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Endogenous endophthalmitis is an infectious disease of the intraocular tissue that is a consequence of bloodstream infection. The efficacy of intravitreal fluconazole injection to assist low-dose oral fluconazole in fungal endophthalmitis remains unknown in older adults with advanced liver and renal disease. In this case report, a 78-year-old man with hepatitis C virus-related liver cirrhosis and hepatocellular carcinoma who also had end-stage renal disease with temporary nephrostomy noticed blurred vision and showed a large retinal infiltrate with vitreous opacity in the right eye. In the clinical diagnosis of endogenous fungal endophthalmitis, he had an intravitreal injection of 0.1% fluconazole in 0.2 - 0.3 mL every 2 weeks four times in total, in addition to a minimum dose of oral fluconazole. One month before the ophthalmic presentation, he developed a fever and computed tomography scan showed ureterolithiasis with hydronephrosis on the right side, indicating that the renal pelvic stone fell into the ureter. He underwent nephrostomy tube insertion on the right side in the diagnosis of obstructive urinary tract infection. In the course, a potassium hydroxide (KOH) preparation of the urine sediments which were obtained from the nephrostomy tube showed yeast-like fungi, suggestive of Candida , 1 week before the development of eye symptoms. One week after the ophthalmic presentation, the nephrostomy tube at 14 Fr (French gauge) which had been inserted 1 month previously was replaced with a new tube with a larger size at 16 Fr because urine excretion from the tube was reduced. Immediately after the exchange of the nephrostomy tube, a large volume of urine was excreted from the tube. In a week, he had no systemic symptoms and serum C-reactive protein became low. In the meantime, the retinal infiltrate became inactive and vitreous opacity resolved. Intravitreal fluconazole injection is a treatment option for fungal endophthalmitis in the case that a patient cannot undergo vitrectomy and cannot take a maximum dose of fluconazole because of poor renal function., Competing Interests: The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (Copyright 2024, Matsuo et al.)

Background: Steatotic liver disease (SLD) is associated with adverse cardiac events. Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a condition characterized by the abnormal accumulation of hepatic lipids that is closely linked to five metabolic disorders: overweight or obesity, impaired glucose regulation, hypertension, hypertriglyceridemia, and low high-density lipoprotein-cholesterol. This retrospective study aimed to stratify the risk of cardiac events in patients with MASLD., Methods: Patients diagnosed with MASLD through ultrasonography were evaluated. We implemented a machine learning-based approach using a survival classification and regression tree (CART) model to stratify patients based on age, and the number of risk scores was investigated as a predictor of adverse outcomes in the derivation cohort. The primary outcomes were major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease., Results: Among 2,962 patients (median age, 62 years; men, 53.5 %), the distribution of risk factors was as follows: one (10.8 %), two (28.5 %), three (33.0 %), four (19.9 %), and five (7.8 %). Over a median follow-up period of 6.8 years, 170 (5.7 %) patients experienced MACE. In the derivation cohort of 2,073 patients, the CART model identified age ≥60 years old and risk factors ≥4 as significant predictors of MACE. These findings were corroborated in a validation cohort of 889 patients. Patients meeting both criteria exhibited the highest risk of MACE (log-rank test, p < 0.001)., Conclusions: Patients aged ≥60 years old with risk factors ≥4 indicates at high risk of MACE in patients with MASLD. This risk stratification system provides a practical tool for identifying high-risk individuals in the MASLD population., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Aims: Many guidelines recommend increases in potassium intake. However, the relationship of dietary potassium intake with incident cardiovascular disease (CVD) has not been examined in those with type 2 diabetes (T2DM), including sodium acting antagonistically with potassium. We investigated these relationships in Japanese patients with T2DM., Materials and Methods: The investigation was part of the JDCP study, a nationwide prospective study begun in 2007. Analysed were 1477 persons with T2DM, 40-75 years of age, who completed a brief-type, self-administered Diet History Questionnaire at baseline. Primary outcome was a CVD event during the follow-up median 7 years (3.9-8.1 years). Hazard ratios (HRs) for CVD were estimated by Cox regression adjusted for confounders of daily potassium intake categorized by tertiles. Tertiles of sodium intake were also analysed., Results: Mean daily potassium intake in tertiles was 1877, 2627 and 3532 mg, respectively, and significant associations were not shown between potassium intake and incidence of CVD. When HRs for CVD were stratified for potassium intake in tertiles (reference group, bottom tertile) and sodium intake (reference group, bottom tertile), potassium intake in the bottom tertile and sodium intake in the second and top tertiles were associated with significantly elevated HR for CVD (2.79 [1.02-7.63] and 3.92 [1.30-11.79], respectively)., Conclusions: Low potassium intake in conjunction with high sodium intake was significantly associated with increased incident CVD in persons with T2DM. However, CVD incidence was not related to high potassium intake, regardless of sodium intake., (Diabetes, Obesity and Metabolism© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: Type 2 diabetes mellitus (T2DM) is a well-known risk factor for hepatocellular carcinoma (HCC). However, HCC is often diagnosed at an advanced stage in patients with diabetes because of the lack of the best criteria for surveillance candidates. The aim of this study was to identify risk factors for HCC development in patients with diabetes with nonviral chronic liver disease., Method: Three hundred thirty T2DM patients with nonviral chronic liver disease who underwent surveillance for HCC by imaging techniques between 2009 and 2020 were enrolled in this multicenter cross-sectional retrospective study. The clinical and laboratory parameters of patients with and without HCC were compared., Results: Age ≥65 years, alcohol intake, lack of hepatic steatosis, triglyceride level <111 mg/dL, Mac2 binding protein glycosylation isomer (M2BPGi) ≥0.9 cut-off index (COI), α-fetoprotein concentration ≥5 ng/mL, and des-γ-carboxy prothrombin concentration ≥26 mAU/mL were independently associated with HCC development. When stratified by age, only alcohol intake (odds ratio [OR] 114.19, p < 0.001) was associated with HCC development in patients aged <65 years, and medication for diabetes mellitus (OR 5.72, p = 0.001), lack of hepatic steatosis (OR 4.47, p = 0.002), lactate dehydrogenase ≥198 IU/L (OR 2.751, p = 0.031), M2BPGi ≥1.18 COI (OR 9.05, p < 0.001), and FIB-4 index ≥2.59 (OR 3.22, p = 0.017) were associated with HCC development in patients aged ≥65 years., Conclusions: In addition to age and advanced liver fibrosis, alcohol intake in younger T2DM patients and medication for DM and lack of hepatic steatosis in older T2DM patients should be considered for HCC surveillance by imaging., (© 2024 Japan Society of Hepatology.)

Background: The fibrosis-4 (FIB4) index, a simple, noninvasive marker used for hepatic diseases, represents adverse outcomes. The aim of the present study was to evaluate whether the FIB4 index can predict adverse outcomes in patients with ST-elevation myocardial infarction (STEMI)., Methods: We investigated patients with STEMI who underwent primary percutaneous coronary intervention (PCI) and were alive at discharge. The cut-off FIB4 index at discharge was investigated using the survival classification and regression tree (CART) model to predict adverse outcomes. The primary outcome was all-cause mortality., Results: Between January 2006 and December 2018, 1354 patients with STEMI (median age, 68 years; men, 76.1%) were investigated. The median value of the FIB4 index was 1.21 (0.84-1.78). The CART model divided the study population into low (FIB4 index <0.945; n = 435), intermediate (0.945 ≤ FIB4 index < 2.185; n = 692), and high (FIB4 index ≥2.185; n = 227) groups based on the significant predictive values for all-cause death. During a median follow-up period of 4.3 years, all-cause death occurred in 208 patients (15.4%). The Kaplan-Meier analysis showed a significant increase in mortality with higher FIB4 index values (log-rank, P < 0.001). The multivariate Cox regression model revealed that the FIB4 index was an independent risk predictor for all-cause death in patients with STEMI [low group as reference vs. intermediate group, hazard ratio: 1.975; 95% confidence interval (CI): 1.166-3.346; P = 0.011 and vs. high group, hazard ratio: 4.633; 95% CI: 2.549-8.418; P < 0.001]., Conclusions: The FIB4 index was associated with the risk of all-cause mortality in patients with STEMI who underwent primary PCI., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The construction industry is actively developing remote-controlled excavators to address labor shortages and improve work safety. However, visually induced motion sickness (VIMS) remains a concern in the remote operation of construction machinery. To predict the occurrence and severity of VIMS, we developed a prototype system that acquires multiple physiological signals with different mechanisms under a low burden and detects VIMS from the collected data. Signals during VIMS were recorded from nine healthy adult males operating excavator simulators equipped with multiple displays and a head-mounted display. Light gradient-boosting machine-based VIMS detection binary classification models were constructed using approximately 30,000 s of time-series data, comprising 23 features derived from the physiological signals. These models were validated using leave-one-out cross-validation on seven participants who experienced severe VIMS and evaluated through area under the curve (AUC) scores. The mean receiver operating characteristic curve AUC score was 0.84, and the mean precision-recall curve AUC score was 0.71. All features were incorporated into the models, with saccade frequency and skin conductance response identified as particularly important. These trends aligned with subjective assessments of VIMS severity. This study contributes to advancing the use of remote-controlled machinery by addressing a critical challenge to operator performance and safety.

