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The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (UCAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture. The UCAR-NKT cells are produced with high yield, purity, and robustness, and they display a stable HLA-ablated phenotype that enables resistance to host cell-mediated allorejection. These UCAR-NKT cells exhibit potent antitumor efficacy to blood cancers and solid tumors, both in vitro and in vivo, employing a multifaceted array of tumor-targeting mechanisms. These cells are further capable of altering the tumor microenvironment by selectively depleting immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells. In addition, UCAR-NKT cells demonstrate a favorable safety profile with low risks of graft-versus-host disease and cytokine release syndrome. Collectively, these preclinical studies underscore the feasibility and significant therapeutic potential of UCAR-NKT cell products and lay a foundation for their translational and clinical development.
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Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Células T Matadoras Naturais , Receptores de Antígenos Quiméricos , Humanos , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Animais , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Imunoterapia Adotiva/métodos , Camundongos , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Edição de Genes , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias/terapia , Neoplasias/imunologia , Linhagem Celular Tumoral , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologiaRESUMO
OBJECTIVE: To report outcomes of urgent juxtarenal/pararenal aneurysms (J/P-AAAs) managed by off-the-shelf multibranched thoracoabdominal endografts (Cook, T-branch). METHODS: In this observational, multicenter, retrospective study, patients with J/P-AAAs treated by urgent endovascular repair by T-branch in 23 European aortic centers, from 2013 to 2023, were analyzed. Contained J/P-AAAs rupture, presence of related symptoms, and aneurysm diameter of >70 mm were considered as indication for urgent repair. Technical success (TS), spinal cord ischemia (SCI), and 30-day/hospital mortality were assessed as early outcomes. Survival, freedom from reinterventions, and target artery instability (TAI) were evaluated during follow-up. RESULTS: Overall, 197 patients (J-AAAs, n = 64 [33%]; P-AAAs, n = 95 [48%]; previous failed endovascular aneurysm repair (EVAR), n = 38 [19%]) were analyzed. The mean age and aneurysm diameter was 75 ± 8 years and 76 ± 4 mm, respectively. The American Society of Anesthesiologists score was 3 and 4 in 118 (60%) and 79 (40%) patients. Rupture, symptoms, and diameter of >70 mm were present in 51 (26%), 110 (56%), and 53 (27%) patients, respectively. An adjunctive proximal thoracic endograft was used in 28 cases (14%). The mean aortic coverage between the upper portion of the endograft and the lowest renal artery was 154 ± 49 mm. Single-stage repair and cerebrospinal fluid drainage were reported in 144 (73%) and 53 (27%) cases, respectively. TS was achieved in 182 (92%) cases (rupture, 84% vs no rupture, 95%; P = .02). Failures consist of TA loss (11 [6%]: renal artery, 9; celiac trunk, 2), type I to III endoleaks (2 [1%]), and 24-h mortality (2 [1%]). Rupture was a risk factor for technical failure (P = .02; odds ratio [OR], 3.8; 95% confidence interval [CI], 1.1-12.1). Overall, 15 patients (8%) had persistent SCI (rupture, 14% vs no rupture, 5%) with 11 (6%) , of paraplegia (rupture, 10% vs no rupture, 5%; P = .001). Rupture (P = .04; OR, 3.1; 95% CI, 1.1-8.9) and adjunctive proximal thoracic endograft (P = .01; OR, 4.1; 95% CI, 1.3-12.9) were risk-factors for SCI. Twenty-two patients (11%) died within 30 days or during a prolonged hospitalization. Previous failed EVAR (P = .04; OR, 3.6; 95% CI, 1.1-12.3), paraplegia (P < .001; OR, 9.9; 95% CI, 1.6-62.2) and postoperative mesenteric complications (P = .03; OR, 10.4; 95% CI, 1.2-93.3), as well as cardiac (P = .03; OR, 8.2; 95% CI, 2.0-33.0) and respiratory (P < .001; OR, 10.1; 95% CI, 2.9-35.2) morbidities were associated with 30-day/hospital mortality. The mean follow-up was 19 ± 5 months. The estimated 3-year survival and freedom from reinterventions was 58% and 77%, respectively. TAI occurred in 27 patients (14%) (occlusion, 15; endoleak, 14) with an estimated 3-year freedom from TAI of 72%. CONCLUSIONS: Urgent repair of J/P-AAAs by T-branch is feasible and effective with satisfactory TS and 30-day/hospital mortality in high-risk patients. However, extensive aortic coverage is necessary, leading to a non-negligible SCI rate, especially in case of aortic rupture or when adjunctive thoracic endografts are necessary. Previous failed EVAR and postoperative mesenteric complications, as well as cardiac and respiratory morbidities were associated with 30-day/hospital mortality and should be subjected to more research for the purposes of improving outcomes.
