We read with great interest the recent paper by Vargas, et al. describing a novel beveled tip aspiration catheter with improved recanalization and patient outcome compared to conventional non-beveled tip catheters in a single-center retrospective study.[1] We want to express our sincere congratulations to the authors on this finding but also want to respectively present our disagreement on the mechanisms explaining the improved performance of the beveled tip catheter as compared to standard catheters.
The authors conclude that a primary reason for higher rate of complete clot ingestion for the beveled tip catheter relates to the area of the catheter tip. It is widely accepted that ingestion force predicts recanalization efficacy, and this force is proportional to tip area (A) and pressure drop (P). The authors note that the beveled tip leads to an ovalized tip area with a total tip area that is approximately 15% larger than a catheter with an equivalent inner diameter but standard non-beveled tip. They then propose that this 15% increase in tip area leads to a corresponding increase of ingestion force, using the standard F=A*P equation. However, this proposition is flawed. While it is true the total force is larger for the beveled tip catheter than a standard catheter, this total force includes two separate force components that are orthogonal to each other, including the ingestion force component (along the catheter’s length) that corks or ingests the clot and...
We read with great interest the recent paper by Vargas, et al. describing a novel beveled tip aspiration catheter with improved recanalization and patient outcome compared to conventional non-beveled tip catheters in a single-center retrospective study.[1] We want to express our sincere congratulations to the authors on this finding but also want to respectively present our disagreement on the mechanisms explaining the improved performance of the beveled tip catheter as compared to standard catheters.
The authors conclude that a primary reason for higher rate of complete clot ingestion for the beveled tip catheter relates to the area of the catheter tip. It is widely accepted that ingestion force predicts recanalization efficacy, and this force is proportional to tip area (A) and pressure drop (P). The authors note that the beveled tip leads to an ovalized tip area with a total tip area that is approximately 15% larger than a catheter with an equivalent inner diameter but standard non-beveled tip. They then propose that this 15% increase in tip area leads to a corresponding increase of ingestion force, using the standard F=A*P equation. However, this proposition is flawed. While it is true the total force is larger for the beveled tip catheter than a standard catheter, this total force includes two separate force components that are orthogonal to each other, including the ingestion force component (along the catheter’s length) that corks or ingests the clot and a perpendicular force directed against the catheter wall, which does not affect ingestion. In fact, the ingestion force is exactly the same between the beveled catheter and standard tip catheters, and is calculated as A*P, where A is simply the area of the ID of the catheter, as with standard catheters.
We think several other possible mechanisms underlie the improved recanalization outcome with the beveled tip catheter as compared to standard catheters. First, as the authors addressed in the discussion, the beveled tip enables better alignment of the catheter’s main axis and the ingestion force to the clot’s main axis , which allows a larger force transmitted to the clot than those with standard catheters.[2] Second, the bevel could partially separate the clot from the vessel wall, reducing the friction and enabling easier clot ingestion. Third, in the cases of the beveled tip advanced to be flush with the clot face, the space between the bevel tip and the bevel base can enable non-contact aspiration,[3] where the clot ingestion is enhanced by the retrograde aspiration blood flow. In comparison, for contact aspiration with standard catheters, the clot blocks the entire catheter tip and no retrograde flow will be created to facilitate clot ingestion.
Overall, the clinical results are very encouraging, and we hope our comments can benefit our community to achieve a more comprehensive understanding of the action mechanism of the beveled tip catheter in our community. Additional mechanistic study is warranted.
References
1. Vargas J, Blalock J, Venkatraman A, et al. Efficacy of beveled tip aspiration catheter in mechanical thrombectomy for acute ischemic stroke. J Neurointerv Surg. Published online 2020:1-5.
2. Bernava G, Rosi A, Boto J, et al. Direct thromboaspiration efficacy for mechanical thrombectomy is related to the angle of interaction between the aspiration catheter and the clot. J Neurointerv Surg. 2020;12(4):396-400.
3. Haussen DC, Bouslama M, Grossberg JA, Nogueira RG. Remote aspiration thrombectomy in large vessel acute ischemic stroke. J Neurointerv Surg. 2017;9(3):250-252.
We congratulate Drs. Srivatsan and colleagues on their paper examining the effects of endovascular coiling of unruptured intracranial aneurysms (UIAs) on cognition using the Montreal Cognitive Assessment (MoCA).1 In particular, we appreciate the efforts made to sample the patients at multiple time points including pre-intervention and at 1-month and 6-months post-intervention. The study found that coiling did not diminish neurocognitive function per the MoCA, with there also being no correlation between follow-up MoCA scores and imaging findings, the overall results being comparable to the authors’ previous paper on MoCA scores following flow diversion for UIAs.2 Intriguingly, the MoCA scores at baseline were on average below the typical cut-off of 26 points, especially given the relatively young population (mean age 55.5 years).
However, as acknowledged by the authors, the ability of the study to discern post-coiling imaging changes was limited by both the small subset of the population that received follow-up imaging (17 of 33 patients, 51.5%) and the smaller subset that underwent MRI (9 patients, 27.3%).1 Diffusion-weighted imaging (DWI) sequences of MRI are most sensitive to identifying post-procedural ischemic injury following neuro-interventional procedures like coiling.3 DWI lesions occur quite frequently; for example, in the ENACT trial (Evaluating Neuroprotection in Aneurysm Coiling Therapy), 68% of patients had new lesions post-procedure, with an average o...
We congratulate Drs. Srivatsan and colleagues on their paper examining the effects of endovascular coiling of unruptured intracranial aneurysms (UIAs) on cognition using the Montreal Cognitive Assessment (MoCA).1 In particular, we appreciate the efforts made to sample the patients at multiple time points including pre-intervention and at 1-month and 6-months post-intervention. The study found that coiling did not diminish neurocognitive function per the MoCA, with there also being no correlation between follow-up MoCA scores and imaging findings, the overall results being comparable to the authors’ previous paper on MoCA scores following flow diversion for UIAs.2 Intriguingly, the MoCA scores at baseline were on average below the typical cut-off of 26 points, especially given the relatively young population (mean age 55.5 years).
