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1.
Org Biomol Chem ; 22(21): 4309-4317, 2024 May 29.
Article En | MEDLINE | ID: mdl-38717394

Methods of selectively synthesizing diorganyl diselenides (R-Se-Se-R) without using harmful reducing agents are presented. We optimized the reaction conditions for the selective formation of the diselenide dianion (Se22-) and the corresponding diorganyl diselenides using basic reagents (e.g., KOH), while suppressing the formation of side products, such as diorganyl selenides (R-Se-R) or multiselenides (R-Sen-R; n ≥ 3). Furthermore, we have suggested and examined the reaction pathways responsible for the formation of the desired diorganyl diselenides 1 and side products 2 and 3. Consequently, the selective synthesis of diverse diorganyl diselenides was achieved with modest to excellent yields (33-99%) using various organyl halides under optimized conditions. The results provide a practical and efficient synthetic method for diorganyl diselenides as a representative class of organoselenium compounds.

2.
Am Heart J ; 271: 48-54, 2024 May.
Article En | MEDLINE | ID: mdl-38401647

BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.


Anticoagulants , Atrial Fibrillation , Clopidogrel , Drug-Eluting Stents , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Female , Humans , Male , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/therapy , Clopidogrel/administration & dosage , Clopidogrel/therapeutic use , Drug Therapy, Combination , Hemorrhage/chemically induced , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Prospective Studies , Stroke/prevention & control , Stroke/etiology , Time Factors , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
3.
AJR Am J Roentgenol ; 222(1): e2329769, 2024 01.
Article En | MEDLINE | ID: mdl-37703195

BACKGROUND. Timely and accurate interpretation of chest radiographs obtained to evaluate endotracheal tube (ETT) position is important for facilitating prompt adjustment if needed. OBJECTIVE. The purpose of our study was to evaluate the performance of a deep learning (DL)-based artificial intelligence (AI) system for detecting ETT presence and position on chest radiographs in three patient samples from two different institutions. METHODS. This retrospective study included 539 chest radiographs obtained immediately after ETT insertion from January 1 to March 31, 2020, in 505 patients (293 men, 212 women; mean age, 63 years) from institution A (sample A); 637 chest radiographs obtained from January 1 to January 3, 2020, in 302 patients (157 men, 145 women; mean age, 66 years) in the ICU (with or without an ETT) from institution A (sample B); and 546 chest radiographs obtained from January 1 to January 20, 2020, in 83 patients (54 men, 29 women; mean age, 70 years) in the ICU (with or without an ETT) from institution B (sample C). A commercial DL-based AI system was used to identify ETT presence and measure ETT tip-to-carina distance (TCD). The reference standard for proper ETT position was TCD between greater than 3 cm and less than 7 cm, determined by human readers. Critical ETT position was separately defined as ETT tip below the carina or TCD of 1 cm or less. ROC analysis was performed. RESULTS. AI had sensitivity and specificity for identification of ETT presence of 100.0% and 98.7% (sample B) and 99.2% and 94.5% (sample C). AI had sensitivity and specificity for identification of improper ETT position of 72.5% and 92.0% (sample A), 78.9% and 100.0% (sample B), and 83.7% and 99.1% (sample C). At a threshold y-axis TCD of 2 cm or less, AI had sensitivity and specificity for critical ETT position of 100.0% and 96.7% (sample A), 100.0% and 100.0% (sample B), and 100.0% and 99.2% (sample C). CONCLUSION. AI identified improperly positioned ETTs on chest radiographs obtained after ETT insertion as well as on chest radiographs obtained of patients in the ICU at two institutions. CLINICAL IMPACT. Automated AI identification of improper ETT position on chest radiographs may allow earlier repositioning and thereby reduce complications.


