Trevo Retriever

The Trevo Stent Retriever is a tiny stent-shaped medical device that is attached to a thin wire. In a minimally invasive procedure that utilizes X-ray, the physician navigates the retriever from the femoral artery, which is located in the upper leg, to the blocked blood artery in the brain. The retriever is designed to ensnare the blood clot and remove it from the body. Originally cleared by the FDA in 2012, the Trevo Retriever has been used in thousands of patients worldwide.

Imahori et al., retrospectively reviewed 50 patients with acute middle cerebral artery occlusion treatment with the Trevo Stent retriever. Patients were divided into groups that achieved (1st-pass recanalization group, n=21) or did not achieve (non-1st-pass recanalization group, n=29) a modified Thrombolysis in Cerebral Ischemia score of 2b or 3 with the 1st-pass procedure. Patients were also divided into a thromboembolic (n=49) and atherosclerotic (n=11) group by occlusion etiology. They evaluated radiographic findings of the Trevo strut, e.g., degree of stent expansion and filling defect of the thrombus in the strut (in-stent thrombus sign) during the 1st-pass procedure among these groups.

The median stent expansion was significantly greater in the 1st-pass recanalization than non-1st-pass recanalization group (60% versus 34%; P<0.01), and in the thromboembolic than atherosclerotic group (45% versus 31%; P<0.01). The receiver operator characteristic curve shows moderate capacity of the prediction for recanalization and etiology, with an area under the curve of 0.83 and 0.73, respectively. The in-stent thrombus sign was significantly more common in the thromboembolic than atherosclerotic groups (86% versus 10%; P<0.01).

Greater stent expansion was associated with recanalization after thrombectomy. The in-stent thrombus sign may be useful for etiology prediction. These radiographic findings could provide useful real-time feedback during procedure, reflecting the clot-stent interaction 1).

1)

Imahori T, Okamura Y, Sakata J, Shose H, Yokote A, Matsushima K, Matsui D, Kobayashi M, Hosoda K, Tanaka K, Fujita A, Kohmura E. Stent expansion and in-stent thrombus sign in the Trevo stent retriever predict recanalization and possible etiology during mechanical thrombectomy: A case series of 50 patients with acute middle cerebral artery occlusion. World Neurosurg. 2018 Dec 28. pii: S1878-8750(18)32910-3. doi: 10.1016/j.wneu.2018.12.087. [Epub ahead of print] PubMed PMID: 30597281.

Cadaveric dura

Cadaveric dura mater graft-associated CJD (dCJD) accounts for a common form of iatrogenic CJD. A report summarizes the epidemiologic features of 154 cases of dCJD identified in Japan during 1975-2017; these cases account for >60% of dCJD cases reported worldwide. The unusually high prevalence of dCJD in Japan was first reported in 1997. In 2008, a single brand of graft (Lyodura [B. Braun Melsungen AG, Melsungen, Germany]), frequently used as a patch in neurosurgical procedures, was identified as the probable vehicle of transmission. No international recall of the implicated Lyodura occurred, the product had a relatively long shelf life, and the grafts were used frequently in Japanese patients with non-life-threatening conditions.

Since 2008, additional cases have been ascertained, reflecting the identification of previously missed cases and the occurrence of new cases with longer latency periods (interval from exposure to symptom onset) for dCJD (up to 30 years), underscoring the importance of maintaining surveillance for dCJD 1).


There is strong evidence that cadaveric dura mater represents a completely unnecessary risk of CJD to the public. The disease in question is fatal, the risks cannot be reliably eliminated and there are clear alternatives. Yet the FDA has not opted to ban the material, even though two other countries, Japan and Britain, have done so without evident problems, and the WHO recommends this course of action. Ironically, the U.S. still permits the import of dura mater sourced from the very countries (Japan and Britain) where the material is no longer used. We hope that the recent attention to BSE will induce the FDA to finally take action to adequately protect the public 2)

Case series

Banerjee et al., describe in detail the clinical and neuroimaging findings in three patients with early-onset symptomatic amyloid-β cerebral amyloid angiopathy following childhood exposure to cadaveric dura (by neurosurgical grafting in two patients, and tumour embolization in a third). The observations provide further in vivo evidence that cerebral amyloid angiopathy might be caused by transmission of amyloid-β seeds (prions) present in cadaveric dura, and has diagnostic relevance for younger patients presenting with suspected cerebral amyloid angiopathy 3).