The principal causes of death among 68,555 patients with diabetes and 164,621 patients without diabetes who died in 208 hospitals throughout Japan between 2011 and 2020 were determined based on a survey of hospital records. 1. The most frequent cause of death in patients with diabetes was malignant neoplasms (38.9%) (lung 7.8%, pancreas 6.5%, liver 4.1%), followed, in order of descending frequency, by infectious diseases (17.0%) and then vascular diseases (10.9%) (cerebrovascular diseases 5.2%, ischemic heart diseases 3.5%, renal failure 2.3%). The proportion of deaths from malignant neoplasms and vascular diseases has trended upward and downward, respectively. Almost all deaths from ischemic heart diseases were due to myocardial infarction, and the proportion of deaths from heart diseases other than ischemic heart diseases was relatively high (9.0%), with most cases due to heart failure. Diabetic coma associated with hyperglycemia accounted for only 0.3% of deaths. 2. The proportion of deaths from malignant neoplasms, infectious diseases, renal failure, ischemic heart diseases, and heart failure was significantly higher in patients with diabetes than in those without diabetes, and the proportion of deaths from cerebrovascular diseases was significantly lower in patients with diabetes. 3. In regard to the relationship between the age and cause of death in patients with diabetes, malignant neoplasms were the most frequent cause of death in all age groups, and the incidence was around 50% for those in their 50s and 60s. The incidence of death due to infectious diseases was highest in patients older than their 70s. The incidence of death due to vascular diseases for patients in their 40s and 50s was higher than that due to infectious diseases. The highest incidence of death due to ischemic heart diseases was observed for patients in their 40s, and that due to renal failure and heart failure in patients older than their 70s. 4. Compared to patients without diabetes, patients with diabetes demonstrated a higher incidence of death due to pancreas cancer, infectious diseases, renal failure, ischemic heart diseases and heart failure and lower incidence of death due to cerebrovascular diseases in all age groups. 5. The average age at death of patients with diabetes was 74.4 years old in men and 77.4 years old in women, which were lower than the average lifespan of the Japanese general population in 2020 by 7.2 and 10.3 years, respectively. However, these differences were smaller than in previous surveys. 6. The average age at death due to all causes, especially due to ischemic heart diseases, cerebrovascular diseases, heart failure, infectious diseases, and diabetic coma, was lower in patients with "poorer" glycemic control than in those with "better" glycemic control. 7. In the total survey population, the average age at death of patients with diabetes was significantly higher than that of patients without diabetes. The average age at death due to malignant neoplasms and cerebrovascular diseases was higher in patients with diabetes than in those without diabetes and that due to renal failure, ischemic heart diseases, and infectious diseases was lower in patients with diabetes than in those without diabetes., Competing Interests: Conflicts of interestNone., (© The Japan Diabetes Society 2024.)

The principal causes of death among 68,555 patients with diabetes and 164,621 patients without diabetes who died in 208 hospitals throughout Japan between 2011 and 2020 were determined based on a survey of hospital records. The most frequent cause of death in patients with diabetes was malignant neoplasms (38.9%) (lung 7.8%, pancreas 6.5%, liver 4.1%), followed, in order of descending frequency, by infectious diseases (17.0%) and then vascular diseases (10.9%) (cerebrovascular diseases 5.2%, ischemic heart diseases 3.5%, renal failure 2.3%). The proportion of deaths from malignant neoplasms and vascular diseases has trended upward and downward, respectively. Almost all deaths from ischemic heart diseases were due to myocardial infarction, and the proportion of deaths from heart diseases other than ischemic heart diseases was relatively high (9.0%), with most cases due to heart failure. Diabetic coma associated with hyperglycemia accounted for only 0.3% of deaths. The proportion of deaths from malignant neoplasms, infectious diseases, renal failure, ischemic heart diseases, and heart failure was significantly higher in patients with diabetes than in those without diabetes, and the proportion of deaths from cerebrovascular diseases was significantly lower in patients with diabetes. With regard to the relationship between the age and cause of death in patients with diabetes, malignant neoplasms were the most frequent cause of death in all age groups, and the incidence was around 50% for those in their 50s and 60s. The incidence of death due to infectious diseases was highest in patients older than their 70s. The incidence of death due to vascular diseases for patients in their 40s and 50s was higher than that due to infectious diseases. The highest incidence of death due to ischemic heart diseases was observed for patients in their 40s, and that due to renal failure and heart failure in patients older than their 70s. Compared with patients without diabetes, patients with diabetes demonstrated a higher incidence of death due to pancreatic cancer, infectious diseases, renal failure, ischemic heart diseases, and heart failure, and a lower incidence of death due to cerebrovascular diseases in all age groups. The average age at death of patients with diabetes was 74.4 years old in men and 77.4 years old in women, which were lower than the average lifespan of the Japanese general population in 2020 by 7.2 and 10.3 years, respectively. However, these differences were smaller than in previous surveys. The average age at death due to all causes, especially due to ischemic heart diseases, cerebrovascular diseases, heart failure, infectious diseases, and diabetic coma, was lower in patients with 'poorer' glycemic control than in those with 'better' glycemic control. In the total survey population, the average age at death of patients with diabetes was significantly higher than that of patients without diabetes. The average age at death due to malignant neoplasms and cerebrovascular diseases was higher in patients with diabetes than in those without diabetes and that due to renal failure, ischemic heart diseases, and infectious diseases was lower in patients with diabetes than in those without diabetes., (© 2024 The Japan Diabetes Society. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The aim of this study was to investigate whether super-resolution deep learning reconstruction (SR-DLR) is superior to conventional deep learning reconstruction (DLR) with respect to interobserver agreement in the evaluation of neuroforaminal stenosis using 1.5T cervical spine MRI. This retrospective study included 39 patients who underwent 1.5T cervical spine MRI. T2-weighted sagittal images were reconstructed with SR-DLR and DLR. Three blinded radiologists independently evaluated the images in terms of the degree of neuroforaminal stenosis, depictions of the vertebrae, spinal cord and neural foramina, sharpness, noise, artefacts and diagnostic acceptability. In quantitative image analyses, a fourth radiologist evaluated the signal-to-noise ratio (SNR) by placing a circular or ovoid region of interest on the spinal cord, and the edge slope based on a linear region of interest placed across the surface of the spinal cord. Interobserver agreement in the evaluations of neuroforaminal stenosis using SR-DLR and DLR was 0.422-0.571 and 0.410-0.542, respectively. The kappa values between reader 1 vs. reader 2 and reader 2 vs. reader 3 significantly differed. Two of the three readers rated depictions of the spinal cord, sharpness, and diagnostic acceptability as significantly better with SR-DLR than with DLR. Both SNR and edge slope (/mm) were also significantly better with SR-DLR (12.9 and 6031, respectively) than with DLR (11.5 and 3741, respectively) (p < 0.001 for both). In conclusion, compared to DLR, SR-DLR improved interobserver agreement in the evaluations of neuroforaminal stenosis using 1.5T cervical spine MRI., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Background: Epicardial adipose tissue (EAT) is closely associated with atrial fibrillation (AF), suggesting that it may be one of the causes of AF progression. However, it is unclear whether AF affects EAT., Objective: This study aimed to demonstrate that sinus rhythm restoration reduces EAT volume (EATV) through left atrial reverse remodeling (LARR)., Methods: We analyzed data from 247 patients who underwent cryoballoon ablation for AF. EATV was assessed by contrast-enhanced computed tomography with a 3-dimensional analysis workstation, evaluating EATV surrounding the entire heart (Total-EATV) and left atrium (LA-EATV) at baseline and 6 months after cryoballoon ablation., Results: At 6 months, all patients but one with persistent AF were in sinus rhythm. Total-EATV and LA-EATV were both significantly decreased in patients with persistent AF (n = 33; Total-EATV: 148.8 ± 53.3 mL to 142.9 ± 53.5 mL [P = .01]; LA-EATV: 26.8 ± 11.3 mL to 25.2 ± 10.7 mL [P = .01]). No changes were observed in patients with paroxysmal AF (n = 214). Persistent AF was more strongly associated with LARR than paroxysmal AF (odds ratio, 2.34; 95% confidence interval, 1.01-5.44; P = .05). LARR showed an independent correlation with both Total-EATV and LA-EATV reduction (odds ratio, 1.78 [P = .04] and 2.80 [P < .001], respectively)., Conclusion: These findings suggest a novel "AF begets EAT" theory, complementing the previously accepted role of EAT as a cause of AF and supporting the "AF begets AF" mechanism., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Durvalumab plus tremelimumab (Durva/Treme) combined immunotherapy is the first-line therapy recommended for unresectable hepatocellular carcinoma (HCC). Since sequential therapy is more effective in improving prognosis, tumor markers have been used as predictive biomarkers for response to systemic therapy. This study aimed to investigate the predictive ability of objective response (OR) by tumor markers for Durva/Treme therapy against HCC. In this multicenter study, 110 patients with HCC who received Durva/Treme therapy were retrospectively enrolled. The OR rate was 15.5%. To aid early decision-making regarding OR, we evaluated the predictors contributing to OR in two steps: before (first step) and 4 weeks after (second step) treatment induction. Changes in tumor markers (alpha-fetoprotein [AFP] and des-gamma-carboxy prothrombin [DCP]) from baseline to 4 weeks after treatment (ΔAFP/ΔDCP) were included as the input factors. In the first step, multivariable analysis identified only the baseline AFP level (odds ratio 3.497, p = 0.029) as a predictor of OR. Patients with AFP ≥ 400 ng/mL had a significantly higher OR rate than those with < 400 ng/mL (28.2 vs. 8.5%, p = 0.011), and there was no significant difference in progression-free survival (PFS) between the two groups. When AFP/DCP response was defined as a ≥10% reduction from baseline, multivariable analysis showed that AFP response (odds ratio 6.023, p = 0.042) and DCP response (odds ratio 11.657, p = 0.006) were both independent predictors of OR in the second step. The PFS of patients with AFP or DCP response was significantly longer than that of patients without AFP or DCP response. The study demonstrated that the use of AFP and DCP can predict the OR of patients with HCC receiving Durva/Treme therapy., Competing Interests: I.S.: Lecture fees from AstraZeneca, and Eisai Co. Ltd., S.S.: Lecture fees from AstraZeneca, Eisai Co. Ltd., T.I.: Lecture fees from AstraZeneca, and Chugai Pharmaceutical Co., Ltd., and research funding from Chugai Pharmaceutical Co., Ltd., H.K.: Research funding from Chugai Pharmaceutical Co., Ltd. T.K.: Lecture fees from ASKA Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Kowa Company, Ltd., AbbVie GK., Eisai Co., Ltd., Novo Nordisk Pharma Ltd., Janssen Pharmaceutical K.K., Otsuka Pharmaceutical Co., Ltd., EA Pharma Co., Ltd. T.T.: Lecture fee from Gilead Sciences, Inc., AbbVie GK., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd. The remaining authors have no conflicts of interest., (Copyright: © 2024 Saeki 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.)