However, as acknowledged by the authors, the ability of the study to discern post-coiling imaging changes was limited by both the small subset of the population that received follow-up imaging (17 of 33 patients, 51.5%) and the smaller subset that underwent MRI (9 patients, 27.3%).1 Diffusion-weighted imaging (DWI) sequences of MRI are most sensitive to identifying post-procedural ischemic injury following neuro-interventional procedures like coiling.3 DWI lesions occur quite frequently; for example, in the ENACT trial (Evaluating Neuroprotection in Aneurysm Coiling Therapy), 68% of patients had new lesions post-procedure, with an average of 4.3 new lesions in the NA-1 arm and 6.7 lesions in the placebo arm when considering just the 147 patients with UIAs.4 Future studies will need to examine the relationship between the burden of such DWI lesions and post-procedural cognitive outcomes in further detail.
Furthermore, although the MoCA is a useful global assessment of cognitive impairment, we suspect that it may have more limited sensitivity in identifying mild post-procedural cognitive changes. As the studies by Drs. Strivatsan and colleagues with post-coiling and post-flow-diversion outcomes have shown, any potential changes are likely to be subtle. As we seek to uncover the phenotype of potential cognitive deficits after endovascular procedures for UIAs, we may seek guidance from the existing literature on vascular cognitive impairment (VCI), which is known to have a preponderance of executive dysfunction, including slowed information processing, impaired set-/task-shifting, and deficits in working memory.5 6 To help assess such domains with greater granularity, the National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) have proposed cognitive testing protocols as part of the NINDS-CSN VCI Harmonization Standards.7 Of the 5-minute, 30-minute, and 60-minute protocols proposed, the 30-minute test protocol (applied in the ENACT trial)4 appears to offer a helpful balance of length and granularity, with specific measures of the aforementioned domains like the Controlled Oral Word Association Test (COWAT – phonemic fluency), semantic fluency, Digit Symbol-Coding, the Hopkins Verbal Learning Test (HVLT), the Trail Making Test, as well as brief assessments of neuropsychiatric symptoms through the Center for Epidemiologic Studies – Depression (CES-D) scale and the Neuropsychiatric Inventory, Questionnaire Version (NPI-Q).7 Future studies of post-procedural cognitive changes should seek to incorporate some or all of these additional tests into their follow-up testing protocols.
References
1. Srivatsan A, Mohanty A, Saleem Y, et al. Cognitive outcomes after unruptured intracranial aneurysm treatment with endovascular coiling. J Neurointerv Surg 2020 doi: 10.1136/neurintsurg-2020-016362 [published Online First: 2020/07/24]
2. Wagner K, Srivatsan A, Mohanty A, et al. Cognitive outcomes after unruptured intracranial aneurysm treatment with flow diversion. J Neurosurg 2019:1-6. doi: 10.3171/2019.9.JNS191910 [published Online First: 2019/11/30]
3. Iosif C, Camilleri Y, Saleme S, et al. Diffusion-weighted imaging-detected ischemic lesions associated with flow-diverting stents in intracranial aneurysms: safety, potential mechanisms, clinical outcome, and concerns. J Neurosurg 2015;122(3):627-36. doi: 10.3171/2014.10.JNS132566 [published Online First: 2015/01/07]
4. Hill MD, Martin RH, Mikulis D, et al. Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2012;11(11):942-50. doi: 10.1016/S1474-4422(12)70225-9
5. Garrett KD, Browndyke JN, Whelihan W, et al. The neuropsychological profile of vascular cognitive impairment--no dementia: comparisons to patients at risk for cerebrovascular disease and vascular dementia. Arch Clin Neuropsychol 2004;19(6):745-57. doi: 10.1016/j.acn.2003.09.008 [published Online First: 2004/08/04]
6. Nyenhuis DL, Gorelick PB, Geenen EJ, et al. The pattern of neuropsychological deficits in Vascular Cognitive Impairment-No Dementia (Vascular CIND). Clin Neuropsychol 2004;18(1):41-9. doi: 10.1080/13854040490507145 [published Online First: 2004/12/15]
7. Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37(9):2220-41. doi: 10.1161/01.STR.0000237236.88823.47
After reading the interesting article by Jeon et al, indeed, the first series of cases of revascularization in cerebral infarction, it is important to point out several aspects related to the cancer patient. Cancer is a heterogeneous group of diseases with some points in common related to cellular behavior in the face of cell division controls and their local and systemic effects. Its incidence and prevalence are increasing, and the borders of treatment are changing, as is the disease itself. Patients with active cancer, therefore, should be approached in a multidisciplinary strategy, for the management of their oncological pathology or associated patient comorbidities. Stroke does not escape this strategy, because it does not have the same clinical impact to treat a patient with an oncological disease in early staging compared to one in advanced staging or in disease progression in palliative care and short calculated survival. It is not possible to establish a general rule of treatment in stroke with active cancer for these reasons, and a careful analysis of which primary tumors, their staging or clinical evolution of response to treatment, are necessary to clarify the clinical picture of stroke treatment in the oncological disease context.
The response from the Stenting and Aggressive Medical Management for
the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial principal
investigators (PIs) is greatly appreciated. Healthy debate helps us weed
out the details that are important in these studies and future trial
design. Although the PIs label some of the editorial comments as
"inaccuracies", one could disagree based on the information listed below....
The response from the Stenting and Aggressive Medical Management for
the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial principal
investigators (PIs) is greatly appreciated. Healthy debate helps us weed
out the details that are important in these studies and future trial
design. Although the PIs label some of the editorial comments as
"inaccuracies", one could disagree based on the information listed below.
So let's look at the numbers and the facts.
First, they state the SAMMPRIS population was the right population to
test, based on the Warfarin versus Aspirin for Symptomatic Intracranial
Disease (WASID) trial data. However, they base this statement on the
criteria of the degree of stenosis, and some standard, but relatively
artificial epidemiological criteria, not focusing on some other important
clinical criteria. For example, the mean time of enrollment from
qualifying event to enrollment was 17 days in the WASID trial and 7 days
in the SAMMPRIS trial, so these are not exactly the same patient
populations. The patients who were stented in SAMMPRIS within 7 days of
their qualifying event did remarkably worse than the patients stented
after day 7, indicating that either these patients had unstable plaque or
some other factor that increased their risk for complications when treated
early. The Wingspan safety trial that led to FDA approval of the Wingspan
stent did NOT include patients who had stroke less than 7 days, so to
stent patients at less than 7 days from the event was another variable
introduced by the SAMMPRIS trial design that was not a part of the
original Food and Drug Administration (FDA) approval of the stent.
