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Background: In the resting conditions, narrowing the window of coronary pressure measurements from the whole cardiac cycle to diastole improves diagnostic performance of coronary pressure–derived physiological index. However, whether this also applies to the hyperemic conditions has not yet been thoroughly evaluated. Objectives: The purpose of this study was to assess whether diastolic fractional flow reserve (diastolic FFR) has better diagnostic performance in identifying ischemia-causing coronary lesions than conventional FFR in a prospective, multicenter, and independent core laboratory–based environment. Methods: In this prospective multicenter registry at 29 Japanese centers, we compared the diagnostic performance of FFR, diastolic FFR, resting distal to aortic coronary pressure (Pd/Pa), and diastolic pressure ratio (dPR) using myocardial perfusion scintigraphy (MPS) as the reference standard in 378 patients with single-vessel coronary disease. Results: Inducible myocardial ischemia was found on MPS in the relevant myocardial territory of the target vessel in 85 patients (22%). In the receiver-operating curve analyses, diastolic FFR had comparable area under the curve (AUC) compared with FFR (AUCdiastolic FFR: 0.66; 95% confidence interval [CI]: 0.58-0.73, vs AUCFFR: 0.66; 95% CI: 0.58-0.74, P = 0.624). FFR and diastolic FFR showed significantly larger AUCs than resting Pd/Pa (0.62; 95% CI: 0.54-0.70; P = 0.033 and P = 0.046) but did not show significantly larger AUCs than dPR (0.62; 95% CI: 0.55-0.70; P = 0.102 and P = 0.113). Conclusions: Diastolic FFR showed a similar diagnostic performance to FFR as compared with MPS. This result reaffirms the use of FFR as the most accurate invasive physiological lesion assessment. (Diagnostic accuracy of diastolic fractional flow reserve (d-FFR) for functional evaluation of coronary stenosis; UMIN000015906)

We demonstrate a dual-comb vibrometer where the pulses of one frequency-comb are split into pulse pairs. We introduce a delay between two pulses of each pulse pair in front of the sample, and after the corresponding two consecutive reflections at the vibrating sample surface, the initially introduced delay is canceled by a modified Sagnac geometry. The remaining phase difference between the two pulses corresponds to the change in the axial position of the surface during the two consecutive reflections. The Sagnac geometry reduces the effect of phase jitter since both pulses propagate through nearly the same optical path (in opposite directions), and spurious signals are eliminated by time gating. We determine the amplitude of surface vibration on a surface-acoustic-wave device with an axial precision of 4 pm. This technique enables the highly accurate determination of extremely small displacements.

Small-cell lung cancer (SCLC) is a subgroup of lung cancer with a high frequency of liver metastasis, which is a predictor of poor prognosis. Diffuse liver metastases of SCLC with no visible nodular lesions in the liver when examined using computed tomography (CT) are relatively rare; however, a few cases with rapid progression to acute liver failure that were diagnosed after death have been reported. In this paper, we report a 63-year-old man with diffuse liver metastases of SCLC that were histologically diagnosed using a transjugular liver biopsy while the patient was alive, even though no lesions were visible during a contrast-enhanced CT examination.