Purpose: To gain insight into patients' visual experiences and satisfaction when using different forms of myopia control lenses., Methods: PubMed, Cochrane Library, Embase, Scopus and Web of Science databases were searched for articles assessing subjective visual quality with myopia control lenses compared with single-vision lenses (SVLs) up to July 10, 2023. Eight-hundred-and-three articles were retrieved, reviewed and any questionnaire items on subjective impressions of lens wear were meta-analysed. Subgroup analyses were based on the magnitude of defocus (add power) of multifocal soft contact lenses (MFSCLs) and age groups. A random-effects model was employed for meta-analysis, and I 2 statistic used to assess the statistical heterogeneity., Results: Nineteen articles fit the criteria, but only six articles involving MFSCLs had relevant data. MFSCLs were associated with lower subjective ratings of vision at different distances compared to SVLs (p < 0.001), but the differences were less than one unit. MFSCLs also yielded lower ratings when moving or walking and/or climbing stairs at -0.38 (-0.69 to -0.07, p = 0.02; I 2  = 85 %, p < 0.001) and for subjective comfort (difference of -0.23, -0.41 to -0.05, p = 0.01; I 2  = 63 %, p < 0.001). Subjective ratings for playing sports were not different between groups. Experience with MFSCLs was rated lower by young adults compared to children for all variables. In both children and young adults, ratings were lower with higher add compared to lower add MFSCLs., Conclusion: Although subjective ratings for vision and comfort were lower with MFSCLs compared to SVLs, the difference was mostly less than one unit. Importantly, young adults rated their visual experience lower compared to children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Several studies investigated endometrial patterns, with respect to pregnancy rates following the transfer of embryos but did not distinguish between single- and multiple-blastocyst procedures. We clarified how the endometrial pattern imaged to transfer a frozen embryo is associated with pregnancy outcomes in single-blastocyst frozen-embryo transfer (sbFET)., Methods: Patients ≤35 years who underwent sbFET on the hormone replacement protocol. We analyzed endometrial patterns' associations with pregnancy outcomes in relation to blastocyst grade and pregnancy-related factors., Results: Of the 1383 cycles, 483 were Lf, 840 were partial-Lf, and 60 were non-Lf. Leaf pattern (Lf): central echogenic line present and continuous. Overall, decreasing distinctness of the central echogenic line was associated with significantly lower rates of clinical pregnancy (Lf: 70.4%; partial-Lf: 58.1%; non-Lf: 28.3%) and live birth (56.3%, 45.5%, and 15.0%) and a higher miscarriage rate (20.0%, 21.7%, and 47.1%). Logistic regressions showed pregnancy and live birth to be significantly more likely and miscarriage less likely in Lf than non-Lf: OR (95% CI): 6.07 (3.24-11.37), 7.43 (3.47-15.39), and 0.20 (0.07-0.57)., Conclusions: Non-Lf presentation was associated with lower rates of pregnancy and live birth, suggesting it signals unsuitable conditions for embryo transfer. We provide information on the pregnancy outcomes of sbFET for endometrial patterns., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s). Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Background and Aims: Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. However, although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events., Methods and Results: We evaluated 4071 patients with NAFLD diagnosed using ultrasonography. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index and NAFLD fibrosis score (NFS). The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. The median age of the evaluated patients was 61 (52-69) years, and 2201 (54.1%) were male. During the median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan-Meier survival analysis demonstrated that MACE increased progressively with the FIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (low group as reference vs. intermediate group, hazard ratio [HR]: 1.860 [95% confidence interval (CI), 1.326-2.610; p < 0.001]; vs. high group, HR:3.325 [95% CI, 2.017-5.479; p < 0.001]), as well as NFS (low NFS group as reference vs. intermediate group, HR: 1.938 [95% CI, 1.391-2.699; p < 0.001]; vs. high group, HR: 3.492 [95% CI, 1.997-6.105; p < 0.001])., Conclusions: The FIB4 index and NFS are associated with the probability of MACE in patients with NAFLD., Clinical Trials: The study design was approved by the ethics review board of Ogaki Municipal Hospital (approval number: 20221124-12, registration date: November 28th, 2022). https://www.ogaki-mh.jp/chiken/kenkyu.html., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: In an aging society, percutaneous coronary intervention (PCI) for super-elderly patients is commonly performed in clinical practice. However, data are scarce regarding the clinical features and outcomes of this population., Methods: This multicenter observational study enrolled patients aged over 90 years who underwent PCI across 10 hospitals between 2011 and 2020. The study included patients presenting with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). The occurrence of all-cause and cardiac deaths during hospitalization and after discharge was investigated., Results: In total, 402 patients (91.9 ± 2.0 years, 48.3 % male) participated in the study, of whom 77.9 % presented with ACS. The rate of in-hospital death was significantly higher in patients with ACS compared to patients with CCS (15.3 % vs. 2.2 %, p < 0.001). The estimated cumulative incidence rates of all-cause death were 24.3 %, 39.5 %, and 60.4 % at 1, 3, and 5 years, respectively. No significant difference was observed in the occurrence of all-cause death between patients with ACS and CCS. Regarding causes of death after discharge, non-cardiac deaths accounted for just over half of the cases., Conclusion: This study highlights the clinical features and long-term clinical course of patients aged over 90 years who underwent PCI in a real-world setting. Patients presenting with ACS exhibited a higher rate of in-hospital mortality compared to those with CCS. Following discharge, both ACS and CCS patients experienced comparable and substantial increases in the incidence rates of both cardiac and non-cardiac mortality over time, and a more holistic management approach is warranted., Competing Interests: Declaration of competing interest H.I. received lecture fees from Astellas Pharma Inc., AstraZeneca Inc., Daiichi-Sankyo Pharma Inc., and MSD K. K. Y.U. received lecture fees from Otsuka Pharma Ltd. T.M. received lecture fees from Bayer Pharmaceutical Co Ltd., Daiichi-Sankyo Co Ltd., Dainippon Sumitomo Pharma Co Ltd., Kowa Co Ltd., MSD K. K., Mitsubishi Tanabe Pharma Co., Nippon Boehringer Ingelheim Co Ltd., Novartis Pharma K. K., Pfizer Japan Inc., Sanofi-Aventis K. K., and Takeda Pharmaceutical Co Ltd. T.M. received unrestricted research grant for Department of Cardiology, Nagoya University Graduate School of Medicine from Astellas Pharma Inc., Daiichi-Sankyo Co Ltd., Dainippon Sumitomo Pharma Co Ltd., Kowa Co Ltd., MSD K. K., Mitsubishi Tanabe Pharma Co., Nippon Boehringer Ingelheim Co Ltd., Novartis Pharma K. K., Otsuka Pharma Ltd., Pfizer Japan Inc., Sanofi-Aventis K. K., Takeda Pharmaceutical Co Ltd., and Teijin Pharma Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Analog and digital quantum simulators can efficiently simulate quantum many-body systems that appear in natural phenomena. However, experimental limitations of near-term devices still make it challenging to perform the entire process of quantum simulation. The purification-based quantum simulation methods can alleviate the limitations in experiments such as the cooling temperature and noise from the environment, while this method has the drawback that it requires global entangled measurement with a prohibitively large number of measurements that scales exponentially with the system size. In this Letter, we propose that we can overcome these problems by restricting the entangled measurements to the vicinity of the local observables to be measured, when the locality of the system can be exploited. We provide theoretical guarantees that the global purification operation can be replaced with local operations under some conditions, in particular for the task of cooling and error mitigation. We furthermore give a numerical verification that the localized purification is valid even when conditions are not satisfied. Our method bridges the fundamental concept of locality with quantum simulators, and therefore is expected to open a path to unexplored quantum many-body phenomena.

