Endovascular treatment of distal anterior cerebral artery aneurysms using flow modulation devices: mid- and long-term results from a two-center study.

Purpose: Flow-diverter (FD) stents have become an established treatment for intracranial aneurysms in recent years, but their use for aneurysms in distal cerebral vessels with small carrier vessel diameters remains controversial. This study describes the method and mid- and long-term outcomes of FD treatment of distal anterior cerebral artery aneurysms (DACAAs) at two neurointerventional centers, to elucidate this topic and provide more in-depth data. Methods: Data for all patients at two neurointerventional centers who were treated with FDs for DACAAs in the pericallosal and supracallosal segment of the anterior cerebral artery were retrospectively analyzed. Data on periprocedural complications, and short-, mid- and long-term follow-up findings were recorded. Results: Forty-one patients were eligible for inclusion in the study. Three FD models were used, one of which had an anti-thrombotic coating. Two periprocedural complications (5%) occurred but did not cause a change in the mRS. In the long-term follow-up, at 29 months and beyond, 83% of assessable patients showed complete occlusion of the aneurysms without new neurological deficits. Conclusion: FDs are a safe and effective treatment approach for DACAAs. This study indicated a low risk of complications, and high closure rates in short-, mid- and long-term follow-up.

Treg-targeted IL-2/anti-IL-2 complex controls graft-versus-host disease and supports anti-tumor effect in allogeneic hematopoietic stem cell transplantation.

Modulating an immune response in opposite directions represents the holy grail in allogeneic hematopoietic stem cell transplantation (allo-HSCT) to avoid insufficient reactivity of donor T cells and hematologic malignancy relapse while controlling the potential development of graft-versus-host disease (GVHD), in which donor T cells attack the recipient's tissues. IL-2/anti-IL-2 complexes (IL-2Cx) represent a therapeutic option to selectively accentuate or dampen the immune response. In dedicated experimental models of allo-HSCT, including also human cells injected in immunodeficient NSG mice, we evaluated side-by-side the therapeutic effect of two IL-2Cx designed either to boost regulatory T cells (Treg) or alternatively to activate effector T cells (Teff), on GVHD occurrence and tumor relapse. We also evaluated the effect of the complexes on the phenotype and function of immune cells in vivo. Unexpectedly, both pro-Treg and pro-Teff IL-2Cx prevented GVHD development. They both induced Treg expansion and reduced CD8+ T-cell numbers, compared to untreated mice. However, only mice treated with the pro-Treg IL-2Cx, showed a dramatic reduction of exhausted CD8+ T cells, consistent with a potent anti-tumor effect. When evaluated on human cells, pro-Treg IL-2Cx also preferentially induced Treg expansion in vitro and in vivo, while allowing the development of a potent anti-tumor effect in NSG mice. Our results demonstrate the clinical relevance of using a pro-Treg, but not a pro-Teff IL2Cx to modulate alloreactivity after HSCT, while promoting a graft-versus-leukemia effect.

The History of Endovascular Stroke Treatment: From Local Intraarterial Fibrinolysis to Stent Retriever Thrombectomy.

