Objective Patients with chronic limb-threatening ischemia (CLTI) are at high risk for delirium because of advanced age and multiple comorbidities. However, the impact of delirium on limb-related outcomes after endovascular therapy (EVT) remains unclear. This study evaluated the association between delirium and clinical outcomes after EVT in patients with CLTI. Methods This retrospective single-center study included patients with CLTI who underwent successful EVT between February 2008 and November 2021. Patients were stratified by the presence of delirium during hospitalization. The primary endpoint was 1-year amputation-free survival (AFS), and the secondary endpoint was 1-year wound healing. Cox proportional hazards regression models were used to identify predictors of poor AFS, whereas Fine–Gray subdistribution hazards regression models were used to evaluate predictors of impaired wound healing, treating death and major amputation as competing events. Results A total of 354 patients (435 limbs) were included, and 69 patients (19.6%) developed delirium. Patients with delirium had greater limb severity and lesion complexity than those without delirium. The cumulative incidence of wound healing at 1 year was significantly lower in the delirium group than in the non-delirium group (16% vs 59%; Gray’s test, P < .01), as was the 1-year AFS rate (35% vs 77%; log-rank P < .01). In multivariable analysis, delirium remained independently associated with impaired wound healing (SHR, 0.26; 95% confidence interval [CI], 0.13–0.54; P < .01) and poor AFS (HR, 3.20; 95% CI, 1.90–5.34; P < .01). Conclusions Delirium is common among patients with CLTI undergoing EVT and is independently associated with impaired wound healing and poor AFS. Early identification of patients at risk for delirium may facilitate multidisciplinary management, although whether prevention of delirium improves clinical outcomes requires further investigation.

Precise navigation of a guidewire tip to a target within the three-dimensional (3D) structure of a coronary artery—controlled from 140 cm away—requires “3D wiring,” a technique involving wire manipulation based on 3D imaging. Hypothesizing that 3D wiring enables the standardization of wiring techniques for chronic total occlusion (CTO) intervention, we have established a 3D wiring method utilizing fluoroscopy and intravascular ultrasound (IVUS). As a first step to visualize guidewire movement within CTO lesions, we collaborated with Terumo Corporation to develop the Navifocus WR in 2012, a CTO-specific IVUS featuring a small diameter and a short tip. Observing guidewire movement during CTO PCI using this IVUS provided the insights necessary to understand how the shaft and tip must be visualized to facilitate effective 3D wiring. We first established angiography-guided 3D wiring using “3D imaging rules” in 2014. Subsequently, to achieve real-time IVUS-guided 3D wiring, we devised the tip detection (TD) method in 2017 and developed the AnteOwl WR IVUS (Terumo Corporation)—a short-tip, pullback-compatible catheter—in 2019, establishing a strategic approach for TD-intra-plaque tracking. Contrary to the traditional view that IVUS guidance is limited to intra-plaque tracking, our 2021 findings show that re-entry is routinely feasible through TD-guided perpendicular puncture (TD-ADR: Antegrade Dissection and Re-entry). This evolution elevated the TD method into a more robust technique for wire crossing. This review aims to systematically organize the theory of 3D wiring and disseminate this knowledge to the global community.

The Task Force on Rotational Atherectomy of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) proposed the expert consensus document to summarize the techniques and evidence regarding rotational atherectomy (RA) in 2020, which was updated in 2023. Because the revascularization strategy to severely calcified lesions has been the hottest topic in contemporary percutaneous coronary intervention (PCI), many literatures related to RA have been published since 2023. Latest advancements have been incorporated in this updated expert consensus document.