Le Fort I (LF1) osteotomy, a common orthognathic procedure for the maxilla aimed at achieving maxillary mobility by separating the pterygomaxillary suture, poses a risk of bad fracture that may lead to complications and inadequate mobility. Our study analyzed two- and three-dimensional computed tomography images to identify the anatomical factors associated with bad fractures due to an LF1 osteotomy. Point 'a' is where the lateral pterygomaxillary suture on the axial image aligns with the zygomatic alveolar line near the line used for an LF1 osteotomy, with the base line connecting the bilateral 'a' points.Two risk factors were identified on the pterygoid side: (i) when the distance from point 'a' to the intersection of the base line and the medial pterygoid plate was <6.0 mm; and (ii) when the distance from the piriform aperture margin to the base line was <44.78 mm. Six risk factors were identified on the maxillary side, including the distance between the most anterior and most lateral points of the internal surface of the maxillary sinus being <31.9 mm. Our analyses revealed that fractures that occur during pterygomaxillary suture separation in an LF1 osteotomy are influenced by anatomical factors of the maxilla and pterygoid process, which form the pterygomaxillary suture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The lingual nerve (LN) is a branch of the mandibular division of the fifth cranial nerve, the trigeminal nerve, arising in the infratemporal fossa. It provides sensory fibers to the mucous membranes of the floor of the mouth, the lingual gingiva, and the anterior two-thirds of the tongue. Although the LN should rarely be encountered during routine and basic oral surgical procedures in daily dental practice, its anatomical location occasionally poses the risk of iatrogenic injury. The purpose of this section is to consider this potential LN injury risk and to educate readers about the anatomy of this nerve and how to treat it., (© 2024 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Background: The fibrosis-4 (FIB-4) index is a noninvasive scoring system that is used to assess the progression of liver fibrosis. This study aimed to assess whether the FIB-4 index is associated with recurrent atrial fibrillation (AF) after catheter ablation in patients with and without heart failure (HF)., Methods: We included 1,184 patients who underwent initial AF catheter ablation between 2016 and 2021. The patients were classified into low-risk (< 1.3), intermediate-risk (1.3-2.67), and high-risk (> 2.67) groups based on their FIB-4 indices at baseline. The patients were divided into HF (n = 552) and non-HF groups (n = 632); the HF group was further divided into paroxysmal AF (PAF) and non-PAF groups. AF recurrence after catheter ablation was then compared among the groups., Results: In the non-HF group, no significant differences in recurrence after ablation were observed between the low-(n = 219), intermediate-(n = 364), and high-risk (n = 49) groups. In contrast, in the HF group, the intermediate-(n = 341) and high-risk (n = 112) groups had significantly higher recurrence rates than the low-risk group (n = 99) (log-rank test, p = 0.005). This association remained significant after multivariate analysis (hazard ratio [HR]:1.374; p = 0.027). The FIB-4 index increased incrementally as the brain natriuretic peptide levels and severity of tricuspid regurgitation increased. The FIB-4 index was an independent predictor of recurrence in the non-PAF HF group (HR:1.498; p = 0.007) but not in the PAF group., Conclusions: The FIB-4 index may be a useful predictor of AF recurrence after catheter ablation in patients with HF, particularly in those with non-PAF., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mutations in Dystonin ( DST ), which encodes cytoskeletal linker proteins, cause hereditary sensory and autonomic neuropathy 6 (HSAN-VI) in humans and the dystonia musculorum ( dt ) phenotype in mice; however, the neuronal circuit underlying the HSAN-VI and dt phenotype is unresolved. dt mice exhibit dystonic movements accompanied by the simultaneous contraction of agonist and antagonist muscles and postnatal lethality. Here, we identified the sensory-motor circuit as a major causative neural circuit using a gene trap system that enables neural circuit-selective inactivation and restoration of Dst by Cre-mediated recombination. Sensory neuron-selective Dst deletion led to motor impairment, degeneration of proprioceptive sensory neurons, and disruption of the sensory-motor circuit. Restoration of Dst expression in sensory neurons using Cre driver mice or a single postnatal injection of Cre-expressing adeno-associated virus ameliorated sensory degeneration and improved abnormal movements. These findings demonstrate that the sensory-motor circuit is involved in the movement disorders in dt mice and that the sensory circuit is a therapeutic target for HSAN-VI.

