Effects of Sprayable, Highly Adhesive Hydrophobized Gelatin Microparticles on Endoscopic Submucosal Dissection: A Swine Model.

INTRODUCTION: Sprayable wound dressings containing hydrophobized microparticles (hMPs) are characterized by strong adhesiveness. We examined the effect of hMPs derived from Alaska pollock gelatin on endoscopic submucosal dissection (ESD) ulcers. METHODS: (1) In an in vivo model of miniature swine gastric ESD, gastric ulcers were created by ESD and then sprayed with hMPs or untreated followed by microscopic examination. (2) In an ex vivo ESD model of resected stomach, a pinhole-shaped perforation was created on the ESD ulcer of resected stomach; hMPs were then sprayed on the perforation; and air leakage and intragastric pressure were measured. (3) In an in vivo duodenal ESD model of miniature swine, duodenal artificial ESD ulcers with pinhole-shaped perforation were examined; ulcers were classified into hMPs-sprayed and nonsprayed groups, and inflammation in the intrinsic muscle layer and serosa were compared between the groups. RESULTS: (1) Histological observation of submucosal tissues showed a decreased number of invading inflammatory cells in hMP-sprayed tissues compared with the control in miniature swine gastric ESD (p < 0.05). In addition, the rates of anti-alpha smooth muscle actin and type I collagen positivity were significantly lower in the hMPs group than in the control group (p < 0.05). (2) Intragastric pressure could not be measured in the nonsprayed group, whereas no air leakage was observed in the sprayed group when pressurized up to 26 mm Hg in the resected stomach model. (3) The sprayed group showed suppressed inflammation of the intrinsic muscular layer and serosa in both cases compared with the nonsprayed group in miniature swine duodenal ESD (p < 0.05). CONCLUSIONS: Sprayable, tissue-adhesive hMPs are a promising medical material for intraoperative and postoperative treatment of ESD-induced wound via anti-inflammation and strong adhesiveness.

First generation versus new generation drug-eluting stents for the treatment of ostial/midshaft lesions in unprotected left main coronary artery: the Milan and New-Tokyo (MITO) registry.

OBJECTIVES: To compare the clinical outcomes following unprotected left main coronary artery (ULMCA) percutaneous coronary intervention (PCI) of ostial/midshaft lesions between first and new generation drug-eluting stents (DES). BACKGROUND: Clinical outcomes after treatment of ostial/midshaft lesions in ULMCA with first generation DES were favorable. However, to date, data regarding treatment for those lesion subsets with new generation DES have not been reported. METHODS: A total of 219 patients with ostial/midshaft lesions in ULMCA treated with first (n = 139) or new generation DES (n = 80) were analyzed. RESULTS: There was a higher prevalence of IVUS use (35.2% vs. 50.0%, P = 0.032) and postdilation (70.5% vs. 93.8%, P < 0.001) with larger maximum balloon diameter (3.81 ± 0.45 vs. 4.08 ± 0.44, P < 0.001) in the new generation DES group. At a median follow-up period of 730 days, there were no significant differences in the propensity-score adjusted analyses, for major adverse cardiac events (MACE) defined as composite endpoint of all-cause death, myocardial infarction, and target vessel revascularization (hazard ratio (HR) [new vs. first generation DES]: 1.22; 95% confidence interval (CI): 0.64-2.31; P = 0.549). Of note, target lesion revascularization rates at 2-years were only 0.9% and 2.7%, for first and new generation DES groups, respectively (P = 0.339). On multivariable analysis, SYNTAX score (HR: 1.06; 95% CI: 1.02-1.11, P = 0.006) and European System for Cardiac Operative Risk Evaluation (HR: 1.14; 95% CI: 1.00-1.31, P = 0.051) were independent predictors for MACE. CONCLUSIONS: This study suggests that new generation DES for ostial/midshaft lesions in ULMCA are associated with favorable clinical outcomes, similar to those observed with first generation DES.

New insights on acute expansion and longitudinal elongation of bioresorbable vascular scaffolds in vivo and at bench test: a note of caution on reliance to compliance charts and nominal length.