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BACKGROUND: During the last years a great progress has been noted in device technology and operator experience in treating complex aortic aneurysms. Fenestrated and branched custom-made devices require detailed preoperative planning and production time that can take up to 12 weeks. During this awaiting period, the aortic related mortality is being increased. To overcome this limitation, off-the shelf standardized multibranched devices were launched in the market for the treatment of pararenal and thoracoabdominal aortic aneurysms (TAAA). Our aim was to systematically evaluate all the published studies of off-the shelf endografts for the treatment of pararenal and thoracoabdominal aortic aneurysms. METHODS: We performed a systematic review to identify all the eligible studies that reported outcomes to the off-the-shelf with inner or outer multibranched devices and then conducted a qualitative synthesis and meta-analysis of the results. The main outcomes were technical success, mortality, target visceral vessel (TVV) instability, major adverse events and reintervention rate. We estimated pooled proportions and 95% confidence intervals (CIs). RESULTS: A total of 1605 study titles were identified by the initial search strategy, of which 13 (8=t-Branch/ 3=E-nside/1=We-Flow/1=TAMBE) were considered eligible for inclusion in the meta-analysis. A total of 595 patients (70% male) were identified among the eligible studies. In terms of procedures, 64.4% were elective, 19.2% (13.4% outer-multibranched group (OMG); 6.1% inner-multibranched group (IMG) were emergent, and 16.4% (15.6% OMG; 0.8% IMG) were urgent. The pooled technical success was 92.1% (95%, CI, 83.8-96.4%) and 96.9% (95%, CI, 92.5-98.8%) for the outer- and inner-multibranched endograft, respectively. The pooled 30-day mortality was 10.4 % (95%, CI, 6.6-16.1%,) and 4.2% (95%, CI, 2.0-8.6%) for the outer and inner branched group respectively. The pooled 30-day and late TVV instability for the outer-branched group was 3.5% (95%, CI, 2.0-6.1%) and 6.2% (95%, CI, 4.7-8.0%) and for the inner branched group 10.4% (95%, CI, 4.5-22.5%) and 1.6% (95%, CI, 0.7-3.3%) respectively. CONCLUSIONS: This pooled analysis indicated good technical success and mortality rate, for both devices despite the high rate of urgent procedures. Pararenal and thoracoabdominal aortic aneurysms can be safely treated using the included devices. However, further studies are required to draw additional conclusions for the inner group due to the small sample size.
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OBJECTIVE: The aim of this study was to report the outcomes of endovascular urgent thoracoabdominal aortic (TAAA) repair, using an off-the-shelf preloaded inner branch device (E-nside; Artivion). METHODS: Data from a physician-initiated national multicenter registry, including patients treated with E-nside endograft (INBREED) were prospectively collected (2020-2024); only urgent cases were included in this study. Primary outcomes were technical success and mortality at 30 days. Secondary outcomes were spinal cord ischemia rate, stroke rate, major adverse events (MAE) as also branch instability at 12 months. RESULTS: Of 185 patients enrolled in the INBREED, 64 (34.5%) were treated in a urgent setting and were included in the study. Reason for urgent repair was presence of aneurysm-related symptoms in 31 patients (48.4%), a contained rupture in eight (12.5%), and a large aneurysm >80 mm in 25 (39.1%). Extent of repair was I to III in 32 patients (50%) and IV in 32 (50%); 18 (28%) had a narrow (<25 mm) paravisceral aortic lumen. An adjunctive proximal thoracic endograft was deployed in 29 patients (45.3%); a distal bifurcated abdominal endograft was used in 33 (51.5%). Two hundred forty-nine target vessels (97.2%) were successfully incorporated through an inner branch from an upper arm (81.2%) or femoral (18.8%) access. A balloon expandable stent was used in 184 (75.7%) target vessels, a self-expandable stent in 59 (24.3%). Mean time for target vessel bridging was 39.9 ± 28.4 minutes per target vessel. Thirty-day cumulative major adverse event (MAE) rate was 28%, and mortality occurred in five patients (9.1%). There was one postoperative stroke (1.6%), and the spinal cord ischemia (SCI) rate was 8% (n = 5). For the 249 target vessels successfully incorporated through an inner branch, 1-year freedom from target vessel instability was 93% ± 3% after 1 year. CONCLUSIONS: The E-nside represents a valid solution for the urgent treatment of TAAAs, including symptomatic and ruptured TAAAs, as well as large asymptomatic TAAAs that cannot wait for a custom-made device. The preloaded inner branches and available proximal and distal graft diameters might be useful in urgent settings and provided satisfactory early and 1-year results, in terms of both endograft and target vessel stability. Further studies are required to assess the clinical role of E-nside for urgent TAAA repair.
