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Abstract Background Lower limb peripheral artery disease classified as Rutherford category IV, is characterized by lower limb ischemic pain both during exertion and at rest. This disease has an unclear course. We aimed to evaluate outcome predictors in this patient group after endovascular therapy. This single-center, retrospective, observational study included 234 consecutive patients (264 limbs), between April 2007 and December 2020. We investigated the disease clinical course after endovascular therapy. The primary endpoint was the wound formation rate 3 years after endovascular therapy. Results The mean observation period was 48.2 ± 8.9 months. The patients (61.9% male; mean age, 76 ± 10 years) presented with diabetes (64.1%), and received hemodialysis with chronic kidney disease (35.0%) and ambulatory treatment (85.0%). The average ankle-brachial index before endovascular therapy was 0.69 ± 0.23. Skin perfusion pressure on the dorsal and plantar sides was 38 ± 13 mmHg and 36 ± 12 mmHg, respectively. The wound incidence rates at 1, 2, and 3 years after endovascular therapy were 8.3%, 11.4%, and 14.4%, respectively. Multivariate analysis revealed the following factors associated with wound formation: P2 in inframalleolar/pedal disease category in the Global Limb Anatomical Staging System (hazard ratio: 1.73, 95% confidence interval: 1.22–2.83, P = 0.01), non-ambulatory status (hazard ratio: 1.09, 95% confidence interval: 1.11–1.36, P = 0.02), intervention up to infrapopliteal lesion (hazard ratio: 1.55, 95% confidence interval: 1.17–2.46, P = 0.03), and patient with chronic kidney disease on hemodialysis (hazard ratio: 1.61, 95% confidence interval: 1.32–2.18, P = 0.03). Conclusions The 3-year incidence of wound onset in this study was 14.4%. Factors associated with this outcome included P2 in the Global Limb Anatomical Staging System, non-ambulatory status, intervention up to infrapopliteal lesion, and patient with chronic kidney disease on hemodialysis.

Key Clinical Message Under challenging common femoral artery access scenarios, the “wall PIERCE” technique, which utilizes a larger puncture needle to pierce the vessel wall along the guidewire, facilitates sheath insertion. This method proved successful in two cases without any complications, presenting a valuable addition to strategies for addressing challenging sheath insertion scenarios.

Background: Endovascular therapy (EVT) is often used for revascularization in patients with chronic limb-threatening ischemia. However, achieving revascularization is challenging. In instances where the guidewire cannot pass through the lesion using an antegrade approach, it is common to incorporate a retrograde approach, such as a trans-collateral approach or distal puncture. However, adding a retrograde approach to cases without below-the-ankle runoff is difficult. In such cases, we have successfully treated patients by directly puncturing the occluded pedal arch under extravascular ultrasound (EVUS) guidance and achieved a pull-through. We herein introduced the method and named it as the Trans-Occluded Pedal arch Access to recanaliZe chronic total occlusion of the tibial artery (TOPAZ) technique. Case Presentation: A man in his 60 s with Rutherford class 6 peripheral artery disease presented with resting pain and gangrene in the left foot. Angiography revealed chronic total occlusion from the proximal posterior tibial artery to the plantar artery. EVT was selected; however, the conventional approach failed. Switching to a trans-pedal approach, we faced challenges, leading to a puncture of the occluded common plantar region using EVUS guidance. Successful revascularization was achieved without calcaneal branch loss. The patient's resting pain was alleviated, and his wounds healed 6 months post-EVT. Conclusions: This case shows the efficacy of the novel TOPAZ technique in addressing difficulties in revascularization when conventional approaches, such as retrograde methods, fail.