Second, they state that the Wingspan stent was not used off-label.
This is not exactly true. The Investigational Device Exemption (IDE) use
of the Wingspan stent in the SAMMPRIS trial was used for expanded
indications compared to the Humanitarian Device Exemption (HDE) FDA
approval. In fact, this was exactly one of the reasons that an IDE
approval was necessary for the trial. Interestingly, if one analyzes the
presenting symptoms, time to treatment, medical failure, and other
factors, only 8% of the patients enrolled in SAMMPRIS would have qualified
for the original Wingspan safety study upon which the FDA granted approval
(FDA Panel Review, March 2012, Baltimore, MD). Therefore, practices such
as treating patients before day 7 post-event, allowing TIA versus stroke
only as an entry criteria, and allowing patients who had not failed
medical therapy into the trial, were markedly expanded indications for the
stent in this trial. For this reason, one could argue that this trial was
not designed for stenting to succeed. Typically, every device trial is
initially designed for the on-label indication, and only later are there
considerations for expanded indications. This was not the paradigm used
in SAMMPRIS. In the subgroup of the 8% of patients in SAMMPRIS that
actually would have qualified for the original Wingspan safety trial,
there was no statistical difference in clinical outcomes between the
stenting and the medical therapy groups.
Third, the argument that even the subgroup of patients who previously
failed anti-platelet therapy did worse with stenting than medical therapy
is easily predictable, if you look how stented patient were managed in the
study. Many major centers test patients for anti-platelet therapy
resistance prior to stent placement, since there is a documented 15%
relative clopidogrel resistance in the population and 10% aspirin
resistance. Patients who are resistant to anti-platelet therapy are more
likely to have a thromboembolic event with a fresh stent placement, as a
nidus for platelet aggregation than someone with a chronic atherosclerotic
stenosis. The SAMMPRIS trial failed to account for possible anti-platelet
therapy resistance as many coronary stenting trials current address. In
fact, it was a protocol violation in SAMMPRIS even to measure the anti-
platelet therapy resistance.
Finally, the argument that interventionalist experience did not play
a role in the results is very short-sighted and is based on poorly
stratified data. It would be difficult to believe that anyone would argue
that less experienced stenters could have equivalent clinical results than
more experienced stenters. The average number of Wingspan stents placed
by interventionalists to qualify as a stenter in the study was 10 Wingspan
stents. This low number, as a distinction between low and high volume
stenters, would not be acceptable in any current stenting trial:
coronary, carotid, peripheral, etc. So technically, both "low volume" and
"high volume" groups analyzed by the PIs were low volume users.
The goals for the future should be to focus our attention on defining
which population will benefit most with revascularization, what is the
best timing for the procedure, and what medical therapy regimen is best
for patients with newly placed intracranial stents, which may not be the
same as the best therapy for those without stents. SAMMPRIS gives a
significant amount of information, but it is a starting point, not an end
to this therapy.
Conflict of Interest:
Dr. Alexander was an investigator in the SAMMPRIS clinical trial. He is a device proctor and consultant for Styker Neurovascular which manufactures the Wingspan stent.
We read with great joy the recent article by Kuhn et al entitled, “ Distal radial access in the anatomical snuffbox for neurointerventions: a feasibility, safety, and proof-of-concept study.” The authors should be congratulated on their work, as well as the use and maturation of the distal radial technique from diagnostic to interventional procedures. The authors detail their use of the Prelude sheaths which we agree are excellent low profile large lumen sheaths for radial access. We typically utilize the Glide Slender sheaths (Terumo) but both are excellent options. We also agree that the distal radial approach can be used for numerous interventions with access sizes from 4 to 6F, including 6F sheathless long 088 guides. Our choice for distal radial sheathless long 088 guides is Infinity LS (Stryker), and for 071 guides the Benchmark (penumbra) via a 6F sheath.
The authors noted their series was the first series to cover numerous neurointerventions with distal transradial access, however we would like to respectfully point out that we published on this topic in January of 2019 (accepted in March of 2019). Our paper by Rajah et al entitled, “ Snuff box radial access: A technical note on distal radial access for neuroendovascular procedures” can be found in Brain Circulation at the following citation available in PUBMED.
Rajah G, Garling RJ, Hudson M, Luqman A. Snuff box radial access: A technical note on distal radial access for neuroe...
We read with great joy the recent article by Kuhn et al entitled, “ Distal radial access in the anatomical snuffbox for neurointerventions: a feasibility, safety, and proof-of-concept study.” The authors should be congratulated on their work, as well as the use and maturation of the distal radial technique from diagnostic to interventional procedures. The authors detail their use of the Prelude sheaths which we agree are excellent low profile large lumen sheaths for radial access. We typically utilize the Glide Slender sheaths (Terumo) but both are excellent options. We also agree that the distal radial approach can be used for numerous interventions with access sizes from 4 to 6F, including 6F sheathless long 088 guides. Our choice for distal radial sheathless long 088 guides is Infinity LS (Stryker), and for 071 guides the Benchmark (penumbra) via a 6F sheath.
The authors noted their series was the first series to cover numerous neurointerventions with distal transradial access, however we would like to respectfully point out that we published on this topic in January of 2019 (accepted in March of 2019). Our paper by Rajah et al entitled, “ Snuff box radial access: A technical note on distal radial access for neuroendovascular procedures” can be found in Brain Circulation at the following citation available in PUBMED.
Rajah G, Garling RJ, Hudson M, Luqman A. Snuff box radial access: A technical note on distal radial access for neuroendovascular procedures. Brain circulation. 2019 Jan;5(1):36.
Our paper details our technique, the pros of anatomic orientation of the hand for both the patient and surgeon, as well as the theoretical safety of the distal radial approach with regards to ischemia. We detail how our access is performed with ultrasound, and depict 4 illustrative case examples with imaging including aneurysm stent coiling, head and neck embolization, posterior fossa parent vessel sacrifice, and carotid stenting via a sheathless approach. We had switched over our entire practice for surgeon (AL) to distal radial access in November of 2018. Since that time all diagnostic angiograms and most interventions were performed via distal radial access including ischemic strokes. We have a distal radial manuscript currently accepted to Brain Circulation detailing our use of a Balloon guide catheter for ischemic stroke, which we admit still has its limitations with the available current guides due to outside diameter (OD) and stiffness. However with newest Balloon guides recently approved by the FDA, such as those made by Q’Apel, Medical boasting an 087 ID with a flexible design may provide for sheathless radial use. A 7F 072 balloon guide is also advertised by the Q’Apel. Kuhn et al explains distal radial access can provide enough support for flow divertor deployment intracranially, we echo this finding, as we have also treated aneurysms and carotid cavernous fistulas via a distal radial approach with flow divertors in tandem or stacked fashion.