OBJECTIVES: We performed systematic optical coherence tomography (OCT) analyses after bioresorbable vascular scaffolds (BVS) implantation in a "real world" setting aiming at evaluating scaffold expansion and longitudinal integrity. BACKGROUND: a comprehensive elucidation of BVS acute performance in the "real-world" setting is lacking. METHODS: acute BVS expansion compared with compliance chart information and longitudinal integrity were assessed in 29 patients (32 lesions) by OCT. In addition, bench experiments with four scaffolds were performed with different combinations of deployment pressures and tube stiffness. RESULTS: scaffold underexpansion, using compliance chart information as reference, was observed in 97% of OCT cross-sections in vivo; however, only 8.3% of the cross-section analyzed revealed BVS area <5 mm(2) . Calcified plaques were more common in the lowest (9.7%) compared with the mid (8.8%) and highest (6.3%) tertiles of scaffold expansion (P = 0.003 and P = 0.001 for lowest vs. mid, and lowest vs. highest, respectively). Seventeen (54.8%) scaffolds were elongated during implantation, but no signs of scaffold fracture were revealed. Elongation and impaired expansion were reproduced in the bench testing when the scaffold was deployed with high pressure in a hard tube. CONCLUSIONS: compliance chart information should not be used to predict final BVS dimensions in the clinical setting. While BVS expansion could be potentially impaired by calcified plaques, they may elongate during deployment. Bench experiments confirmed the elongation phenomenon when BVS were deployed with high pressure in hard tubes.

The impact of main branch restenosis on long term mortality following drug-eluting stent implantation in patients with de novo unprotected distal left main bifurcation coronary lesions: the Milan and New-Tokyo (MITO) Registry.

BACKGROUND: In-stent restenosis (ISR) remains one of the main limitations for percutaneous coronary intervention of unprotected distal left main (UDLM). This study aims to demonstrate the impact of main-branch ISR (MB-ISR) on mortality and to clarify the optimal strategy. METHODS: Between 2002 and 2008, 482 consecutive UDLM patients treated with drug eluting stent (sirolimus and paclitaxel) were evaluated. RESULTS: During follow-up period (median 52.6 months), MB-ISR occurred in 29, SB-ISR in 65, and MB/SB-ISR in 24. Multivariable analysis demonstrated that the independent predictors of MB-ISR were calcification (HR 2.284, p = 0.016), true-bifurcation (HR 2.331, p = 0.024), insulin-dependent diabetes mellitus (insulin-DM) (HR 2.259, p = 0.048). Furthermore, final proximal postdilatation (FPPD) (HR 0.548, p = 0.077), full LM cover approach (FCA) (HR 0.605, p = 0.093) and greater MLD (HR 0.611, p = 0.062) had a tendency to reduce MB-ISR. Furthermore, the occurrence of MB-ISR within 1-year was associated with cardiac-death (HR 2.734, p = 0.017). CONCLUSIONS: The patients with MB-ISR had more comorbidities and complex lesions, resulting in higher risk of cardiac mortality as compared to the patients without MB-ISR. Presence of calcification, true-bifurcation and insulin-DM were associated with MB-ISR following UDLM intervention, while FCA, FPPD, and greater MLD seemed to be associated with the low occurrence of MB-ISR.

Impact of rotational atherectomy on heavily calcified, unprotected left main disease.

BACKGROUND: There is little data on percutaneous coronary intervention (PCI) using rotational atherectomy (Rota) for severely calcified unprotected left main (ULM) lesions. METHODS AND RESULTS: Between January 2005 and August 2011, 64 consecutive patients who underwent drug-eluting stent implantation using Rota were retrospectively evaluated. Of these, 54.7% and 20.3% patients had diabetes and were undergoing hemodialysis (HD), respectively. The mean EuroSCORE and SYNTAX score was 5.6 and 35.4, respectively. Procedural success, defined as residual stenosis <30%, was achieved in 95.3% of patients without fatal complications. Periprocedural myocardial infarction occurred in 7.8% patients. At the 1-year follow up, cardiac death was observed in 6.3% of patients, and target lesion revascularization (TLR) and TLR in the main branch (TLR-MB) were required in 18.8% and 10.9% patients, respectively. Optimal stent expansion was achieved in the majority of 33 patients with available intravascular ultrasound (IVUS) data. However, 5 of 9 HD patients who underwent IVUS required TLR-MB despite optimal stent expansion. The rate of TLR-MB was significantly lower in the non-HD patients than in the HD patients (2.1% vs. 46.2%; P=0.003). CONCLUSIONS: PCI using Rota for calcified ULM lesions might guarantee high procedural success and a low complication rate. Although acceptable results were obtained at the 1-year follow up for non-HD patients, the rate of TLR-MB was considerably high for HD patients despite optimal stent expansion.