Severely calcified ostial occlusion of the deep femoral artery (DFA) is a condition that is technically challenging to manage. Surgical reconstruction has been traditionally considered the most reliable treatment option, and evidence on feasible endovascular strategies remains limited. Herein, we report the case of a woman in her 80 s who presented with Rutherford class 5 lower-extremity arterial disease and a nonhealing ulcer of the right first toe. A long-segment occlusion of the superficial femoral artery (SFA) with heavy calcification and an ostial occlusion of the DFA were observed on angiography. The SFA was successfully revascularized with stent placement. However, revascularization of the DFA origin was required to secure a collateral source because of the risk of acute limb ischemia due to multiple implanted stent grafts. The antegrade and retrograde wiring attempts were not successful owing to severe calcification and jailed stent struts. Therefore, a modified stylet puncture-based direct orifice puncture of the DFA origin was performed via manipulation of a Bent bAre Metal needle for Breaking calcified ObstructiOn using a High-precisiOn Orifice puncture into the Keystone DFA (referred to as the "BAMBOO HOOK") technique. A pull-through was established, and balloon angioplasty yielded sufficient lumen gain despite the jailed stent struts. Hemostasis was secured via prolonged balloon inflation, and complete wound healing was achieved approximately 3 months after minor toe amputation. The bamboo hook technique can be a feasible endovascular approach for recanalizing severely calcified ostial occlusions of the DFA.

Combination therapy with atherectomy and intravascular lithotripsy (IVL) has emerged as a promising strategy for the treatment of severely calcified occlusive coronary lesions, which potentially enhances procedural efficacy without increasing complication risk. The Dual-Prep Registry is a multicenter, prospective registry designed to evaluate the safety and efficacy of IVL after atherectomy in severely calcified lesions. Combined use was selectively applied when the risk of complications was anticipated to be high with a larger atherectomy burr size, or when it was deemed non-beneficial due to unfavorable guidewire bias. All adverse events were adjudicated by a clinical events committee. Kaplan–Meier analysis was performed to evaluate the primary endpoint of major adverse cardiovascular events (MACE; composite endpoint of cardiac death, myocardial infarction, and target vessel revascularization [TVR]) at 1 year. A total of 118 cases (120 lesions) were enrolled across 20 facilities. Significant comorbidities included diabetes in 56.8 https://jrct.mhlw.go.jp .

Drug-coated balloons (DCBs) are increasingly used in femoropopliteal (FP) endovascular therapy (EVT) to limit permanent scaffold implantation. Although this paradigm shift has substantially altered treatment strategies, its effects on real-world clinical outcomes remain unclear. Temporal trends in device selection and clinical outcomes after FP EVT were evaluated in contemporary practice. This multicenter, retrospective study included patients who underwent EVT for de novo FP artery disease at six institutions between July 2017 and December 2023. Patients were stratified into three equal, chronological eras (early, middle, and late). Trends in device use were evaluated, and clinical outcomes, including primary patency and restenosis patterns, were compared. Overall, 2815 patients were included in the analysis. DCB use increased substantially across eras (24.5

Objective To evaluate the association between procedural duration and periprocedural outcomes in patients with chronic limb-threatening ischemia (CLTI) who underwent endovascular therapy (EVT). Methods This retrospective single-center study included 347 consecutive patients (428 limbs) with CLTI who underwent successful EVT for de novo lesions between February 2008 and January 2021. Patients were stratified by procedural location into a prolonged group (>2 h; 203 limbs) and a standard group (≤2 h; 225 limbs). The primary endpoint was in-hospital mortality, and the secondary endpoint was postprocedural complications. Multivariate logistic regression analysis was performed to identify independent predictors of postprocedural complications. Results The prolonged group showed greater limb severity and lesion complexity, including a higher prevalence of Wound, Ischemia, and Foot Infection (WIfI) stage 4 (51.5% vs. 36.9%, P < 0.01), chronic total occlusion (65.2% vs. 48.4%, P < 0.01), and Global Limb Anatomic Staging System (GLASS) infrapopliteal grade 4 (71.1% vs. 53.1%, P < 0.01). In-hospital mortality did not differ significantly between the groups (2.0% vs. 0.4%; P = 0.14). However, postprocedural complications occurred significantly more frequently in the prolonged group (9.9% vs. 2.7%; P < 0.01). Multivariate analysis identified prolonged procedural duration as an independent predictor of postprocedural complications (odds ratio [OR], 3.30; 95% confidence interval [CI], 1.23–8.85; P = 0.02), along with bedridden status (OR, 4.15; 95% CI, 1.64–10.6; P < 0.01) and GLASS inframalleolar grade 2 (OR, 3.29; 95% CI, 1.34–8.10; P < 0.01). Conclusions Prolonged procedural duration was independently associated with an increased risk of postprocedural complications in patients with CLTI undergoing EVT. Thus, procedural time may serve as a marker of lesion complexity and procedural burden and may assist intraprocedural decision-making.