We again applaud the authors on their work, and are excited to see the field moving toward more distal radial access during the current radial revolution in the neuro endovascular world. We agree with the authors this technique is a safe and effective way to perform a variety of endovascular procedures and should be in every surgeons armamentarium.
Kaminsky et al1 present an interesting study regarding the logistics of patients eligible for endovascular stroke therapy (EVT). They conclude that whether patients with large vessel occlusion (LVO) are first admitted to a hospital with or without this treatment does not affect patient outcome.
However, there are some difficulties interpreting the main statistical multivariate analyses. Firstly, although there is a clear presentation of how the main multivariate logistic regression analysis is performed, the covariates included in the model are not presented, and the model is not shown in any table. Secondly, the authors have included variables solely based on the strength of their association with the outcome, and not based on the potential of the variable to confound the relationship between the variable of interest (which center the patient is admitted to first), and the outcome. In this setting, it is our opinion that selecting covariates based on an etiological model, that focuses on the variable of interest, and includes covariates based on the potential for confounding, would be the best strategy.2 We disagree with the authors` choice of a prognostic model.
We urge the authors to provide a table showing the main analysis, or even repeat the main analysis using an etiological approach to model building and variable selection.
Despite these shortcomings, we commend the authors for undertaking such a relevant clinical study, and we...
Kaminsky et al1 present an interesting study regarding the logistics of patients eligible for endovascular stroke therapy (EVT). They conclude that whether patients with large vessel occlusion (LVO) are first admitted to a hospital with or without this treatment does not affect patient outcome.
However, there are some difficulties interpreting the main statistical multivariate analyses. Firstly, although there is a clear presentation of how the main multivariate logistic regression analysis is performed, the covariates included in the model are not presented, and the model is not shown in any table. Secondly, the authors have included variables solely based on the strength of their association with the outcome, and not based on the potential of the variable to confound the relationship between the variable of interest (which center the patient is admitted to first), and the outcome. In this setting, it is our opinion that selecting covariates based on an etiological model, that focuses on the variable of interest, and includes covariates based on the potential for confounding, would be the best strategy.2 We disagree with the authors` choice of a prognostic model.
We urge the authors to provide a table showing the main analysis, or even repeat the main analysis using an etiological approach to model building and variable selection.
Despite these shortcomings, we commend the authors for undertaking such a relevant clinical study, and we agree on the need for randomized trials in this field.
1. Kaminsky AL, Mione G, Omorou Y, et al. Outcome of patients with large vessel occlusion stroke after first admission in telestroke spoke versus comprehensive stroke center. J Neurointerv Surg 2019 doi: 10.1136/neurintsurg-2019-015342
2. Tripepi G, Jager KJ, Dekker FW, et al. Testing for causality and prognosis: etiological and prognostic models. Kidney International 2008;74(12):1512-15. doi: https://doi.org/10.1038/ki.2008.416
Haussen et al described a technique of blind exchange with mini-pinning technique (BEMP) for distal occlusion thrombectomy. The authors are to be commended for a well-written article show-casing an important technique for reperfusing distal occlusions in eloquent territories. We recently used a variation of this technique for mechanical thrombectomy in a large proximal vessel occlusion to great effect.
A 64-year-old man with atrial fibrillation presented to our institution with a right ICA terminus occlusion and NIHSS 17. Mechnical thrombectomy with a Solitaire retriever and 6F aspiration catheter (Solumbra technique) was attempted, but could not be performed due to marked tortuosity of the aortic arch and right cervical ICA, which prevented the aspiration catheter from reaching the clot. Two passes were attempted with the stentriever alone, without success (TICI 0). Therefore, a Trevo stentriever was advanced through the right ICA occlusion via a Markman microcatheter, the microcatheter was removed, and a 3MAX aspiration catheter was advanced over the retriever delivery wire. The stent was left in place for 5 minutes, and the thrombus was retrieved under continuous aspiration after partial ingestion/corking of the thrombus into the 3MAX aspiration catheter (BEMP). This was performed for a total of 2 passes, at the end of which there was complete revascularization of the right MCA territory (TICI 3).
The BEMP technique described by Haussen et al is an import...
Haussen et al described a technique of blind exchange with mini-pinning technique (BEMP) for distal occlusion thrombectomy. The authors are to be commended for a well-written article show-casing an important technique for reperfusing distal occlusions in eloquent territories. We recently used a variation of this technique for mechanical thrombectomy in a large proximal vessel occlusion to great effect.
A 64-year-old man with atrial fibrillation presented to our institution with a right ICA terminus occlusion and NIHSS 17. Mechnical thrombectomy with a Solitaire retriever and 6F aspiration catheter (Solumbra technique) was attempted, but could not be performed due to marked tortuosity of the aortic arch and right cervical ICA, which prevented the aspiration catheter from reaching the clot. Two passes were attempted with the stentriever alone, without success (TICI 0). Therefore, a Trevo stentriever was advanced through the right ICA occlusion via a Markman microcatheter, the microcatheter was removed, and a 3MAX aspiration catheter was advanced over the retriever delivery wire. The stent was left in place for 5 minutes, and the thrombus was retrieved under continuous aspiration after partial ingestion/corking of the thrombus into the 3MAX aspiration catheter (BEMP). This was performed for a total of 2 passes, at the end of which there was complete revascularization of the right MCA territory (TICI 3).
The BEMP technique described by Haussen et al is an important one to keep in mind for any neurovascular center with a busy stroke practice. In addition to distal occlusions, it can also be used as a salvage technique for large proximal occlusions that would be otherwise inaccessible to large bore aspiration catheters.
