point, we normally say a rote clinical retrospective. And I don't want people to conflate retrospective study design and the statement rote clinical retrospective, because what it essentially, in this sense of a rote clinical retrospective we're just talking about, the authors are giving their perspective on their experience.
In this case, they've been able to follow patients for an extended period of time, which is a value add. They had 37 patients included, though, so, I mean, it's not a tremendous number of individuals. The median NRS score for pain during walking improved from 7 preoperatively to 2 at 5 years, with mutually exclusive interquartile range. And this also surpasses the minimal clinically important difference for this outcome. All their graphs showed incorporation, but the vast majority, 87%, who had CT imaging at five years demonstrated evidence of cyst formation.
And the authors don't quite know what to make of this, which I thought was interesting unto itself, you know, they say that recent systematic reviews did not identify a relationship between cyst formation and clinical symptoms. Cysts and clinical failure has not been conclusively established as those two parameters being linked. So they say cyst development is not currently considered failure, but it remains under investigation and potentially cyst becomes symptomatic over the long term and thus they say we need longer follow up, of course. But when it's like close to 90% of your patients have cysts and it seems like they don't quite know what to make of this. If they say, like I don't love the sound of.
Cyst development is not currently considered failure.
[00:08:43] Speaker B: Right.
[00:08:45] Speaker A: That seems like quite a big caveat. Like, so it could become failure later, like, and then 90% of your patients have failed. I don't know.
That was the first kind of false note in this that just left me sort of.
All right, so they're doing okay now. Now these are challenging conditions to treat, of course, and you know, if it's part of just you're, you're saving somebody from having a total ankle at a younger age where then they're going to have complications or need to go to a fusion and maybe in the long term you avoid. And I'm just, I'm just sort of postulate. These are all just my kind of thoughts on it. Not necessarily that this is a cogent, established cascade, but I could see you're doing this to delay to something else, even if you know that in the end it's not really going to work out.
[00:09:39] Speaker B: I think they were being very honest.
You could have these asymptomatic cysts. We don't know the meaning of them. They're present, we're reporting on it. But our definition of failure was arthrodesis and it happened in a low number, like 5%, I think, of patients. So I think it's conceivable. But yeah, jury's out on what those cysts mean.
[00:09:56] Speaker A: Yeah. Also their cases of failure were not included in the five year outcome and they have a number of reasons for that.
Another thing that I think again, it's 37 patients, but when you start talking about, you know, complications, there's only a 3% complication rate and no patients reported issues suggesting donor site morbidity. Now, as somebody who works in the spine space and you know, iliac crest bone grafting and harvesting is a regular part of many individuals practice less, less and less these days, but certainly have seen it enough.
Nobody had iliac crest Bone graft, donor site morbidity is just like do it in, do it in some more people.
[00:10:39] Speaker B: Yes, exactly. That was hard to believe.
[00:10:42] Speaker A: Yeah. So, I mean, nothing to put on hold here. I think it, it is useful to have these types of follow ups. I had a colleague who said nothing dampens the enthusiasm for surgery as much as long term follow up.
[00:10:56] Speaker B: And, and that, that, the truth that
[00:10:58] Speaker A: may, that may play out in this context. Yeah, I think, I think, you know, for you in joints and me and spine, I like the idea of one surgery for one problem and then the ideal is that you're done.
And when they have this, you know, kind of sort of Damocles where it's like 87% have the cysts and well, maybe in another five years they've all failed or something, you know, I guess. Stay tuned. It's a real cliffhanger, you know, like 1930s radio serial fash.
The damsel is tied on the train tracks and the train is coming.
[00:11:32] Speaker B: What's going to happen?
[00:11:33] Speaker A: Call back in five years.
[00:11:37] Speaker B: Yeah, I thought it was a well conducted study. I was a little curious.
The cohort was all young patients and they all had BMI between 26 and 30. So I'm wondering, is this applicable in heavier patients or older patients? They also included smokers. And I'm wondering what was the spread on the failures? Were a lot of that 5% that went on to arthrodesis, were those mostly in smokers?
