Ultra-high-resolution CT vs. invasive angiography for detecting hemodynamically significant coronary artery disease: Rationale and methods of the CORE-PRECISION multicenter study.

BACKGROUND: Direct coronary arterial evaluation via computed tomography (CT) angiography is the most accurate noninvasive test for the diagnosis of coronary artery disease (CAD). However, diagnostic accuracy is limited in the setting of severe coronary calcification or stents. Ultra-high-resolution CT (UHR-CT) may overcome this limitation, but no rigorous study has tested this hypothesis. METHODS: The CORE-PRECISION is an international, multicenter, prospective diagnostic accuracy study testing the non-inferiority of UHR-CT compared to invasive coronary angiography (ICA) for identifying patients with hemodynamically significant CAD. The study will enroll 150 patients with history of CAD, defined as prior documentation of lumen obstruction, stenting, or a calcium score ≥400, who will undergo UHR-CT before clinically prompted ICA. Assessment of hemodynamically significant CAD by UHR-CT and ICA will follow clinical standards. The reference standard will be the quantitative flow ratio (QFR) with <0.8 defined as abnormal. All data will be analyzed in independent core laboratories. RESULTS: The primary outcome will be the comparative diagnostic accuracy of UHR-CT vs. ICA for detecting hemodynamically significant CAD on a patient level. Secondary analyses will focus on vessel level diagnostic accuracy, quantitative stenosis analysis, automated contour detection, in-depth plaque analysis, and others. CONCLUSION: CORE-PRECISION aims to investigate if UHR-CT is non-inferior to ICA for detecting hemodynamically significant CAD in high-risk patients, including those with severe coronary calcification or stents. We anticipate this study to provide valuable insights into the utility of UHR-CT in this challenging population and for its potential to establish a new standard for CAD assessment.

Preliminary Investigation of a Rapid and Feasible Therapeutic Drug Monitoring Method for the Real-Time Estimation of Blood Pazopanib Concentrations.

Pazopanib is a multi-kinase inhibitor used to treat advanced/metastatic renal cell carcinoma and advanced soft tissue tumors; however, side effects such as diarrhea and hypertension have been reported, and dosage adjustment based on drug concentration in the blood is necessary. However, measuring pazopanib concentrations in blood using the existing methods is time-consuming; and current dosage adjustments are made using the results of blood samples taken at the patient's previous hospital visit (approximately a month prior). If the concentration of pazopanib could be measured during the waiting period for a doctor's examination at the hospital (in approximately 30 min), the dosage could be adjusted according to the patient's condition on that day. Therefore, we aimed to develop a method for rapidly measuring blood pazopanib concentrations (in approximately 25 min) using common analytical devices (a tabletop centrifuge and a spectrometer). This method allowed for pazopanib quantification in the therapeutic concentration range (25-50 µg/mL). Additionally, eight popular concomitant medications taken simultaneously with pazopanib did not interfere with the measurements. We used the developed method to measure blood concentration in two patients and obtained similar results to those measured using the previously reported HPLC method. By integrating it with the point of care and sample collection by finger pick, this method can be used for measurements in pharmacies and patients' homes. This method can maximize the therapeutic effects of pazopanib by dose adjustment to control adverse events.

One-Month Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy After Biodegradable Polymer Drug-Eluting Stent Implantation　- The REIWA Region-Wide Registry.

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain.Methods and Results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Detailed Lipid Profiles and Lipid-related Residual Risk after 12-week 10 mg Rosuvastatin Treatment for Acute Myocardial Infarction.

Objective We aimed to reveal detailed on-treatment lipid profiles, lipid-related surrogate markers, and factors predicting failure to achieve the guideline-recommended lipid management goal following guideline-recommended statin treatment in Japanese patients with acute myocardial infarction (AMI). Methods and Results Sixty AMI patients who underwent coronary intervention and had received rosuvastatin 10 mg/day since the start of their hospitalization were assessed for on-treatment lipid-related profiles, including high-sensitivity C-reactive protein, small dense low-density lipoprotein cholesterol (sd LDL-C), and lipoprotein (a), at the 12-week follow-up. Patients who failed to achieve the guideline-recommended lipid management at 12 weeks were defined as the "unachieved group." Univariate and multivariate logistic regression analyses were performed to evaluate the predictors of inclusion in the unachieved group after high-dose statin treatment. Despite the use of high-dose rosuvastatin, 61.7% of the enrolled AMI patients were included in the unachieved group. In addition, the unachieved group had higher sd LDL-C and lipoprotein (a) levels than the achieved group. Logistic regression analyses demonstrated that low baseline high-density lipoprotein cholesterol (HDL-C) levels and the absence of diabetes were predictors of inclusion in the unachieved group. Conclusion More than half of the Japanese AMI patients treated with rosuvastatin 10 mg/day did not achieve the guideline-recommended goal of lipid management and still had lipid-related residual risk at 12 weeks. Particular attention should be paid to patients with low baseline HDL-C levels and those without diabetes with regard to their on-treatment lipid profiles.

