Tailoring CD19xCD3-DART exposure enhances T-cells to eradication of B-cell neoplasms.

Many patients with B-cell malignancies can be successfully treated, although tumor eradication is rarely achieved. T-cell-directed killing of tumor cells using engineered T-cells or bispecific antibodies is a promising approach for the treatment of hematologic malignancies. We investigated the efficacy of CD19xCD3 DART bispecific antibody in a broad panel of human primary B-cell malignancies. The CD19xCD3 DART identified 2 distinct subsets of patients, in which the neoplastic lymphocytes were eliminated with rapid or slow kinetics. Delayed responses were always overcome by a prolonged or repeated DART exposure. Both CD4 and CD8 effector cytotoxic cells were generated, and DART-mediated killing of CD4+ cells into cytotoxic effectors required the presence of CD8+ cells. Serial exposures to DART led to the exponential expansion of CD4 + and CD8 + cells and to the sequential ablation of neoplastic cells in absence of a PD-L1-mediated exhaustion. Lastly, patient-derived neoplastic B-cells (B-Acute Lymphoblast Leukemia and Diffuse Large B Cell Lymphoma) could be proficiently eradicated in a xenograft mouse model by DART-armed cytokine induced killer (CIK) cells. Collectively, patient tailored DART exposures can result in the effective elimination of CD19 positive leukemia and B-cell lymphoma and the association of bispecific antibodies with unmatched CIK cells represents an effective modality for the treatment of CD19 positive leukemia/lymphoma

Multiscale Effect of Hierarchical Self-Assembled Nanostructures on Superhydrophobic Surface

In this work, we describe self-assembled surfaces with a peculiar multiscale organization, from the nanoscale to the microscale, exhibiting the Cassie–Baxter wetting regime with extremely low water adhesion: floating drops regime with roll-off angles < 5°. These surfaces comprise bundles of hierarchical, quasi-one-dimensional (1D) TiO2 nanostructures functionalized with a fluorinated molecule (PFNA). While the hierarchical nanostructures are the result of a gas-phase self-assembly process, their bundles are the result of the capillary forces acting between them when the PFNA solvent evaporates. Nanometric features are found to influence the hydrophobic behavior of the surface, which is enhanced by the micrometric structures up to the achievement of the superhydrophobic Cassie–Baxter state (contact angle (CA) ≫ 150°). Thanks to their high total and diffuse transmittance and their self-cleaning properties, these surfaces could be interesting for several applications such as smart windows and photovoltaics where light management and surface cleanliness play a crucial role. Moreover, the multiscale analysis performed in this work contributes to the understanding of the basic mechanisms behind extreme wetting behaviors

Multiscale Effect of Hierarchical Self-Assembled Nanostructures on Superhydrophobic Surface

In this work, we describe self-assembled surfaces with a peculiar multiscale organization, from the nanoscale to the microscale, exhibiting the Cassie–Baxter wetting regime with extremely low water adhesion: floating drops regime with roll-off angles < 5°. These surfaces comprise bundles of hierarchical, quasi-one-dimensional (1D) TiO₂ nanostructures functionalized with a fluorinated molecule (PFNA). While the hierarchical nanostructures are the result of a gas-phase self-assembly process, their bundles are the result of the capillary forces acting between them when the PFNA solvent evaporates. Nanometric features are found to influence the hydrophobic behavior of the surface, which is enhanced by the micrometric structures up to the achievement of the superhydrophobic Cassie–Baxter state (contact angle (CA) ≫ 150°). Thanks to their high total and diffuse transmittance and their self-cleaning properties, these surfaces could be interesting for several applications such as smart windows and photovoltaics where light management and surface cleanliness play a crucial role. Moreover, the multiscale analysis performed in this work contributes to the understanding of the basic mechanisms behind extreme wetting behaviors

Mid-term results on a new self-expandable covered stent combined with branched stent-grafts: insights from a multicenter Italian registry