A nationwide survey and information documented 57 patients with Creutzfeldt-Jakob disease (CJD) who had received dura mater grafts during the period between January 1979 and September 1999. At least 54 of these 57 patients received the same brand of dura mater graft from the same processor. Mean age at disease onset in the 57 patients with dural grafts was younger (51.9 years) than that in patients with sporadic CJD (63 years) (p < 0. 0001). Initial symptoms were cerebellar ataxia, disorientation, and visual or oculomotor disturbance 4).

Case reports

A 31-year-old woman 56 months after she received a cadaveric dura mater graft after the removal of a giant pituitary adenoma. Creutzfeldt-Jakob disease was confirmed by a brain autopsy and the existence of an abnormal isoform of prion protein, verified by both immunohistochemical and Western blot analysis. Moreover, prion protein gene analysis was shown in this case to possess a wild-type genotype 5).

References

1)

Ae R, Hamaguchi T, Nakamura Y, Yamada M, Tsukamoto T, Mizusawa H, Belay ED, Schonberger LB. Update: Dura Mater Graft-Associated Creutzfeldt-Jakob Disease – Japan, 1975-2017. MMWR Morb Mortal Wkly Rep. 2018 Mar 9;67(9):274-278. doi: 10.15585/mmwr.mm6709a3. PubMed PMID: 29518068; PubMed Central PMCID: PMC5844283.
3)

Banerjee G, Adams ME, Jaunmuktane Z, Lammie GA, Turner B, Wani M, Sawhney IMS, Houlden H, Mead S, Brandner S, Werring DJ. EARLY-ONSET CEREBRAL AMYLOID ANGIOPATHY FOLLOWING CHILDHOOD EXPOSURE TO CADAVERIC DURA. Ann Neurol. 2018 Dec 31. doi: 10.1002/ana.25407. [Epub ahead of print] PubMed PMID: 30597599.
4)

Hoshi K, Yoshino H, Urata J, Nakamura Y, Yanagawa H, Sato T. Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts in Japan. Neurology. 2000 Sep 12;55(5):718-21. PubMed PMID: 10980745.
5)

Yamada S, Aiba T, Endo Y, Hara M, Kitamoto T, Tateishi J. Creutzfeldt-Jakob disease transmitted by a cadaveric dura mater graft. Neurosurgery. 1994 Apr;34(4):740-3; discussion 743-4. Review. PubMed PMID: 8008177.

Neoantigen vaccination

Neoantigens arise from somatic mutations that differ from wild type antigens and are specific to each individual patient, which provide tumor specific targets for developing personalized cancer vaccines. Decades of work has increasingly shown the potential of targeting neoantigens to generate effective clinical responses. Current clinical trials using neoantigen targeting cancer vaccines, including in combination with checkpoint blockade monoclonal antibodies, have demonstrated potent T-cell responses against those neoantigens accompanied by antitumor effects in patients. Personalized neoantigen vaccines represent a potential new class of cancer immunotherapy 1).


They are exempt from central tolerance, can generate robust immune responses and can function as bona fide antigens that facilitate tumour rejection.

It is a truly personalized therapy because most neoantigens are derived from unique mutations in each tumor genome.

Keskin et al., demonstrated that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load, and an immunologically ‘cold’ tumour microenvironment.

They used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase 1/Phase 1 B randomized controlled trial. Patients who did not receive dexamethasone-a highly potent corticosteroid that is frequently prescribed to treat cerebral edema in patients with glioblastoma-generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, they provided evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma 2).

References

1)

Aldous AR, Dong JZ. Personalized neoantigen vaccines: A new approach to cancer immunotherapy. Bioorg Med Chem. 2018 Jun 1;26(10):2842-2849. doi: 10.1016/j.bmc.2017.10.021. Epub 2017 Oct 19. Review. PubMed PMID: 29111369.
2)

Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, Oliveira G, Giobbie-Hurder A, Felt K, Gjini E, Shukla SA, Hu Z, Li L, Le PM, Allesøe RL, Richman AR, Kowalczyk MS, Abdelrahman S, Geduldig JE, Charbonneau S, Pelton K, Iorgulescu JB, Elagina L, Zhang W, Olive O, McCluskey C, Olsen LR, Stevens J, Lane WJ, Salazar AM, Daley H, Wen PY, Chiocca EA, Harden M, Lennon NJ, Gabriel S, Getz G, Lander ES, Regev A, Ritz J, Neuberg D, Rodig SJ, Ligon KL, Suvà ML, Wucherpfennig KW, Hacohen N, Fritsch EF, Livak KJ, Ott PA, Wu CJ, Reardon DA. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2018 Dec 19. doi: 10.1038/s41586-018-0792-9. [Epub ahead of print] PubMed PMID: 30568305.
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