BACKGROUND: Acute thromboembolic occlusions of large intracranial arteries are associated with high rates of permanent disability and mortality. Intravenous thrombolysis (IVT) in these patients resulted in an inadequate rate of recanalization and has had limited clinical success. Various endovascular procedures have been attempted to remove intracranial thrombi and reopen occluded vessels. These technical innovations led to the publication of initial case reports, but the methods ultimately did not endure. Endovascular treatment of acute cerebral ischemia was performed only rarely and in selected centers as part of individualized curative attempts. The Solitaire stent was originally developed to treat intracranial aneurysms through stent-assisted coil occlusion. The suggestion that this stent could also be used for intracranial thrombectomy was made as early as 2003 and was clinically confirmed in 2008. Releasing a Solitaire stent into an embolically occluded large cerebral artery, with an incubation time of approximately 3 minutes and slow retraction of the stent, has led to unprecedented success rates of thrombus removal and (sub)total recanalization in more than 90 % of patients. METHODS: This review article aimed to describe the steps in the development of endovascular stroke therapy, beginning with intra-arterial thrombolysis and early technical innovations leading to the eventual success of stent retriever thrombectomy. CONCLUSION: The potential for mechanical recanalization of acutely occluded large cerebral arteries could not be fully exploited until the advent of stent retriever thrombectomy. The entire concept of stroke treatment fundamentally changed after complete and rapid recanalization first became possible. Randomized controlled trials have shown superiority of stent retriever thrombectomy over IVT. An unparalleled boom in endovascular stroke therapy followed. KEY POINTS: · The history of endovascular stroke treatment was marked by setbacks in the first three decades.. · Stent retriever thrombectomy is the first procedure enabling recanalization of acute large intracranial artery occlusions in more than 90 % of patients.. · Stent retriever thrombectomy has transformed stroke care and neuroradiology in unprecedented ways.. · Further technical improvements will enable even faster, safer, complete recanalization in the near future.. · Further improvements in clinical outcomes will probably be determined by aspects beyond endovascular methods alone..

The pivotal role of timing of intravenous thrombolysis bridging treatment prior to endovascular thrombectomy.

Background: The role of intravenous thrombolysis (IVT) as bridging treatment prior to endovascular thrombectomy (EVT) is under debate and better patient selection is needed. Objectives: As the efficacy and safety of IVT diminish with time, we aimed to examine the impact of bridging treatment within different time frames from symptom onset. Design: A retrospective registry study. Methods: Data were extracted from ongoing prospective EVT registries in two large tertiary centers. The current study included IVT-eligible patients with onset to door (OTD) < 4 h. We examined the efficacy and safety of bridging treatment through a comparison of the IVT + EVT group with the direct-EVT group by different time frames. Results: In all, 408 patients (age 71.1 ± 14.6, 50.6% males) were included, among them 195 received IVT + EVT and 213 underwent direct EVT. Both groups had similar characteristics. In the IVT + EVT group only, longer OTD was associated with lower rates of favorable outcome (p = 0.021) and higher rates of hemorrhagic transformation (HT; p = 0.001). In patients with OTD ⩽ 2 h, IVT + EVT compared to direct EVT had higher rates of TICI 2b-3 (86.2% versus 80.7%, p = 0.038). In patients with OTD > 2 h, IVT + EVT had lower rates of favorable outcome (33.3% versus 56.9%, p = 0.021), worse discharge National Institutes of Health Stroke Scale [7 (2-13) versus 3 (1-8), p = 0.024], and higher rates of HT (34.0% versus 8.5%, p < 0.001). Discussion: In this study, we found OTD times to have a significant effect on the impact of IVT bridging treatment. Our study shows that among patients with OTD < 2 h bridging treatment may be associated with higher rates of successful recanalization. By contrast, in patients with OTD > 2 h, bridging treatment was associated with worse outcomes. Further time-sensitive randomized trials are needed.

Impact of high-resolution intracranial vessel wall magnetic resonance imaging on diagnosis in patients with embolic stroke of unknown source.

BACKGROUND: The mechanism responsible for stroke in patients with embolic stroke of unknown source (ESUS) often remains unknown despite extensive investigations. We aimed to test whether high-resolution intracranial vessel wall MR imaging (icVWI) can add to the diagnostic yield in these patients. PATIENTS AND METHODS: Patients with ESUS were prospectively included into an ongoing registry. Patients that underwent icVWI as part of their diagnostic workup were compared to those that did not have an icVWI. Patients with icVWI positive for intracranial vulnerable plaques were than compared to those without evidence of plaque vulnerability on VWI. RESULTS: A total of 179 patients with ESUS were included and 48 of them (27%) underwent icVWI. Patients that had an icVWI scan were significantly younger, had lower rates of ischemic heart disease and prior disability as well as significantly lower stroke severity. On regression analysis the only factor that remained associated with not obtaining an icVWI scan was increasing age (Odds ratio [OR] 0.97/year, 95% confidence intervals [CI] 0.95-0.97). Among patients that had an icVWI scan 28 (58%) had evidence of plaque enhancement on VWI in the same distribution of the stroke and the remaining 20 studies were negative. The relative proportion of stroke presumed to be secondary to intracranial non-stenotic atheromatous disease increased from 15% in patients without icVWI scans to 58% among patients with icVWI scans (p = 0.001). On regression analysis the only factor that was associated with vulnerable plaques on icVWI was smoking (OR 11.05 95% CI 1.88-65.17). CONCLUSIONS: icVWI can add significant information relevant to stroke pathogenesis and treatment in patients with ESUS and a negative initial exhaustive diagnostic workup.