An In-depth Single-center Retrospective Assessment of In-Hospital Outcomes in Acute Myocardial Infarction Patients with and without Diabetes.

Objective This study examined variations in in-hospital mortality causes and identified independent mortality predictors among patients with acute myocardial infarction (AMI) with and without diabetes mellitus (DM). Methods We examined factors influencing in-hospital mortality in a single-center retrospective observational study. Separate multivariate analyses were conducted for both groups to identify independent predictors of in-hospital mortality. Patients This study included consecutive patients admitted to Iwate Medical University Hospital between January 2012 and December 2017 with a diagnosis of AMI. Results Of 1,140 patients meeting the AMI criteria (average age: 68.2±12.8 years old, 75% men), 408 (35.8%) had diabetes. The DM group had a 1.87-times higher 30-day mortality rate, a lower prevalence of ST-elevated MI (56.6% vs. 65.3% in non-DM, p=0.004), and more frequent non-cardiac causes of death (32% vs. 14% in non-DM, p=0.046) than the non-DM group. Independent predictors of in-hospital mortality in both groups were cardiogenic shock (CS) [DM: hazard ratio (HR) 6.59, 95% confidence interval (CI) 2.90-14.95; non-DM: HR 4.42, 95% CI 1.99-9.77] and renal dysfunction (DM: HR 5.64, 95% CI 1.59-20.04; non-DM: HR 5.92, 95% CI 1.79-19.53). Among patients with DM, a history of stroke was an additional independent predictor of in-hospital mortality (HR 2.59, 95% CI 1.07-6.31). Conclusion Notable disparities were identified in the causes of death and predictive factors of mortality between these two groups of patients with AMI. To further improve AMI outcomes, individualized management and prioritizing non-cardiac comorbidities during hospitalization may be crucial, particularly in patients with DM.

New risk stratification for adjuvant nivolumab for high-risk muscle-invasive urothelial carcinoma.

Objectives: We aim to evaluate the risk of recurrence after neoadjuvant chemotherapy followed by radical cystectomy, particularly in ypT2 disease in patients with urothelial carcinoma, because it is not clear if all eligible patients with high-risk muscle-invasive urothelial carcinoma should be treated with adjuvant nivolumab. Materials and Methods: We analysed the radiological and clinicopathological features, including cT and ypT stages, of 197 patients who had undergone two to four cycles of cisplatin-based neoadjuvant chemotherapy and radical cystectomy without adjuvant chemotherapy. We stratified the risk of postoperative recurrence by these factors. Results: The median observation period was 29.6 (interquartile range, 11.4-71.7) months, and disease recurrence was observed in 58 patients. Multivariate analysis revealed that ypT stage (P = 0.019) and lymphovascular invasion (P = 0.015) were independent risk factors for postoperative recurrence. The ypT2 group (n = 38) had significantly better recurrence-free survival than the ypT3 group (n = 41) (median recurrence-free survival: not reached vs. 13.4 months, respectively, P = 0.005). In ypT2 disease, the cT2 and ypT2 group (n = 15), which was diagnosed as cT2 preoperatively and then diagnosed as ypT2 postoperatively, had significantly better recurrence-free survival than the cT3/4 and ypT2 group (n = 23) (median recurrence-free survival: not reached vs. 63.1 months, respectively, P = 0.034). There was no significant difference in recurrence-free survival between the ypT ≤ 1 (n = 106) and the cT2 and ypT2 groups (median recurrence-free survival: not reached in both, P = 0.962). Conclusion: Patients with cT2 and ypT2 stage have a relatively low risk of recurrence and thus have a lower need for adjuvant nivolumab, particularly those with ypT2.