Some guidance on that. So I think there'll be more to tell when these are the experts who designed this particular technique. When others start publishing on this, you know, what is the results? Can they match the results that these authors had?
So again, more to come.
[00:12:15] Speaker A: Absolutely.
[00:12:17] Speaker B: Okay, so the next paper, this is Clinical outcomes of Pyrocarbon Hemiarthroplasty, a short term multicenter study by Hatsideikis and associates. There is a commentary and a visual summary.
This was an industry sponsored multicenter study by Stryker conducted in 18 US centers to evaluate the short term outcomes of their pyrocarbon shoulder hemiarthroplasty implant. The clinical context of this paper is the issue of shoulder arthroplasty in younger active patients in whom total shoulder replacement is not the optimal solution due to accelerated polyethylene glenoid failure. While hemiarthroplasty remains a favorable option, there are potential issues of pain and erosion at the native glenoid secondary to friction between cobalt chromium humeral head against the glenoid due to inelasticity of the cobalt chromium. One solution to this that the authors propose could be pyrocarbon, a ceramic like carbon material with a lower coefficient of friction than cobalt chrome which when coated with a graphite substrate has a Young's modulus of elasticity similar to bone.
Prior data has shown reduced revision rate after pyrocarbon hemiarthroplasty. The authors aim to evaluate short term results of the Tornier pyrocarbon with the Tornier Flex stem from Stryker compared to a historical control group of patients with hemiary arthroplasty performed with cobalt chromium heads. It was a prospective single arm study with a US FDA approved investigational device exemption. There were 190 subjects 33 of these did not meet screening criteria so this left 157 patients. Majority were men. The patients had surgery between 2015 and 2017. The implant had three parts. It was a solid pyrocarbon humeral head that was factory assembled onto a cobalt chromium double tape taper neck which was impacted onto a short titanium humeral stem.
The historical control was the cobalt chrome group was identified in a database of patients who underwent cobalt chromium hemiarthroplasty using the Tornier Flex or the Equalis by Stryker between 2003 and 2014 and they agreed to participate in the Tornier Post market outcomes registry. Patients were identified from this database through a propensity score subclassification to compare outcomes with the study. Cohort of patients with pyrocarbon hemiarthroplasty.
Indications included primary glenohumeral osteoarthritis, osteonecrosis or post traumatic arthritis in the order of most common to least common in both cohorts. Covariates used in the propensity score classification were age, sex, bmi, indication for surgery, dexterity and laterality and the outcomes included the constant activity and pain scores, baseline adjusted constant score, size of the hospital in which the surgery took place and whether the clinical setting was private or academic.
The statistical analysis was performed by an outside blinded consulting group to maintain the largest possible pyrocarbon HA cohort size and therefore statistical power. They performed iterative trimming of the control cohort which was implemented rather than a one to one propensity score matching process. The covariate balancing within sub classes was addressed and pool standardized mean difference of less than 0.1 was considered evidence of covariate balance. Iterative trimming of control subjects who fell outside the established standardized mean difference was repeated until a propensity score subclass was balanced and achieved and this left 169 control subjects.
The primary outcome measure was composite clinical success or CCS rate which they define as a greater than or equal to 17 point increase in the constant score, no revision or reoperation or device related adverse event and no implant failure or dissociation.
Of the 157 patients in the pyroparping group, 10 were excluded due to loss to follow up and one was excluded from missing baseline data.
They used a tipping point analysis to assess the robustness of the missing data. Assumptions the surgical technique was described. The treatment of the glenoid varied depending on the amount of wear and technique was dependent on the surgeon preference and not specifically based on the classification of wear. In the description of the surgical technique the authors indicated that posteriorly eroded glenoids were left untreated or were reshaped with a bur or reamer according to the surgeon discretion in order to remove the central ridge at the junction between the neoglenoid and the paleoglenoid. I was fascinated by the word paleoglenoid which translate as old or ancient glenoid. It turns out the Walt classification glenoid based on erosion and morphology of the glenoid. The authors made reference to this classification later in the paper but as a non shoulder surgeon I had to look it up here. Type A demonstrates concentric wear, B is asymmetric wear with posterior wear in a concave glenoid and type C dysplastic with retroversion and D is anteverted glenoid.