In endovascular therapy (EVT) for femoropopliteal artery (FPA) lesions, studies examining the relationship between lesion morphology and hemodynamic status are limited. The purpose of this study was to investigate FPA lesion characteristics, including imaging findings and their cutoff values that can predict hemodynamic significance after balloon angioplasty. This single-center retrospective study enrolled 50 de novo FPA lesions from 43 patients treated under intravascular ultrasound (IVUS) usage between June 2022 and March 2023. As a physiological parameter, the pressure gradient was measured, and the cutoff value of the residual pressure gradient (RPG) was defined as a systolic pressure > 10 mmHg through the lesions after balloon angioplasty. The pressure gradients were measured using a 0.014-inch wire-guided, rapid exchange-type microcatheter, Navvus II (Acist, Eden Prairie, Minnesota, USA). Predictive risk factors for RPG were analyzed using the random forest (RF) method. The relationship between the variables, RPG, and the cutoff points of each predictor was assessed using the partial dependence plot (PDP) method. RPG was observed in 20% of the lesions after balloon angioplasty. The RF model revealed that the percent diameter stenosis (%DS) and minimum lumen area (MLA) on IVUS assessment were strong predictive factors for RPG after balloon angioplasty. The PDP model revealed that a higher %DS (cutoff 30%) and smaller MLA (cutoff 10 mm 2 ) could predict RPG after balloon angioplasty. Conventional lesion parameters such as %DS and MLA can predict hemodynamic significance during EVT for FPA lesions., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

The aim of this study was to investigate the effect of iterative motion correction (IMC) on reducing artifacts in brain magnetic resonance imaging (MRI) with deep learning reconstruction (DLR). The study included 10 volunteers (between September 2023 and December 2023) and 30 patients (between June 2022 and July 2022) for quantitative and qualitative analyses, respectively. Volunteers were instructed to remain still during the first MRI with fluid-attenuated inversion recovery sequence (FLAIR) and to move during the second scan. IMCoff DLR images were reconstructed from the raw data of the former acquisition; IMCon and IMCoff DLR images were reconstructed from the latter acquisition. After registration of the motion images, the structural similarity index measure (SSIM) was calculated using motionless images as reference. For qualitative analyses, IMCon and IMCoff FLAIR DLR images of the patients were reconstructed and evaluated by three blinded readers in terms of motion artifacts, noise, and overall quality. SSIM for IMCon images was 0.952, higher than that for IMCoff images (0.949) (p < 0.001). In qualitative analyses, although noise in IMCon images was rated as increased by two of the three readers (both p < 0.001), all readers agreed that motion artifacts and overall quality were significantly better in IMCon images than in IMCoff images (all p < 0.001). In conclusion, IMC reduced motion artifacts in brain FLAIR DLR images while maintaining similarity to motionless images., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-free survival (PFS), therapeutic response and adverse events (AEs) were assessed. The objective response rate (ORR) and disease control rates (DCR) were 15.8 and 53.3%, respectively. The median PFS was 3.9 months. The incidence rates of AEs of any grade and those grade 3 or higher were 83.3 and 36.7%, respectively. Liver injury was the most frequent AE of any grade and grade 3 or higher. Although there was no significant difference in ORR and PFS between the first and later line groups (ORR 15.8 vs. 15.7%, P=0.986; PFS 4.5 vs. 3.6 months, P=0.213), there was a significant difference in DCR between the two groups (65.8 vs. 45.9%, P=0.034). No significant differences were noted between the first- and later-line treatment groups regarding the incidence rate of AEs. Decision tree analysis revealed that poor liver function and advanced age were significant variables for discontinuation owing to AEs. In conclusion, Dur/Tre as first-line therapy had better disease control responses compared with later-line therapy; however, this regimen should be carefully administered to patients with deteriorating hepatic function or advanced age., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Shimose et al.)

Background: Evidence regarding the association between hyperuricemia and arrhythmia recurrence after catheter ablation for paroxysmal atrial fibrillation (AF) is scarce. We investigated whether hyperuricemia predicts arrhythmia recurrence after catheter ablation for paroxysmal AF and the relationship between hyperuricemia and alcohol consumption in AF recurrence., Methods: Patients who underwent catheter ablation for paroxysmal AF were divided into the hyperuricemia (index serum uric acid [UA] >7.0 mg/dL; n  = 114) and control (UA ≤7.0 mg/dL; n  = 609) groups and were followed for a median of 24 (12-48) months after ablation., Results: The hyperuricemia group had more patients with an alcohol intake of ≥20 g/day (33.3% vs. 22.7%, p  = .017) and a lower incidence of AF-free survival ( p  = .019). Similarly, those with an alcohol intake of ≥20 g/day had a lower incidence of AF-free survival than other patients. Multivariate Cox regression analysis revealed the following independent predictors of AF recurrence (adjusted hazard ratio, 95% confidence interval): hyperuricemia (1.64, 1.12-2.40), female gender (1.91, 1.36-2.67), brain natriuretic peptide level >100 pg/mL (1.59, 1.14-2.22), and alcohol consumption ≥20 g/day (1.49, 1.03-2.15) (all p  < .05). In addition, causal mediation analysis revealed that alcohol consumption of ≥20 g/day directly affected AF recurrence, independent of hyperuricemia., Conclusions: Patients with hyperuricemia may be at a high risk of arrhythmia recurrence after catheter ablation for paroxysmal AF. Although high alcohol consumption may contribute to increased UA levels, the presence of hyperuricemia may independently predict AF recurrence., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Rationale and Objectives: To determine if super-resolution deep learning reconstruction (SR-DLR) improves the depiction of cranial nerves and interobserver agreement when assessing neurovascular conflict in 3D fast asymmetric spin echo (3D FASE) brain MR images, as compared to deep learning reconstruction (DLR)., Materials and Methods: This retrospective study involved reconstructing 3D FASE MR images of the brain for 37 patients using SR-DLR and DLR. Three blinded readers conducted qualitative image analyses, evaluating the degree of neurovascular conflict, structure depiction, sharpness, noise, and diagnostic acceptability. Quantitative analyses included measuring edge rise distance (ERD), edge rise slope (ERS), and full width at half maximum (FWHM) using the signal intensity profile along a linear region of interest across the center of the basilar artery., Results: Interobserver agreement on the degree of neurovascular conflict of the facial nerve was generally higher with SR-DLR (0.429-0.923) compared to DLR (0.175-0.689). SR-DLR exhibited increased subjective image noise compared to DLR (p ≥ 0.008). However, all three readers found SR-DLR significantly superior in terms of sharpness (p < 0.001); cranial nerve depiction, particularly of facial and acoustic nerves, as well as the osseous spiral lamina (p < 0.001); and diagnostic acceptability (p ≤ 0.002). The FWHM (mm)/ERD (mm)/ERS (mm -1 ) for SR-DLR and DLR was 3.1-4.3/0.9-1.1/8795.5-10,703.5 and 3.3-4.8/1.4-2.1/5157.9-7705.8, respectively, with SR-DLR's image sharpness being significantly superior (p ≤ 0.001)., Conclusion: SR-DLR enhances image sharpness, leading to improved cranial nerve depiction and a tendency for greater interobserver agreement regarding facial nerve neurovascular conflict., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: The proportion of young females among the patients who undergo percutaneous coronary intervention (PCI) is relatively small, and information on their clinical characteristics is limited. This study investigated the clinical characteristics and prognostic factors for future cardiac events in young females who underwent PCI., Methods: This multicenter observational study included 187 consecutive female patients aged < 60 years who underwent PCI in seven hospitals. The primary composite endpoint was the incidence of cardiac death, nonfatal myocardial infarction, and target vessel revascularization., Results: The mean patient age was 52.1 ± 6.1 years and 89 (47.6%) had diabetes, and renal dysfunction (an estimated glomerular filtration rate < 60 mL/min/1.73 m 2 ) was observed in 38 (20.3%). During a median follow-up of 3.3 years, the primary endpoint occurred in 28 patients. The Cox proportional hazards models showed that renal dysfunction was an independent predictor for the primary endpoint (hazard ratio 3.04, 95% confidence interval 1.25-7.40, p = 0.01), as well as multivessel disease (hazard ratio 2.79, 95% confidence interval 1.12-6.93, p = 0.03). Patients with renal dysfunction had a significantly higher risk for the primary endpoint than those without renal dysfunction., Conclusions: Renal dysfunction was strongly associated with future cardiac events in young females who underwent PCI., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Odontomas, often found adjacent to impacted teeth, are tumors of abnormal tissue morphology arising from the tooth germ and are usually asymptomatic. They are often found by accident on X-ray images, and the eruption of permanent teeth is often caused by odontomas. In most cases, the tooth is extracted with the permanent tooth or orthodontic treatment is performed after extraction. However, the criteria are not clear. We encountered two cases of dental eruption in which permanent teeth, which originally seemed to be suitable for orthodontic treatment, spontaneously erupted after odontoma removal. It is necessary to examine the indications and timing of tooth extraction., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kunisada et al.)