Geographic disparity of pathophysiological coronary artery disease characteristics: Insights from ASET trials.

BACKGROUND: The geographical disparity in the pathophysiological pattern of coronary artery disease (CAD) among patients undergoing percutaneous coronary intervention (PCI) is unknown. OBJECTIVES: To elucidate the geographical variance in the pathophysiological characteristics of CAD. METHODS: Physiological indices derived from angiography-based fractional flow reserve pullbacks from patients with chronic coronary syndrome enrolled in the ASET Japan (n = 206) and ASET Brazil (n = 201) studies, which shared the same eligibility criteria, were analysed. The pathophysiological patterns of CAD were characterised using Murray law-based quantitative flow ratio (µQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the µQFR pullback pressure gradient index. RESULTS: Significant functional stenoses pre-PCI (µQFR ≤0.80) were more frequent in ASET Japan compared to ASET Brazil (89.9% vs. 67.5%, p < 0.001), as were rates of a post-PCI µQFR <0.91 (22.1% vs. 12.9%, p = 0.013). In the multivariable analysis, pre-procedural µQFR and diffuse disease were independent factors for predicting a post-PCI µQFR <0.91, which contributed to the different rates of post-PCI µQFR ≥0.91 between the studies. Among vessels with a post-PCI µQFR <0.91, a consistent diffuse pattern of CAD pre- and post-PCI occurred in 78.3% and 76.7% of patients in ASET Japan and Brazil, respectively; only 6.3% (Japan) and 10.0% (Brazil) of vessels had a major residual gradient. Independent risk factors for diffuse disease were diabetes mellitus in ASET Japan, and age and male gender in Brazil. CONCLUSIONS: There was geographic disparity in pre-procedural angiography-based pathophysiological characteristics. The combined pre-procedural physiological assessment of vessel µQFR and diffuseness of CAD may potentially identify patients who will benefit most from PCI.

An optimal method of hydrogel spacer insertion for stereotactic body radiation therapy of prostate cancer.

PURPOSE: This study aimed to explore an ideal method for hydrogel spacer insertion by analyzing the efficacy and safety of our originally developed apex expansion method. MATERIALS AND METHODS: Overall, 100 patients with low- and intermediate-risk localized prostate cancer treated with stereotactic body radiation therapy were included. A hydrogel spacer was inserted in 64 and 36 patients using the conventional and apex expansion methods, respectively. For dosimetry, we trisected the rectum into the upper rectum, middle rectum, and lower rectum on the sagittal section of magnetic resonance imaging. We compared the dose to each part of the rectum between the two methods using dose-volume histograms. Genitourinary and gastrointestinal toxicity assessments were conducted until 3 months of follow-up. RESULTS: The whole rectal dose in the apex expansion method group was lower than that in the conventional method group, which was significant in all dose regions (V5-V35). Similarly, in the apex expansion method group, the dose to the middle rectum was lower in the low- to high-dose region (V10-V35), and the dose to the lower rectum was lower in the middle- to high-dose region (V15-35). No Grade ≥ 3 toxicity or procedure-related complications were observed. Additionally, Grade 2 genitourinary and gastrointestinal toxicities during the treatment showed no significant differences between the two methods. CONCLUSION: The apex expansion method may be safe and effective in achieving a more efficient rectal dose reduction by expanding the anterior perirectal space in the prostatic apex area.

Preprocedural physiological assessment of coronary disease patterns to predict haemodynamic outcomes post-PCI.