Artificial Intelligence , Intubation, Intratracheal , Male , Humans , Female , Middle Aged , Aged , Retrospective Studies , Intubation, Intratracheal/methods , Trachea , Radiography
4.
Diabetes Obes Metab ; 26(3): 829-839, 2024 Mar.
Article En | MEDLINE | ID: mdl-37994242

AIM: This study evaluated the safety and efficacy of a moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with metabolic syndrome (MetS) and atherosclerotic cardiovascular disease. MATERIALS AND METHODS: In this post-hoc subgroup analysis of the RACING trial, patients were analysed based on the presence of MetS. MetS was defined as meeting at least three of the five following criteria: (a) elevated waist circumference; (b) elevated triglycerides; (c) reduced high-density lipoprotein cholesterol; (d) elevated blood pressure; and (e) elevated fasting glucose. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. RESULTS: Of the 3780 patients enrolled in the RACING trial, 1703 (45.1%) had MetS at baseline. The primary outcome rate was 10.1% and 10.3% in patients with MetS receiving ezetimibe combination therapy versus high-intensity statin monotherapy (hazard ratio = 0.97; 95% confidence interval = 0.72-1.32; p = .868). Lower rates of intolerance-related drug discontinuation or dose reduction (3.9% vs. 8.0%; p < .001) and lower low-density lipoprotein cholesterol levels (57 vs. 65 mg/dl; p < .001) were observed with ezetimibe combination therapy versus high-intensity statin monotherapy. Furthermore, the rate of new-onset diabetes was 18.5% and 19.1% in each group (p = .822). There were no significant interactions between MetS and therapy regarding study outcomes in the total population. CONCLUSIONS: In patients with MetS and atherosclerotic cardiovascular disease, a moderate-intensity statin with ezetimibe combination therapy had comparable cardiovascular benefits with those of high-intensity statin monotherapy. Meanwhile, ezetimibe combination therapy was associated with lower drug intolerance and low-density lipoprotein cholesterol levels, but there was no apparent between-group difference in new-onset diabetes.


Anticholesteremic Agents , Atherosclerosis , Cardiovascular Diseases , Diabetes Mellitus , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Metabolic Syndrome , Humans , Anticholesteremic Agents/adverse effects , Atherosclerosis/complications , Atherosclerosis/drug therapy , Atherosclerosis/prevention & control , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Cholesterol, LDL , Diabetes Mellitus/drug therapy , Drug Therapy, Combination , Ezetimibe/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Metabolic Syndrome/complications , Metabolic Syndrome/drug therapy , Treatment Outcome
5.
Korean Circ J ; 54(2): 63-75, 2024 Feb.
Article En | MEDLINE | ID: mdl-38111184

BACKGROUND AND OBJECTIVES: Evidence regarding the efficacy and safety of intracardiac echocardiography (ICE) for guidance during transcatheter aortic valve replacement (TAVR) is limited. This study aimed to compare the clinical efficacy and safety of ICE versus transesophageal echocardiography (TEE) for guiding TAVR. METHODS: This prospective cohort study included patients who underwent TAVR from August 18, 2015, to June 31, 2021. Eligible patients were stratified by echocardiographic modality (ICE or TEE) and anesthesia mode (monitored anesthesia care [MAC] or general anesthesia [GA]). Primary outcome was the 1-year composite of all-cause mortality, rehospitalization for cardiovascular cause, or stroke, according to the Valve Academic Research Consortium-3 (VARC-3) definition. Propensity score matching was performed, and study outcomes were analyzed for the matched cohorts. RESULTS: Of the 359 eligible patients, 120 patients were matched for the ICE-MAC and TEE-GA groups, respectively. The incidence of primary outcome was similar between matched groups (18.3% vs. 20.0%; adjusted hazard ratio, 0.94; 95% confidence interval [CI], 0.53-1.68; p=0.843). ICE-MAC and TEE-GA also had similar incidences of moderate-to-severe paravalvular regurgitation (PVR) (4.2% vs. 5.0%; adjusted odds ratio, 0.83; 95% CI, 0.23-2.82; p=0.758), new permanent pacemaker implantation, and VARC-3 types 2-4 bleeding. CONCLUSIONS: ICE was comparable to TEE for guidance during TAVR for the composite clinical efficacy outcome, with similar incidences of moderate-to-severe PVR, new permanent pacemaker implantation, and major bleeding. These results suggest that ICE could be a safe and effective alternative echocardiographic modality to TEE for guiding TAVR.