Objectives: We analyzed the 2-year clinical outcomes of patients with de novo femoropopliteal (FP) lesions who underwent drug-coated balloon (DCB) angioplasty and the angiographic predictors of restenosis. Methods: This single-center, retrospective, and observational study evaluated 129 de novo FP lesions treated with DCB angioplasty without bailout stenting. Clinical outcomes and risk factors for loss of primary patency were analyzed using univariate and multivariate Cox proportional hazards regression models. Results: The participants were aged 48–93 (mean: 73.6 ± 9.8) years, and 31% were women. Approximately 33% of the patients were receiving regular dialysis, and 35% of the affected limbs had critical ischemia. The mean lesion length was 132 ± 96 mm, and the mean reference vessel diameter (RVD) was 4.7 ± 0.8 mm. Forty-three (33%) limbs had chronic total occlusion of the target artery segment. Fifty-seven (44%) and 72 (56%) lesions were treated with DCB angioplasty using IN.PACT Admiral and Lutonix, respectively. The primary patency and amputation-free survival at 2 years were 59.3% and 89.5%, respectively. RVD was found to be an independent predictor of loss of primary patency. Based on the receiver operating characteristic analysis, an RVD of 4.2 mm was the best predictor of loss of primary patency at 2 years. Conclusions: The short-term clinical outcome of DCB angioplasty for de novo FP lesions was acceptable. Moreover, an RVD of

Abstract MYC is one of the most commonly dysregulated proto-oncogenes in cancer. MYC promotes cancer initiation and maintenance by regulating multiple biological processes, such as proliferation and stem cell function. Here, we show that developmental regulator RUNX3 targets MYC protein for rapid degradation through the glycogen synthase kinase-3 beta-F-box/WD repeat-containing protein 7 (GSK3β-FBXW7) proteolytic pathway. The evolutionarily conserved Runt domain of RUNX3 interacts directly with the basic helix–loop–helix leucine zipper of MYC, resulting in the disruption of MYC/MAX and MYC/MIZ-1 interactions, enhanced GSK3β-mediated phosphorylation of MYC protein at threonine-58 and its subsequent degradation via the ubiquitin-proteasomal pathway. We therefore uncover a previously unknown mode of MYC destabilization by RUNX3 and provide an explanation as to why RUNX3 inhibits early-stage cancer development in gastrointestinal and lung mouse cancer models.

Abstract Background Sedation during cardiac catheter examination in neonates with complex congenital heart disease is challenging, as even the slightest change in the circulatory or respiratory status can lead to hemodynamic collapse. Here, we report a case wherein we achieved adequate sedation with a high-flow nasal cannula (HFNC) for catheter examination in a neonate with a congenital cardiac anomaly. Case presentation An 11-day-old boy with hypoplastic left heart syndrome was scheduled for a cardiac catheter examination prior to the Norwood procedure. He underwent bilateral pulmonary artery banding (PAB) on day 1 and was receiving dobutamine, milrinone, alprostadil, and dexmedetomidine in addition to air and nitrogen insufflation via HFNC, which was applied following extubation on day 3 and nitrogen therapy on day 6 owing to persistent pulmonary overcirculation symptoms (tachypnea and low arterial blood pressure) despite bilateral PAB. A catheter examination was performed on day 11 with careful monitoring of expired carbon dioxide and observation of chest wall motion. Adequate sedation was provided with supplemental midazolam and fentanyl along with HFNC without tracheal intubation. Conclusions The findings from this case suggest that HFNC is a safe and effective tool for oxygenation during cardiac catheter examination under sedation in neonates.

Abstract Purpose To compare the impact of Chocolate and conventional balloons on vessel preparation in percutaneous transluminal angioplasty. Materials and methods This single-center retrospective study included 111 endovascular therapy consecutive cases of femoropopliteal lesions using drug-coated balloon strategy with a 1:1 pre-dilation balloon diameter between February 2020 and August 2021, divided into the Chocolate percutaneous transluminal angioplasty (n = 48) and conventional (n = 63) groups. Before the availability of Chocolate balloons in Japan (December 2020), a standard semi-compliant or non-compliant balloon was used for vessel preparation. The primary endpoint was rate of severe dissection after pre-dilatation. Secondary endpoints were angiographic percent diameter stenosis, bailout stent rate, primary patency rate, and freedom from target-lesion-revascularization rate at six months. Results There was no significant difference in patient and lesion characteristics. The procedural characteristics comprised balloon length 90 ± 37 and 149 ± 95 mm (P = 0.004) and inflation pressure 11 ± 3 and 16 ± 7 atm (P