Successful healing of aneurysmal false lumen using a second-generation drug-eluting stent in spontaneous coronary artery dissection: a case report.

BACKGROUND: According to 2023 ESC Guideline, conservative medical management is generally recommended for the treatment of spontaneous coronary artery dissection (SCAD) except for patients with signs of ongoing myocardial ischemia. However, in some cases, invasive treatment (coronary artery bypass graft surgery or percutaneous coronary intervention (PCI)) is performed because of the progression of aneurysm in SCAD. Although there is no established strategy for the management of coronary aneurysm in SCAD, we report a case of successful healing of aneurysmal false lumen (AFL) using a second-generation drug-eluting stent (DES) in SCAD. CASE PRESENTATION: A 44-year-old woman without any cardiovascular risk factors was transferred to our hospital due to inferior myocardial infarction. Coronary angiography (CAG) showed multiple SCADs in the coronary artery. We performed PCI to the distal right coronary artery (RCA) because the RCA showed severe stenosis (99%) with bradycardia. Six days after the first PCI, SCAD relapsed in the mid left anterior descending artery (LAD). Furthermore, AFL was observed by intravascular ultrasound imaging. To avoid enlargement of the AFL and progression of the dissection toward the proximal site of the LAD, we performed PCI to the mid LAD to seal the entry tear of the dissection using a second-generation DES. CAG revealed that the AFL in the mid LAD completely diminished at 1 year after PCI. CONCLUSIONS: The implantation of a second-generation DES might be one of therapeutic options for sealing AFL in SCAD patients.

Trends of Early Helicobacter pylori-Uninfected Gastric Cancer in an Aging Regional Area.

Background/Objectives: We aimed to determine the trends over time and current status of early Helicobacter pylori-uninfected gastric cancer (HpUIGC) treatment in a region with an aging population. Methods: This retrospective, multi-center observational study was conducted at seven major general hospitals in Kagoshima Prefecture. From January 2009 to July 2022, 2091 patients who received endoscopic resection (ER) for early gastric cancer (EGC) were retrospectively enrolled, of which 35 were identified as early HpUIGC cases. Results: The number of ERs for EGC demonstrated a significant increasing trend from 2010 to 2021 (p = 0.01 for trend). Furthermore, the 12-year period from 2010 to 2021 was divided into an early and late phase every 6 years. In the early phase, there were 5 cases (0.7%) of early HpUIGC, while in the late phase, there were 25 cases (2.1%), indicating a significant increase in the proportion of ERs for early HpUIGC cases in the late phase (p = 0.02). Conclusions: The proportion of ERs for early HpUIGC, which are more common in relatively young patients, may be increasing as a proportion of all ERs for GC, even in areas of Japan with an aging population.

Frequency-domain optical coherence tomography assessment of unprotected left main coronary artery disease-a comparison with intravascular ultrasound.

OBJECTIVES: To investigate safety and feasibility of imaging unprotected left main (ULM) using frequency-domain optical coherence tomography (FD-OCT) compared with intravascular ultrasound (IVUS). BACKGROUND: IVUS has been used to assess and guide percutaneous coronary intervention (PCI) of ULM disease. FD-OCT offers 10-fold higher axial resolution than IVUS and its high-speed image acquisition obviates the need for proximal balloon occlusion. METHODS: We prospectively enrolled 35 consecutive patients with ULM disease. FD-OCT and IVUS assessments were attempted pre- and post-PCI and compared in regards to safety, ability to image the region of interest (ROI), number of pullbacks, volume of contrast and ability to detect malapposition, dissection, and thrombus. RESULTS: Patients were followed for 1 year when FD-OCT imaging was repeated. FD-OCT required more repeated pullbacks to image the ROI compared to IVUS. Mean lumen and stent areas were similar between FD-OCT and IVUS (11.24 ± 2.66 vs. 10.85 ± 2.47 mm(2) , P = 0.13 and 10.44 ± 2.33 vs. 10.49 ± 2.32 mm(2) , P = 0.82, respectively), whereas imaged stent length was shorter with FD-OCT. Malapposition areas and volumes were larger and more edge dissections were detected by FD-OCT. There were no clinical adverse events and no complications associated with FD-OCT at baseline and 1-year follow-up. All dissections were healed, whereas stent malapposition was still detected at follow-up. CONCLUSIONS: FD-OCT assessment of ULM is feasible and safe. Direct comparisons with IVUS reveal that FD-OCT achieved imaging completeness less often, whereas it was more sensitive in detecting malapposition and edge dissections, and similar to IVUS in the assessment of lumen and stent dimensions.