The type B biconcave glenoids are further classified as having two articular facets, the posterior neoglenoid which represents the region of new glenohumeral contact and the anterior paleoglenoid, the remaining anterior native glenoid articular surface. After describing their surgical technique, the authors describe their post op regimen and then they give the outcome measures of the study which were quite extensive. The PROMS included the adjusted constant store, the American Shoulder and Elbow Surgeon's ases score, the VAs for pain, single assessment, numeric evaluation or the SANE score and the EQ5D.
Clinical outcomes included the constant strength score, active range of Motion, adjusted constant and ASES scores. These outcome measures were all evaluated using the Walch glenoid classification and glenoid treatment method. Patients were stratified into noneroded or centrally eroded glenoids and the results were compared by comparing those who underwent glenoid reaming to those who did not undergo glenoid reaming and again that was just based on surgeon preference, not based on classification.
Adverse events and revisions were recorded through the study period when the first implant was performed in December 2015 through the study end date on July 2019 for 43 months.
X rays were taken and the two board certified radiologists were used to assess Walsh classification.
Descriptive stats were evaluated and linear regression was performed to evaluate it. If Walch glenoid type or treatment of the glenoid was predictive of constant or ASES scores and a survival analysis was performed.
So as mentioned 10 patients were lost to follow up. They had 144 in the study cohort. The mean age of patients was 52 years ranging from 17 sorry 19 to 73 years of age and mean follow up duration was 24.4 months with a range of 22 to 32 months. There were significant improvements from baseline to short term follow up. The largest increase in constant and ASES scores occurred in patients with Walsh Type A2 and B2 Glenoids and A slightly greater increases in ASES scores in patients with osteonecrosis and post traumatic arthritis.
They found that patients who underwent glenoid reaming had the lowest mean improvement in constant and ASDS scores compared to other glenoid treatments. The greatest difference in constant scores was comparing reaming with drilling and or microfracture in favor of the latter. The differences in scores was also significant when comparing reaming with glenoidplasty or with or without drilling or microfacture and the authors describe the historical control with propensity score analysis.
So there are some stylistic things about this paper. I would have liked the authors to have developed the background a little bit more to discuss the current use of the specific implant. They gave a bit of background on pyrocarbon heads but it wasn't apparent that this was an investigation device until they mentioned it sort of as an afterthought in the methods. Also, a little bit more background on the current indications for treatment of the glenoid and classification would have been helpful.
I think the main limitations of the study is the temporal bias in the pyrocarbon group and the cobalt chromium group. The study arm had surgery between 2015 and 2017 whereas the controls included patients that had surgery more than a decade, almost a decade and a half earlier than the study patients from 2003 to 2014. I think this could lead to many confounders as to why the clinical outcome scores were superior including evolution of post op care, differences in soft tissue handling, surgical technique, patient optimization and a whole host of other things that could make these two cohorts very different. The authors included a very complex way of managing substantial missing data for which controls seemed like they had a lot of effort just to really cover the fact that the two groups were not comparable and the data was just not there to compare for all these outcome measures. This reminds me of a really elegant analogy, Andrew, you made many moons ago on this podcast of a Potemkin village where Grigori Potemkin created these fake villages in Crimea to show Catherine the Great on her trip. There's, you know, bringing these housing facades and livestock and happy, you know, healthy citizens to make it look like there was a thriving village, when in fact there was not. I think same sort of thing here. The authors did a lot of work to sort of statistically maneuver the data set when in fact there just wasn't enough data to compare the two groups. I think they did a lot, but they could have just simply kept this as a one armed study and reported on the results of this new implant.
So I'd be interested to hear your thoughts, Andrew.
[00:21:04] Speaker A: I love that you brought in the Potemkit village. That's so great.
