13 research outputs found
First Experience of Three Neurovascular Centers With the p64MW-HPC, a Low-Profile Flow Diverter Designed for Proximal Cerebral Vessels With Antithrombotic Coating
Background: In the last decade, flow diversion (FD) has been established as
hemodynamic treatment for cerebral aneurysms arising from proximal and distal cerebral
arteries. However, two significant limitations remain—the need for 0.027” microcatheters
required for delivery of most flow diverting stents (FDS), and long-term dual anti-platelet
therapy (DAPT) in order to prevent FDS-associated thromboembolism, at the cost
of increasing the risk for hemorrhage. This study reports the experience of three
neurovascular centers with the p64MW-HPC, a FDS with anti-thrombotic coating that
is implantable via a 0.021” microcatheter.
Materials and methods: Three neurovascular centers contributed to this retrospective
analysis of patients that had been treated with the p64MW-HPC between March 2020
and March 2021. Clinical data, aneurysm characteristics, and follow-up results, including
procedural and post-procedural complications, were recorded. The hemodynamic effect
was assessed using the O’Kelly–Marotta Scale (OKM).
Results: Thirty-two patients (22 female, mean age 57.1 years) with 33 aneurysms
(27 anterior circulation and six posterior circulation) were successfully treated with
the p64MW-HPC. In 30/32 patients (93.75%), aneurysmal perfusion was significantly
reduced immediately post implantation. Follow-up imaging was available for 23
aneurysms. Delayed aneurysm perfusion (OKM A3: 8.7%), reduction in aneurysm size
(OKM B1-3: 26.1%), or sufficient separation from the parent vessel (OKM C1-3 and
D1: 65.2%) was demonstrated at the last available follow-up after a mean of 5.9
months. In two cases, device thrombosis after early discontinuation of DAPT occurred.
One delayed rupture caused a caroticocavernous fistula. The complications were
treated sufficiently and all patients recovered without permanent significant morbidity.
Conclusion: Treatment with the p64MW-HPC is safe and feasible and achieves
good early aneurysm occlusion rates in the proximal intracranial circulation, which are
comparable to those of well-established FDS. Sudden interruption of DAPT in the
early post-interventional phase can cause in-stent thrombosis despite the HPC surface
modification. Deliverability via the 0.021” microcatheter facilitates treatment in challenging
vascular anatomies
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
First Experience of Three Neurovascular Centers With the p64MW-HPC, a Low-Profile Flow Diverter Designed for Proximal Cerebral Vessels With Antithrombotic Coating
Background: In the last decade, flow diversion (FD) has been established as
hemodynamic treatment for cerebral aneurysms arising from proximal and distal cerebral
arteries. However, two significant limitations remain—the need for 0.027” microcatheters
required for delivery of most flow diverting stents (FDS), and long-term dual anti-platelet
therapy (DAPT) in order to prevent FDS-associated thromboembolism, at the cost
of increasing the risk for hemorrhage. This study reports the experience of three
neurovascular centers with the p64MW-HPC, a FDS with anti-thrombotic coating that
is implantable via a 0.021” microcatheter.
Materials and methods: Three neurovascular centers contributed to this retrospective
analysis of patients that had been treated with the p64MW-HPC between March 2020
and March 2021. Clinical data, aneurysm characteristics, and follow-up results, including
procedural and post-procedural complications, were recorded. The hemodynamic effect
was assessed using the O’Kelly–Marotta Scale (OKM).
Results: Thirty-two patients (22 female, mean age 57.1 years) with 33 aneurysms
(27 anterior circulation and six posterior circulation) were successfully treated with
the p64MW-HPC. In 30/32 patients (93.75%), aneurysmal perfusion was significantly
reduced immediately post implantation. Follow-up imaging was available for 23
aneurysms. Delayed aneurysm perfusion (OKM A3: 8.7%), reduction in aneurysm size
(OKM B1-3: 26.1%), or sufficient separation from the parent vessel (OKM C1-3 and
D1: 65.2%) was demonstrated at the last available follow-up after a mean of 5.9
months. In two cases, device thrombosis after early discontinuation of DAPT occurred.
One delayed rupture caused a caroticocavernous fistula. The complications were
treated sufficiently and all patients recovered without permanent significant morbidity.
Conclusion: Treatment with the p64MW-HPC is safe and feasible and achieves
good early aneurysm occlusion rates in the proximal intracranial circulation, which are
comparable to those of well-established FDS. Sudden interruption of DAPT in the
early post-interventional phase can cause in-stent thrombosis despite the HPC surface
modification. Deliverability via the 0.021” microcatheter facilitates treatment in challenging
vascular anatomies
First Experience of Three Neurovascular Centers With the p64MW-HPC, a Low-Profile Flow Diverter Designed for Proximal Cerebral Vessels With Antithrombotic Coating
Background: In the last decade, flow diversion (FD) has been established as
hemodynamic treatment for cerebral aneurysms arising from proximal and distal cerebral
arteries. However, two significant limitations remain—the need for 0.027” microcatheters
required for delivery of most flow diverting stents (FDS), and long-term dual anti-platelet
therapy (DAPT) in order to prevent FDS-associated thromboembolism, at the cost
of increasing the risk for hemorrhage. This study reports the experience of three
neurovascular centers with the p64MW-HPC, a FDS with anti-thrombotic coating that
is implantable via a 0.021” microcatheter.
Materials and methods: Three neurovascular centers contributed to this retrospective
analysis of patients that had been treated with the p64MW-HPC between March 2020
and March 2021. Clinical data, aneurysm characteristics, and follow-up results, including
procedural and post-procedural complications, were recorded. The hemodynamic effect
was assessed using the O’Kelly–Marotta Scale (OKM).
Results: Thirty-two patients (22 female, mean age 57.1 years) with 33 aneurysms
(27 anterior circulation and six posterior circulation) were successfully treated with
the p64MW-HPC. In 30/32 patients (93.75%), aneurysmal perfusion was significantly
reduced immediately post implantation. Follow-up imaging was available for 23
aneurysms. Delayed aneurysm perfusion (OKM A3: 8.7%), reduction in aneurysm size
(OKM B1-3: 26.1%), or sufficient separation from the parent vessel (OKM C1-3 and
D1: 65.2%) was demonstrated at the last available follow-up after a mean of 5.9
months. In two cases, device thrombosis after early discontinuation of DAPT occurred.
One delayed rupture caused a caroticocavernous fistula. The complications were
treated sufficiently and all patients recovered without permanent significant morbidity.
Conclusion: Treatment with the p64MW-HPC is safe and feasible and achieves
good early aneurysm occlusion rates in the proximal intracranial circulation, which are
comparable to those of well-established FDS. Sudden interruption of DAPT in the
early post-interventional phase can cause in-stent thrombosis despite the HPC surface
modification. Deliverability via the 0.021” microcatheter facilitates treatment in challenging
vascular anatomies