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OBJECTIVE: Fenestrated-branched endovascular aortic repair (FB-EVAR) has shown favorable outcomes for repair of complex aneurysms and thoracoabdominal aortic aneurysms (TAAA). Physician-modified endografting (PMEG) and the Gore Thoracoabdominal Multibranch Endoprosthesis (TAMBE) provide custom and off-the-shelf devices for FB-EVAR, respectively. This study compares the outcomes of TAMBE and PMEG at a single institution. METHODS: A retrospective review of patients who underwent TAMBE as part of the multicenter pivotal trial or PMEG as part of a prospective physician sponsored investigational device exemption at a single institution between 2020-2022 were completed. Patient demographics, characteristics, perioperative and midterm outcomes were compared. RESULTS: A total of 68 patients were included, with 12 in the TAMBE group and 56 in the PMEG group. Baseline characteristics were comparable between groups. Aneurysm type was most often TAAA in both groups (58% TAMBE and 52% PMEG). TAMBE had a higher rate of upper extremity access (100% vs 63%, P=.013) and longer mean procedure time (247 ± 36 vs 189 ± 49 minutes, P<.001). Other intraoperative metrics were similar between groups. Technical success was 100% in TAMBE and 95% in PMEG (P=0.412). There was no 30-day mortality in either group. No major adverse events occurred with TAMBE, while in PMEG cases, 2% had respiratory failure, 2% required dialysis, and 4% experienced spinal cord ischemia. While overall endoleak rates were similar (50% of TAMBE vs 41% of PMEG, P=0.57), type II accounted for all of the endoleaks in the TAMBE group, while type I or III endoleaks were seen in 11% of PMEG patients. At the median follow-up of 26.7 months for the TAMBE group and 21.2 months for the PMEG group, target vessel instability was seen in 10.4% of TAMBE, and 6.9% of PMEG targeted branches (P=0.401). Reintervention was required in 33% of TAMBE patients and 27% of PMEG patients (P=.646). Estimated freedom from reintervention at 3 years were similar (56% TAMBE vs. 62% PMEG, log-rank P=0.910). Freedom from visceral renal target vessel instability at 3 years was 89% for both groups (log-rank P=0.459). Kaplan Meier 3-year estimated survival was 100% for patients in the TAMBE group and 77% for patients in the PMEG group (log-rank P=.157). CONCLUSIONS: At experienced centers, FB-EVAR can be completed with PMEG or TAMBE with comparable, excellent perioperative and midterm outcomes. Reinterventions are frequently needed for both TAMBE and PMEG.
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INTRODUCTION: The aim of this study is to present single-center outcomes in patients treated with in situ laser fenestration thoracic endovascular aortic repair (LFTEVAR) for various aortic arch pathologies and assess the impact of increasing experience. METHODS: The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was followed. A retrospective analysis of prospectively collected single aortic center data was conducted, including baseline information and peri- and post-operative outcomes of consecutive patients managed with LFTEVAR for aortic arch pathologies. Patients were enrolled from April 1, 2017 to January 31, 2023. The cohort was dichotomized to compare early (2017-2019) and late experience (2020-2023). Primary outcomes were peri-operative mortality and cerebrovascular morbidity. RESULTS: Thirty patients were included (63.3% males, mean age 69.8±9.6 years); 21.4% presented with aortic ruptures. Aortic aneurysm involving the aortic arch was the most frequent pathology (53.3%). Forty target vessels (TVs) were revascularized, including 19 left subclavian arteries (47.5%) and 17 left common carotid arteries (42.5%). Double fenestrations were performed in 10 patients. The proximal landing zone was Ishimaru zone 0 in 5 patients (16.7%) and zone 1 in 13 patients (43.3%). Technical success was 93%. No spinal cord ischemia was recorded, and 3 patients (10%) suffered a post-operative stroke, of which 1 was major (3.3%). The median follow-up was 12 months (range=1-48 months). Thirty-day and follow-up mortality rates were 13.5% and 15.3%, respectively. Target vessel instability was 10%, of which 3.8% required reintervention. There was no statistically significant difference in outcomes between the early and late experience groups. CONCLUSIONS: Laser fenestration thoracic endovascular aortic repair of the aortic arch performed in experienced aortic centers is associated with low early mortality and stroke rates. It is a safe and effective therapeutic option in patients considered unfit for open repair. CLINICAL IMPACT: Custom-made devices for arch pathologies requiring urgent repair are not an option because of manufacturing delays. Off-the-shelf devices with single branch arch prostheses, and outside IFU techniques such as parallel-grafts and surgeon-modified endografts have been proposed in this setting. Another off-the-shelf alternative is in situ laser fenestration thoracic endovascular repair (LFTEVAR), which addresses many limitations of the other off-the-shelf options. Our study reports the outcomes of 30 patients treated with LFTEVAR, showing that it is a viable therapeutic option in patients considered unfit for open repair acknowledging that sufficient experience with complex endovascular aortic repair is mandatory to achieve acceptable outcomes in these high-risk patients with challenging aortic anatomies.