White adipocytes are a major component of white adipose tissue (WAT) and help to maintain systemic metabolic homeostasis by storing energy and secreting adipokines. In mice deficient in the protein WWP1 (WW domain-containing E3 ubiquitin protein ligase 1), oxidative stress in adipocytes increases but insulin resistance induced by obesity improves. However, the specific roles of WWP1 in adipocytes remain unclear. Here, we show that in 3T3L1 adipocytes, WWP1 localized in the Golgi apparatus via its C2 domain, where it protected the Golgi apparatus from monensin-induced disruption. By contrast, WWP1 knockdown by short hairpin RNA failed to protect the Golgi apparatus and enhanced Golgi apparatus disruption by monensin. The Golgi apparatus acts as a central organelle to establish accurate protein glycosylation of proteoglycans containing glycosaminoglycans, including chondroitin sulfate and heparan sulfate (HS). WWP1 overexpression increased chondroitin sulfate and HS levels, whereas WWP1 knockdown decreased them. Furthermore, obesity-related increases in HS were prevented by WWP1 knockout in adipose tissue. In summary, our results demonstrate a novel role for WWP1 in maintaining Golgi apparatus morphology and proteoglycan synthesis in adipocytes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: The number of dementia patients is increasing with population aging. Preclinical detection of dementia in patients is essential for access to adequate treatment. In previous studies, dementia patients showed texture recognition difficulties. Onomatopoeia or sound symbolic words (SSW) are intuitively associated with texture impressions and are less likely to be affected by aphasia and description of material perception can be easily obtained. In this study, we aimed to create a test of texture recognition ability expressed by SSW to detect the presence of mild cognitive disorders., Methods: The sound symbolic words texture recognition test (SSWTRT) is constructed from 12 close-up photos of various materials and participants were to choose the best SSW out of 8 choices to describe surface texture in the images in Japanese. All 102 participants seen in Juntendo University Hospital from January to August 2023 had a diagnosis of possible iNPH (age mean 77.9, SD 6.7). The answers were scored on a comprehensive scale of 0 to 1. Neuropsychological assessments included MMSE, FAB, and the Rey Auditory Verbal Learning Test (RAVLT), Pegboard Test, and Stroop Test from the EU-iNPH Grading Scale (GS). In study 1 the correlation between SSWTRT and the neuropsychological tests were analyzed. In study 2, participants were divided into two groups: the Normal Cognition group (Group A, n  = 37) with MMSE scores of 28 points or above, and the Mild Cognitive Impairment group (Group B, n  = 50) with scores ranging from 22 to 27 points, and its predictability were analyzed., Results: In study 1, the total SSWTRT score had a moderate correlation with the neuropsychological test results. In study 2, there were significant differences in the SSWTRT scores between groups A and B. ROC analysis results showed that the SSWTR test was able to predict the difference between the normal and mildly impaired cognition groups., Conclusion: The developed SSWTRT reflects the assessment results of neuropsychological tests in cognitive deterioration and was able to detect early cognitive deficits. This test not only relates to visual perception but is likely to have an association with verbal fluency and memory ability, which are frontal lobe functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kamohara, Nakajima, Nozaki, Ieda, Kawamura, Horikoshi, Miyahara, Akiba, Ogino, Karagiozov, Miyajima, Kondo and Sakamoto.)

Members of the T-cell immunoglobulin and mucin (TIM) family, which is crucial for T-cell function, are implicated in autoimmunity. TIM-1 and -3 play distinct roles in autoimmunity, with TIM-1 acting as a costimulatory molecule and TIM-3 regulating Th1 responses. We investigated the therapeutic potential of anti-TIM-1 (RMT1-10) and anti-TIM-3 (RMT3-23) antibodies in an autoimmune arthritis model. Zymosan A was used to induce arthritis in female SKG mice. The arthritis scores, histology, mRNA expression, cytokine levels, micro-computed tomography, and flow cytometry results were obtained. The application of RMT1-10 reduced the arthritis scores, histological damage, and CD4+ T-cell infiltrations, and it suppressed interleukin (IL)-6 and -17A and reduced TIM-3 mRNA expressions. RMT3-23 also lowered arthritis severity, improved histology, and reduced serum levels of tumor necrosis factor (TNF)-α and IL-17A. RMT3-23 inhibited intracellular TNF-α and IL-6 and early apoptosis. An amelioration of autoimmune arthritis was achieved by blocking the TIM-1 and -3 signaling pathways via RMT1-10 and RMT3-23 administration, leading to a widespread decrease in inflammatory cytokines. Both antibodies exhibited therapeutic effects, suggesting TIM-1 and -3 as potential targets for rheumatoid arthritis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This is the first case report in which computed tomography (CT) images of a patient with emphysematous pyelonephritis (EPN) capture the time course of emphysema from onset to resolution through conservative treatment. To re-evaluate EPN, including refractory urinary tract infections, CT scans after 72 h might be helpful., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: The effects of aspirin-free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated., Methods and Results: We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT-3 (Short and Optimal Duration of Dual Antiplatelet Therapy-3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46-2.35]; no-OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73-1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64-3.62]; no-OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83-1.42]; P for interaction =0.46)., Conclusions: The no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Background/aim: Oncotype DX Breast Recurrence Score ® test (ODx) is a gene profiling assay predicting the benefit of adjuvant chemotherapy for early-stage hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Meanwhile, to avoid unnecessary financial burden on the patient, many studies have attempted to establish alternatives to ODx using conventional clinicopathological factors, but these have not yet been successful. Thus, we retrospectively investigated clinicopathological factors to establish alternatives to ODx., Patients and Methods: Data from 114 Japanese women who underwent ODx were retrospectively examined to investigate the relationship between ODx recurrence score (RS) and clinicopathological features, including MUC1 staining patterns on immunohistochemical assessment. An RS of 0-25 was defined as low, and 26-100 as high., Results: Ninety patients (79%) had low RS and 24 patients (21%) had high RS. Univariate analysis revealed that low tumor grade, high progesterone receptor (PgR) expression, and low Ki67 labeling index (LI) were significantly associated with low RS (p=0.025, p<0.001, and p<0.001, respectively). Tumors with an apical pattern of MUC1 staining also frequently had a low RS (p=0.024). In multivariate analysis, PgR expression and Ki67 LI were independent factors associated with RS (p<0.001, for both). When the ODx results were categorized with a combination of these two factors, only 2% of the PgR-high and Ki67-low group (one in 51 cases) had a high RS., Conclusion: PgR expression and Ki67 LI were independent factors correlated with RS. MUC1 staining pattern also has the potential to be a useful marker. We believe that it is crucial to continue attempts to identify patients who are unlikely to benefit from ODx., Competing Interests: The Authors have no potential conflicts of interest to disclose., (Copyright 2024, International Institute of Anticancer Research.)