Objective: To investigate the technical periprocedural and mid-term outcomes of endovascular repairs with multibranched (BEVAR) or iliac-branch devices (IBD) combined with a new self-expanding covered stent. Methods: The COBRA (COvera in BRAnch) registry is a physician-initiated, multicenter, ambispective, observational registry (ClinicalTrials.gov Identifier: NCT04598802) enrolling patients receiving a BEVAR or IBD procedure mated with Bard Covera Plus (Tempe, Arizona, USA) covered stent, designed to evaluate the outcomes of the covered stent mated with patient-specific and off-the-shelf branched stent-graft. Primary endpoints were technical success, branch instability, and freedom from aortic and branch-related reintervention within 30 days and at follow-up. Preoperative characteristics, comorbidities, and outcomes definition were graded according to the Society for Vascular Surgery reporting standards. Results: Two hundred eighty-four patients [76 years (70-80); 79% males] in 24 centers were enrolled for a total of 708 target vessels treated. The CSs were mated with an off-the-shelf graft in 556 vessels (79%) and a custom-made graft in 152 (21%). Three-hundred-seven adjunctive relining stents in 277 vessels (39%) were deployed, of which 116 (38%) proximal, 66 (21%) intrastent and 125 (41%) distal. Adjunctive relining stent placement was more frequent when landing in a vessel branch instead of the main trunk (59%vs39%, p=.031), performing a percutaneous access (49%vs35%, p<.001), using a stent with a diameter ≥8mm (44%vs36%, p=.032) and a length ≥80mm (65%vs55%, p=.005), when a post-dilatation was not performed (45%vs29%, p<.001) and when an inner-branch configuration was used (55%vs35%, p<.001). Perioperative technical bridging success was 98%. Eight patients (3%) died in the perioperative period. Two deaths (1%) were associated with renal branch occlusion followed by acute kidney injury and paraplegia. Follow-up data were available for 638 vessels (90%) at a median of 32 months (Q1, Q3: 21,46). A branch instability was reported in 1% of branches. Forty-six (17%) patients died during follow-up, nine (3%) of them due to aortic-related causes. Primary patency rates at one year, two and three years were 99% (581/587), 99% (404/411), and 97% (272/279) respectively. Branch instability was associated with patient-specific devices (9% vs 4%, p=.014) and intrastent adjunctive stent placement (12% vs 2%, p=.003), especially when a bare metal balloon-expandable stent was used (25%vs3%, p<.001). Conclusions: The use of this new self-expanding covered stent mated with branched endografts proved to be safe and feasible with high technical procedural success rates. Low rates of branch instability were observed at mid-term follow-up. Comparative studies with other commercially available covered stents are warranted

The "Woundosome" Concept and Its Impact on Procedural Outcomes in Patients With Chronic Limb-Threatening Ischemia

This editorial assembles endovascular specialists from diverse clinical backgrounds and nationalities with a global call to address key challenges to enhance revascularization in chronic limb-threatening ischemia (CLTI) patients.- Dedicated below-the-ankle (BTA) angiography and revascularization is underutilized in ischemic foot treatment. Existing guidelines do not address comprehensive BTA vessel analysis. CLTI trials also often lack data on in-line arterial flow to the ischemic lesion and BTA vessel evaluation, hindering outcome assessment.- Dedicated multi-planar angiographic evaluation of the distal microcirculation is key: Direct arterial flow or good-quality collaterals are crucial in influencing wound healing and need to be assessed diligently to the level of the distal ischemic wound territory, termed “woundosome.”- An important primary emphasis of future trials should be on validating technologies and strategies for assessing tissue perfusion before, during, and after revascularization undertaken to heal tissue loss in CLTI patients. This will allow determination of a potentially significant delta in tissue perfusion prior to and following intervention at the “woundosome” level. Once changes in arterial perfusion have been identified as positively correlated to wound healing, these could serve as a much-needed novel primary technical outcome measure for patients with tissue loss undergoing surgical, hybrid, or endovascular revascularization