7.
Am J Med ; 136(10): 1026-1034.e1, 2023 10.
Article En | MEDLINE | ID: mdl-37356644

BACKGROUND: The optimal antiplatelet therapy (APT) for patients undergoing non-cardiac surgery within 1 year after percutaneous coronary intervention (PCI) is not yet established. METHODS: Patients who underwent non-cardiac surgery within 1 year after second-generation drug-eluting stent implantation were included from a multicenter prospective registry in Korea. The primary endpoint was 30-day net adverse clinical event (NACE), including all-cause death, major adverse cardiovascular event (MACE), and major bleeding events. Covariate adjustment using propensity score was performed. RESULTS: Among 1130 eligible patients, 708 (62.7%) continued APT during non-cardiac surgery. After propensity score adjustment, APT continuation was associated with a lower incidence of NACE (3.7% vs 5.5%; adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = .019) and MACE (1.1% vs 1.9%; adjusted OR, 0.35; 95% CI, 0.12-0.99; P = .046), whereas the incidence of major bleeding events was not different between the 2 APT strategies (1.7% vs 2.6%; adjusted OR, 0.61; 95% CI, 0.25-1.50; P = .273). CONCLUSIONS: The APT continuation strategy was chosen in a substantial proportion of patients and was associated with the benefit of potentially reducing 30-day NACE and MACE with similar incidence of major bleeding events, compared with APT discontinuation. This study suggests a possible benefit of APT continuation in non-cardiac surgery within 1 year of second-generation drug-eluting stent implantation.


Drug-Eluting Stents , Percutaneous Coronary Intervention , Humans , Platelet Aggregation Inhibitors/therapeutic use , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Hemorrhage/drug therapy
8.
Exp Mol Med ; 55(6): 1232-1246, 2023 06.
Article En | MEDLINE | ID: mdl-37258580

SIRT1, a member of the mammalian sirtuin family, is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase with key roles in aging-related diseases and cellular senescence. However, the mechanism by which SIRT1 protein homeostasis is controlled under senescent conditions remains elusive. Here, we revealed that SIRT1 protein is significantly downregulated due to ubiquitin-mediated proteasomal degradation during stress-induced premature senescence (SIPS) and that SIRT1 physically associates with anaphase-promoting complex/cyclosome (APC/C), a multisubunit E3 ubiquitin ligase. Ubiquitin-dependent SIRT1 degradation is stimulated by the APC/C coactivator Cdh1 and not by the coactivator Cdc20. We found that Cdh1 depletion impaired the SIPS-promoted downregulation of SIRT1 expression and reduced cellular senescence, likely through SIRT1-driven p53 inactivation. In contrast, AROS, a SIRT1 activator, reversed the SIRT1 degradation induced by diverse stressors and antagonized Cdh1 function through competitive interactions with SIRT1. Furthermore, our data indicate opposite roles for Cdh1 and AROS in the epigenetic regulation of the senescence-associated secretory phenotype genes IL-6 and IL-8. Finally, we demonstrated that pinosylvin restores downregulated AROS (and SIRT1) expression levels in bleomycin-induced mouse pulmonary senescent tissue while repressing bleomycin-promoted Cdh1 expression. Overall, our study provides the first evidence of the reciprocal regulation of SIRT1 stability by APC/C-Cdh1 and AROS during stress-induced premature senescence, and our findings suggest pinosylvin as a potential senolytic agent for pulmonary fibrosis.