Aims: We aimed to elucidate the association between malnutrition and the occurrence of bleeding events in patients with heart failure., Methods and Results: We evaluated the nutritional status of patients with heart failure [n = 2044, median (inter-quartile range) age 69.0 (59.0-78.0) years, 1209 (59.1%) males] using the Geriatric Nutritional Risk Index (GNRI). The primary endpoint was a composite of bleeding events such as haemorrhagic stroke or gastrointestinal bleeding. According to the survival classification and regression tree analysis, the accurate cut-off point of GNRI for predicting the primary endpoint was 106.2. We divided the patients into two groups based on GNRI levels: high GNRI group (GNRI ≥ 106.2, n = 606, 29.6%) and low GNRI group (GNRI < 106.2, n = 1438, 70.4%). We compared the patients' characteristics and prognosis between the two groups. The low GNRI group was older [72.0 (63.0-79.0) vs. 63.0 (53.0-73.0) years, P < 0.001] and had a lower prevalence of male sex (56.9% vs. 64.5%, P = 0.001). There were no differences in the use of antiplatelet agents and anticoagulants between the two groups. Levels of B-type natriuretic peptide were higher [321.1 (123.3-667.4) vs. 111.6 (42.6-235.4) pg/mL, P < 0.001] and levels of haemoglobin were lower [12.4 (10.8-13.7) vs. 14.2 (12.9-15.4) g/dL, P < 0.001] in the low GNRI group. The Kaplan-Meier analysis demonstrated that bleeding event rates were higher in the low GNRI group (log-rank P < 0.001). The multivariable Cox proportional hazard analysis revealed that low GNRI (hazard ratio 1.952, 95% confidence interval 1.002-3.805, P = 0.049) was associated with bleeding events., Conclusions: Heart failure patients with poor nutritional status, determined by GNRI under 106.2, experienced high bleeding event rates. Comprehensive management is required to avoid bleeding event in those populations., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The treatment efficiency and predictors of atezolizumab plus bevacizumab therapy for unresectable hepatocellular carcinoma in real-world practice have not been established. This study aimed to assess the efficacy and safety of atezolizumab plus bevacizumab and to investigate predictors of progression-free survival and overall survival. Patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab therapy in 19 hospitals were enrolled before treatment and observed prospectively. The outcomes of 222 patients in this cohort were analyzed. The objective response rate and disease control rate were 22.0% and 70.6%, respectively, whereas the median progression-free survival was 5.7 months. Independent risk factors for shortened progression-free survival were younger age (<75 years; 3.9 months vs. 8.6 months), higher number of intrahepatic tumors (≥5; 4.0 months vs. 7.9 months), macrovascular invasion (2.3 months vs. 6.7 months), and higher neutrophil-to-lymphocyte ratio (≥3.03; 3.0 months vs. 7.8 months). The median overall survival was not reached; however, independent risk factors for shortened overall survival were absence of hyperlipidemia, higher number of intrahepatic tumors (≥5), macrovascular invasion, higher α-fetoprotein level (≥400 ng/mL), worse Child-Pugh score (≥6), and higher neutrophil-to-lymphocyte ratio (≥3.03). Severe adverse events (grade ≥3) were observed in 96 patients (36.0%), with proteinuria being the most frequent. In conclusion, patients with older age, lower number of intrahepatic tumors, absent macrovascular invasion, and lower neutrophil-to-lymphocyte ratio are expected to have better progression-free survival with atezolizumab plus bevacizumab therapy for unresectable hepatocellular carcinoma., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Tetsuo Takehara has received lecture fees and research grants from Chugai Pharmaceutical Co., Ltd, Eisai Co., Ltd. Takahiro Kodama has received lecture fees from Chugai Pharmaceutical Co., Ltd and AstraZeneca K.K. All other authors declare no conflicts of interest., (Copyright: © 2024 Kai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Drug-induced convulsion is a serious concern in drug development, such that the convulsion liability of drug candidates must be evaluated in preclinical safety studies. However, information on the differences among species regarding their sensitivity to convulsions induced by convulsant drugs in humans remains limited. Here, we selected 11 test articles from several pharmacological classes and compared the sensitivities of three types of laboratory animal to convulsion. All 11 test articles were examined in mice via intraperitoneal injection and in rats via intravenous bolus; and 6 of the 11 test articles, selected mainly based on availabilities of data on drug plasma concentrations in humans at convulsion, were examined in non-human primates (NHPs) via intravenous infusion. Plasma concentrations of the test articles shortly after convulsion onset or 5 min after administration were measured. All 11 articles tested in mice, 10 of 11 articles tested in rats, and all 6 articles tested in NHPs induced convulsion with premonitory signs. Although there was a general tendency that rats and NHPs exhibited convulsions at lower plasma drug concentrations than did mice, the plasma concentrations at convulsion onset were generally comparable, within 3-fold differences, across the animal species. We conclude that the mice, rats, and NHPs examined in the present study generally showed similar sensitivities to convulsion induced by the test articles. Thus, each of these laboratory animals can be used for the assessment of convulsion risk in the early stages of drug development, depending on throughput, cost, and test article-specific requirements.