BACKGROUND: Even with intracoronary imaging-guided stent optimisation, suboptimal haemodynamic outcomes post-percutaneous coronary intervention (PCI) can be related to residual lesions in non-stented segments. Preprocedural assessment of pathophysiological coronary artery disease (CAD) patterns could help predict the physiological response to PCI. AIMS: The aim of this study was to assess the relationship between preprocedural pathophysiological haemodynamic patterns and intracoronary imaging findings, as well as their association with physiological outcomes immediately post-PCI. METHODS: Data from 206 patients with chronic coronary syndrome enrolled in the ASET-JAPAN study were analysed. Pathophysiological CAD patterns were characterised using Murray law-based quantitative flow ratio (µQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the pullback pressure gradient (PPG) index. Intracoronary imaging in stented segments after stent optimisation was also analysed. RESULTS: In the multivariable analysis, diffuse disease - defined by the pre-PCI µQFR-PPG index - was an independent factor for predicting a post-PCI µQFR <0.91 (per 0.1 decrease of PPG index, odds ratio 1.57, 95% confidence interval: 1.07-2.34; p=0.022), whereas the stent expansion index (EI) was not associated with a suboptimal post-PCI µQFR. Among vessels with an EI ≥80% and post-PCI µQFR <0.91, 84.0% of those vessels had a diffuse pattern preprocedure. There was no significant difference in EI between vessels with diffuse disease and those with focal disease. The average plaque burden in the stented segment was significantly larger in vessels with a preprocedural diffuse CAD pattern. CONCLUSIONS: A physiological diffuse pattern preprocedure was an independent factor in predicting unfavourable immediate haemodynamic outcomes post-PCI, even after stent optimisation using intracoronary imaging. Preprocedural assessment of CAD patterns could identify patients who are likely to exhibit superior immediate haemodynamic outcomes following PCI.

Safety and feasibility of intravascular ultrasound-guided robotic percutaneous coronary intervention.

OBJECTIVE: Previous studies have demonstrated the benefit of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) for preventing longitudinal geographic miss (LGM). However, it is yet unclear whether IVUS guidance is useful for robotic-PCI (robotic-assisted perctaneous coronary intervention [R-PCI]). METHODS: A total of 58 consecutive patients with stable angina who underwent IVUS-guided R-PCI were enrolled. The stent landing position was angiographically marked using a balloon marker before stenting, followed by measurements of the expected stent length using balloon pullback. Subsequently, prestenting IVUS was performed to determine stent landing. All pre-PCI IVUS images were assessed for lesion length and percent plaque volume (%PV) using both IVUS and angiographic marking. LGM was defined as a residual %PV >50% at either the distal or proximal stent edge, any stent edge dissection, or additional stent deployment immediately after stenting. RESULTS: The included patients had an average age of 67.1 ± 10.1 years. IVUS guidance had significantly longer lesion lengths compared with angiographic marking. Based on IVUS-guided stent deployment, nine cases exhibited LGM immediately after stenting. IVUS-marked landing points had a significantly smaller %PV and significantly larger lumen area compared with those for angiography. CONCLUSION: IVUS-guided R-PCI was well-tolerated and may be better at preventing LGM compared with angiography-guided R-PCI.

Evaluation of the thickness of coronary calcium by 60-MHz intravascular ultrasound: head-to-head comparison with optical frequency domain imaging.

The region behind the coronary calcium could not be visualized by intravascular ultrasound (IVUS) because of acoustic shadow. However, some pathological studies have shown that IVUS delineated the vessel border behind thin coronary calcium sheets. This study aimed to reveal whether recent IVUS can visualize the region behind thin coronary calcium sheets. Using 534 cross-sectional optical frequency domain images (OFDI), including severe calcified coronary lesions, calcium sheet thickness was measured by every 1°. Accordingly, the visibility of the vessel border behind the coronary calcium sheet was evaluated using 60-MHz IVUS images, which were longitudinally linked with OFDI ones. After carefully coordinating with the axial position, the association between the IVUS-derived permeability of the coronary calcium sheet and calcium thickness was evaluated. The maximum and mean calcium thickness by OFDI was 0.88 ± 0.39 and 0.62 ± 0.30 mm, respectively. By 60-MHz IVUS, 12.1% of the coronary calcium sheets had permeable segments. Comparing between OFDI and IVUS images, 48.6% of the coronary calcium sheets with maximum thickness ≤ 0.3 mm were sometimes permeable by 60-MHz IVUS, whereas most > 0.5 mm thick calcium sheets were impermeable. In the receiver operating characteristic curve analysis, the best cutoff values for the maximum and mean thickness of permeable calcium were 0.48 and 0.31 mm, respectively. Thus, 60-MHz IVUS can occasionally visualize the region behind a thin coronary calcium sheet. When using 60-MHz IVUS, this finding may be a predictive marker of calcium sheet with a thickness of < 0.5 mm.

Comparing In-Hospital Outcomes for Acute Myocardial Infarction Patients in High-Volume Hospitals Performing Primary Percutaneous Coronary Intervention vs. Regional General Hospitals.