Summary: We present a detailed protocol to identify and validate IGF2BP1 target genes in pluripotent human embryonic carcinoma cells (NTERA-2). We first identify the target genes through RNA-immunoprecipitation (RIP) sequencing. We then validate the identified targets through the use of RIP-qPCR assays, determine the m6A status of target genes by m6A-IP, and perform functional validation by quantifying changes in mRNA or protein expression levels upon knockdown of IGF2BP1 or methyltransferases in NTERA-2.For complete details on the use and execution of this protocol, please refer to Myint et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background & Aims: RUNX transcription factors play pivotal roles in embryonic development and neoplasia. We previously identified the single missense mutation R122C in RUNX3 from human gastric cancer. However, how RUNX3R122C mutation disrupts stem cell homeostasis and promotes gastric carcinogenesis remained unclear. Methods: To understand the oncogenic nature of this mutation in vivo, we generated the RUNX3R122C knock-in mice. Stomach tissues were harvested, followed by histologic and immunofluorescence staining, organoid culture, flow cytometry to isolate gastric corpus isthmus and nonisthmus epithelial cells, and RNA extraction for transcriptomic analysis. Results: The corpus tissue of RUNX3R122C/R122C homozygous mice showed a precancerous phenotype such as spasmolytic polypeptide-expressing metaplasia. We observed mucous neck cell hyperplasia; massive reduction of pit, parietal, and chief cell populations; as well as a dramatic increase in the number of rapidly proliferating isthmus stem/progenitor cells in the corpus of RUNX3R122C/R122C mice. Transcriptomic analyses of the isolated epithelial cells showed that the cell-cycle–related MYC target gene signature was enriched in the corpus epithelial cells of RUNX3R122C/R122C mice compared with the wild-type corpus. Mechanistically, RUNX3R122C mutant protein disrupted the regulation of the restriction point where cells decide to enter either a proliferative or quiescent state, thereby driving stem cell expansion and limiting the ability of cells to terminally differentiate. Conclusions: RUNX3R122C missense mutation is associated with the continuous cycling of isthmus stem/progenitor cells, maturation arrest, and development of a precancerous state. This work highlights the importance of RUNX3 in the prevention of metaplasia and gastric cancer.

Summary: We reported earlier that IQGAP3 is an important stem cell factor in rapidly proliferating isthmus stem cells in the stomach and that IQGAP3 expression is robustly induced in terminally differentiated chief cells and de-differentiated cells following tissue damage. The elevated IQGAP3 expression in cancer and its association with metastasis suggest a fundamental role for IQGAP3 in proliferating cancer stem cells. What causes IQGAP3 upregulation in cancer is unclear. Here, we show that IGF2BP1 and IQGAP3 expression levels are highest in the blastocyst, with both decreasing during adulthood. This suggests that IQGAP3, like IGF2BP1, is an early developmental gene that is aberrantly upregulated upon re-expression of IGF2BP1 during carcinogenesis. IGF2BP1 binds and stabilizes m6A-modified IQGAP3 transcripts. Downstream targets of IGF2BP1, namely SRF and FOXM1, also upregulate IQGAP3 expression. These multiple layers of IQGAP3 regulation, which may safeguard against inappropriate stem cell proliferation, present additional drug targets to inhibit IQGAP3-driven malignant growth.

Osteoarthritis is caused by an imbalance between extracellular matrix synthesis and degradation. Here, the authors show that both strands of microRNA-455, -5p and -3p, target HIF2α and regulate cartilage homeostasis, and show that overexpression of these miRNAs is protective against osteoarthritis in mice.