Belatacept inhibit human B cell germinal center development in immunodeficient mice.

The humoral response mediated by alloantibodies directed against donor HLA molecules (DSAs) is one of the main causes of graft loss in kidney transplantation. Understanding the pathophysiology leading to humoral kidney rejection as the development of therapeutic tools is therefore a main objective in the field of solid organ transplantation and necessitate adapted experimental models. Among the immunosuppressive agents used in renal transplantation, belatacept, a fusion protein targeting T costimulatory molecules has shown its ability to prevent more efficiently the secretion of DSA by different mechanisms including a direct action on plasma cells but also on B lymphocytes and follicular helper T lymphocytes (Tfh) cooperation. This cellular cooperation occurs within germinal centers (GC), the seat of B lymphocytes differentiation. Here, we aimed to develop a dedicated mouse model in which human GC would be functional to study the effect of belatacept on GC formation and the ability of B lymphocytes to secrete immunoglobulin. We next demonstrate that belatacept inhibits the formation of these GCs, by inhibiting the frequency of Tfh and B lymphocytes. This alters the B maturation and therefore the generation of plasma cells and consequently, immunoglobulin secretion.

Does Malignancy Status Effect Outcomes in Patients With Large Vessel Occlusion Stroke and Cancer Who Underwent Endovascular Thrombectomy?

Background Cancer is associated with an increased risk of acute ischemic stroke, including large vessel occlusions. Whether cancer status affects outcomes in patients with large vessel occlusions that undergo endovascular thrombectomy remains unknown. Methods and Results All consecutive patients undergoing endovascular thrombectomy for large vessel occlusions were recruited into a prospective ongoing multicenter database, and the data were retrospectively analyzed. Patients with active cancer were compared with patients with cancer in remission. Association of cancer status with 90-day functional outcome and mortality were calculated in multivariable analyses. We identified 154 patients with cancer and large vessel occlusions that underwent endovascular thrombectomy (mean age, 74±11; 43% men; median National Institutes of Health Stroke Scale 15). Of the included patients, 70 (46%) had a remote history of cancer or cancer in remission, and 84 (54%) had active disease. Outcome data at 90 days poststroke were available for 138 patients (90%) and was classified as favorable in 53 (38%). Patients with active cancer were younger and more often smoked but did not significantly differ from those without malignancy in other risk factors, stroke severity, stroke subtype, or procedural variables. Favorable outcome rates among patients with active cancer did not significantly differ compared with those seen in patients without active cancer, but mortality rates were significantly higher among patients with active cancer on univariate and multivariable analyses. Conclusions Our study suggests that endovascular thrombectomy is safe and efficacious in patients with history of malignancy as well as in those with active cancer at the time of stroke onset, although mortality rates are higher among patients with active cancer.

Gait analysis of leprosy patients with foot drop using principal component analysis.