The 3CL protease (3CLpro) is a viral cysteine protease of SARS-CoV-2 and is responsible for the main processing of the viral polyproteins involved in viral replication and proliferation. Despite the importance of 3CLpro as a drug target, the intracellular dynamics of active 3CLpro, including its expression and subcellular localization in SARS-CoV-2-infected cells, are poorly understood. Herein, we report an activity-based probe (ABP) with a clickable alkyne and an irreversible warhead for the SARS-CoV-2 3CL protease. We designed and synthesized two ABPs that contain a chloromethyl ketone (probe 2 ) or 2,6-dichlorobenzoyloxymethyl ketone (probe 3 ) reactive group at the P1' site. Labeling of recombinant 3CLpro by the ABPs in the purified and proteome systems revealed that probe 3 displayed ligand-directed and selective labeling against 3CLpro. Labeling of transiently expressed active 3CLpro in COS-7 cells also validated the good target selectivity of probe 3 for 3CLpro. We finally demonstrated that endogenously expressed 3CLpro in SARS-CoV-2-infected cells can be detected by fluorescence microscopy imaging using probe 3 , suggesting that active 3CLpro at 5 h postinfection is localized in the juxtanuclear region. To the best of our knowledge, this is the first report investigating the subcellular localization of active 3CLpro by using ABPs. We believe that probe 3 will be a useful chemical tool for acquiring important biological knowledge of active 3CLpro in SARS-CoV-2-infected cells.

Smile reconstruction using the branches that supply the zygomaticus major muscle as a motor source is an established procedure in facial reanimation surgery for facial paralysis. However, the anatomy of the nerve to the muscle remains unclear. Therefore, we herein examined the topographical anatomy of the nerve to the zygomaticus major muscle to obtain more detailed information on donor nerve anatomy. Preserved cadaver dissection was performed under a microscope on 13 hemifaces of 8 specimens. The branches that innervate the zygomaticus major muscle and their peripheral routes medial to the muscle were traced and examined. A median of four (ranges 2-4) branches innervated the zygomaticus major muscle. The proximal two branches (near the muscle origin) arose from the zygomatic branch, the second of which was the major branch. The distal branches (near the oral commissure) arose from the buccal branch or zygomaticobuccal plexus. The vertical distance from the caudal margin of the zygomatic arch to the major branch intersecting point was 19 ± 4.0 mm, while the horizontal distance parallel to the Frankfort plane was 29 ± 5.2 mm. The proximal two branches innervating the zygomaticus major muscle were detected in the majority of specimens. The anatomical findings obtained herein on the nerve to the zygomaticus major muscle will allow for more reliable donor selection in facial reanimation surgery., (© 2023 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Background: Cisplatin (CDDP) plays a central role in chemotherapy for head and neck squamous cell carcinoma (HNSCC), but drug resistance in HNSCC chemotherapy remains a problem, and the mechanism of CDDP resistance is unclear. We investigated CDDP-resistance mechanisms mediated by extracellular vesicles (EVs) and ATPase copper transporting beta (ATP7B) in HNSCC., Methods: We established CDDP-resistant sublines of HNSCC cells and verified their ATP7B expression. We used an EV secretion inhibitor (GW4869) and ATP7B short hairpin (sh)RNA transfection to examine the correlation between EV secretion and ATP7B expression., Results: The CDDP-resistant HNSCC sublines showed decreased CDDP sensitivity and increased ATP7B expression. GW4869 suppressed ATP7B expression, and ATP7B shRNA transfection suppressed EV secretion. The suppressions of EV secretion and ATP7B expression both enhanced CDDP's cell-killing effect., Conclusions: EVs were involved in the ATP7B-mediated mechanism underlying CDDP resistance. Further clarification of the EV-induced CDDP-resistance mechanism may lead to novel therapeutic strategies for HNSCC., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Nicorandil is widely used as a vasodilator for the physiological assessment of coronary arteries because of its usefulness and safety; however, there are no data on its use in peripheral arteries., Aims: To identify the utility of nicorandil and its appropriate dose for the physiological assessment on the femoropopliteal artery., Methods: We retrospectively enrolled patients from three institutes in which physiological assessment was carried out with various doses of nicorandil before treatment. Twenty-four femoropopliteal artery stenotic lesions from 22 patients were included. The nicorandil doses used were 2, 4, and 6 mg. Twenty-two lesions were also assessed using 30 mg of papaverine. The pressure gradient (PG) and peripheral fractional flow reserve (pFFR) were calculated based on the mean and systolic pressure levels. We examined the correlation of each parameter with the peak systolic velocity ratio (PSVR) based on the duplex ultrasound images using Spearman's rank correlation coefficient. Systemic blood pressure was assessed for safety., Results: The correlations were higher for mean pressure-based parameters than for systolic pressure-based parameters. As the nicorandil dose increased, the correlations among PG, pFFR, and PSVR also increased (mean pressure-based PG: 2 mg, r = 0.360; 4 mg, r = 0.498; 6 mg, r = 0.694, mean pressure-based pFFR: 2 mg, r = -0.479; 4 mg, r = -0.469; 6 mg, r = -0.641). The blood pressure after the administration of 6 mg of nicorandil was low, and the median systemic mean pressure was 65 mmHg., Conclusion: A 4 mg dose of nicorandil is effective and safe for the mean pressure-based physiological assessment of lesions in the femoropopliteal artery., (© 2024 Wiley Periodicals LLC.)

Purpose: Surgical thromboendarterectomy has been the gold standard treatment for common femoral artery (CFA) disease. However, endovascular therapy (EVT) is conducted in certain patients with CFA lesions because of multiple comorbidities. The interwoven nitinol stent (IWS) has been developed to prevent stent fracture. Thus, this study aimed to evaluate the feasibility of EVT using IWS for CFA lesions in clinical practice., Materials and Methods: This retrospective multicenter registry analyzed patients who had symptomatic lower-extremity artery disease due to CFA lesions and underwent EVT using IWS between 2019 and 2021. The primary endpoint was restenosis 2 years after EVT., Results: This study enrolled a total of 177 patients with 196 CFA lesions. The 2-year estimate of freedom from restenosis was 88.0%. The 2-year freedom rates from the target-lesion revascularization, major amputation, and all-cause death were 92.9%, 99.0%, and 75.2%, respectively. The clinical features significantly associated with restenosis risk were the reference vessel diameter (RVD, per 1.0 mm, hazard ratio [HR], 0.24 [0.08-0.70]; p=0.009), external iliac artery (EIA) involvement (HR=4.03 [1.56-10.4]; p=0.004), superficial femoral artery (SFA) involvement (HR=3.05 [1.00-9.25]; p=0.049), body mass index (BMI; per 1.0, HR=0.85 [0.73-0.99]; p=0.032), occlusion of deep femoral arteries (DFAs) at baseline (HR=7.89 [2.04-30.5]; p=0.003), and chronic limb-threatening ischemia (CLTI, HR=2.63 [1.02-6.78]; p=0.045). Their significant association was also confirmed by the random survival forest analysis. During a median follow-up of 12.0 months, guiding sheaths were inserted via CFAs implanted IWSs in 73 cases (37.2%), and no patients had cannulation-related complications, such as failed hemostasis, fracture of IWS, and stent occlusion., Conclusions: Endovascular therapy using IWS in CFA lesions showed acceptable 2-year patency rates at 88.0% and might preserve the arterial access via the ipsilateral CFAs. Small RVD, involving EIA and SFA lesions, emaciation, occluded DFA, and CLTI are associated with poor 2-year patency rates following EVT, thus, IWS implantation in CFA lesions may be an option for patients unsuitable for surgical revascularization., Clinical Impact: This retrospective multicenter registry enrolled 177 patients with 199 CFA lesions treated with EVT using interwoven nitinol stents, because surgical thromboendarterectomy was difficult due to their multiple comorbidities. The 2-year estimate of freedom from restenosis was acceptable at 88.0%. The 2-year freedom rate from major amputation was also high at 99.0%. Moreover, during a median follow-up of 12.0 months, guiding sheaths were inserted via CFAs implanted IWSs in 73 cases, and no patients had cannulation-related complications such as failed hemostasis, fracture of IWS, and stent occlusion., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