Dear Editor,
We would like the thank Drs. Berndt, Zimmer, Kaesmacher, and Boeckh-Behrens for their interest in our study titled “Clot permeability and histopathology: Is a clot’s perviousness on CT imaging correlated with its histologic composition?” We read their letter with interest. The authors have been pioneers in stroke clot analysis and we greatly respect their academic rigor and expertise.
While we agree that there are certainly some methodological differences between our two studies, we do not believe that these are to blame for the differences in results. Rather, we feel that the observed differences in results between our studies could be due to differences in our patient populations.
Our group has previously shown that there is indeed a correlation between clot composition and etiology. In a recently published article in Stroke we found that large artery atherosclerosis clots were more likely to be platelet rich than those of a cardioembolic origin.1 To date, however, we have yet to find any definite correlation between etiology and RBC density or fibrin density, and we think it is too early to make any definite conclusions on the association between clot composition and etiology.
We agree that the association between perviousness, clot composition, etiology and clinical outcome is not conclusively clarified yet, and hence warrants further research, especially in a larger patient group in a multi-centric setting. Currently, our gr...
Dear Editor,
We would like the thank Drs. Berndt, Zimmer, Kaesmacher, and Boeckh-Behrens for their interest in our study titled “Clot permeability and histopathology: Is a clot’s perviousness on CT imaging correlated with its histologic composition?” We read their letter with interest. The authors have been pioneers in stroke clot analysis and we greatly respect their academic rigor and expertise.
While we agree that there are certainly some methodological differences between our two studies, we do not believe that these are to blame for the differences in results. Rather, we feel that the observed differences in results between our studies could be due to differences in our patient populations.
Our group has previously shown that there is indeed a correlation between clot composition and etiology. In a recently published article in Stroke we found that large artery atherosclerosis clots were more likely to be platelet rich than those of a cardioembolic origin.1 To date, however, we have yet to find any definite correlation between etiology and RBC density or fibrin density, and we think it is too early to make any definite conclusions on the association between clot composition and etiology.
We agree that the association between perviousness, clot composition, etiology and clinical outcome is not conclusively clarified yet, and hence warrants further research, especially in a larger patient group in a multi-centric setting. Currently, our group is collaborating with multiple centers across the United States and Canada in the Stroke Thromboembolism Registry of Imaging and Pathology and are in the process of performing histological and imaging analysis of over 1200 collected clots from stroke patients. Combining our findings with those of other ongoing multicenter studies may ultimately help us reach meaningful conclusions regarding the association between clot composition and imaging, outcomes and etiology.
References:
[1] Fitzgerald S, Dai D, Wang S, et al. Platelet-rich emboli in cerebral large vessel occlusion are associated with a large artery atherosclerosis source. Stroke 2019;50(7):1907-1910.
Recently, we have read with great interest the article by Benson et al. “Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?” [1].
It is pleasing, that research in the field of thrombus characterization by perviousness and its association to thrombus composition is emerging. Benson et al. report a higher clot perviousness for RBC rich clots in comparison to fibrin dominant thrombi [1]. These results stand in contrast to our previously published study [2], that shows an association between perviousness and fibrin rich clots. We furthermore validated those findings in a large collective by showing a relationship between perviousness and cardioembolic origin. Further research to this special topic is scarce. However, there is another experimental and therefore well controllable study on artificial clots, that showed a strong association of fibrin content and contrast agent uptake [3], similar as it has been shown for in vivo thrombi in our study [2].
Consequently, these contradictory results demand further explanations. In our opinion, the differing results might be caused by methodological differences, which we want to discuss.
First, thrombus localizations should be taken into account. Benson et al. used a collective of 57 thrombi with different thrombus locations (38 MCA, 6 ICA, 5 ICA/MCA, 3 basilar artery, 2 posterior cerebral artery, 2 ICA/MCA/ACA, 1 ICC/MCA). It is at least questiona...
Recently, we have read with great interest the article by Benson et al. “Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?” [1].
It is pleasing, that research in the field of thrombus characterization by perviousness and its association to thrombus composition is emerging. Benson et al. report a higher clot perviousness for RBC rich clots in comparison to fibrin dominant thrombi [1]. These results stand in contrast to our previously published study [2], that shows an association between perviousness and fibrin rich clots. We furthermore validated those findings in a large collective by showing a relationship between perviousness and cardioembolic origin. Further research to this special topic is scarce. However, there is another experimental and therefore well controllable study on artificial clots, that showed a strong association of fibrin content and contrast agent uptake [3], similar as it has been shown for in vivo thrombi in our study [2].
Consequently, these contradictory results demand further explanations. In our opinion, the differing results might be caused by methodological differences, which we want to discuss.
First, thrombus localizations should be taken into account. Benson et al. used a collective of 57 thrombi with different thrombus locations (38 MCA, 6 ICA, 5 ICA/MCA, 3 basilar artery, 2 posterior cerebral artery, 2 ICA/MCA/ACA, 1 ICC/MCA). It is at least questionable, if histological composition can be compared between different circulations as it is known that there are different pathophysiological mechanisms (e.g. more underlying stenosis in the posterior circulation) as well as different flow conditions that would influence thrombus evolution and consequently composition [4].
Second, and more important, using an in-homogenous collective for perviousness assessment would stringently lead to technical difficulties in data acquisition: to make measurements comparable, direct contact from fresh flooding contrast agent in CTA is required, preventing the problem of a stationary blood column, which can be observed in occlusions of the ICA, for example. From own experience, identifying exact thrombus location is challenging for cases of ICA occlusions, that complicates the perviousness assessment. To circumvent these risks for falsified measurements, we used in our study a homogenous collective of 32 MCA occlusions. It would be interesting if Benson et al. would reproduce their results in the subgroup of 38 MCA occlusions.
Third, technical issues about perviousness assessment should be discussed as they differ between the groups. We used a co-registration process for native CT and CTA images to exactly identify the thrombus, although the thrombus is not visible in the native CT scan. Benson et al. did not apply a co-registration process between native CT and CTA images, and they excluded patients, “if the inciting clot was too small to be visualized”. Especially fibrin-rich clots are not obviously visible on native CT, and they can be included in the analysis by using a co-registration process to avoid a systematical selection bias.
Fourth, we excluded patients because of non-occluding thrombi when contrast agent passed the thrombus. We think, that perviousness cannot be assessed adequately for these cases, because perviousness would be measured artificially high. Consequently, these cases also present with tendentially better clinical outcome. It would be interesting, if such cases are included in the study of Benson et al. and how they present.