BACKGROUND: Peripheral nerve injury caused by leprosy can lead to foot drop, resulting in an altered gait pattern that has not been previously described using 3D gait analysis. METHODS: Gait kinematics and dynamics were analyzed in 12 patients with unilateral foot drop caused by leprosy and in 15 healthy controls. Biomechanical data from patients' affected and unaffected limbs were compared with controls using inferential statistics and a standard distance, based on principal components analysis (PCA). FINDINGS: Patients walked slower than controls (0.8 ± 0.2 vs. 1.1 ± 0.2 m/s, p = 0.003), with a reduced stance and increased swing percentage. The affected limb increased (p < 0.05) plantar flexion at the initial contact (-16.8o ± 8.3), terminal stance (-29.1o ± 11.5), and swing (-12.4o ± 6.2) in the affected limb compared to unaffected (-6.6o ± 10.3; -14.6o ± 11.6; 2.4o ± 7.6) and controls (-5.4o ± 2.5; -18.8o ± 5.8; -1.4o ± 3.9). Increased pelvic tilt and knee adduction/abduction range, with lower hip adduction, were observed. The second peak of ground reaction force (98.6 ± 5.2 %BW), ankle torque (0.99 ± 0.33 Nm/kg), and net ankle work in stance (-0.03 ± 5.4 J/Kg) decreased in the affected limb compared to controls (104.1 ± 5.5 %BW; 1.24 ± 0.4 Nm/kg; -4.58 ± 5.19 J/kg; p < 0.05). There were decreasing multivariate standard distances in the affected limb compared with the unaffected and controls. PCA loading factors highlighted the major differences between groups. INTERPRETATION: Leprosy patients with foot drop presented altered gait patterns in affected and unaffected limbs. There were remarkable differences in ankle kinematics and dynamics. Rehabilitation devices, such as ankle foot orthosis or tendon transfer surgeries to increase ankle dorsiflexion, could benefit these patients and reduce deviations from normal gait.

Pathologic Response to Neoadjuvant Sequential Chemoradiation Therapy in Locally Advanced Breast Cancer: Preliminary, Translational Results from the French Neo-APBI-01 Trial.

BACKGROUND: Radiation therapy (RT), a novel approach to boost the anticancer immune response, has been progressively evaluated in the neoadjuvant setting in breast cancer (BC). PURPOSE: We aimed to evaluate immunity-related indicators of response to neoadjuvant chemoradiation therapy (NACRT) in BC for better treatment personalization. PATIENTS AND METHODS: We analyzed data of the first 42 patients included in the randomized phase 2 Neo-APBI-01 trial comparing standard neoadjuvant chemotherapy (NACT) and NACRT regimen in locally advanced triple-negative (TN) and luminal B (LB) subtype BC. Clinicopathological parameters, blood counts and the derived parameters, total tumor-infiltrating lymphocytes (TILs) and their subpopulation, as well as TP53 mutation status, were assessed as predictors of response. RESULTS: Twenty-one patients were equally assigned to each group. The pathologic complete response (pCR) was 33% and 38% in the NACT and NACRT groups, respectively, with a dose-response effect. Only one LB tumor reached pCR after NACRT. Numerous parameters associated with response were identified, which differed according to the assigned treatment. In the NACRT group, baseline hemoglobin of ≥13 g/dL and body mass index of <26 were strongly associated with pCR. Higher baseline neutrophils-to-lymphocytes ratio, total TILs, and T-effector cell counts were favorable for pCR. CONCLUSION: This preliminary analysis identified LB and low-TIL tumors as poor responders to the NACRT protocol, which delivered RT after several cycles of chemotherapy. These findings will allow for amending the selection of patients for the trial and help better design future trials of NACRT in BC.

[GLIOBLASTOMA MULTIFORME AFTER STEREOTACTIC RADIOSURGERY TREATMENT FOR ARTERIO-VENOUS MALFORMATION].

INTRODUCTION: Stereotactic radiosurgery (SRS) is a minimally invasive option commissioned in the treatment of intracranial arteriovenous malformations (AVMs). As long-term follow-up data became available, some late adverse effects have been reported, including SRS-induced neoplasia. However, the exact incidence of this adverse effect is unknown. In this article we present and discuss the topic with an unusual case of a young patient who was treated with SRS for AVM and developed a malignant brain tumor.

Effect of lethal total body irradiation on bone marrow chimerism, acute graft-versus-host disease, and tumor engraftment in mouse models: impact of different radiation techniques using low- and high-energy X-rays.