Volumetric characterization of human coronary calcification by frequency-domain optical coherence tomography.

BACKGROUND: Coronary artery calcification (CAC) presents unique challenges for percutaneous coronary intervention. Calcium appears as a signal-poor region with well-defined borders by frequency-domain optical coherence tomography (FD-OCT). The objective of this study was to demonstrate the accuracy of intravascular FD-OCT to determine the distribution of CAC. METHODS AND RESULTS: Cadaveric coronary arteries were imaged using FD-OCT at 100-µm frame interval. Arteries were subsequently frozen, sectioned and imaged at 20-µm intervals using the Case Cryo-Imaging automated system(TM). Full volumetric co-registration between FD-OCT and cryo-imaging was performed. Calcium area, calcium-lumen distance (depth) and calcium angle were traced on every cross-section; volumetric quantification was performed offline. In total, 30 left anterior descending arteries were imaged: 13 vessels had a total of 55 plaques with calcification by cryo-imaging; FD-OCT identified 47 (85%) of these plaques. A total of 1,285 cryo-images were analyzed and compared with corresponding co-registered 257 FD-OCT images. Calcium distribution, represented by the mean depth and the mean calcium angle, was similar, with excellent correlation between FD-OCT and cryo-imaging respectively (mean depth: 0.25±0.09 vs. 0.26±0.12mm, P=0.742; R=0.90), (mean angle: 35.33±21.86° vs. 39.68±26.61°, P=0.207; R=0.90). Calcium volume was underestimated in large calcifications (3.11±2.14 vs. 4.58±3.39mm(3), P=0.001) in OCT vs. cryo respectively. CONCLUSIONS: Intravascular FD-OCT can accurately characterize CAC distribution. OCT can quantify absolute calcium volume, but may underestimate calcium burden in large plaques with poorly defined abluminal borders.

Hepatocyte growth factor ameliorates dextran sodium sulfate­induced colitis in a mouse model by altering the phenotype of intestinal macrophages.

Hepatocyte growth factor (HGF) serves key roles in cell motility, proliferation and immunoregulatory functions. However, the effect of HGF on macrophages is unclear. The present study aimed to elucidate the effect of HGF on the phenotypic alterations of intestinal lamina propria mononuclear cells (LPMCs). Colitis was induced in a mouse model using dextran sodium sulfate (DSS). Subsequently, LPMCs were isolated from the mice with chronic colitis and the expression levels of cytokine­encoding genes in the LPMCs were determined. CD11b­positive macrophages isolated from LPMCs were cultured with HGF, and alterations in the levels of M1 or M2 markers were evaluated by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and flow cytometry. In addition, the cytokine levels were assessed using RT­qPCR and ELISA. HGF shifted the phenotype of macrophages from M1 to M2­like, as determined by increased mRNA expression levels of arginase­1, CD206 and IL­10, and reduced mRNA expression levels of CD86 and IL­6 in mice with DSS­induced colitis. Moreover, HGF could ameliorate DSS­induced colitis owing to its immunosuppressive effect on immune cells. These findings indicated that HGF treatment may not only promote the regeneration of epithelial cells but also lead to tissue repair by phenotypic alteration of M1 macrophages to M2­like macrophages.

Focal Type 2 Autoimmune Pancreatitis Mimicking Pancreatic Cancer: Treatment with Neoadjuvant Chemotherapy and Surgery.