People will say that I'm a cynic at heart, which is fine, it's a reasonable charge. But I, I always get suspicious when I mean, of course, you know, there can be industry funding. That's a reality. And, and, and I've done industry funded research as well. So I mean, I'm not, I'm not casting aspersions, I'm. But when the primary affiliations of authors is the company, that, that really is kind of a flag for me. Not, you know, they're, they should be transparent. They're being transparent. But at the same time, I think that should give everyone kind of pause. And I think that the points that you raised are exactly the ones that, that I would bring up in going through this.
I felt they should probably have just done, you know, in the background. They say that this is a prospective single arm multi center study, but actually that's not it. It wasn't a prospective single arm multicenter study. What they actually did was they tried to do a, what I would characterize as a retrospective causal inference study using propensity score. They have some perspective data, they have a lot of retrospective data which isn't clean and is prone to confounding from secular trends, just as you said. So I won't belabor that point. But it's a very messy control cohort, if you could even characterize it as a control cohort. And they, they didn't Treat it in a straight up fashion. They do a lot of, you know, they if you.
So the first thing, I want to take one step back. The first thing for the edification of our listeners, the ideal propensity score setting.
You can't just go ahead and do propensity score whenever you feel like it. For it to really work in a causal inference sense, the controls and the cases should have had the opportunity to have the whichever procedure it was that they got.
So you want ostensibly equal access to the procedure, you want adequate representation across the spectrum of disease, and you want comparable temporal assessments and outcome measures.
This study, I would say, probably doesn't have any of those things.
Maybe you can argue about the spectrum of disease. I'm not entirely sure about that one. But definitely they didn't have comparable access to the procedures. One was done in an intentional way with industry funding. And there's much higher potential for, we would say selection or you know, you're really careful about which patients you're going to include versus who gets the hemi arthroplasty, let alone the fact that there's such a difference in the time window over which things were collected and they could have accounted for the time of surgery in there.
Adjusted analyses. That's not ideal, but it would been something that they could have done further.
So I think that if you want to just look at this as similar to what we talked about with the topic trial, a clinical retrospective of this multicenter experience with the pyrocarbon hemiarthroplasty. I think that's fine. To say it's anything more than that or to sort of really hang your hat on a causal inference analysis of sorts. I think that part needs to go on hold for me.
[00:24:34] Speaker B: Agree.
Okay, so moving on to our featurette. Your case is on hold.
We have a paper entitled low cognitive function and somatic psychological symptoms are correlated with a greater risk of delirium and after total knee arthroplasty. A prospective cohort study by Lee There is a commentary. I actually wrote this commentary infographic and it's 30 days free.
This was a prospective cohort to evaluate the correlation of preoperative cognitive and psychological factors with post op delirium after total knee arthroplasty. Post op delirium after total joint arthroplasty is reported at 0 to 7.1% of patients after hip or knee arthroplasty and is associated with significant morbidity, length of stay and cost.
This study included 574 patients ages 60 and older who underwent primary total knee arthroplasty at two major tertiary care centers in Korea. Patients were excluded if they had a diagnosis of dementia. Patients underwent testing one day prior to surgery, including cognitive evaluation with the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease, also known as CIRAD C E R AAD Neuropsychological Battery, which comprises nine tests including J1 for verbal fluency, J2 the Boston Naming Test, J3 the Mini Mental Status Examination, J4 Word List Learning, J5 Constructional Praxis, J6 Wordless Recall, J7 Wordless Recognition, J8 Constructional Practice Recall, and J9 Trail Making Test Parts A and B so very complex psychological testing. Preoperatively, the Cirret Total 2 score was calculated by summing the J1, J2, J4, 5, 6, 7, and 8 scores. Subjective cognitive symptoms were assessed through the Subjective Memory Complaints Questionnaire and the Caregiver Reported cognitive decline was evaluated by the Sole Informant Report Questionnaire for Dementia Psychological and Somatic Symptom Assessments including the Hospital Anxiety and Depression Scale or the HADS Scale to evaluate anxiety and depressive symptoms, the Pittsburgh Sleep Quality Index Global Score, which is the sum of seven component scores to assess overall sleep quality and the Patient Health Questionnaire 15 PHQ 15 to gauge the burden of somatic symptoms. Preoperative pain intensity was assessed during the Numeric Rating Scale or the nrs.