PURPOSE: Effects of X­ray energy levels used for myeloablative lethal total body irradiation (TBI) delivery prior to bone marrow transplantation (BMT) in preclinical mouse models were examined. MATERIALS AND METHODS: In mouse models, single-fraction myeloablative TBI at a lethal dose was delivered using two different X­ray devices, either low (160 kV cabinet irradiator) or high energy (6 MV linear accelerator), before semi-allogeneic hematopoietic stem-cell transplantation (HSCT) to ensure bone marrow (BM) chimerism, graft-versus-host disease (GVHD), and tumor engraftment. Recipient mice were clinically followed for 80 days after bone marrow transplantation (BMT). Flow cytometry was performed to assess donor chimerism and tumor engraftment in recipient mice. RESULTS: Both X­ray irradiation techniques delivered a 10 Gy single fraction of TBI, presented a lethal effect, and could allow near-complete early donor chimerism on day 13. However, low-energy irradiation increased T cells' alloreactivity compared to high-energy irradiation, leading to clinical consequences for GVHD and tumor engraftment outcomes. The alloreactive effect differences might be attributed to the distinction in inflammatory status of irradiated recipients at donor cell infusion (D0). Delaying donor cell administration (D1 after lethal TBI) attenuated T cells' alloreactivity and clinical outcomes in GVHD mouse models. CONCLUSION: Different X­ray irradiation modalities condition T cell alloreactivity in experimental semi-allogeneic BMT. Low-energy X­ray irradiator induces a post-TBI inflammatory burst and exacerbates alloreactive reactions. This technical and biological information should be considered in interpreting GVHD/ graft-versus-leukemia effect results in mice experimental models of BMT.

Coating (Coating to Optimize Aneurysm Treatment in the New Flow Diverter Generation) study. The first randomized controlled trial evaluating a coated flow diverter (p64 MW HPC): study design.

BACKGROUND: Due to its high efficacy, flow diversion is increasingly used in the management of unruptured and recanalized aneurysms. Because of the need for perioperative dual antiplatelet treatment (DAPT), flow diversion is not indicated for the treatment of ruptured aneurysms. To overcome this major limitation, surface modification-'coating'-of flow diverters has been developed to reduce platelet aggregation on the implanted device, reduce thromboembolic complications, and facilitate the use of coated flow diverter treatment in patients with single antiplatelet treatment (SAPT). COATING (Coating to Optimize Aneurysm Treatment in the New Flow Diverter Generation) is a prospective, randomized, multicenter trial that aims to determine whether the use of the coated flow diverter p64 MW HPC under SAPT is non-inferior (or even superior) to the use of the bare flow diverter p64 MW under DAPT in relation to thromboembolic and hemorrhagic complications. METHODS: Patients with unruptured or recanalized aneurysms for which endovascular treatment with a flow diverter is indicated will be enrolled and randomly assigned on a 1:1 ratio to one of two treatment groups: p64 MW HPC with SAPT or p64 MW with DAPT. RESULTS: The primary endpoint is the number of diffusion-weighted imaging lesions visualized via MRI assessed within 48 hours (±24 hours) of the index procedure. Secondary primary endpoints are comparing safety and efficacy in both arms. CONCLUSIONS: This randomized controlled trial is the first to directly compare safety and efficacy of coated flow diverters under SAPT with bare flow diverters under DAPT. TRIAL REGISTRATION NUMBER: http://clinicaltrials.gov/ - NCT04870047.

Diagnostic Yield of High-Resolution Vessel Wall Magnetic Resonance Imaging in the Evaluation of Young Stroke Patients.

(1) Background: The mechanism responsible for stroke in patients younger than 50 often remains unknown. This study was designed to assess whether high-resolution intracranial vessel wall MR imaging (icVWI) may be instrumental in determining stroke cause. (2) Methods: Young stroke patients with and without an identified cause of stroke despite an exhaustive investigation were prospectively included. Patients who underwent icVWI were compared to those who did not. We next compared patients with and without intracranial vulnerable plaques on icVWI. (3) Results: Overall, 47 young stroke patients were identified over the span of 2 years and included in this study. Of those, 20 (42%) underwent intracranial icVWI. Cancer prevalence was higher among patients who did not have an icVWI study (19% vs. 0% p = 0.042) but there were no other significant differences between patients who had an icVWI study and those who did not have an icVWI. Among patients who had an icVWI, 11 (55%) had vulnerable plaques and the remaining nine studies were negative. Patients with positive icVWI scans had significantly higher stroke severity at admission (mean ± SD NIHSS score 5.5 ± 3.5 vs. 1.7 ± 2.3, p = 0.012). Patients with positive icVWI scans were more often treated with antiplatelets upon discharge (100% vs. 67%, p = 0.038). (4) Conclusions: icVWI can add significant information relevant to stroke pathogenesis and secondary prevention among young stroke patients with a negative exhaustive diagnostic workup.