Background Although endovascular therapy is often used for revascularization in patients with chronic limb-threatening ischemia, highly calcified lesions below the knee still remain challenging and difficult to treat. To treat such lesions, a hard-tip guidewire or a bidirectional approach can be used to aid the passage of the guidewire and thereby perform balloon dilatation. In contrast, when a severe calcified lesion is present at a highly flexural area, such as the origin of the anterior tibial artery (ATA), passing the guidewire is extremely difficult because the route of the guidewire is restricted.Case report A male patient in his 60 s with Rutherford 5 peripheral artery disease presented with resting pain in the right foot, gangrene of the right fifth toe, and an ulcer due to stasis dermatitis near the right heel. Lower limb angiography revealed severe stenosis with calcification of the right popliteal artery and tibio-peroneal trunk (TPT) as well as obstruction with severe calcification in the ATA. Herein, we have proposed this technique—ProxiMal Anterior tibial artery direct puncture with Needle (P-MAN) for recanalizing highly calcified obstructive lesions.Discussion When a severe calcified lesion is present at a highly flexural area, such as the origin of the ATA, by directly puncturing the severe calcified portion of the ATA origin with a needle from the body surface, the calcification can be penetrated and cracked, and devices such as guidewires and balloons can pass through the lesion.

The runt-related transcription factors (RUNX) play prominent roles in cell cycle progression, differentiation, apoptosis, immunity and epithelial–mesenchymal transition. There are three members in the mammalian RUNX family, each with distinct tissue expression profiles. RUNX genes play unique and redundant roles during development and adult tissue homeostasis. The ability of RUNX proteins to influence signaling pathways, such as Wnt, TGFβ and Hippo-YAP, suggests that they integrate signals from the environment to dictate cell fate decisions. All RUNX genes hold master regulator roles, albeit in different tissues, and all have been implicated in cancer. Paradoxically, RUNX genes exert tumor suppressive and oncogenic functions, depending on tumor type and stage. Unlike RUNX1 and 2, the role of RUNX3 in stem cells is poorly understood. A recent study using cancer-derived RUNX3 mutation R122C revealed a gatekeeper role for RUNX3 in gastric epithelial stem cell homeostasis. The corpora of RUNX3R122C/R122C mice showed a dramatic increase in proliferating stem cells as well as inhibition of differentiation. Tellingly, RUNX3R122C/R122C mice also exhibited a precancerous phenotype. This review focuses on the impact of RUNX3 dysregulation on (1) stem cell fate and (2) the molecular mechanisms underpinning early carcinogenesis.

Introduction: Radial artery occlusion after puncture is a serious complication of radial artery access for endovascular therapy (EVT). Herein, we show the feasibility of ultrasound-guided trans-occluded radial access (TORA) for EVT after radial artery occlusion. Case: We describe the technique performed under ultrasound guidance for EVT for right external iliac artery stenosis in a 73-year-old man with intermittent claudication. Conclusion: TORA provides a safe and feasible alternative access after radial artery occlusion.

Abstract Background and Aims A balloon‐expandable stent (BES) is generally used for ostial lesions of the common iliac artery (CIA) owing to the positional ease of stent adjustment. However, there are potential risks such as vessel dissection and perforation due to vessel overstretching during. In our hospital, we performed endovascular therapy (EVT) for CIA ostial lesions via a novel method named “the flower stenting method,” using a self‐expandable stent. This study aimed to analyze the efficacy and safety of this method. Methods This study was single‐center, retrospective, and observational. We enrolled 83 patients (91 limbs) who underwent EVT with SMART stent (Cordis, Miami, Florida) for CIA ostial lesions from 2007 to 2014. The primary endpoint was the rate of freedom from target lesion revascularization (TLR) in 5 years, and the secondary endpoint was the success rate of stent placement for the CIA ostium. Results The average patient age was 72.3 ± 9.4 years, 71% of the patients were men, 19% were receiving hemodialysis, and 60% had diabetes. Additionally, 38% of the lesions were Trans‐Atlantic Inter‐Society Consensus C/D lesions, while 37% were chronic total occlusion lesions. The average lesion length was 36 ± 23 mm, and the average vessel diameter was 10.7 ± 1.4 mm. The rate of freedom from TLR was 97.3% at 5 years, and the success rate of only stent placement was 90.1%. Conclusion The flower stenting method leads to acceptable outcomes and is useful for accurate stent deployment.