A technical review of bail-out procedures to place Najuta stent-graft into the ascending aorta

BackgroundThe Najuta stent-graft (Kawasumi Laboratories Inc., Tokyo, Japan) is usually easily advanced to the correct deployment position in the ascending aorta thanks to the pre-curved delivery J-sheath with all fenestrations automatically oriented towards the supra-aortic vessels. Aortic arch anatomy and delivery system stiffness could however represent limitations for proper endograft advancement, especially when the aortic arch bends sharply. The aim of this technical note is to report a series of bail-out procedures that could be useful to overcome the difficulties encountered during the Najuta stent-graft advancement up to the ascending aorta.Main bodyThe insertion, positioning and deployment of a Najuta stent-graft requires a through-and-through guidewire technique using a .035 '' 400 cm hydrophilic nitinol guidewire (Radifocus (TM) Guidewire M Non-Vascular, Terumo Corporation, Tokyo, Japan) with right brachial and both femoral accesses. When standard maneuver to put the endograft tip into the aortic arch, some bail-out procedures can be applied to obtain proper positioning. Five techniques are described into the text: positioning of a coaxial extra-stiff guidewire; positioning of a long introducer sheath down to the aortic root from the right brachial access; inflation of a balloon inside the ostia of the supra-aortic vessels; inflation of a balloon inside the aortic arch (coaxial to the device); and transapical access technique. This is a troubleshooting guide for allowing physicians to overcome various difficulties with the Najuta endograft as well as for other similar devices.Short conclusionTechnical issues in advancing the delivery system of Najuta stent-graft could occur. Therefore, the rescue procedures described in this technical note could be useful to guarantee the correct positioning and deployment of the stent-graft

Preliminary results from an Italian National Registry on the outcomes of the Najuta fenestrated aortic arch endograft

Introduction: Arch pathology represents one of the last frontiers in aortic aneurysms endovascular management. Several companies recently developed dedicated branched and fenestrated endografts specifically designed for the aortic arch, aiming to overcome some of the issues associated with standard thoracic endograft and supra-aortic vessels extra-anatomical debranching. This study aimed to evaluate early outcomes obtained with a custom-made fenestrated endograft approved for thoracic aortic aneurysms exclusion. Methods: All consecutive patients treated with the Najuta endograft (Kawasumi Laboratories, Inc, Tokyo, Japan) in Italy were prospectively enrolled and included in the study population. Anatomical characteristics and perioperative data were retrospectively analyzed. Study endpoints were technical success, 30-day clinical success, overall survival, supra-aortic vessel patency, endoleak and need for reintervention or surgical conversion. Results: During the period 2018-2022, seventy-six patients received a Najuta endograft in Italy and were enrolled in the study. Median age was 72 (IQR 69-76) years and 80.3% were male. Most of the patients received treatment for atherosclerotic aneurysms (80.3%) while the others for post-dissection aneurysms (7.9%), penetrating aortic ulcer (9.2%), or type I endoleak correction after previous thoracic endovascular repair (2.6%). Overall, 161 supra-aortic vessels were preserved through a dedicated fenestration. Technical success was achieved in 74/76 (97.4%) of procedures; both failures were associated with endoleak detection at final angiography (one type I and one type III endoleak). Two distal migrations occurred during the implanting procedure. Clinical success at 30 days was 94.7%. Two early reinterventions were needed within 30 days after index procedure: in one case an aortic false lumen coils embolization was performed, since distal re-entry caused enlargement of the post dissection thoracic aneurysm. The other procedure consisted of a femoral pseudoaneurysm repair. Median follow-up was 7 (IQR 3-15) months; no supra-aortic vessel occlusions occurred and no patients needed surgical conversion. Conclusion: Early results suggest that in selected patients with aortic arch pathology needing a proximal landing, an endovascular approach with the Najuta system is safe and effective, especially for those at high surgical risk. A strict follow-up with high-quality computed tomography angiography images and eventual long-term complications evaluation is needed to confirm these initial experience findings