Correction: Ponzo et al. Nucleolin Therapeutic Targeting Decreases Pancreatic Cancer Immunosuppression. Cancers 2022, 14, 4265.

In the original publication [...].

Tandem occlusions involving the internal carotid and anterior cerebral arteries-A rare form of stroke: Results from the multicenter EVATRISP collaboration study.

Background: Patients with stroke secondary to isolated anterior cerebral artery (ACA) occlusions have poor outcomes. Whether tandem occlusions (TO) of the extracranial internal carotid (ICA) and the ACA carry even worse outcomes that remain unknown. Methods: Patients with TO involving ICA and ACA occlusions were identified from 14 participating centers from the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) project which is a multicenter, observational, cohort study with prospective accrual of data followed by retrospective data analysis. Patients with isolated ACA stroke served as controls. Results: Included were 92 patients with isolated ACA and 16 patients with ICA-ACA TO stroke. On univariate analyses, patients with TO had more severe strokes on admission [median NIHSS (IQR) 13.5 (9-21) vs. 8 (5-12), p = 0.003] and were more often treated with thrombectomy (81 vs. 40%, p = 0.002). Mortality rates were higher among TO patients (31 vs. 11%, p = 0.03). Rates of favorable functional outcomes were numerically lower among TO patients (38 vs. 60%) but the difference was not statistically significant (p = 0.09). On multivariate analyses, the presence of TO did not modify the chances for favorable outcomes. Conclusion: TO stroke with ICA and isolated ACA involvement is rare and results in more severe initial neurological deficits and higher mortality compared to those seen in patients with isolated ACA stroke.

Visualization of both proximal M2-MCA segments in patients (the Tilted-V Sign) with acute M1-MCA occlusion stroke is associated with better procedural and prognostic outcomes.

Introduction: We aimed to assess the clinical significance of M1-MCA occlusion with visualization of both MCA-M2 segments ["Tilted-V sign" (TVS)] on initial CT angiography (CTA) in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT). Methods: Data for patients with consecutive AIS undergoing EVT for large vessel occlusion (LVO) in two academic centers are recorded in ongoing databases. Patients who underwent EVT for M1-MCA occlusions ≤ 6 h from symptom onset were included in this retrospective analysis. Results: A total of 346 patients met the inclusion criteria; 189 (55%) had positive TVS. Patients with positive TVS were younger (68 ± 14 vs. 71 ± 14 years, P = 0.028), with similar rates of vascular risk factors and baseline modified Rankin scores (mRS) 0-2. The rates of achieving thrombolysis in cerebral ischemia (TICI) 2b-3 were similar to the two groups (79%), although successful first-pass recanalization was more common with TVS (64 vs. 36%, p = 0.01). On multivariate analysis, higher collateral score [odds ratio (OR) 1.38 per unit increase, p = 0.008] and lower age (OR 0.98 per year increase, p = 0.046) were significant predictors of TVS. Patients with positive TVS had higher post-procedural Alberta Stroke Program Early CT Score (ASPECTS; 6.9 ± 2.2 vs. 5.2 ± 2.3, p = 0.001), were discharged with lower National Institutes of Health Stroke Score (NIHSS; 6±6 vs. 9±7, p = 0.003) and higher rates of mRS 0-2 (29.5 vs. 12%, p = 0.001), and had lower rates of 90-day mortality (13.2 vs. 21.6%, p = 0.038). However, TVS was not an independent predictor of functional independence (OR 2.51; 95% CI 0.7-8.3). Conclusion: Tilted-V Sign, an easily identifiable radiological marker, is associated with fewer recanalization attempts, better functional outcomes, and reduced mortality.