OBJECTIVE:Extravascular ultrasound (EVUS) has been reported to be a feasible modality for facilitating guidewire passage in femoropopliteal (FP) chronic total occlusions (CTOs). However, predictors of procedural success remain uncertain. We aimed to identify the lesion and imaging characteristics associated with successful EVUS-guided wiring within 30 minutes and to develop a simplified scoring system. METHODS:We retrospectively analyzed 299 FP-CTO lesions in 250 patients who were treated with EVUS-guided wiring between April 2012 and December 2023. Successful wiring was defined as the guidewire passage under EVUS guidance within 30 minutes. Clinical, angiographic, and EVUS parameters were assessed, including the "Doppler flow sign," which is defined as ultrasound detection of intraluminal flow within the CTO. Multivariate logistic regression analysis was performed to identify independent predictors, and a simplified EVUS CTO score was developed. RESULTS:Successful wiring within 30 minutes was achieved for 140 lesions (47%). Independent predictors were shorter lesion length (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.86-0.92), absence of calcification (OR = 0.30, 95% CI = 0.14-0.64), presence of a Doppler flow sign (OR = 2.45, 95% CI = 1.17-5.10), and absence of popliteal involvement (OR = 0.47, 95% CI = 0.24-0.94). The EVUS CTO score (range, 0-4) demonstrated stepwise increases in success rates as follows: 14% (0-1 point), 39% (2 points), 72% (3 points), and 90% (4 points). CONCLUSIONS:The EVUS CTO score serves as a useful tool for stratifying lesion complexity, predicting early procedural success, and aiding in case selection, operator training, and procedural planning for FP-CTO interventions.Clinical ImpactThis study identifies key predictors of successful extra-vascular ultrasound (EVUS)-guided wiring within 30 minutes in femoropopliteal chronic total occlusions and introduces a simple EVUS CTO score. This scoring system allows clinicians to stratify lesion complexity and predict early technical success, thereby improving case selection and procedural planning. By anticipating procedural difficulty, EVUS-guided intervention can be performed more efficiently, potentially reducing procedure time and radiation exposure. These findings support a more structured and practical approach to EVUS-guided peripheral intervention.

The gastrointestinal tract is frequently subjected to tissue damage caused by various environmental stressors. Adult stem cells conduct tissue repair through regenerative programs with striking parallels to carcinogenesis, implying that dysregulated repair mechanisms initiate cancer development. Previously, we identified Iqgap3 as a marker of rapidly proliferating stem cells within the isthmus of gastric glands, a region essential for maintaining tissue homeostasis. Following tissue injury, we observed upregulation of Iqgap3 expression and activation of Myc signaling pathways, particularly within the fully differentiated chief cell population. Given that Myc is a major oncoprotein, our findings implicate Iqgap3 as a critical mediator in the stomach repair process and carcinogenesis. To understand how the role of Iqgap3 in tissue repair may be hijacked for carcinogenesis, we developed a conditional knockout (cKO) mouse model that attenuates Iqgap3 expression in gastric epithelial cells. Tissue damage and Iqgap3 deletion were induced by high-dose tamoxifen (HDT) treatment. Iqgap3-cKO mice were markedly compromised in tissue repair, exhibiting reduced cellular proliferation and chief cell population even one month after tissue injury. Transcriptomic analyses revealed that Iqgap3 deficiency suppressed the Myc signaling pathway and stem cell activity in the stomach, indicating a causal link between Iqgap3 and Myc during tissue regeneration. Furthermore, Iqgap3 depletion in oncogenic KrasG12D-induced metaplasia mouse model and KrasG12D-induction with Apc-depleted dysplasia mouse model protected against formation of metaplasia and dysplasia. Mechanistically, Iqgap3 deficiency led to reduced expression of neoplastic factors, such as CD44, Aqp5 and Trop2. Interestingly, Myc phosphorylation was attenuated in Iqgap3-cKO mice. We further showed that Iqgap3 directly interacted with Myc, which reinforces a role of Iqgap3 in enhancing Myc activity. Our findings highlight the critical roles of the Iqgap3-Myc axis in the regulation of stem cell activity, gastric tissue regeneration and precancerous metaplasia and dysplasia development. These insights provide a mechanistic framework for understanding the intersection of tissue repair and early carcinogenic processes. Junichi Matsuo, Mitsuhiro Shimura, Jungwon Lee, Linda S. Chuang, Wei Peng Yong, Yoshiaki Ito. Iqgap3 and Myc interaction regulates damaged stomach repair and early gastric carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 121.