Wwp2 is an HECT-type E3 ubiquitin ligase abundantly expressed in articular cartilage. Here, the authors show that in mice, loss of Wwp2 leads to upregulated Runx2-Adamts5 signaling in articular cartilage and development of osteoarthritis, and that disease severity is reduced by injection of Wwp2 mRNA

The transcription factor RUNX3 plays a key role in the restriction point of cell cycle. Here the authors showed that RUNX3 binds and opens chromatin structure of restriction point associated genes, by sequential recruitment of chromatin remodeling complex, transcription complex and cell cycle regulators.

Aims. We aimed to evaluate the efficacy of stentless strategy by drug-coated balloon (DCB) angioplasty following directional coronary atherectomy (DCA) for left main (LM) bifurcation lesions. Methods. A total of 38 patients who underwent DCB angioplasty following DCA for LM bifurcation lesions were retrospectively enrolled. The primary endpoint was target vessel failure (TVF) at 12 months. Secondary endpoints included procedure-related major events during the hospitalization, major adverse cardiac events at 12 months, ischemia-driven target lesion revascularization (TLR) at 12 months, and bleeding complications defined as the Bleeding Academic Research Consortium criteria ≥2 at 12 months. Results. Among these 38 lesions, 31 lesions were de novo LM bifurcation lesions and 7 lesions were stent edge restenosis at the left anterior descending (LAD) ostium. The mean % plaque area (%PA) after DCA was 44.0 ± 7.4%. TVF at 12 months occurred in 1 lesion (3.2%) of de novo LM bifurcation lesion and in 3 lesions (42.9%) of stent edge restenosis at the LAD ostium. All events of TVF were ischemia-driven TLR by percutaneous coronary intervention. Among 4 TLR cases, %PA after DCA was high (55.9%) in the de novo LM bifurcation lesions; on the other hand, %PA after DCA was low (42.4%, 38.7%, and 25.7% in the 3 cases) in stent edge restenosis at the LAD ostium. No procedure-related major events were observed during hospitalization. There was no cardiac death, no myocardial infarction, no coronary artery bypass grafting, and no bleeding complications at 12 months. Conclusions. Stentless strategy by DCB angioplasty following DCA for de novo LM bifurcation lesions resulted in acceptable outcomes. On the other hand, its efficacy was limited for stent edge restenosis at the LAD ostium even after aggressive debulking by DCA.

Introduction. The proportion of patients with comorbid atrial fibrillation (AF) and peripheral artery disease (PAD) has increased in this era. This study aimed to assess the relationship between AF and totally occlusive in-stent restenosis (ISR) in femoropopliteal (FP) lesions. Methods. In this study, 363 patients (461 stents) who underwent endovascular therapy with de novo stent implantation in our hospital between April 2007 and December 2016 were retrospectively evaluated. The patients were divided into two groups according to the AF status (AF group, 61 patients; sinus group, 302 patients). The primary endpoint was the incidence of totally occlusive ISR within 3 years. The secondary endpoint was the incidence of acute limb ischemia (ALI) due to FP stent occlusion. Results. Baseline characteristics were similar, except for higher age and a lower prevalence of dyslipidemia in the AF group. The incidence of a totally occlusive ISR was higher in the AF group than in the sinus group (29.5% vs. 14.6%, p=0.004). A multiple Cox regression model suggested that presence of AF (hazard ratio, 2.10) and CTO lesion (hazard ratio, 1.97) which were the independent predictors of a totally occlusive ISR within 3 years. The incidence of ALI was significantly higher in the AF group than in the sinus group (3.9% vs. 0%, p=0.0001). In the AF group, the introduction of an anticoagulant did not prevent the occurrence of totally occlusive ISR (p=0.71) for ALI (p=0.79). Conclusions. AF is independently associated with totally occlusive ISR of FP stents; however, anticoagulant use does not prevent stent occlusion.