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PURPOSE: To analyze the early performance and efficacy of the first commercially available off-the-shelf precannulated multibranched endograft in the endovascular repair of pararenal abdominal aortic aneurysms (PAAAs). The device received European marketing approval in late 2020. MATERIALS AND METHODS: Between January 2021 and June 2023, a retrospective analysis of prospectively collected data from all consecutive patients with pAAAs undergoing implantation of the E-nside precannulated inner-branched endograft was conducted in 2 centers. The primary outcome measure was technical success defined as the composite endpoint of successful (1) delivery of the 24F endograft, (2) use of the precannulation tubes, and (3) implantation of the bridging stent-grafts (BSGs) to the target vessels. Main secondary endpoints were mortality, target vessel instability (TVI), absence of type I or III endoleak, reintervention, spinal cord ischemia, and supra-celiac aortic coverage. RESULTS: Twenty-one patients (20 men, mean age: 71 years) were included in this study with a mean follow-up of 14±7.7 months. Nine patients had a symptomatic aneurysm (43%). Technical success amounted to 95% (in one patient, an iliofemoral conduit was necessary to advance the device). One out of 112 BSGs (1%, right renal artery) occluded at 30 days, resulting in freedom from TVI and reintervention rate at 12 months of 95%. No type I or III endoleaks were identified during follow-up. One patient (5%) died at 13 months due to non-aneurysm-related death, and 1 patient (5%) developed spinal cord ischemia. No other major perioperative complications were observed. Mean supra-celiac aortic coverage reached 52±8%. CONCLUSIONS: Given the imperative need for an off-the-shelf endograft tailored to address PAAAs, the E-nside stent-graft demonstrated encouraging outcomes in this study. Nevertheless, it is essential to emphasize that the extent of aortic coverage mandates the production of a truncated variant. CLINICAL IMPACT: The endovascular repair of urgent pararenal aortic aneurysms remains still an unsolved problem in the endovascular era since there are no available off-the-shelf dedicated fenestrated or branched endografts. This paper confirms the safety and efficacy of the off-the-shelf precannulated inner branched endograft for this specific indication.
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OBJECTIVE: The upside-down configuration of a Gore Excluder contralateral leg endoprosthesis has been used to overcome diameter differences in the endovascular treatment of aortoiliac aneurysms. Our goal was not to describe the technique but to study the applicability and safety. MATERIAL AND METHODS: Patients were retrospectively enrolled. The indication and details of the procedure were at the discretion of the treating physicians. A case report form was completed including baseline characteristics, indication for treatment, procedural data, and outcomes during follow-up. RESULTS: A total of 31 subjects were enrolled with a range of indications, including 3 patients treated in the emergency setting (9.7%). In 64.5% (n=20), it was a primary intervention for a common iliac aneurysm (n=10), internal iliac aneurysm (n=4), or abdominal aortic aneurysm (n=6). In 11 subjects (35.5%), treatment was performed after previous aortoiliac interventions, including anastomotic iliac artery aneurysm (n=5), type III endoleak (n=3), and endograft thrombus (n=3). Median follow-up was 13 months (range=1-142 months). During follow-up, 2 patients required an upside-down contralateral leg-related secondary intervention, one for an occlusion and another for a type Ia endoleak. There was no type Ib or III endoleak, and no migration, kinking/stenosis, or conversion to open repair was observed. The aneurysm-related mortality was 3.3% (n=1). CONCLUSION: An upside-down contralateral leg is a valuable technique that can be used to achieve adequate aneurysm exclusion or resolve complications. It is associated with a limited number of complications. CLINICAL IMPACT: This article studies the use of an upside-down iliac endograft. We describe a wide range of indications in which this previously published technique has been applied. In elective and acute settings and as primary and revision intervention an upside-down iliac endograft was performed successfully. Furthermore, follow-up data is presented showing the effectiveness of the technique. Knowledge of this procedure is a valuable addition to the skillset of every interventionalist.