The KCB01 (KIZASHI™) is a novel cutting balloon catheter with blades integrally formed with the balloon. It is designed to overcome the drawbacks of conventional cutting balloons in terms of lesion delivery, crossability and procedural complications while maintaining the same dilation capacity. To evaluate the efficacy and safety of the KCB01, a prospective, open-label, single-arm study was conducted at nine sites in Japan on percutaneous coronary intervention-eligible patients with stenotic lesions that exhibited residual indentation even after conventional balloon dilation at nominal pressure. Seventy-six patients were enrolled between November 2022 and June 2023, and 73 eligible patients were included in the primary analysis. The mean age was 73.5 ± 7.4 years, and 79.5

Genetic alterations in the RUNX family genes and their co-factor CBFB are frequently observed in cancer. In breast cancer, RUNX1 and CBFB are identified as significantly mutated genes, while RUNX3 expression is often silenced through hypermethylation. These observations highlight the importance of RUNX genes in mammary homeostasis. Previous studies on luminal-type breast cancer demonstrated that RUNX3 restoration inhibits tumor progression by destabilizing the estrogen receptor α (ERα) protein. However, despite the therapeutic promise of reactivating RUNX3 in breast cancer, its role in hormone receptor-negative subtypes remains inadequately understood. Furthermore, RUNX3 has been reported to exhibit dualistic roles and depending on the cancer type and stage, may function as either tumor suppressor or oncogene. Yet, the molecular mechanisms underlying this duality remain unclear. To investigate the role of RUNX3 in breast pathogenesis, we developed the MMTV-PyMT; Krt8-CreERT2; Rosa26-lsl-RUNX3 mouse model and analysed the effect of conditional induction of RUNX3 expression in Krt8+ mammary epithelial cells and tumor cells within the MMTV-PyMT-driven breast cancer. Without RUNX3 induction, MMTV-PyMT mice developed an average of eight tumors per mouse, and transcriptomic analyses revealed robust activation of the Myc-signaling pathway. Conversely, the induction of RUNX3 significantly suppressed tumor growth, concomitant with a diminished c-Myc expression. This observation underscores the tight relationship between RUNX3 and c-Myc and identifies RUNX3-mediated suppression of Myc pathway as a major aspect of RUNX3 tumor suppressive role. Remarkably, histological analyses of RUNX3-induced breast tumors showed two distinct clusters of cancer cells: proliferating RUNX3-positive cells and non-proliferating RUNX3-positive cells. Spatial transcriptomic profiling revealed elevated c-Myc expression and suppressed RUNX1 expression in the proliferating RUNX3-positive cells compared to non-proliferating RUNX3-positive cells. This observation raises the intriguing possibility that interplay between RUNX1 and RUNX3 determines cellular proliferative potential and implicates RUNX1 as a regulator of RUNX3’s paradoxical traits. Consistently, overexpression of RUNX3 in human breast cancer cells induced significant cell death and upregulated RUNX1 expression. Our findings suggest the convergence of RUNX1 and RUNX3 pathways in driving cell states within the tumor microenvironment and establish a causal link between RUNX3, c-Myc activity, and tumor growth dynamics. This study provides critical insights into dual roles of RUNX3 in breast cancer pathogenesis. Nawaphat Jangphattananont, Junichi Matsuo, Wei Peng Yong, Linda SH Chuang, Yoshiaki Ito. RUNX3 restoration in breast tumors leads to profound growth regression via c-Myc inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6708.