High-spin organic tetraradicals with significant intramolecular exchange interactions have high potential for advanced technological applications and fundamental research, but those synthesized to date possess limited stability and processability. In this work, we have designed a tetraradical based on the Blatter's radical and nitronyl nitroxide radical moieties and successfully synthesized it by using the palladium-catalyzed cross-coupling reaction of a triiodo-derivative of the 1,2,4-benzotriazinyl radical with gold(I) nitronyl nitroxide-2-ide complex in the presence of a newly developed efficient catalytic system. The molecular and crystal structure of the tetraradical was confirmed by X-ray diffraction analysis. The tetraradical possesses good thermal stability with decomposition onset at ∼150 °C under an inert atmosphere and exhibits reversible redox waves at -0.54 and 0.45 V versus Ag/AgCl. The magnetic properties of the tetraradical were characterized by SQUID magnetometry of polycrystalline powders and EPR spectroscopy in various matrices. The collected data, analyzed by using high-level quantum chemical calculations, confirmed that the tetraradical has a triplet ground state and a nearby excited quintet state. The unique high stability of the prepared triazinyl-nitronylnitroxide tetraradical is a new milestone in the field of creating high-spin systems., (© 2023 Wiley-VCH GmbH.)

Aim: The accuracy of the DISFORM (diameter reduction, spiral shape, flow impairment, or adverse morphology) classification system has not been validated., Methods: This retrospective multicenter observational study enrolled 288 consecutive patients with lower extremity artery disease who underwent endovascular therapy with drug-coated balloons for femoropopliteal lesions between January 2018 and December 2021. Patients were classified into DISFORM I-IV groups. Primary patency (PP) and freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months, and recurrence predictors at 12 months were investigated., Results: In total, 183, 66, 11, and 28 patients were classified into DISFORM I, II, III, and IV groups, respectively. In the DISFORM I, II, III, and IV groups, the PP rates were 75.3%, 91.1%, 87.5%, and 50.0%, respectively, and freedom from CD-TLR rates were 86.0%, 91.6%, 88.9%, and 76.7%, respectively, at 12 months. In the DISFORM I-III and IV groups, the PP rates were 79.4% and 50.0%, respectively, and freedom from CD-TLR rates were 87.5% and 76.7%, respectively, at 12 months. Multivariate analysis showed that chronic limb-threatening ischemia, DISFORM IV, and Lutonix™ use were independent predictors of PP loss at 12 months., Conclusion: DISFORM IV had a lower PP rate than DISFORM I-III in midterm phase.

Introduction: In Japan, telemedicine has gradually expanded due to deregulation in response to the COVID-19 pandemic. However, its current status remains unclear, as it is primarily provided by general practitioners. Meanwhile, telemedicine has begun to be utilized for low-dose estrogen-progestin (LEP) prescriptions for dysmenorrhea., Methods: We conducted a retrospective analysis of medical record data from two gynecology clinics and performed an exploratory evaluation between a group that combined telemedicine and in-person visits during the initial 6 months of LEP treatment, and another group with only in-person visits., Results: After propensity score matching, 89 and 83 patients were eligible for the telemedicine and in-person groups, respectively, with 53 patients in both. The characteristics of both groups were similar after matching. There were no significant differences in the probability of abnormal uterine bleeding during the first 6 months of treatment (25% and 43% in each group; p  = 0.064), side effects, or treatment efficacy between the two groups. The withdrawal rate at 6 months was significantly higher in the telemedicine group than in the in-person group (13% and 0%, p  = 0.013). The average copayment for patients who covered 30% of the total cost was also significantly higher in the telemedicine group after 1 and 3 months of LEP prescription., Conclusion: The appropriate combination of telemedicine and in-person visits is currently employed in hospital visits, which does not differ significantly from in-person visits. Given the retrospective nature of this study and the limited number of cases, further investigation is necessary in the future., Competing Interests: Telemedicine at both facilities A and B used CLINICS® (provided Medley, Inc.), a telemedicine system in Japan. However, this study did not aim to validate the telemedicine system. In addition, the co-researcher, the first author of this article, was both a visiting researcher at Yokohama City University and an employee of Medley, Inc. However, this study did not receive any funding from the company. The Conflict of Interest Review Committee granted permission to conduct this study on the condition that the aforementioned information was stated in the protocol, disclosure documents, and published article, and that the researcher did not engage in statistical analysis work.Y.I. is employed at Medley, Inc., and receives a regular salary. The remaining authors have nothing to disclose., (© Yumi Inoo et al., 2024; Published by Mary Ann Liebert, Inc.)

Aim: Lower-extremity artery disease (LEAD) is a high-risk factor for bleeding. However, the specific risk factors for bleeding in patients with LEAD remain unclear. We aimed to identify risk factors for bleeding in patients with LEAD after endovascular treatment (EVT)., Methods: This multicenter, retrospective, observational study included 732 consecutive patients with LEAD who underwent EVT between January 2018 and December 2019. Patient characteristics, laboratory data, target lesions, and medications were compared between patients with and without chronic limb-threatening ischemia (CLTI). Predictive bleeding risk factors were explored using Cox regression analysis with differential models., Results: In model 1, a body mass index (BMI) ＜18.5 kg/m 2 , prior heart failure, high bleeding risk, use of single antiplatelet therapy (SAPT) plus warfarin, and CLTI were predictive bleeding risk factors (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.13-3.52; p＜0.01; HR 2.15; 95% CI 1.28-3.55; p＜0.01; HR 3.40; 95% CI 1.28-3.55; p＜0.01; HR 2.05; 95% CI 1.33-5.84; p＜0.01; respectively). In model 2, a BMI ＜18.5 kg/m 2 , prior heart failure, anemia (＜11 g/dL), low platelet count (＜10*10 4 /µL), chronic kidney disease, use of single antiplatelet therapy (SAPT) plus warfarin, and CLTI were independent risk factors for bleeding (model 2: HR 2.05; 95% CI 1.12-3.56; p=0.02; HR 2.35; 95% CI 1.39-3.90; p＜0.01; HR 2.71; 95% CI 1.64-4.50; p＜0.01; HR 2.66; 95% CI 1.00-5.89; p=0.05; HR 2.47; 95% CI 1.25-5.45; p＜0.01; HR 2.79; 95% CI 1.24-5.63; p=0.01; respectively) Conclusions: CLTI is a residual and predictive risk factor for bleeding in patients with LEAD. We have to pay attention to the bleeding events of patients with CLTI after EVT during follow-up.

Dystonin (DST), also known as bullous pemphigoid antigen 1 (BPAG1), encodes cytoskeletal linker proteins belonging to the plakin family. The DST gene produces several isoforms, including DST-a, DST-b, and DST-e, which are expressed in neural, muscle, and cutaneous tissues, respectively. Pathogenic DST mutations cause hereditary sensory and autonomic neuropathy type 6 (HSAN-VI) and epidermolysis bullosa simplex (EBS); therefore, it is important to elucidate the roles of DST isoforms in multiple organs. Recently, we have used several Dst mutant mouse strains, in which the expression of Dst isoforms is disrupted in distinct patterns, to gain new insight into how DST functions in multiple tissues. This review provides an overview of the roles played by tissue-specific DST isoforms in neural, muscle, and cutaneous tissues., (© 2023. The Author(s), under exclusive licence to Japanese Association of Anatomists.)