From the majority of histological studies, an association between fibrin-rich clots and cardioembolic origin is known [5, 6]. This fact makes the perviousness assessment interesting as it can predict stroke cause early on (for detailed discussion see [2]). Benson et al. report a cardioembolic origin as most common (59.6% of thrombi). They also report that 66.7% appeared pervious, however with higher RBC density. It would be interesting if their data would show a possible correlation between histological thrombus composition and etiology, and, secondly, a correlation between perviousness and etiology.
Benson et al. based their hypotheses on a positive correlation between pervious clots and good clinical outcome, that seems plausible as the dependent tissue behind an occlusion is better supplied with blood and nutrients when the clot is pervious [7]. RBC-rich clots show better clinical outcome, that is, among others, based on an easier removal in mechanical thrombectomy [8]. Due to the predominant subgroup of cardioembolic, presumably fibrin-rich clots in the anterior circulation, these clots dominate the analyses. Possibly, the assumed tendency between perviousness and good clinical outcome is based on this predominant subgroup. Consequently, it would not contradict the possible association between higher perviousness and fibrin-rich clots.
In summary, association between perviousness, clot composition, etiology and clinical outcome is not conclusively clarified yet and warrants further research, especially in a larger patient group in a multi-centric setting.
Literature
1. Benson JC, Fitzgerald ST, Kadirvel R, Johnson C, Dai D, Karen D et al. Clot permeability and histopathology: is a clot's perviousness on CT imaging correlated with its histologic composition? J Neurointerv Surg. 2019. doi:10.1136/neurintsurg-2019-014979.
2. Berndt M, Friedrich B, Maegerlein C, Moench S, Hedderich D, Lehm M et al. Thrombus Permeability in Admission Computed Tomographic Imaging Indicates Stroke Pathogenesis Based on Thrombus Histology. Stroke. 2018;49(11):2674-82. doi:10.1161/STROKEAHA.118.021873.
3. Borggrefe J, Kottlors J, Mirza M, Neuhaus VF, Abdullayev N, Maus V et al. Differentiation of Clot Composition Using Conventional and Dual-Energy Computed Tomography. Clin Neuroradiol. 2017. doi:10.1007/s00062-017-0599-3.
4. Boeckh-Behrens T, Pree D, Lummel N, Friedrich B, Maegerlein C, Kreiser K et al. Vertebral Artery Patency and Thrombectomy in Basilar Artery Occlusions. Stroke. 2019;50(2):389-95. doi:10.1161/STROKEAHA.118.022466.
5. Sporns PB, Hanning U, Schwindt W, Velasco A, Minnerup J, Zoubi T et al. Ischemic Stroke: What Does the Histological Composition Tell Us About the Origin of the Thrombus? Stroke. 2017;48(8):2206-10. doi:10.1161/STROKEAHA.117.016590.
6. Boeckh-Behrens T, Kleine JF, Zimmer C, Neff F, Scheipl F, Pelisek J et al. Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke. Stroke. 2016;47(7):1864-71. doi:10.1161/STROKEAHA.116.013105.
7. Santos EM, Marquering HA, den Blanken MD, Berkhemer OA, Boers AM, Yoo AJ et al. Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke. Stroke. 2016;47(3):732-41. doi:10.1161/STROKEAHA.115.011187.
8. Hashimoto T, Hayakawa M, Funatsu N, Yamagami H, Satow T, Takahashi JC et al. Histopathologic Analysis of Retrieved Thrombi Associated With Successful Reperfusion After Acute Stroke Thrombectomy. Stroke. 2016;47(12):3035-7. doi:10.1161/STROKEAHA.116.015228.
Proprietary nature of intravascular medical device coatings limits safety testing
Dear Dr. Albuquerque:
We are glad that our work has generated interest and discussion in the field [1]. Four years have elapsed since a need for updated device coating testing was officially announced [2], however complexities on the matter and persistent knowledge gaps limit safety studies of devices currently on the market for clinical intravascular use [3,4]. Standardized in vitro particulate generation testing is needed. However, available literature shows that preclinical device testing is not fully predictive of clinical response. Therefore, in vitro and animal studies cannot replace investigation in humans. Currently, lack of consensus on the following prevent meaningful testing in humans: I) optimal clinical testing methods; ii) definitions of permissible risk; iii) adverse cellular, organ, and temporal-specific effects of distinct coating biomaterials; and iv) effects of pre-existing comorbid conditions. Nevertheless, in vitro testing that does not incorporate clinical data has limited utility for safety guidance. Likewise, in vivo studies that do not incorporate biomaterial factors are incomplete. Thus, the proprietary nature of intravascular device coatings remains a significant limitation to clinical device testing and safety assurances. Growing data [2-6] suggest that it may be time for this to be addressed.
1. Chopra AM, Hu YC, Cruz JP. The Device Specific...
Proprietary nature of intravascular medical device coatings limits safety testing
Dear Dr. Albuquerque:
We are glad that our work has generated interest and discussion in the field [1]. Four years have elapsed since a need for updated device coating testing was officially announced [2], however complexities on the matter and persistent knowledge gaps limit safety studies of devices currently on the market for clinical intravascular use [3,4]. Standardized in vitro particulate generation testing is needed. However, available literature shows that preclinical device testing is not fully predictive of clinical response. Therefore, in vitro and animal studies cannot replace investigation in humans. Currently, lack of consensus on the following prevent meaningful testing in humans: I) optimal clinical testing methods; ii) definitions of permissible risk; iii) adverse cellular, organ, and temporal-specific effects of distinct coating biomaterials; and iv) effects of pre-existing comorbid conditions. Nevertheless, in vitro testing that does not incorporate clinical data has limited utility for safety guidance. Likewise, in vivo studies that do not incorporate biomaterial factors are incomplete. Thus, the proprietary nature of intravascular device coatings remains a significant limitation to clinical device testing and safety assurances. Growing data [2-6] suggest that it may be time for this to be addressed.
1. Chopra AM, Hu YC, Cruz JP. The Device Specific Nature of Polymer Coating Emboli: An Optimal Approach For Future Investigations Related to Polymer Embolism. Journal of Neurointerventional Surgery.