Demographic and clinical data included age, body mass index, sex, history of delirium, comorbidities, and the Charleston Comorbidity Index. Cci.
The use of glasses or hearing aids was documented. Socioeconomic factors including educational level, employment status, medical coverage type, marital and parental status, history of alcohol use and history of smoking were documented. Lab tests including bun, creatinine, gfr, albumin, sodium, potassium, erythrocyte, sedimentation rate, and CRP were taken and use of preoperative medications including opioids, sedatives, antidepressants, antipsychotics, antiepileptics, and cholinergic agents were also documented.
Regarding environmental conditions, noise levels were measured before and after the preoperative interview and the mean of these levels were used for analysis. A sound level meter was placed 1 meter from the patient's bed and recorded noise in decibels and illuminance or lux levels in the patient's hospital room and bed position relative to the window were recorded, so a lot of detail they were getting in this preoperative assessment.
Surgical protocols were standardized for anesthetic type and post op pain management. Post op evaluations were conducted daily from postoperative days one through five, so the patients were inpatient during that time by trained research evaluators. All patients were screened using two standardized tools, the 4A test and the CONFUSION assessment or CAM score.
Post operative delirium was defined as a CAM positive result.
The delirium rating scale revised 98 was administered to patients who scored positive on the 4 at but did not meet camera criteria. In order to identify sub syndromal delirium, the cohort developed delirium in 4.2% of cases. Most of these occurred on post op day one and certainly by post op day zero and day one rather and the third score total score was not statistically different between patients with and without delirium. However, the mini mental status domain did reveal a significant difference. Logistic regression analysis revealed that after adjusting for age, bmi, Charleston Comorbidity Index, noise level and pain, both MSE or the MINI mental and the PHQ15 were significant predictors of post op delirium.
PSQI did not reach significance.
Other associated factors included preoperative use of sedatives and antidepressants and somewhat unexpectedly, patients with postdoc delirium were exposed to lower in hospital noise rates rather compared to those without delirium. However, after adjustment for covariates, noise level was not found to be independently associated with post op delirium.
So in summary, I thought this was a very meaningful study. It's one that we could not have performed very easily. Here in the US patients were admitted pre op one day and were kept for five days postoperatively. Whereas here in the US most patients are either discharged same day or within 23 hours of observation after total knee arthroplasty. At first glance I thought well maybe that's what contributed to their delirium. As we all know that being in an unfamiliar environment and being hospitalized can increase delirium risk. However, all cases of delirium happened on day zero or day one.
So I entitled the commentary for this paper Keeping it simple the Mini Mental and The Patient Health Questionnaire 15 Outperformance Complex Psychiatric assessments as a predictor of postoperative delirium following total knee arthroplasty. Sort of channeling the Keep it simple stupid series of how to books because they did such a complicated testing to find it. Only the sort of the Mini Mental and the PHQ were predictive of post operative delirium. But I think it's a study that had to be done. They conducted it in a very methodologically sound way and I think this case is not on hold.
[00:30:44] Speaker A: Yes, really well done study.
Normally we say when there's a comment you don't have to take it from us, you can read the comment. But this case they have to take it from you one way or the other.
This is an area that is of particular clinical and research interest for me. I have published on delirium after spine surgery as a secondary complication or downstream event for patients of more advanced age.
Then also Antonia Chen and I have participated in the DECADE study which was an NIH funded study that was looking at outcomes for patients with cognitive impairment following a number of different surgeries. One of Those of which Dr. Chen was not the co author, was published in JBGS on odontoid fractures. The one where Dr. Chen and I were both co authors was on total knee arthroplasty and that was not published in jbjs. But we were not looking at delirium was a particular outcome, but we were not specifically looking at delirium. We were looking at a broader kind of battery of outcomes. And these are elective procedures and patients who have cognitive dysfunction or cognitive impairment. You may be setting them up for a really bad experience.