White adipose tissue (WAT) is critical for whole-body energy metabolism, and its dysfunction leads to various metabolic disorders. In recent years, many studies have suggested that impaired mitochondria may contribute to obesity-related decline in adipose tissue function, but the detailed mechanisms remain unclear. To investigate these mechanisms, we carried out a comprehensive analysis of WAT from mice with diet-induced obesity. We discovered the transcription factor Parkin interactive substrate (PARIS or ZNF746), which suppresses the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a key regulator of mitochondrial biogenesis, to be accumulated in adipose progenitor cells from obese mice. Furthermore, we demonstrated that 3T3-L1 preadipocytes with overexpression of PARIS protein exhibited decreased mitochondrial biogenesis and impaired adipogenesis. Our results suggest that the accumulation of PARIS protein may be a novel component in the pathogenesis of obesity-related dysfunction in WAT., (© 2023. The Author(s).)

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics., Competing Interests: Competing interests statement:The authors declare no competing interest.

Psoriasis is an immune-mediated inflammatory disease of the skin, which is characterized by epidermal hyperkeratosis and neutrophil infiltration. The interleukin (IL)-17/IL-23 pathway and associated cytokines play major roles in the pathogenesis and exacerbation of psoriasis. The IL-18/IL-18 receptor (R) α signaling pathway is important for Th1 cytokine production and differentiation of Th1 cells; however, its role in the pathogenesis of psoriasis remains unknown. In this study, we investigated the effect of the IL-18Rα-mediated signaling pathway in the pathogenesis of psoriasis in Il18ra- deficient mice ( Il18ra - / - ) and wild-type imiquimod (IMQ)-induced psoriatic dermatitis model mice. Blocking this pathway exacerbated IMQ-induced psoriatic skin inflammation. Il18ra deficiency led to significant increases in the levels of IL-1β, IL-6, IL-8, IL-17A, IL-23, and chemokine (C-X-C motif) ligand 2 in skin lesions. Gr1-positive cells highly infiltrated psoriatic skin lesions in Il18ra - / - mice compared to those in wild-type mice. Citrullinated histone H3-positive area was relatively broad in Il18ra - / - mice. These results suggest that IL-18Rα-mediated signaling pathways may inhibit psoriatic skin inflammation by regulating infiltration and activation of neutrophil and other innate immune cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Akazawa, Nozaki, Yamazawa, Ishimura, Ashida, Okada, Kinoshita and Matsumura.)