Aims. To evaluate the vascular response after directional coronary atherectomy (DCA) for left main (LM) bifurcation lesion. Methods. This study was a retrospective, single-center study enrolling 31 patients who underwent stentless therapy using DCA followed by drug-coated balloon (DCB) angioplasty for LM bifurcation lesion. We compared intravascular ultrasound (IVUS) findings before and after DCA. Results. After DCA, the lumen and vessel areas significantly increased, whereas the plaque area (PA) and %PA were significantly reduced. When the lesions were divided into small vessel and large vessel groups using the median value of the vessel area, the maximum balloon pressure of the DCA catheter was greater in the large vessel group. Changes in the lumen and vessel areas were also significantly greater in the large vessel group. On the other hand, the changes in PA and %PA were similar between groups. Conclusions. The main vascular responses associated with lumen enlargement after DCA were plaque reduction and vessel expansion. Contribution of vessel expansion to lumen enlargement was larger than the effect of plaque reduction in large vessel lesions.

This study aimed to assess the safety and feasibility of the ULtrasound-guided uSe Of exoSEAL technique (ULSOSEAL technique) in patients at a high risk of complications following the use of ExoSeal. ExoSeal is a novel, completely extravascular hemostatic device that can treat punctures of the common femoral artery; however, it is not preferable for use in cases that require hemostasis of complex puncture sites. From November 2019 to August 2020, the ULSOSEAL technique was performed in 35 patients with implanted stents (6 patients, 17%), severe calcification (32 patients, 91%), and plaque (7 patients, 20%) around the puncture site; the presence of these conditions is usually undesirable when using ExoSeal. The antegrade approach was used in 22 patients (71%). The size of the ExoSeal used was 5 Fr (13 patients, 37%), 6 Fr (21 patients, 60%), and 7 Fr (1 patient, 2%). Technical success was achieved in 34 patients (97%), while ExoSeal malfunction occurred in 1 patient. There was no incidence of vessel occlusion, pseudoaneurysm, arteriovenous fistula, infection, and secondary bleeding. One patient developed a hematoma (>5 cm in size); however, it occurred before the use of ExoSeal due to side leakage from the inserted sheath. The ULSOSEAL technique was safe and feasible for hemostasis in patients who were considered unsuitable for the ExoSeal device.

A 68-year-old man was scheduled to undergo percutaneous coronary intervention for in-stent total occlusion of the severely tortuous right coronary artery. Intravascular ultrasound revealed heavy in-stent calcification. Lesion atherectomy was required; however, severe proximal vessel tortuosity was detected. We introduced a 7-Fr guide-extension catheter beyond the severely tortuous part and performed rotational atherectomy with a 1.5 mm burr. However, the balloon could not expand; therefore, we changed to an orbital atherectomy system. Subsequently, the balloon successfully expanded, and intravascular ultrasound revealed an enlarged lumen. Severe proximal vessel tortuosity limits the use of atherectomy devices; however, a guide-extension catheter delivers the atherectomy device beyond the tortuosity. The delivery of the orbital atherectomy system inside the guide-extension catheter is easy due to its low profile; the debulking effect increases with the number of passes and rotational speed. This strategy is a useful option for treating severe calcified lesions with proximal vessel tortuosity.