And there were non negligible numbers of individual in both of our elective arms, the total knee and we also had a lumbar fusion arm where these patients were ending up in hospice with trachs and pegs. And so I applaud these authors for highlighting the importance of doing these studies because a lot of that pre surgical cognitive impairment is unrecognized for many. It may be subclinical and then it comes out after the fact. And you know, to your point, we are trying to get grant funding for a prospective study to expand on that decade's work which was done retrospectively.
We're in the process of seeing if we can obtain grant funding for multi center study between UT Southwestern and our facilities here in Boston to look at this in a prospective way after total knees and elective spine surgery specific to this study. Just a few points of edification from the method standpoint for the interested reader and learner. The first thing is that While they had 574 patients, they actually had a very low number involved with the incidence of POD for which there was just 24 patients for 4%. And with that 24 patients, you can't really do a whole lot. They're trying to look at risk factors. They use an exploratory approach and one that we would not endorse as providing actionable information. So a caution there. You know, they they made a bunch of what they call univariate but really bivariate comparisons and then based on performance they put that in a multivariable analysis with just 24 patients with the outcome, you don't really have enough even for a meaningful bivariate comparison. You should really have 20 patients with the outcome of interest per variable that you're trying to include for conservative models.
So they just don't really have enough to meaningfully speak to risk factors. By and large, I think it's that doesn't necessarily detract from the work itself. I think it's just important for people to realize who are trying to use this to model and inform how they're going to conduct studies. And then also recognizing that I would characterize this as while it is level two, it's exploratory in terms of its outlook.
[00:34:22] Speaker B: Yep.
Yeah, I appreciate your insight as our stats guru. That's very helpful.
Moving on to our honorable mentions, we have Transthyretin amyloid Maidri fibrosis and proliferation of tenosynovial fibroblasts in carpal tunnel syndrome by Yamanaka and Associates. This is a basic Science investigation. The phenomenon that trans thyritic amyloid deposition in the tenosynovium in carpal tunnel syndrome is a potential early manifestation of systemic amyloidosis. The effect on tenosynovial fibroblasts and carpal tunnel syndrome remain unclear. The authors aimed to clarify how specific TTR amyloids affect tenosynovial fibroblasts and CTs.
Synovial tissue from 20 patients undergoing carpal tunnel release was evaluated for TTR. Amyloid expressions of genes related to fibrosis, inflammation and oxidative stress were compared between TTR positive and TTR negative groups. Fibroblasts isolated from TTR negative patients were treated with in vitro wild type or Val30 Met mutant recombinant TTR and analyses included quantitative RT, PCR, pyrocereous red staining, MTT assay evaluating cell proliferation, reactive oxygen species or ROS activity measurements and senescence related gene expression.
Their findings were that in TTR positive tissue fibrosis related genes including COL1A1, COL3A1, TGFB1 and ACTA2. The inflammatory mediator TNFKB1 and oxidative stress related genes were significantly upregulated whereas SOD2 was downregulated with in vitro treatment. In the TTR negative group, both wild type and val 30 MET TTR increased col3a1, Illinois 6 and cxcla8. That's a mouthful expression. Whereas val 30 MET TTR further enhanced il1b expression. Picocerus red staining confirmed increased collagen deposition. MTT assays revealed increased cell viability, indicating enhanced fibroblast proliferation in both groups. The senescence related gene CDKN2D and GAD D45A were downregulated, suggesting enhanced proliferative activity. Reactive oxygen species activity did not differ significantly between groups. The authors conclude that TTR amyloid was found to promote expression of fibrosis inflammation and oxidative stress related genes, inhibit senescence pathways, and enhance collagen deposition and fibroblast proliferation in fibroblasts from patients with CTs.
And there you have it folks, our April 15th edition or issue of JBJS.
And that concludes our episode for today. We will see you for our next episode of your case is on hold.