Background: We aimed to investigate the diagnostic value of energy loss (EL) and baseline CT fractional flow reserve (CT-FFR) computed using computational fluid dynamics to predict functional progression of coronary stenosis in patients with type 2 diabetes mellitus., Methods: This single-center prospective study included 61 patients with type 2 diabetes mellitus (mean age, 61 years ±9 [SD]; 43 men) showing 20-70 % stenosis who underwent serial coronary CT performed at 2-year interval between October 2015 and March 2020. A mesh-free simulation was performed to calculate the CT-FFR and EL. Functional progression was defined as ≥ 0.05 decrease in CT-FFR on the second coronary CT. Models using baseline CT-FFR and EL were compared by analyzing the receiver operating characteristic (ROC) curve., Results: Of the 94 vessels evaluated, 25 vessels (27 %) showed functional progression. EL at distal stenosis (EL dis ) of vessels with functional progression was higher than that of vessels without functional progression (27.6 W/m 3 [interquartile range (IQR): 15.0, 53.0] vs. 5.7 W/m 3 [IQR: 2.3, 10.1], p  < 0.001). Multivariable analysis showed that EL dis (per unit Ln(EL); odds ratio, 11.8; 95 % CI: 4.0-34.9; p < 0.001) remained as a predictor of functional progression after adjustment for diameter stenosis and baseline CT-FFR. The area under the ROC curve using EL dis (0.89; 95 % CI: 0.82-0.96) was higher than that using baseline CT-FFR (0.71; 95 % CI: 0.59-0.83; p  < 0.001)., Conclusion: When EL dis and baseline CT-FFR were considered, EL dis was a better predictor of functional progression of coronary stenosis., (© 2023 The Authors.)