Tendons and ligaments are pivotal connective tissues that tightly connect muscle and bone. In this study, we developed a novel approach to generate tendon/ligament-like tissues with a hierarchical structure, by introducing the tendon/ligament-specific transcription factor Mohawk (MKX) into the mesenchymal stem cell (MSC) line C3H10T1/2 cells, and by applying an improved three-dimensional (3D) cyclic mechanical stretch culture system. In our developed protocol, a combination of stable Mkx expression and cyclic mechanical stretch synergistically affects the structural tendon/ligament-like tissue generation and tendon related gene expression. In a histological analysis of these tendon/ligament-like tissues, an organized extracellular matrix (ECM), containing collagen type III and elastin, was observed. Moreover, we confirmed that Mkx expression and cyclic mechanical stretch, induced the alignment of structural collagen fibril bundles that were deposited in a fibripositor-like manner during the generation of our tendon/ligament-like tissues. Our findings provide new insights for the tendon/ligament biomaterial fields.

The body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of Hox genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of Hox genes are not fully understood. In this study, we demonstrated that the Lin28a/let-7 pathway is critical for axial elongation. Lin28a–/– mice exhibited axial shortening with mild skeletal transformations of vertebrae, which were consistent with results in mice with tail bud-specific mutants of Lin28a. The accumulation of let-7 in Lin28a–/– mice resulted in the reduction of PRC1 occupancy at the Hox cluster loci by targeting Cbx2. Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior Hox genes, which was rescued by the knockdown of let-7. These results suggest that the Lin28/let-7 pathway is involved in the modulation of the ‘Hox code’ via Polycomb regulation during axial patterning.

A 63 year-old woman with claudication underwent endovascular therapy for diffuse stenosis of the right superficial femoral artery in our hospital. We performed paclitaxel-coated balloon angioplasty using the IN.PACT™ Admiral™ and achieved acceptable results. After 42 days, we performed follow-up optical frequency domain imaging for the right superficial femoral artery lesion treated with paclitaxel-coated balloon and observed several high-intensity regions with attenuation on the lumen surface. Sustained drug availability is a notable characteristic of paclitaxel-coated balloon. To the best of our knowledge, this is the first report on the visualization of sustained drug retention on the lumen surface using follow-up optical frequency domain imaging after paclitaxel-coated balloon angioplasty in a human patient with superficial femoral artery disease.

Objectives. To compare feasibility and safety between ultrasound-guided and conventional distal transradial access (dTRA). Background. Distal transradial access, a new technique for coronary angiography (CAG) and percutaneous coronary interventions (PCI), is safe and feasible and will become popular worldwide. Ultrasound-guided dTRA has been advocated to reduce failure rate and access-site complications. However, to date, the comparison of feasibility and safety between ultrasound-guided and conventional dTRA has not been reported. Method. Overall, 137 patients (144 procedures) who underwent CAG or PCI using dTRA between September 2018 and February 2019 were investigated. These patients were classified into two groups: C (dTRA with conventional punctures; 76 patients, 79 procedures) and U (dTRA with ultrasound-guided punctures; 61 patients, 65 procedures) groups. Successful procedural rate, procedural outcomes, and complication rate during hospital stays were compared between the two groups. Results. The procedural success rate was significantly higher in the U group than in the C group (97% vs. 87%, P=0.0384). However, the rate of PCI, puncture time, total fluoroscopy time, the volume of contrast medium, the rate of access-site ecchymosis, and incidence of nerve disorder were similar between the two groups. Additionally, radial artery occlusion after the procedure did not occur in this study. Conclusion. The ultrasound-guided dTRA for CAG or PCI was associated with a lower failure rate than conventional dTRA. However, there were no significant differences in puncture time and complication rate between the two procedures.