Epigenesis, Genetic , Sirtuin 1 , Animals , Mice , Anaphase-Promoting Complex-Cyclosome/genetics , Anaphase-Promoting Complex-Cyclosome/metabolism , Cell Cycle Proteins/metabolism , Cellular Senescence , Sirtuin 1/genetics , Sirtuin 1/metabolism , Ubiquitin/metabolism , Ubiquitination
9.
J Am Coll Cardiol ; 81(14): 1339-1349, 2023 04 11.
Article En | MEDLINE | ID: mdl-37019580

BACKGROUND: The routine use of high-intensity statins should be considered carefully in elderly patients because of their higher risk of intolerance or adverse events. OBJECTIVES: We evaluated the impact of moderate-intensity statin with ezetimibe combination therapy compared with high-intensity statin monotherapy in elderly patients with atherosclerotic cardiovascular disease (ASCVD). METHODS: In this post hoc analysis of the RACING (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases) trial, patients were stratified by age (≥75 years and <75 years). The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke. RESULTS: Among the 3,780 enrolled patients, 574 (15.2%) were aged ≥75 years. The rates of the primary endpoint were not different between the moderate-intensity statin with ezetimibe combination therapy group and the high-intensity statin monotherapy group among patients aged ≥75 years (10.6% vs 12.3%; HR: 0.87; 95% CI: 0.54-1.42; P = 0.581) and those <75 years (8.8% vs 9.4%; HR: 0.94; 95% CI: 0.74-1.18; P = 0.570) (P for interaction = 0.797). Moderate-intensity statin with ezetimibe combination therapy was associated with lower rates of intolerance-related drug discontinuation or dose reduction among patients aged ≥75 years (2.3% vs 7.2%; P = 0.010) and those <75 years (5.2% vs 8.4%; P < 0.001) (P for interaction = 0.159). CONCLUSIONS: Moderate-intensity statin with ezetimibe combination therapy showed similar cardiovascular benefits to those of high-intensity statin monotherapy with lower intolerance-related drug discontinuation or dose reduction in elderly patients with ASCVD having a higher risk of intolerance, nonadherence, and discontinuation with high-intensity statin therapy. (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases [RACING Trial]; NCT03044665).


Anticholesteremic Agents , Atherosclerosis , Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Ezetimibe , Anticholesteremic Agents/therapeutic use , Cardiovascular Diseases/etiology , Drug Therapy, Combination , Atherosclerosis/drug therapy , Lipids , Treatment Outcome
10.
Eur Heart J Case Rep ; 7(1): ytad028, 2023 Jan.
Article En | MEDLINE | ID: mdl-36733687

Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a multi-organ disorder resulting from mitochondrial DNA (mtDNA) mutations. We report a case of suspected MELAS syndrome that progressed to left ventricular dysfunction 24 years after an initial diagnosis of atrioventricular block (AVB). Case summary: A 51-year-old woman was referred to heart failure clinic because of dyspnoea on exertion and progressive cardiomegaly. She had a dual-chamber pacemaker implanted for 24 years because of a high-degree AVB. She was treated for diabetes mellitus for 23 years and used hearing aids for 12 years because of sensorineural hearing loss. Transthoracic echocardiography revealed reduced left ventricular ejection fraction (26%), with increased thickness and unusual texture of the myocardium. The absence of abnormal findings on serum and urine protein electrophoresis suggested that light-chain amyloidosis was unlikely. In addition, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy revealed no definite uptake in the myocardium. Endomyocardial biopsy revealed a hypertrophy of myocytes in haematoxylin-eosin staining, and electron microscopy revealed a disarrangement of mitochondrial cristae, which were suggestive of mitochondrial cardiomyopathy. A mtDNA test detected the m.3243A > G mutation in the MT-TL1 gene. According to these findings, MELAS syndrome was the most probable diagnosis despite the absence of common symptoms such as stroke-like episodes or lactic acidosis. Discussion: The patient had progressed to heart failure with reduced ejection fraction 24 years after the first cardiac manifestation. An identification of the mutation in the MT-TL1 gene, indicative of MELAS syndrome, enabled the diagnosis of MELAS syndrome without typical manifestations.