A 51-year-old man was referred to our hospital for the further examination of main pancreatic duct interruption. Imaging findings showed a 25-mm-diameter mass lesion located in the pancreatic head. Endoscopic ultrasonography (EUS)-guided fine-needle aspiration (FNA) was performed on the mass. Cytology suggested adenocarcinoma, but the histological diagnosis was not confirmed. We made a comprehensive diagnosis of resectable pancreatic cancer. The mass shrank after preoperative adjuvant chemotherapy, and the patient underwent surgery. The final pathological diagnosis was type 2 autoimmune pancreatitis (AIP). Two years after surgery, AIP had not recurred in the remaining pancreas.

Characterization of plaque phenotypes exhibiting an elevated pericoronary adipose tissue attenuation: insights from the REASSURE-NIRS registry.

Inflammation has been considered to promote atheroma instability. Coronary computed tomography angiography (CCTA) visualizes pericoronary adipose tissue (PCAT) attenuation, which reflects coronary artery inflammation. While PCAT attenuation has been reported to predict future coronary events, plaque phenotypes exhibiting high PCAT attenuation remains to be fully elucidated. The current study aims to characterize coronary atheroma with a greater vascular inflammation. We retrospectively analyzed culprit lesions in 69 CAD patients receiving PCI from the REASSURE-NIRS registry (NCT04864171). Culprit lesions were evaluated by both CCTA and near-infrared spectroscopy/intravascular ultrasound (NIRS/IVUS) imaging prior to PCI. PCAT attenuation at proximal RCA (PCATRCA) and NIRS/IVUS-derived plaque measures were compared in patients with PCATRCA attenuation ≥ and < -78.3 HU (median). Lesions with PCATRCA attenuation ≥ -78.3 HU exhibited a greater frequency of maxLCBI4mm ≥ 400 (66% vs. 26%, p < 0.01), plaque burden ≥ 70% (94% vs. 74%, p = 0.02) and spotty calcification (49% vs. 6%, p < 0.01). Whereas positive remodeling (63% vs. 41%, p = 0.07) did not differ between two groups. On multivariable analysis, maxLCBI4mm ≥ 400 (OR = 4.07; 95%CI 1.12-14.74, p = 0.03), plaque burden ≥ 70% (OR = 7.87; 95%CI 1.01-61.26, p = 0.04), and spotty calcification (OR = 14.33; 95%CI 2.37-86.73, p < 0.01) independently predicted high PCATRCA attenuation. Of note, while the presence of only one plaque feature did not necessarily elevate PCATRCA attenuation (p = 0.22), lesions harboring two or more features were significantly associated with higher PCATRCA attenuation. More vulnerable plaque phenotypes were observed in patients with high PCATRCA attenuation. Our findings suggest PCATRCA attenuation as the presence of profound disease substrate, which potentially benefits from anti-inflammatory agents.

Non-mercaptalbumin is significantly associated with the coronary plaque burden and the severity of coronary artery disease.

Human non-mercaptalbumin (HNA), oxidized form of serum albumin, has been reported as a useful marker in oxidative stress-related diseases; however, few reports have examined the association between HNA and the severity of coronary artery disease (CAD). The present study evaluated whether the HNA fraction is correlated with coronary artery stenosis in 140 patients considered to have a high risk of CAD or who were suspected of having acute coronary syndrome. The severity of CAD was defined by the number of stenotic coronary vessels and a severity score system (the Gensini score). HNA measurements were performed using our newly established high-performance liquid chromatography methodology. The results had shown that HNA was significantly increased in patients with three-vessel disease, compared with those without CAD or with single-vessel disease (p = 0.025), and was positively correlated with the Gensini score (ρ = 0.421, p < 0.001). A multivariate analysis showed that the number of stenotic vessels was an independent and significant factor associated with HNA (ρ = 1.246, p = 0.012). A logistic regression analysis showed that HNA was a strong predictor of multivessel CAD (odds ratio, 1.12; 95% confidence interval, 1.020-1.229; p = 0.017). These findings indicate that the measurement of HNA could be clinically practical for predicting the severity of coronary artery stenosis.

Structural changes induced by ligand binding drastically increase the thermostability of the Ser/Thr protein kinase TpkD from Thermus thermophilus HB8.