Summary: The Fanconi anemia (FA) pathway is a pivotal genome maintenance network that orchestrates the repair of DNA interstrand crosslinks (ICLs). The tumor suppressors RUNX1 and RUNX3 were shown to regulate the FA pathway independent of their canonical transcription activities, by controlling the DNA damage-dependent chromatin association of FANCD2. Here, in further biochemical characterization, we demonstrate that RUNX3 is modified by PARP-dependent poly(ADP-ribosyl)ation (PARylation), which in turn allows RUNX binding to DNA repair structures lacking transcription-related RUNX consensus motifs. SILAC-based mass spectrometric analysis revealed significant association of RUNX3 with core DNA repair complexes, including PARP1, even in unstressed cells. After DNA damage, the increased interaction between RUNX3 and BLM facilitates efficient FANCD2 chromatin localization. RUNX-Walker motif mutations from breast cancers are impaired for DNA damage-inducible PARylation, unveiling a potential mechanism for FA pathway inactivation in cancers. Our results reinforce the emerging paradigm that RUNX proteins are tumor suppressors with genome gatekeeper function. : Tay et al. demonstrate that the tumor suppressor genes RUNX1 and RUNX3 have an important regulatory role in the genome maintenance pathway controlled by FANCD2. DNA damage induces PARP-dependent PARylation of RUNX proteins, leading to their interaction with BLM to control the loading of FANCD2 on DNA damage sites. Keywords: RUNX1, RUNX3, Fanconi anemia, interstrand crosslink repair, PARP1, poly(ADP-ribosyl)ation, BLM, SILAC, DNA repair, FANCD2

Abstract A 23‐year‐old male with manifest Wolff–Parkinson–White syndrome presented with a first occurrence of ventricular fibrillation (VF). Initially, we anticipated the occurrence of atrial fibrillation, causing rapid antegrade conduction over the accessory pathway and, thus, resulting in hemodynamic deterioration. Electrophysiological study revealed that the atrioventricular accessory pathway was located at the mid‐septum. After eliminating the pathway, a J‐point elevation was revealed in the inferior and lateral leads. In addition, program ventricular stimulation induced VF, and the administration of isoproterenol suppressed VF. In our case, VF occurrence can be attributed to early repolarization syndrome and ventricular preexcitation‐modified J‐point elevation.

The Hippo–YAP signaling pathway serves roles in cell proliferation, stem cell renewal/maintenance, differentiation and apoptosis. Many of its functions are central to early development, adult tissue repair/regeneration and not surprisingly, tumorigenesis and metastasis. The Hippo pathway represses the activity of YAP and paralog TAZ by modulating cell proliferation and promoting differentiation to maintain tissue homeostasis and proper organ size. Similarly, master regulators of development RUNX transcription factors have been shown to play critical roles in proliferation, differentiation, apoptosis and cell fate determination. In this review, we discuss the multiple interactions of RUNX with the Hippo–YAP pathway, their shared collaborators in Wnt, TGFβ, MYC and RB pathways, and their overlapping functions in development and tumorigenesis.

Homeobox protein Mohwak (Mkx) is involved in tendon and ligament development. Here the authors show that Mkx in the outer annulus fibrosus of the intervertebral disc plays a role in maintenance of the IVD, showing that stem cells overexpressing Mkx enhance therapeutic IVD regeneration in mice.

A 62-year-old man with effort angina underwent percutaneous coronary intervention in our hospital. The target lesion was severely calcified at the mid part of the right coronary artery. Pre-procedural intravascular imaging and optical frequency domain imaging showed a calcified nodule at the lesion. We performed rotational atherectomy with a 2.0 mm burr and observed an increase in the lumen area; however, a large amount of calcified nodule persisted. We decided to perform rotational atherectomy with a burr size of 2.25 mm; however, distal embolization of the calcified nodule occurred. We failed to retrieve the embolus; hence, we performed balloon dilatation with a 2.0-mm balloon, which was successfully performed. Yet, the lesion with the embolus immediately recoiled. Finally, a drug-eluting stent was implanted in both the distal lesion with the embolus and the lesion with the calcified nodule. Final coronary angiography showed good results. We confirmed good stent expansion and that calcified nodule was compressed outside the stent. Atherectomy of a calcified nodule is effective at achieving sufficient stent expansion and reducing the risk of vessel perforation. However, we experienced distal embolization of the calcified nodule at the time of rotational atherectomy and so distal embolization should be considered at the time of treatment of calcified nodule.