2. U.S. Food and Drug Administration Lubricious Coating Separation From Intravascular Medical Devices FDA Safety Communication. Silver Spring MD: FDA; 2015. Available at: https://wayback.archive-it.org/7993/20161022044037/http://www.fda.gov/Me.... Accessed September 11, 2019.
3. Mehta RI, Rai AT, Vos JA, et al. Intrathrombus polymer coating deposition: a pilot study of 91 patients undergoing endovascular therapy for acute large vessel stroke. Part I: Histologic frequency. Journal of NeuroInterventional Surgery Published Online First: 18 May 2019. doi: 10.1136/neurintsurg-2018-014684
4. Mehta RI , Mehta RI. Hydrophilic polymer embolism: implications for manufacturing, regulation, and postmarketsurveillance of coated intravascular medical devices. J Patient Saf 2018 [Epub ahead of print 19 Mar 2019].doi:10.1097/PTS.0000000000000473
5. Mehta RI , Mehta RI , Solis OE , et al. Hydrophilic polymer emboli: an under-recognized iatrogenic cause of ischemia and infarct. Mod Pathol 2010;23:921–30.doi:10.1038/modpathol.2010.74
6. Mehta RI , Mehta RI. Hydrophilic polymer embolism: an update for physicians. Am J Med 2017;130:e287–90.doi:10.1016/j.amjmed.2017.01.032
Sincerely,
Rashi I. Mehta, MD
West Virginia University
Department of Neuroradiology
Ansaar T. Rai, MD
West Virginia University
Department of Neuroradiology
James W. Simpkins, PhD
West Virginia University
Department of Physiology and Pharmacology
Center for Basic and Translational Stroke Research
Rockefeller Neuroscience Institute
Rupal I. Mehta, MD
University of Rochester
Center for Translational Neuromedicine
Acknowledgments: RIM (Rashi I Mehta) is supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health (5U54GM104942-03). RIM (Rupal I Mehta) is supported by a grant from the National Institute of Neurological Disorders and Stroke (K08NS089830).
Competing interests: ATR serves as a consultant for Stryker Corporation.
We read with great interest the recent paper by Vargas, et al. describing a novel beveled tip aspiration catheter with improved recanalization and patient outcome compared to conventional non-beveled tip catheters in a single-center retrospective study.[1] We want to express our sincere congratulations to the authors on this finding but also want to respectively present our disagreement on the mechanisms explaining the improved performance of the beveled tip catheter as compared to standard catheters.
The authors conclude that a primary reason for higher rate of complete clot ingestion for the beveled tip catheter relates to the area of the catheter tip. It is widely accepted that ingestion force predicts recanalization efficacy, and this force is proportional to tip area (A) and pressure drop (P). The authors note that the beveled tip leads to an ovalized tip area with a total tip area that is approximately 15% larger than a catheter with an equivalent inner diameter but standard non-beveled tip. They then propose that this 15% increase in tip area leads to a corresponding increase of ingestion force, using the standard F=A*P equation. However, this proposition is flawed. While it is true the total force is larger for the beveled tip catheter than a standard catheter, this total force includes two separate force components that are orthogonal to each other, including the ingestion force component (along the catheter’s length) that corks or ingests the clot and...
Show MoreWe congratulate Drs. Srivatsan and colleagues on their paper examining the effects of endovascular coiling of unruptured intracranial aneurysms (UIAs) on cognition using the Montreal Cognitive Assessment (MoCA).1 In particular, we appreciate the efforts made to sample the patients at multiple time points including pre-intervention and at 1-month and 6-months post-intervention. The study found that coiling did not diminish neurocognitive function per the MoCA, with there also being no correlation between follow-up MoCA scores and imaging findings, the overall results being comparable to the authors’ previous paper on MoCA scores following flow diversion for UIAs.2 Intriguingly, the MoCA scores at baseline were on average below the typical cut-off of 26 points, especially given the relatively young population (mean age 55.5 years).
However, as acknowledged by the authors, the ability of the study to discern post-coiling imaging changes was limited by both the small subset of the population that received follow-up imaging (17 of 33 patients, 51.5%) and the smaller subset that underwent MRI (9 patients, 27.3%).1 Diffusion-weighted imaging (DWI) sequences of MRI are most sensitive to identifying post-procedural ischemic injury following neuro-interventional procedures like coiling.3 DWI lesions occur quite frequently; for example, in the ENACT trial (Evaluating Neuroprotection in Aneurysm Coiling Therapy), 68% of patients had new lesions post-procedure, with an average o...
Show MoreAfter reading the interesting article by Jeon et al, indeed, the first series of cases of revascularization in cerebral infarction, it is important to point out several aspects related to the cancer patient. Cancer is a heterogeneous group of diseases with some points in common related to cellular behavior in the face of cell division controls and their local and systemic effects. Its incidence and prevalence are increasing, and the borders of treatment are changing, as is the disease itself. Patients with active cancer, therefore, should be approached in a multidisciplinary strategy, for the management of their oncological pathology or associated patient comorbidities. Stroke does not escape this strategy, because it does not have the same clinical impact to treat a patient with an oncological disease in early staging compared to one in advanced staging or in disease progression in palliative care and short calculated survival. It is not possible to establish a general rule of treatment in stroke with active cancer for these reasons, and a careful analysis of which primary tumors, their staging or clinical evolution of response to treatment, are necessary to clarify the clinical picture of stroke treatment in the oncological disease context.
The response from the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial principal investigators (PIs) is greatly appreciated. Healthy debate helps us weed out the details that are important in these studies and future trial design. Although the PIs label some of the editorial comments as "inaccuracies", one could disagree based on the information listed below....
Dear Editor:
We read with great joy the recent article by Kuhn et al entitled, “ Distal radial access in the anatomical snuffbox for neurointerventions: a feasibility, safety, and proof-of-concept study.” The authors should be congratulated on their work, as well as the use and maturation of the distal radial technique from diagnostic to interventional procedures. The authors detail their use of the Prelude sheaths which we agree are excellent low profile large lumen sheaths for radial access. We typically utilize the Glide Slender sheaths (Terumo) but both are excellent options. We also agree that the distal radial approach can be used for numerous interventions with access sizes from 4 to 6F, including 6F sheathless long 088 guides. Our choice for distal radial sheathless long 088 guides is Infinity LS (Stryker), and for 071 guides the Benchmark (penumbra) via a 6F sheath.