ABSTRACTBackground and AimsWhen dealing with severely calcified lesions in endovascular therapy (EVT) for lower extremity artery disease (LEAD), navigating through severely calcified chronic total occlusion (CTO) using hard‐tip guidewires can be challenging. To address this issue, we employed a novel highly intensive penetration (HIP) technique. This technique involves modifying the tail of a 0.035‐inch guidewire to enhance its penetration capability, thus enabling effective navigation through the calcified lesion and facilitating the EVT procedure. This study aimed to assess the feasibility and safety of the HIP technique.MethodsThis single‐center, retrospective study enrolled 27 consecutive patients (29 limbs) who underwent the HIP technique for the recanalization of calcified femoropopliteal CTO lesions that were resistant to penetration by high‐tip load (≧ 40 g) guidewires between January 2015 and April 2023. Statistical analyses were performed using JMP 13 software.ResultsThe mean patient age was 75.9 ± 10.1 years. The proportion of men, patients with hypertension, patients with diabetes mellitus, and patients on hemodialysis was 78%, 59%, 41%, and 44%, respectively. The crossover approach was selected for 55% of the patients. The reference vessel diameter was 5.3 ± 0.6 mm, and the lesion length was 19.7 ± 12.0 cm. The target lesions were predominantly located in the superficial femoral artery (76%). In‐stent occlusion was treated in 14% of patients. The HIP technique was successfully performed in 79% of patients, and the complication rate of vascular perforation was 7%.ConclusionThe HIP technique demonstrates remarkable effectiveness in navigating through highly calcified lesions, offering a reliable method for successful recanalization in challenging cases.

The scaffold protein IQGAP3 is highly upregulated in most epithelial cancers. While recent studies have highlighted its pivotal roles in cancer cell proliferation and metastasis, a deeper mechanistic understanding of IQGAP3 is currently lacking. We have here used TurboID to map IQGAP3 proximity partners and identified the Wnt signaling members Axin1 and CK1α as IQGAP3-interacting proteins. Our functional studies demonstrated that overexpression of IQGAP3 increases β-catenin levels, while IQGAP3 depletion reduces β-catenin levels in gastric cancer cells. Mechanistically, IQGAP3 disrupts Axin1-CK1α interaction, thereby inhibiting β-catenin phosphorylation and ultimately leading to its accumulation. Importantly, we discovered that IQGAP3 itself is regulated by Wnt signaling, suggesting its involvement in a positive feedback loop in Wnt/β-catenin signaling through interactions with Axin1 and CK1α. These findings identify IQGAP3 as a novel mediator of β-catenin stabilization and underscore its potential as a target for cancer therapy.

BackgroundThe elevation of IQGAP3 expression in diverse cancers indicates a key role for IQGAP3 in carcinogenesis. Although IQGAP3 was established as a proliferating stomach stem cell factor and a regulator of the RAS-ERK pathway, how it drives cancer growth remains unclear.ObjectiveWe define the function of IQGAP3 in gastric cancer (GC) development and progression.DesignWe studied the phenotypic changes caused by IQGAP3 knockdown in three molecularly diverse GC cell lines by RNA-sequencing. In vivo tumorigenesis and lung metastasis assays corroborated IQGAP3 as a mediator of oncogenic signalling. Spatial analysis was performed to evaluate the intratumoral transcriptional and functional differences between control tumours and IQGAP3 knockdown tumours.ResultsTranscriptomic profiling showed that IQGAP3 inhibition attenuates signal transduction networks, such as KRAS signalling, via phosphorylation blockade. IQGAP3 knockdown was associated with significant inhibition of MEK/ERK signalling-associated growth factors, including TGFβ1, concomitant with gene signatures predictive of impaired tumour microenvironment formation and reduced metastatic potential. Xenografts involving IQGAP3 knockdown cells showed attenuated tumorigenesis and lung metastasis in immunodeficient mice. Accordingly, immunofluorescence staining revealed significant reductions of TGFβ/SMAD signalling and αSMA-positive stromal cells; digital spatial analysis indicated that IQGAP3 is indispensable for the formation of two phenotypically diverse cell subpopulations, which played crucial but distinct roles in promoting oncogenic functions.ConclusionIQGAP3 knockdown suppressed the RAS-TGFβ signalling crosstalk, leading to a significant reduction of the tumour microenvironment. In particular, IQGAP3 maintains functional heterogeneity of cancer cells to enhance malignant growth. IQGAP3 is thus a highly relevant therapy target in GC.