BACKGROUND: It has been reported that patients with acute myocardial infarction (AMI) transferred to low-volume primary percutaneous coronary intervention (PCI) hospitals (<115/year) in low population density areas experience higher in-hospital mortality rates. This study compared in-hospital outcomes of patients admitted to high-volume primary PCI hospitals (≥115/year) with those for other regional general hospitals.Methods and Results: Retrospective analysis was conducted on data obtained from 2,453 patients with AMI admitted to hospitals in Iwate Prefecture (2014-2018). Multivariate analysis revealed that the in-hospital mortality rate of AMI among patients in regional general hospitals was significantly higher than among patients in high-volume hospitals. However, no significant difference in mortality rate was observed among patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI. Although no significant difference was found in the in-hospital mortality rate of patients with Killip class I STEMI, significantly lower in-hospital mortality rates were observed in patients admitted in high-volume hospitals for Killip classes II, III, and IV. CONCLUSIONS: Although in-hospital outcomes for patients with STEMI undergoing primary PCI were similar, patients with heart failure or cardiogenic shock exhibited better in-hospital outcomes in high-volume primary PCI hospitals than those in regional general hospitals.

Impact of cilostazol on prevention of late failure of autologous vein grafts.

OBJECTIVES: The effectiveness of postoperative medication for the prevention of late graft failure is controversial. We conducted the present study to investigate whether cilostazol improved the mid-term outcomes after infrainguinal autologous vein bypass for chronic limb-threatening ischemia (CLTI). METHODS: From April 1994 to March 2022, we performed 590 de novo infrainguinal bypass procedures using autologous vein grafts (AVGs) in three hospitals. The bypass grafts were classified according to the postoperative prescription of cilostazol. The loss of graft patency and major adverse limb events (MALEs) were set as endpoints. Patients who died within 30 days and grafts that lost primary patency within 30 days after surgery were excluded. Data up to 3 years were analyzed. The cumulative primary patency (PP), assisted primary patency (AP), secondary patency (SP), and freedom from MALE (ffMALE) rates were calculated by the Kaplan-Meier method and compared between the cilostazol group and the non-cilostazol group. After a propensity score matching, same statistical analyses were performed. In addition, a Cox proportional hazards regression analysis that included preoperative factors, intraoperative factors, and postoperative medications was performed to identify whether cilostazol is an independent predictor for the outcomes. RESULTS: A total of 523 AVGs met inclusion criteria. Kaplan-Meier curves showed that the cilostazol group was superior to the non-cilostazol group in all outcomes, while the cilostazol group was superior to the non-cilostazol group in AP and SP after a propensity score matching. A multivariable analysis showed that non-use of cilostazol was identified as an independent predictor for loss of AP, SP, and ffMALE. CONCLUSIONS: Cilostazol improved the mid-term outcomes after infrainguinal autologous vein bypass.

Experience of Balloon Aortic Valvuloplasty for Severe Aortic Stenosis in Patients Scheduled for Open Surgery for Chronic Limb-Threatening Ischemia.

Objectives: To estimate the effectiveness of balloon aortic valvuloplasty (BAV) for severe aortic stenosis (SAS) in patients scheduled for open surgery for chronic limb-threatening ischemia. Materials and Methods: Clinical data of patients from 2012 to 2018 were retrieved and summarized. The early outcomes and survival after BAV and open bypass were retrospectively investigated. Results: BAV was performed on seven dialysis patients. One patient died of mesenteric infarction 3 days after BAV; however, six patients were able to undergo open bypass at an average of 10 days (7-19 days) after BAV. One patient died of hemorrhagic shock before the wound healed; five patients underwent limb salvage. Four of these five patients could not undergo surgical aortic open valve replacement owing to advanced age or poor cardiac function and died within 2 years. Only one patient who underwent radical surgery after a bypass survived more than 4 years. Conclusion: BAV enabled open surgery and limb salvage in patients with SAS. Although BAV alone cannot ensure long-term survival, the procedure will continue to be important as a bridge technique to radical surgery, such as transcatheter aortic valve implantation and aortic valve repair, which are often avoided owing to infection.

Synthesis, structures and reactions of acylsulfenyl iodides with theoretical investigations.