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PURPOSE: The treatment of thoracoabdominal aortic aneurysms (TAAAs) using branched endovascular aortic repair (BEVAR) is safe and effective. During deployment, the superior mesenteric artery (SMA) branch can unintentionally open into the celiac trunk (CT) ostium and switched catheterization of the SMA from the CT branch and the CT from the SMA branch can be used as an alternative technique in these cases. This study aimed to investigate the outcome of exchanging the intended target vessels (TVs) for the CT and SMA branches during BEVAR. MATERIALS AND METHODS: A single-center retrospective analysis of patients with TAAAs who underwent BEVAR, using off-the-shelf or custom-made devices (CMDs), with an unintended exchange of TVs for the CT and SMA branches was performed. RESULTS: Between 2014 and 2023, 397 patients were treated with BEVAR for TAAA. Eighteen (4.5%) of those patients were treated with an exchange of TVs for the CT and SMA branches. T-branch was used in 9 cases (50%) and the remaining patients were treated with CMDs. Twelve patients were treated electively, 3 were symptomatic and 3 presented with rupture. Of 36 mesenteric TVs in those 18 patients, 34 (94%) were catheterized successfully, including all 18 SMAs and 16 of the 18 CTs. No branch stenosis or occlusion of the switched mesenteric TVs was detected during follow-up. During 30-day follow-up, 3 patients died and during a median follow-up of 3 (interquartile range [IQR]: 1-15) months 3 more patients died. None of the deaths or the 2 unintended reinterventions was induced by the mesenteric TV exchange. The median hospital stay was 14 (IQR: 9-22) days with a median of 4 (IQR: 2-11) days at the intensive care unit. CONCLUSION: The exchange of the mesenteric TVs for the CT and SMA branches during BEVAR with off-the-shelf and CMD endografts is feasible with good TV patency and freedom from TV-related reinterventions. This alternative technique should be considered in selected cases when direct catheterization via the intended branch is deemed more time-consuming or not feasible. CLINICAL IMPACT: This is the first description of using an exchange of target vessels for the celiac trunk and the superior mesenteric artery branches in patients with thoracoabdominal aortic aneurysms undergoing BEVAR, using off-the-shelf or custom-made devices. The high success rate as well as the good clinical results without any branch stenosis or occlusion during follow-up highlight the feasibility of this alternative technique. It could help in challenging cases when catheterization of the intended target vessels is not possible or too time consuming, resulting in higher success rates of BEVAR and better clinical results.
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OBJECTIVE: To investigate outcomes of a novel, off the shelf multibranched endovascular stent graft for the treatment of thoraco-abdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PAAA). METHODS: A prospective, single centre study including 15 patients (mean age, 63.4 ± 10.7 years; 13 male) with TAAA or PAAA treated from October 2019 to March 2021 with a G-Branch endograft (Lifetech Scientific, Shenzhen, China) featuring a mixed multibranch design with two inner and two outer branches for reconstruction of the visceral and bilateral renal arteries, respectively. Follow up assessments were scheduled before discharge and at 30 days, six and 12 months after the index procedure. Annual telephone interviews were performed beyond the initial 12 months. The Kaplan-Meier method was used to estimate cumulative mortality and morbidity rates after endovascular repair. RESULTS: Technical success was achieved in all 15 patients. Nine patients (60%) had TAAA and six (40%) had PAAA (mean maximum aneurysm diameter, 73.7 ± 15.8 mm). The median follow up was 31.4 months (range, 10.1 - 44.0 months). At 30 days, there was no death and 7% morbidity (one case of temporary spinal cord ischaemia on Day 4). At one year, the mortality rate was 7% (one death from stroke at 10 months) and morbidity was 13% (one other case of renal function decline at six months). There were no aneurysm dilatations, re-interventions, or access related complications, and two (13%) persistent type II endoleaks. The one year primary branch patency rate was 100% for the four renovisceral arteries in all 13 patients who underwent computed tomography examinations. One patient died of hepatocellular carcinoma 29 months post-operatively, resulting in an estimated three year mortality rate of 13%. CONCLUSION: The G-Branch endograft yielded high technical success with good early and midterm outcomes for the treatment of TAAA and PAAA. A large multicentre study is warranted.
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Aneurisma da Aorta Abdominal , Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Aneurisma da Aorta Torácica/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Fatores de Tempo , Stents/efeitos adversos , Aneurisma da Aorta Abdominal/cirurgia , Artéria Renal/cirurgia , Procedimentos Endovasculares/efeitos adversos , Desenho de PróteseRESUMO
Human mucosal-associated invariant T (MAIT) cells are characterized by their expression of an invariant TCR α chain Vα7.2-Jα33/Jα20/Jα12 paired with a restricted TCR ß chain. MAIT cells recognize microbial peptides presented by the highly conserved MHC class I-like molecule MR1 and bridge the innate and acquired immune systems to mediate augmented immune responses. Upon activation, MAIT cells rapidly proliferate, produce a variety of cytokines and cytotoxic molecules, and trigger efficient antitumor immunity. Administration of a representative MAIT cell ligand 5-OP-RU effectively activates MAIT cells and enhances their antitumor capacity. In this review, we introduce MAIT cell biology and their importance in antitumor immunity, summarize the current development of peripheral blood mononuclear cell-derived and stem cell-derived MAIT cell products for cancer treatment, and discuss the potential of genetic engineering of MAIT cells for off-the-shelf cancer immunotherapy.