The authors noted their series was the first series to cover numerous neurointerventions with distal transradial access, however we would like to respectfully point out that we published on this topic in January of 2019 (accepted in March of 2019). Our paper by Rajah et al entitled, “ Snuff box radial access: A technical note on distal radial access for neuroendovascular procedures” can be found in Brain Circulation at the following citation available in PUBMED.
Rajah G, Garling RJ, Hudson M, Luqman A. Snuff box radial access: A technical note on distal radial access for neuroe...
Show MoreDear Editor,
Kaminsky et al1 present an interesting study regarding the logistics of patients eligible for endovascular stroke therapy (EVT). They conclude that whether patients with large vessel occlusion (LVO) are first admitted to a hospital with or without this treatment does not affect patient outcome.
Show MoreHowever, there are some difficulties interpreting the main statistical multivariate analyses. Firstly, although there is a clear presentation of how the main multivariate logistic regression analysis is performed, the covariates included in the model are not presented, and the model is not shown in any table. Secondly, the authors have included variables solely based on the strength of their association with the outcome, and not based on the potential of the variable to confound the relationship between the variable of interest (which center the patient is admitted to first), and the outcome. In this setting, it is our opinion that selecting covariates based on an etiological model, that focuses on the variable of interest, and includes covariates based on the potential for confounding, would be the best strategy.2 We disagree with the authors` choice of a prognostic model.
We urge the authors to provide a table showing the main analysis, or even repeat the main analysis using an etiological approach to model building and variable selection.
Despite these shortcomings, we commend the authors for undertaking such a relevant clinical study, and we...
Haussen et al described a technique of blind exchange with mini-pinning technique (BEMP) for distal occlusion thrombectomy. The authors are to be commended for a well-written article show-casing an important technique for reperfusing distal occlusions in eloquent territories. We recently used a variation of this technique for mechanical thrombectomy in a large proximal vessel occlusion to great effect.
A 64-year-old man with atrial fibrillation presented to our institution with a right ICA terminus occlusion and NIHSS 17. Mechnical thrombectomy with a Solitaire retriever and 6F aspiration catheter (Solumbra technique) was attempted, but could not be performed due to marked tortuosity of the aortic arch and right cervical ICA, which prevented the aspiration catheter from reaching the clot. Two passes were attempted with the stentriever alone, without success (TICI 0). Therefore, a Trevo stentriever was advanced through the right ICA occlusion via a Markman microcatheter, the microcatheter was removed, and a 3MAX aspiration catheter was advanced over the retriever delivery wire. The stent was left in place for 5 minutes, and the thrombus was retrieved under continuous aspiration after partial ingestion/corking of the thrombus into the 3MAX aspiration catheter (BEMP). This was performed for a total of 2 passes, at the end of which there was complete revascularization of the right MCA territory (TICI 3).
The BEMP technique described by Haussen et al is an import...
Show MoreDear Editor,
We would like the thank Drs. Berndt, Zimmer, Kaesmacher, and Boeckh-Behrens for their interest in our study titled “Clot permeability and histopathology: Is a clot’s perviousness on CT imaging correlated with its histologic composition?” We read their letter with interest. The authors have been pioneers in stroke clot analysis and we greatly respect their academic rigor and expertise.
While we agree that there are certainly some methodological differences between our two studies, we do not believe that these are to blame for the differences in results. Rather, we feel that the observed differences in results between our studies could be due to differences in our patient populations.
Our group has previously shown that there is indeed a correlation between clot composition and etiology. In a recently published article in Stroke we found that large artery atherosclerosis clots were more likely to be platelet rich than those of a cardioembolic origin.1 To date, however, we have yet to find any definite correlation between etiology and RBC density or fibrin density, and we think it is too early to make any definite conclusions on the association between clot composition and etiology.
We agree that the association between perviousness, clot composition, etiology and clinical outcome is not conclusively clarified yet, and hence warrants further research, especially in a larger patient group in a multi-centric setting. Currently, our gr...
Show MoreRecently, we have read with great interest the article by Benson et al. “Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?” [1].
Show MoreIt is pleasing, that research in the field of thrombus characterization by perviousness and its association to thrombus composition is emerging. Benson et al. report a higher clot perviousness for RBC rich clots in comparison to fibrin dominant thrombi [1]. These results stand in contrast to our previously published study [2], that shows an association between perviousness and fibrin rich clots. We furthermore validated those findings in a large collective by showing a relationship between perviousness and cardioembolic origin. Further research to this special topic is scarce. However, there is another experimental and therefore well controllable study on artificial clots, that showed a strong association of fibrin content and contrast agent uptake [3], similar as it has been shown for in vivo thrombi in our study [2].
Consequently, these contradictory results demand further explanations. In our opinion, the differing results might be caused by methodological differences, which we want to discuss.
First, thrombus localizations should be taken into account. Benson et al. used a collective of 57 thrombi with different thrombus locations (38 MCA, 6 ICA, 5 ICA/MCA, 3 basilar artery, 2 posterior cerebral artery, 2 ICA/MCA/ACA, 1 ICC/MCA). It is at least questiona...
Proprietary nature of intravascular medical device coatings limits safety testing
Dear Dr. Albuquerque:
We are glad that our work has generated interest and discussion in the field [1]. Four years have elapsed since a need for updated device coating testing was officially announced [2], however complexities on the matter and persistent knowledge gaps limit safety studies of devices currently on the market for clinical intravascular use [3,4]. Standardized in vitro particulate generation testing is needed. However, available literature shows that preclinical device testing is not fully predictive of clinical response. Therefore, in vitro and animal studies cannot replace investigation in humans. Currently, lack of consensus on the following prevent meaningful testing in humans: I) optimal clinical testing methods; ii) definitions of permissible risk; iii) adverse cellular, organ, and temporal-specific effects of distinct coating biomaterials; and iv) effects of pre-existing comorbid conditions. Nevertheless, in vitro testing that does not incorporate clinical data has limited utility for safety guidance. Likewise, in vivo studies that do not incorporate biomaterial factors are incomplete. Thus, the proprietary nature of intravascular device coatings remains a significant limitation to clinical device testing and safety assurances. Growing data [2-6] suggest that it may be time for this to be addressed.
1. Chopra AM, Hu YC, Cruz JP. The Device Specific...
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