A series of acylsulfenyl iodides (RCOSI) were synthesized by the reactions of carbothioic acid group 11-16 element derivatives with iodine or N-iodosuccinimides in moderate to good yields. The structure of the PhCOSI was nearly square planar based on the X-ray analysis, where the C[double bond, length as m-dash]O⋯I distance (3.153(5) Å) was significantly shorter than the sum of the van der Waals radii of the atoms (Σr vdW), indicating close contact within the molecule. The distances between an iodine atom and the neighbouring two iodine atoms were also less than Σr vdW, perhaps due to the energy lowering effect of the interactions. The acylsulfenyl iodides readily reacted with alkenes and alkynes to give the expected addition products in moderate to good yields at approximately 0 °C. A new synthesis of acylated sulfines, sulfenamides and sulfenochalcogenides using acylsulfenyl iodides is also described. Theoretical calculations were performed on PhCOSI with the Sapporo-TZP(+1s1p) basis sets at the MP2 level, which perfectly reproduced the observed structures. Similar calculations were performed on the reactions, exemplified by those of MeCOSI and CH2[double bond, length as m-dash]CH2, together with those of MeSI and CH2[double bond, length as m-dash]CH2. Mechanisms for both reactions were proposed, which were very similar. The proposed mechanism for the former was understood based on that of the latter. For both mechanisms, the episulfuranes and episulfonium ions played an important role. The dynamic and static nature of the bonds in the COSI group of PhCOSI and MeCOSI were elucidated based on QTAIM dual functional analysis.

Quantitative determination of plasma cabozantinib concentration using HPLC-UV and its application to patients with renal cell carcinoma.

Cabozantinib is an oral small-molecule tyrosine kinase inhibitor that has become a standard of care for advanced renal cell carcinoma (RCC). However, cabozantinib is associated with a high rate of adverse events. Therefore, individualised cabozantinib administration and monitoring could help maximise its therapeutic efficacy and avoid serious adverse events. This study developed and validated a method to determine cabozantinib concentration in plasma using HPLC-UV. Sorafenib, an internal standard, was added to the plasma sample containing cabozantinib. A calibration curve for cabozantinib showed good linearity (R2 = 1.00), between 25 and 4,000 ng/ml. The recovery rate was above 92.1%, and the intra- and inter-day coefficients of variation were smaller than 5.2 and 6.8%, respectively. Then, we applied the method for monitoring cabozantinib blood levels in three patients with advanced RCC who were taking cabozantinib at a dose of 20, 40 or 60 mg/day. Grade 3 adverse events were more likely to occur in patients with high dosing and blood level of cabozantinib. Owing to its simplicity, the developed method can be used in general hospitals, and is expected to help maximise drug efficacy and minimise serious adverse events in many patients with RCC undergoing cabozantinib treatment.

Importance of Flow Waveform and Flow Volume as Prognostic Indicators for the Patency of Infra-Inguinal Autologous Vein Bypass.

OBJECTIVE: To investigate the association of the intra-operative flow waveform and the flow volume with graft prognosis of the infra-inguinal vein bypass. METHODS: This was a retrospective study of intra-operative flowmetry performed for infra-inguinal autologous vein bypass between 2011 and 2020. Flow waveforms were classified as type 0 - IV according to the Kyushu University (KU) classification. The patients (n = 340) were divided into three groups based on the flow waveform predicting the graft patency: type 0/I (long patency), type II (no early occlusion but late occlusion possible), and type III/IV (early occlusion). The graft occlusion rates of popliteal artery bypass (PAB) and infrapopliteal artery bypass (IPAB) within 30 days of surgery were compared between type 0/I + II and type III/IV groups, while the midterm graft patency rates were compared between type 0/I and type II groups. Additionally, a multivariate analysis was performed to identify independent risk factors for early and late graft occlusion. RESULTS: The early graft occlusion rates of type 0/I + II and type III/IV groups were 3.9% and 0%, respectively, (p = 1.0) for PAB, and 5.3% and 46.2%, respectively, (p < .001) for IPAB. The two year primary patency rates of type 0/I and type II groups were 91% and 75%, respectively, (p = .030) for PAB, and 58% and 63%, respectively, (p = .72) for IPAB. Independent risk factors for early occlusion were none in PAB and flow waveform (type IV) in IPAB. Independent risk factors for patency loss in PAB were flow waveform (type II), end stage renal disease, and dual antiplatelet use, and those in IPAB were older age, women, lower flow volume, and iterative bypass. CONCLUSION: Intra-operative flowmetry is useful for predicting the graft prognosis in infra-inguinal vein bypass and this is dependent on the distal target artery.