Background: This study aimed to investigate the association between proteinuria and long-term prognosis in patients with coronary artery disease., Methods: This was a single-center observational study. A total of 1351 patients were identified who underwent percutaneous coronary intervention, and whose urine data were available. Patients were divided into two groups according to the presence (n = 245) or absence (n = 1106) of proteinuria. All-cause and cardiovascular deaths were primarily evaluated., Results: The prevalence rates of hypertension and diabetes were significantly higher, and the baseline estimated glomerular filtration rate (eGFR) was lower in patients with proteinuria than in those without proteinuria. During the median follow-up of 4.1 years (interquartile range, 1.7-6.8 years), the occurrences of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria. Multivariable Cox regression analysis indicated that the presence of proteinuria was a significant predictor of cardiovascular death as well as age, BMI, reduced eGFR, and left ventricular ejection fraction. When stratified into four groups based on eGFR category (eGFR <60 or ≥60 ml/min/1.73 m2) and absence or presence of proteinuria, the incidence rates of all-cause and cardiovascular deaths were highest in patients with proteinuria and eGFR less than 60 ml/min/1.73 m2. Furthermore, the incidence rates of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria among both diabetic and nondiabetic patients., Conclusion: Proteinuria is associated with the long-term prognosis, and all-cause and cardiovascular deaths in patients with coronary artery disease, regardless of eGFR and the presence or absence of diabetes mellitus., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

We present a unified approach to analyzing the cost of various quantum error mitigation methods on the basis of quantum estimation theory. By analyzing the quantum Fisher information matrix of a virtual quantum circuit that effectively represents the operations of quantum error mitigation methods, we derive for a generic layered quantum circuit under a wide class of Markovian noise that, unbiased estimation of an observable encounters an exponential growth with the circuit depth in the lower bound on the measurement cost. Under the global depolarizing noise, we in particular find that the bound can be asymptotically saturated by merely rescaling the measurement results. Moreover, we prove for random circuits with local noise that the cost grows exponentially also with the qubit count. Our numerical simulations support the observation that, even if the circuit has only linear connectivity, such as the brick-wall structure, each noise channel converges to the global depolarizing channel with its strength growing exponentially with the qubit count. This not only implies the exponential growth of cost both with the depth and qubit count, but also validates the rescaling technique for sufficiently deep quantum circuits. Our results contribute to the understanding of the physical limitations of quantum error mitigation and offer a new criterion for evaluating the performance of quantum error mitigation techniques.

Functional mitral regurgitation (FMR) often coexists with atrial fibrillation (AF) and may have a causal relation with AF persistence and exacerbation of heart failure (HF). The purpose of this study was to investigate the impact of FMR on AF catheter ablation (AFCA) outcomes and improvement in FMR after AFCA in patients with HF with preserved ejection fraction (HFpEF) and nonparoxysmal AF. Excluding patients with primary valve disease or post-mitral valve repair, 280 patients with HFpEF who underwent CA for nonparoxysmal AF were retrospectively included. All patients completed 1-year follow-up and were assessed for FMR, AF recurrence and HF parameters, including echocardiography. At baseline, FMR was present in 153 (54.6%) patients (mild, n = 112; moderate, n = 40; severe, n = 1), and these were decreased to 70 (25%) significantly 1 year after AFCA (mild, n = 64; moderate, n = 6), 119 patients (78%) had improvement in MR (a decrease of ≥1 level in the severity from baseline to 1 year on echocardiography). Overall, 274 patients (97.9%) had sinus rhythm at the 1-year examination, and recurrent AF-free survival did not differ in patients with and without MR improvement (83.2% vs 82.4%, p = 0.908). However, the MR improvement group had a significantly lower cardiothoracic ratio, left atrial diameter, E/e', and B-type natriuretic peptide levels after 1 year than those in the MR nonimprovement group. In conclusion, the majority of the HFpEF patients with nonparoxysmal AF had improvement of FMR after AFCA with the high maintenance of sinus rhythm, leading to a virtuous cycle of cardiac function., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The topology of the network of load transmitting connections plays an essential role in the cascading failure dynamics of complex systems driven by the redistribution of load after local breakdown events. In particular, as the network structure is gradually tuned from regular to completely random a transition occurs from the localized to mean field behavior of failure spreading. Based on finite size scaling in the fiber bundle model of failure phenomena, here we demonstrate that outside the localized regime, the load bearing capacity and damage tolerance on the macro-scale, and the statistics of clusters of failed nodes on the micro-scale obey scaling laws with exponents which depend on the topology of the load transmission network and on the degree of disorder of the strength of nodes. Most notably, we show that the spatial structure of damage governs the emergence of the localized to mean field transition: as the network gets gradually randomized failed clusters formed on locally regular patches merge through long range links generating a percolation like transition which reduces the load concentration on the network. The results may help to design network structures with an improved robustness against cascading failure., (© 2023. The Author(s).)

Aim: Patients with chronic limb-threatening ischemia (CLTI) have a high bleeding risk (HBR) and mortality rate. The 2-year life expectancy is an important factor in deciding the appropriate treatment strategy. This study aimed to assess the influence of HBR on the prognosis of patients with CLTI., Methods: A total of 259 patients with CLTI who underwent endovascular therapy (EVT) (mean age, 76.2 years; male, 62.9%) between January 2018 and December 2019 were evaluated. The Academic Research Consortium for HBR (ARC-HBR) criteria were applied to each patient, and the ARC-HBR scores were calculated. The cut-off score for predicting all-cause mortality within two years was derived using a survival classification and regression tree (CART) model. Causes of death and the association between ARC-HBR scores and major bleeding events within two years were also investigated., Results: Based on the CART model, patients were divided into three groups (low HBR score 0-1.0, 48 patients; moderate HBR score 1.5-3.0, 176 patients; and high HBR score ≥ 3.5, 35 patients). During the study period, 82 patients (39.6%) died due to cardiac (n=23) and non-cardiac causes (n=59). All-cause mortality increased significantly with increasing ARC-HBR scores. Cox multivariate analysis revealed a significant association between high ARC-HBR scores and the risk of all-cause mortality within two years. Major bleeding events increased significantly with increasing ARC-HBR scores., Conclusions: The ARC-HBR score could predict 2-year mortality in patients with CLTI who underwent EVT. Thus, this score can help determine the best revascularization strategy for patients with CLTI.

Purpose: To compare the diagnostic performance of 1.5 T versus 3 T magnetic resonance angiography (MRA) for detecting cerebral aneurysms with clinically available deep learning-based computer-assisted detection software (EIRL aneurysm® [EIRL&#95;an]), which has been approved by the Japanese Pharmaceuticals and Medical Devices Agency. We also sought to analyze the causes of potential false positives., Methods: In this single-center, retrospective study, we evaluated the MRA scans of 90 patients who underwent head MRA (1.5 T and 3 T in 45 patients each) in clinical practice. Overall, 51 patients had 70 aneurysms. We used MRI from a vendor not included in the dataset used to create the EIRL&#95;an algorithm. Two radiologists determined the ground truth, the accuracy of the candidates noted by EIRL&#95;an, and the causes of false positives. The sensitivity, number of false positives per case (FPs/case), and the causes of false positives were compared between 1.5 T and 3 T MRA. Pearson's χ 2 test, Fisher's exact test, and the Mann‒Whitney U test were used for the statistical analyses as appropriate., Results: The sensitivity was high for 1.5 T and 3 T MRA (0.875‒1), but the number of FPs/case was significantly higher with 3 T MRA (1.511 vs. 2.578, p < 0.001). The most common causes of false positives (descending order) were the origin/bifurcation of vessels/branches, flow-related artifacts, and atherosclerosis and were similar between 1.5 T and 3 T MRA., Conclusion: EIRL&#95;an detected significantly more false-positive lesions with 3 T than with 1.5 T MRA in this external validation study. Our data may help physicians with limited experience with MRA to correctly diagnose aneurysms using EIRL&#95;an., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vascular closure devices (VCDs) are widely used to achieve rapid hemostasis after percutaneous intervention via the common femoral artery (CFA), with well-established efficacy and safety. Although VCD-related artery occlusion is rare, it can be critical. A 72-year-old female underwent endovascular therapy (EVT) for stent occlusion in the left superficial femoral artery through a 7-Fr guiding sheath from the right CFA. After the procedure, an acute right popliteal artery (POP-A) occlusion, associated with the EXOSEAL VCD plug, occurred. The plug material was successfully removed using a bidirectional approach. The migration plug was blocked to prevent distal vessel migration and pushed gently to close the antegrade system, using an over-the-wire balloon from the retrograde site. We named this the "Push balloon INto vessel and Close Embolus from Retrograde site" (PINCER) technique. Finally, the plug was successfully removed using biopsy forceps. Acute limb ischemia (ALI) caused by EXOSEAL is a rare condition. Removal of the emboli by EVT is clinically significant because it is minimally invasive. However, it is sometimes difficult to remove the embolus using only antegrade approach; thus, the bidirectional approach using the PINCER technique can be effective in these situations.