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Células T Invariantes Associadas à Mucosa , Neoplasias , Humanos , Células T Invariantes Associadas à Mucosa/metabolismo , Leucócitos Mononucleares/metabolismo , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/genética , Imunoterapia , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/metabolismoRESUMO
PURPOSE: The purpose of this pilot cross-sectional study was to compare the operating room (OR) efficiency and intraoperative staff task load when performing individualised versus off-the-shelf (OTS) total knee arthroplasty (TKA). METHODS: A consecutive series of 28 patients randomised (1:1) to receive either OTS TKA or individualised TKA were included. The OR staff workload was assessed with the NASA Task Load Index (TLX), a subjective grading system assessing mental demand, physical demand, temporal demand, performance, effort and frustration on a scale from 0 (very low) to 20 (very high). The time for patient preparation, surgical time, closure and total OR time was recorded to assess OR efficiency. Effect sizes of differences between OTS and individualised TKA were expressed as mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Patients in both cohorts were similar in age (OTS vs. individualised TKA (median [IQR]), 67 [63-76] vs. 71 [68-79]; p = 0.207) and body mass index (BMI) (29 [24-33] vs. 29 [26-31]; p = 0.807), and there were no significant differences in other preoperative characteristics. The OR staff perceived individualised TKA as less demanding than OTS TKA: Individualised TKA was rated significantly better across the six domains of the NASA TLX: mental demand by 5.6 points, physical demand by 6.3 points, temporal demand by 5.3 points, performance by 3.6 points, effort by 5.9 points and frustration by 5.8 points. Individualised TKA resulted in statistically significantly shorter mean total OR time (MD, 10 min; p = 0.018). CONCLUSION: The staff in the OR found that individualised TKA is less mentally, physically and temporally demanding than OTS TKA. The average total time spent in the OR during individualised TKA is 10 min less than during OTS TKA. CLINICAL TRIAL REGISTRATION: This study constitutes a part of a larger registered randomised controlled trial comparing patient satisfaction following OTS versus individualised TKA (NCT04460989). LEVEL OF EVIDENCE: Level III.
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This paper presents an innovative technique, Advanced Predictor of Electrical Parameters, based on machine learning methods to predict the degradation of electronic components under the effects of radiation. The term degradation refers to the way in which electrical parameters of the electronic components vary with the irradiation dose. This method consists of two sequential steps defined as 'recognition of degradation patterns in the database' and 'degradation prediction of new samples without any kind of irradiation'. The technique can be used under two different approaches called 'pure data driven' and 'model based'. In this paper, the use of Advanced Predictor of Electrical Parameters is shown for bipolar transistors, but the methodology is sufficiently general to be applied to any other component.
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In the face of rising population, erratic climate, resource depletion, and increased exposure to natural hazards, environmental monitoring is increasingly important. Satellite data form most of our observations of Earth. On-the-ground observations based on in situ sensor systems are crucial for these remote measurements to be dependable. Providing open-source options to rapidly prototype environmental datalogging systems allows quick advancement of research and monitoring programs. This paper introduces Loom, a development environment for low-power Arduino-programmable microcontrollers. Loom accommodates a range of integrated components including sensors, various datalogging formats, internet connectivity (including Wi-Fi and 4G Long Term Evolution (LTE)), radio telemetry, timing mechanisms, debugging information, and power conservation functions. Additionally, Loom includes unique applications for science, technology, engineering, and mathematics (STEM) education. By establishing modular, reconfigurable, and extensible functionality across components, Loom reduces development time for prototyping new systems. Bug fixes and optimizations achieved in one project benefit all projects that use Loom, enhancing efficiency. Although not a one-size-fits-all solution, this approach has empowered a small group of developers to support larger multidisciplinary teams designing diverse environmental sensing applications for water, soil, atmosphere, agriculture, environmental hazards, scientific monitoring, and education. This paper not only outlines the system design but also discusses alternative approaches explored and key decision points in Loom's development.