Use of the 11-Item Modified Frailty Index to Determine Accurate Prognosis and Revascularization Strategy in Patients Undergoing Vascular Bypass Surgery for Intermittent Claudication.

BACKGROUND: In cases of intermittent claudication (IC) where traditionally noninvasive management yields unsatisfactory results, revascularization strategy in IC patients is generally decided based on anatomical considerations and the availability of a saphenous vein graft. Life expectancy should also be considered. This study aimed to investigate the relationship between the 11-item modified frailty index (mFI-11) and the overall survival (OS) in patients with IC who underwent vascular bypass surgery to facilitate revascularization strategy selection. METHODS: We reviewed the records of 144 consecutive patients (153 lower limbs) who underwent infrainguinal bypass for IC between 2011 and 2020. Patients were divided into 2 groups based on their mFI-11 score: high frailty (H), mFI score >0.3; and low frailty (L), mFI score ≤0.3. The OS was compared among the 2 groups. Rates of graft patency and freedom from major adverse limb event (ffMALE) were also determined and compared. RESULTS: Five-year OS in the L and H groups was 92% and 55% (P < 0.001). Multivariate analysis showed that mFI, age, and end-stage renal disease were independent predictors of OS. Five-year rates of primary and secondary patency and ffMALE for vein grafts were 81%, 91%, and 94%, respectively; those for prosthetic grafts were 65%, 80%, and 84%, respectively; the differences were not significant. CONCLUSIONS: The mFI-11 was a helpful tool in predicting OS for patients with IC who underwent vascular bypass surgery. Those with H should not undergo open revascularization; however, for IC patients who have either not responded to a regimen of exercise and medication, or have specifically requested a more aggressive approach, obtaining a good score in frailty assessment is useful in determining whether or not bypass surgery would be a viable option.

Comparison of MECHANISM of early and late vascular responses following treatment of ST-elevation acute myocardial infarction with two different everolimus-eluting stents: a randomized controlled trial of biodegradable versus durable polymer stents.

The early and mid-term arterial healing profile of biodegradable polymer-coated everolimus-eluting stents (BP-EES) is unclear, especially in ST-segment elevation myocardial infarction (STEMI) culprit lesions. This study aimed to compare early- and mid-term arterial healing between durable polymer-coated everolimus-eluting stents (DP-EES) and BP-EES in STEMI patients. In a prospective, multicenter, non-inferiority trial, STEMI patients were randomized to receive BP-EES (n = 60) or DP-EES (n = 60). The primary endpoint of this study was the mean percentage of covered struts (%covered struts) on FD-OCT 2 weeks post-PCI. Key secondary endpoints included the percentage of uncovered struts, frequency of abnormal intra-stent tissue, and percentage of malapposed struts by FD-OCT 2 weeks and 12 months post-PCI. They underwent serial frequency-domain optical coherence tomography (FD-OCT) evaluations immediately after percutaneous coronary intervention, and at 2 weeks and at 12 months after the procedure. The primary endpoint of %covered struts at 2 weeks was 71.4% in BP-EES and 72.3% in DP-EES [risk difference - 0.94%, lower limit of one-sided 95% confidence interval (CI) - 5.6; Pnon-inferiority = 0.0756]. At 12 months, the mean percentage of uncovered struts was significantly lower [1.73% (95% CI 0.28-3.17) vs. 4.81% (95% CI 3.52-6.09); p = 0.002], and the average malapposed volume was significantly smaller in the BP-EES group than in the DP-EES group (p = 0.002). At 12 months, BP-EES had a significantly larger average neointimal area with a significantly smaller average intra-stent tissue unevenness score than DP-EES, suggesting more uniform neointimal coverage with BP-EES. Strut coverage was comparable between BP-EES and DP-EES at 2 weeks. Non-inferiority could not be proven because of an insufficient sample size. The significantly better arterial healing with BP-EES at 12 months suggests a safer profile for STEMI culprit lesions.Trial registration: jRCTs022180024 https://jrct.niph.go.jp/en-latest-detail/jRCTs022180024.