Thermophilic proteins maintain their structure at high temperatures through a combination of various factors. Here, we report the ligand-induced stabilization of a thermophilic Ser/Thr protein kinase. Thermus thermophilus TpkD unfolds completely at 55 °C despite the optimum growth temperature of 75 °C. Unexpectedly, we found that the TpkD structure is drastically stabilized by its natural ligands ATP and ADP, as evidenced by the increase in the melting temperature to 80 °C. Such a striking effect of a substrate on thermostability has not been reported for other protein kinases. Conformational changes upon ATP binding were observed in fluorescence quenching and limited proteolysis experiments. Urea denaturation of Trp mutants suggested that ATP binding affects not only the ATP-binding site, but also the remote regions. Our findings shed light on thermoadaptation of thermophilic proteins.

Impact of Abnormal Remote Stress Myocardial Blood Flow by Dynamic CT Perfusion on Clinical Outcomes.

The objective of this study was to investigate the incremental prognostic value for adverse events of myocardial blood flow (MBF) derived from stress computed tomography perfusion (CTP) at remote myocardium over cardiac risk factors and ischemia. We prospectively analyzed 242 patients who underwent dynamic CTP and CT angiography. Adverse events were defined as a composite of all-cause mortality, non-fatal myocardial infarction, unstable angina, heart failure requiring hospitalization, peripheral artery disease, and stroke. MBF value was calculated in each myocardial segment and ischemia was defined as mild decrease in MBF in two consecutive segments or moderate decrease in a single segment accompanied with a coronary stenosis ≥50%. The mean MBF of the non-ischemic segments was defined as remote MBF. We divided the patients into two groups by median MBF value of 1.15 ml/min/g. During a median follow-up of 18 months, 18 patients had adverse events. Annual event rate showed a significant difference between patients with low (≤1.15 ml/min/g) and high (>1.15 ml/min/g) MBF (6.1% vs 1.8%, p = 0.02). Univariate analysis showed that low MBF was a significant predictor of events (hazard ratio (HR): 3.4; 95% confidence interval (CI): 1.2 to 12.0; p = 0.02). This relationship maintained significant after adjusted for the presence of ischemia and cardiac risk factors (HR: 3.0; 95%CI: 1.1 to 11.1; p = 0.04). In conclusion, MBF value ≤1.15 ml/min/g derived from dynamic CTP in remote myocardium is significantly related with poor outcome and this relationship was independent of myocardial ischemia and cardiac risk factors.

Feasibility of dynamic myocardial CT perfusion using single-source 64-row CT.

BACKGROUND: Dynamic myocardial computed tomography perfusion (CTP) is an emerging technique to diagnose significant coronary stenosis. However, this procedure has not been reported using single-source 64-row CT. OBJECTIVE: To investigate the radiation dose and the diagnostic performance of dynamic CTP to diagnose significant stenosis by catheter exam. METHODS: We prospectively included 165 patients who underwent CTP exam under adenosine stress using a single-source 64-row CT. MBF was calculated using the deconvolution technique. Quantitative perfusion ratio (QPR) was defined as the myocardial blood flow (MBF) of the myocardium with coronary stenosis divided by the MBF of the myocardium without significant stenosis or infarct. Of the 44 patients who underwent subsequent coronary angiography, we assessed the diagnostic performance to diagnose ≥50% stenosis by quantitative coronary analysis (QCA). RESULTS: The average effective dose of dynamic CTP and the entire scans were 2.5 ±â€¯0.7 and 7.3 ±â€¯1.8 mSv, respectively. The MBF of the myocardium without significant stenosis was 1.20 ±â€¯0.32 ml/min/g, which significantly decreased to 0.98 ±â€¯0.24 ml/min/g (p < 0.01) in the area with ≥50% stenosis by CT angiography. The QPR of the myocardium with QCA ≥50% stenosis was significantly lower than 1 (0.84 ±â€¯0.32, 95% confidence interval (CI), 0.77-0.90, p < 0.001). The accuracy to detect QCA ≥50% stenosis was 82% (95%CI, 74-88%) using CT angiography alone and significantly increased to 87% (95%CI, 80-92%, p < 0.05) including QPR. CONCLUSION: Dynamic myocardial CTP could be performed using 64-row CT with a low radiation dose and would improve the diagnostic performance to detect QCA ≥50% stenosis than CT angiography alone.