Transporter-mediated drug-drug interaction (DDI) is of clinical concern, and the quantitative prediction of DDIs is an indispensable part of drug development. Cell-based inhibition assays, in which a representative probe substrate and a potential inhibitor are coincubated, are routinely performed to assess the inhibitory potential of new molecular entities on drug transporters. However, the inhibitory effect of cyclosporine A (CsA) on organic anion transporting polypeptide (OATP) 1B1 is substantially potentiated with CsA preincubation, and this effect is both long-lasting and dependent on the preincubation time. This phenomenon has also been reported with transporters other than OATP1Bs, but it is considered more prevalent among OATP1Bs and organic cation transporters. Regulatory agencies have also noted this preincubation effect and have recommended that pharmaceutical companies consider inhibitor preincubation when performing in vitro OATP1B1 and OATP1B3 inhibition studies. Although the underlying mechanisms responsible for the preincubation effect are not fully understood, a trans -inhibition mechanism was recently demonstrated for OATP1B1 inhibition by CsA, in which CsA inhibited OATP1B1 not only extracellularly ( cis -inhibition) but also intracellularly ( trans -inhibition). Furthermore, the trans -inhibition potency of CsA was much greater than that of cis -inhibition, suggesting that trans -inhibition might be a key driver of clinical DDIs of CsA with OATP1B substrate drugs. Although confidence in transporter-mediated DDI prediction is generally considered to be low, the predictability might be further improved by incorporating the trans -inhibition mechanism into static and dynamic models for preincubation-dependent inhibitors of OATP1Bs and perhaps other transporters. SIGNIFICANCE STATEMENT: Preincubation time-dependent, long-lasting inhibition has been observed for OATP1B1 and other solute carrier transporters in vitro. Recently, a trans -inhibition mechanism for the preincubation effect of CsA on OATP1B1 inhibition was identified, with the trans -inhibition potency being greater than that of cis -inhibition. The concept of trans -inhibition may allow us to further understand the mechanism of transporter-mediated DDIs not only for OATP1B1 but also for other transporters and to improve the accuracy and confidence of DDI predictions., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Purpose: To investigate whether vorticity could predict functional plaque progression better than high-risk plaque (HRP) and lesion length (LL) in individuals with type 2 diabetes mellitus., Materials and Methods: This single-center prospective study included 61 participants (mean age, 61 years ± 9 [SD]; 43 male participants) who underwent serial coronary CT angiography at 2 years, with 20%-70% stenosis at initial CT between October 2015 and March 2020. The number of the following HRP characteristics was recorded: low attenuation, positive remodeling, spotty calcification, and napkin-ring sign. Vorticity was calculated using a mesh-free simulation. A decrease in CT fractional flow reserve larger than 0.05 indicated functional progression. Models using HRP and LL and vorticity were compared using receiver operating characteristic curve analysis., Results: Of the 94 vessels evaluated, 25 vessels (27%) showed functional progression. Vessels with functional progression showed higher vorticity at distal stenosis (984 sec -1 ; IQR: 730-1253 vs 443 sec -1 ; IQR: 295-602; P < .001) than vessels without progression. The area under the receiver operating characteristic curve of vorticity (0.91; 95% CI: 0.84, 0.97) was higher than that of HRP and LL (0.69; 95% CI: 0.56, 0.82; P < .01). Diagnostic accuracy of vorticity (85%; 80 of 94 vessels; 95% CI: 76, 92) was higher than that of HRP and LL (72%; 68 of 94 vessels; 95% CI: 62, 81; P = .004)., Conclusion: In participants with type 2 diabetes mellitus, vorticity at distal stenosis was a better predictor of functional plaque progression than HRP and LL. Keywords: Coronary Artery, Vorticity, Functional Plaque Progression, Type 2 Diabetes, Vasculature, CT Angiography, Computational Fluid Dynamics, Fractional Flow Reserve Supplemental material is available for this article. © RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: N.T. No relevant relationships. S.F. No relevant relationships. T. Mita No relevant relationships. D.T. No relevant relationships. Y.N. No relevant relationships. R.F. No relevant relationships. A.K. No relevant relationships. Y.K. No relevant relationships. K.T. No relevant relationships. M.H. No relevant relationships. M.K. No relevant relationships. K.K.K. No relevant relationships. H.W. Grants from Takeda Pharmaceuticals, Nippon Boehringer Ingelheim, Kissei Pharmaceutical, Novo Nordisk, Mitsubishi Tanabe Pharma, LifeScan Japan, Kyowa Kirin, Sumitomo Pharma, Eli Lilly, Taisho Pharmaceutical, Abbott, Ono Pharmaceutical, Soiken, Sanwa Kagaku, and Kowa; payment from Bayer Pharma Japan, Teijin Pharma, Sanofi-Aventis, Novo Nordisk, Nippon Boehringer Ingelheim, Eli Lilly, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Daiichi Sankyo Company, Abbott, Kowa, Taisho Pharmaceutical, Astellas Pharma, Kissei Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Sanwa Kagaku, Takeda Pharmaceuticals. T. Minamino No relevant relationships. S.A. No relevant relationships., (© 2023 by the Radiological Society of North America, Inc.)

This study aimed to investigate the bleeding risk associated with percutaneous transhepatic gallbladder interventions in patients with acute cholecystitis receiving antithrombotic therapy. In this retrospective study, 194 consecutive patients who underwent percutaneous transhepatic gallbladder interventions for acute cholecystitis between April 2011 and April 2021 were enrolled. Patients were sorted into four groups: no prior antithrombotic therapy, discontinued antithrombotic drugs, single antithrombotic drug continued perioperatively, and multiple antithrombotic drugs continued perioperatively. The risk of postoperative bleeding after percutaneous transhepatic gallbladder interventions was evaluated via multivariate logistic regression analysis. Of the 116 (59.8%) patients receiving antithrombotic therapy, 32 (16.5%) discontinued antithrombotic drugs before their respective procedure, 50 (25.8%) continued a single antithrombotic drug, and 34 (17.5%) continued multiple antithrombotic drugs during the perioperative period. The rates of significant and severe bleeding were 10.3% (20/194) and 3.1% (6/194), respectively. The rate of significant bleeding was significantly higher in patients who continued multiple antithrombotic drugs than in patients who received no prior antithrombotic therapy (P = 0.006). In the multivariate logistic regression analysis, the continuation of multiple antithrombotic drugs during the perioperative period was a risk factor for significant bleeding after percutaneous transhepatic gallbladder interventions. In conclusion, the perioperative continuation of multiple antithrombotic drugs is a risk factor for postoperative bleeding after percutaneous transhepatic gallbladder interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Iwamoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)