ICG Flow 800 technology targeted STA-MCA microvascular bypass for exclusion of deep-seated fusiform MCA aneurysm: 2-dimensional operative video.

The authors present the case of an 18-year-old male with a deep-seated left fusiform dissecting M3 aneurysm for which endovascular treatment was not applicable. At the open surgery, they used the less commonly reported FLOW 800 fluorescent indocyanine green (ICG) videoangiography, before and after parental aneurysmal artery temporary clipping, to locate the distal outflow branch of the aneurysm and use it as the recipient artery for a superficial temporal artery-M4 bypass, excluding the aneurysm by clipping the parental artery. Repeated ICG FLOW 800 angiography confirmed bypass patency and adequate blood flow. The aneurysm's exclusion from circulation was confirmed by digital subtraction angiography postoperatively. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21183.

Endovascular thrombectomy is beneficial for functional nonagenarians - a multicenter cohort analysis.

INTRODUCTION: The use of endovascular thrombectomy (EVT) has dramatically increased in recent years. However, most existing studies used an upper age limit of 80 and data regarding the safety and efficacy of EVT among nonagenarians is still lacking. METHODS: 767 consecutive patients undergoing EVT for large vessel occlusion (LVO) in three participating centers were recruited into a prospective ongoing database. Demographic, clinical and imaging characteristics were documented. Statistical analysis was done to evaluate EVT outcome among nonagenarians compared to younger patients. RESULTS: The current analysis included 41 (5.4%) patients older than 90 years. Compared to younger patients, nonagenarians were more often female (78% versus 50.3%, p ≤ 0.001), had worse baseline mRS scores (2 [0-3] versus 0 [0-2], p < 0.001), higher rates of hypertension and hyperlipidemia and a higher admission NIHSS (20 [14-23] versus 16 [11-20], p < 0.001). No differences were found between groups regarding the involved vessel, stroke etiology, time from symptoms to door or symptoms to EVT, successful recanalization rates and hemorrhagic transformation rates. Nonagenarians had worse mRS at 90 days (5 [3-6] versus 3 [2-5], p = 0.001), similar discharge NIHSS (5 [1-11] versus 4 [1-11], p = 0.78) and higher mortality rates (36.6% versus 15.8%, p < 0.001). All nonagenarians with baseline mRS 4 have died within 90 days. 36.4% of nonagenarian patients with baseline MRS of 3 or less had favorable outcome. DISCUSSION: This study demonstrates that nonagenarian stroke patients with baseline mRS of 3 or less benefit from EVT with no significant difference in the rate of favorable outcome compared to octogenarians.

Nucleolin Therapeutic Targeting Decreases Pancreatic Cancer Immunosuppression.

Background: The pancreatic ductal adenocarcinoma (PDAC) microenvironment is highly fibrotic and hypoxic, with poor immune cell infiltration. Recently, we showed that nucleolin (NCL) inhibition normalizes tumour vessels and impairs PDAC growth. Methods: Immunocompetent mouse models of PDAC were treated by the pseudopeptide N6L, which selectively inhibits NCL. Tumour-infiltrating immune cells and changes in the tumour microenvironment were analysed. Results: N6L reduced the proportion of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) and increased tumour-infiltrated T lymphocytes (TILs) with an activated phenotype. Low-dose anti-VEGFR2 treatment normalized PDAC vessels but did not modulate the immune suppressive microenvironment. RNAseq analysis of N6L-treated PDAC tumours revealed a reduction of cancer-associated fibroblast (CAF) expansion in vivo and in vitro. Notably, N6L treatment decreased IL-6 levels both in tumour tissues and in serum. Treating mPDAC by an antibody blocking IL-6 reduced the proportion of Tregs and MDSCs and increased the amount of TILs, thus mimicking the effects of N6L. Conclusions: These results demonstrate that NCL inhibition blocks the amplification of lymphoid and myeloid immunosuppressive cells and promotes T cell activation in PDAC through a new mechanism of action dependent on the direct inhibition of the tumoral stroma.