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INTRODUCTION: Total knee arthroplasty (TKA) can be performed with either conventional off-the-shelf (OTS) or customized individually-made (CIM) implants. The evidence for CIM implants is limited and variable, and the aim of this review was to compare clinical and radiological outcomes between CIM and OTS implants. METHODS: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Studies reporting on clinical, radiological, or alignment outcomes for CIM and OTS implants were selected. The studies were appraised using the Methodical index for non-randomized studies tool. RESULTS: Twenty-three studies fulfilled the inclusion criteria. The studies comprised 2856 CIM and 1877 OTS TKAs. Revision rate was higher with CIM (5.9%) compared to OTS (3.7%) implants [OR 1.23(95% CI 0.69-2.18)]. Manipulation under anesthesia (MUA) was higher in CIM (2.2%) compared to OTS (1.1%) group [OR 2.95(95% CI 0.95-9.13)] and complications rate was higher in CIM (5%) vs. OTS (4.5%) [OR 1.45(95% CI 0.53-3.96)] but neither reached statistical significance. Length of stay was significantly shorter in CIM group 2.9 days vs. 3.5 days [MD - 0.51(95% CI - 0.82 to - 0.20)]. Knee Society Score showed no difference between CIM and OTS groups for Knee 90.5 vs. 90.6 [MD - 0.27(95% CI - 4.27 to 3.73)] and Function 86.1 vs. 83.1 [MD 1.51(95% CI - 3.69 to 6.70)]. CONCLUSION: CIM implants in TKA have theoretical benefits over OTS prostheses. However, in this present review, CIM implants were associated with higher revisions, MUA, and overall complication rates. There was no difference in outcome score and CIM implants did not improve overall target alignment; however, more CIM TKAs were found to be in the HKA target zone compared to OTS TKAs. The findings of this review do not support the general utilization of CIM over OTS implants in TKA.
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Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Articulação do Joelho/cirurgia , Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Resultado do TratamentoRESUMO
Chimeric antigen receptor-transduced autologous T (CAR-T) cell therapy targeting CD19 has revolutionized the treatment of CD19-positive hematological tumors, including acute lymphoblastic leukemia and large B-cell lymphoma. However, despite the high response rate, many problems such as exceedingly high cost, complex logistics, insufficient speed, and manufacturing failures have become apparent. One solution for these problems is to use an allogeneic cell as an effector cell for genetic modification with CAR. Allogeneic, or "off-the-shelf", CAR-expressing immune-effector cells include 1) genome-edited, T-cell receptor (TCR) gene-deleted CAR-T cells generated using healthy adult donor T cells, 2) induced pluripotent stem cell-derived CAR-T cells, and 3) CAR NK cells. NK cells are notorious for their poor ex-vivo expansion and low susceptibility to genetic modification. In this article, I will review the current state and future prospects of allogeneic CAR cell therapies, with special reference to CAR NK cells.
Assuntos
Células Matadoras Naturais , Humanos , Células Matadoras Naturais/imunologia , Transplante Homólogo , Receptores de Antígenos Quiméricos/imunologia , Imunoterapia Adotiva/métodosRESUMO
Respiratory syncytial virus (RSV)-associated viral infections are a major public health problem affecting the immunologically naïve/compromised populations. Given the RSV-associated morbidity and the limited treatment options, we sought to characterize the cellular immune response to RSV to develop a targeted T cell therapy for off-the-shelf administration to immunocompromised individuals. Here we report on the immunological profiling, as well as manufacturing, characterization and antiviral properties of these RSV-targeted T cells. A randomized, phase 1/2 clinical trial evaluating their safety and activity in haematopoietic stem cell transplant recipients as an off-the-shelf multi-respiratory virus-directed product is currently underway (NCT04933968, https://clinicaltrials.gov).
Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Antivirais/uso terapêutico , Imunoterapia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Linfócitos TRESUMO
The accelerated development of antitumor immunotherapies in recent years has brought immunomodulation into the spotlight. These include immunotherapeutic treatments with dendritic cell (DC)-based vaccines which can elicit tumor-specific immune responses and prolong survival. However, this personalized treatment has several drawbacks, including being costly, labor-intensive, and time consuming. This has sparked interest in producing artificial dendritic cells (aDCs) to open up the possibility of standardized "off-the-shelf" protocols and circumvent the cumbersome and expensive personalized medicine. aDCs take advantage of materials that can be designed and tailored for specific clinical applications. Here, an overview of the immunobiology underlying antigen presentation by DCs is provided in an attempt to select the key features to be mimicked and/or improved through the development of aDCs. The inherent properties of aDCs that greatly impact their performance in vivo and, consequently, the fate of the triggered immune response are also outlined.
Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Células Dendríticas , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Medicina de PrecisãoRESUMO
OBJECTIVES: To analyze device designs, similarities and overlaps of custom-made fenestrated arch endografts intended for mid/distal arch thoracic endovascular aortic repair. MATERIALS AND METHODS: A multicenter cross-sectional study analyzing custom-made anonymized graft plans was performed. Graft plans were included from a cohort of mid/distal aortic arch repairs using custom-made fenestrated aortic endografts treated at 8 centers. Grafts targeting >2 arteries were excluded. No patient/clinical data were analyzed. A descriptive analysis was performed followed by an analysis of overlap of the designs to reach a common design in which the greatest number of grafts would overlap. RESULTS: One hundred thirty-one graft plans were included. All grafts were custom-made grafts from the COOK Medical Fenestrated arch platform. Ninety-four (71.8%) had a scallop-and-single-fenestration design, 33 (25.2%) had a single fenestration and 4 (4.3%) a single scallop. For analysis purposes, these latter 4 grafts were excluded. Two main graft plans (Plans 1 and 2) were proposed after analysis with similar configuration (1 scallop with 30 mm width, 20 mm height, 12:00 position; 1 preloaded fenestration with 8 mm diameter, 26 mm from the top of the graft and 12:00 position; tapered, with a 193 mm length and 32 mm distal diameter) but with 2 different proximal diameters of 38 mm (Plan 1) and 44 mm (Plan 2), reaching an overall feasibility of 85.8% (n=109), being 47.2% (n=60) and 38.6% (n=49) for each design, respectively. CONCLUSION: The degree of overlap between the studied fenestrated and/or scalloped thoracic endovascular aneurysm repair (TEVAR) graft designs was high. Future studies analyzing these designs in a real-world cohort of patients are needed to further address off-the-shelf feasibility. CLINICAL IMPACT: In a multicenter study analyzing 127 fenestrated aortic arch endograft plans from 9 aortic centers, we found that the degree of overlap between the studied fenestrated and/or scalloped arch graft designs was high and that 2 proposed graft designs would be theoretically applicable in 85.8% of cases. Future studies analyzing these designs in a real-world cohort of patients are needed to further address off-the-shelf feasibility.
RESUMO
OBJECTIVE: To preliminarily evaluate the safety and efficacy of the WeFlow-JAAA endograft, a novel off-the-shelf device designed for the repair of juxtarenal abdominal aortic aneurysms (JRAAAs) and pararenal abdominal aortic aneurysms (PRAAAs). METHODS: This prospective single-arm first-in-human clinical trial included patients with JRAAAs (infrarenal necks ≤10 mm) or PRAAAs with at least a 5 mm sealing zone below the superior mesenteric artery (SMA) who underwent endovascular repair using the WeFlow-JAAA endograft system. With this system, the celiac artery was addressed with a wide scallop, the renal arteries (RAs) were addressed with 2 standard inner branches, and the SMA was addressed with a "mini-inner-cuff" reinforced fenestration. The primary efficacy endpoint was the clinical success at 12 months. The primary safety endpoint was the freedom from major adverse events (MAEs) in the first 30 days after surgery. RESULTS: Fifteen patients (all men; mean age 68.5±6.0 years) were enrolled between October 2019 and August 2021. The median infrarenal neck length was 0 mm (IQR, 0-4 mm). Technical success was achieved in all patients. No MAEs occurred in the first 30 days. The mean fluoroscopy time was 73.1±27.8 minutes, and the mean volume of contrast media was 130.7±29.4 mL. Clinical success was maintained in all patients at 12 months. No aortic-related deaths, aneurysm rupture, type I or type III endoleak, or open surgery conversion occurred during the follow-up period. The secondary intervention was required only in 1 patient who developed an occluded right RA stent 14 months after the procedure. CONCLUSION: The WeFlow-JAAA endograft device appears to be safe and efficacious in selected patients with JRAAAs or PRAAAs with more than 5 mm sealing zone below SMA. Large-scale, multicenter, and prospective studies with long-term follow-ups are ongoing to validate our findings in China. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04745546 (URL: Guo's Visceral Arteries Reconstruction: The First in Man Study of WeFlow-JAAA Stent Graft System-Full-Text View-ClinicalTrials.gov). CLINICAL IMPACT: The first-in-human clinical trial of the WeFlow-JAAA endograft system demonstrates promising safety and efficacy in treating juxtarenal abdominal aortic aneurysms (JRAAAs) and partial pararenal abdominal aortic aneurysms (PRAAAs). This innovative off-the-shelf device offers a potential alternative to traditional endovascular aortic repair. The successful outcomes, including technical success in all patients, freedom from major adverse events, and maintenance of clinical success at 12 months, suggest a potential shift in clinical practice towards using the WeFlow-JAAA endograft system for selected patients. This study paves the way for larger-scale, multicenter, prospective studies to further validate its long-term safety and efficacy, offering clinicians a new option for managing complex abdominal aortic aneurysms.