11.
Article En | MEDLINE | ID: mdl-36554572

Insomnia is a common health problem that can lead to various diseases and negatively impact quality of life. Pharmacopuncture is a new type of acupuncture that involves applying herbal medicine extracts to acupoints. Korean medicine doctors frequently use it to treat insomnia disorder. However, there is insufficient evidence to support the effectiveness and safety of pharmacopuncture for insomnia disorder. We designed a pragmatic randomized controlled trial to compare the effectiveness of pharmacopuncture and acupuncture for insomnia disorder. This multi-site, randomized, acupuncture-controlled trial will enroll 138 insomnia patients. The subjects will be randomly assigned to one of two groups, pharmacopuncture or acupuncture, at a 2:1 ratio. For 4 weeks, the participants will receive ten sessions of pharmacopuncture or acupuncture treatment and will be followed up for 4 weeks after the treatment ends. The Pittsburgh Sleep Quality Index score is the primary outcome measure. Insomnia severity index score, sleep parameters recorded using actigraphy and sleep diaries, physical symptoms associated with insomnia, emotions, quality of life, medical costs, and safety are the secondary outcome measures. The findings of this trial willprovide evidence that will be useful in clinical decision-making for insomnia treatment strategies.


Acupuncture Therapy , Acupuncture , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/therapy , Quality of Life , Acupuncture Therapy/methods , Sleep , Treatment Outcome , Randomized Controlled Trials as Topic
12.
Molecules ; 27(24)2022 Dec 16.
Article En | MEDLINE | ID: mdl-36558124

Studies on the selective synthetic method for dialkyl ditellurides 1, a representative class of organyl tellurium compounds, were presented. Considering the difficulty in conducting previous harsh reactions and in suppressing the formation of dialkyl tellurides 2 as side products, we optimized reaction conditions for selective syntheses of sodium ditelluride and the corresponding dialkyl ditellurides 1. We reduced tellurium to sodium ditelluride by using NaBH4 and subsequently, treated the obtained sodium ditelluride with alkyl halides (RX) to give the target compounds 1. Consequently, by applying various alkyl halides (RX) we achieved the selective syntheses of dialkyl ditellurides 1 (13 examples with 4 new compounds) in modest to good yields. We also suggested the mechanistic pathways to dialkyl ditellurides 1.


Tellurium
13.
Molecules ; 27(19)2022 Oct 10.
Article En | MEDLINE | ID: mdl-36235301

The syntheses of novel 1-acyloxyindole compounds 1 and the investigations on reaction pathways are presented. Nitro ketoester substrate 2, obtained in a two-step synthetic process, underwent reduction, intramolecular addition, nucleophilic 1,5-addition, and acylation to afford 1-acyloxyindoles 1 in one pot. Based on the systematic studies, we established the optimized reaction conditions for 1 focusing on the final acylation step of the intermediate 1-hydroxyindole 8. With the optimized conditions, we succeeded in synthesizing 21 examples of new 1-acyloxyindole derivatives 1 in modest yields (Y = 24 - 35%). Among the 1-acyloxyindole compounds, 1-acetoxyindole compounds 1x were generally unstable, and their yields were relatively lower than the other 1-acyloxyindoles. We expect that a bulkier alkyl or aromatic group on R2 could stabilize the 1-acyloxyindole compounds. Significantly, one-pot reactions of a four-step sequence successfully generated compounds 1 that are all new and might be difficult to be synthesized otherwise.


Molecular Structure , Acylation
14.
Molecules ; 27(16)2022 Aug 16.
Article En | MEDLINE | ID: mdl-36014475

The studies on the selective synthesis of dialkyl selenide compounds 1 were presented. Overcoming the complexity and difficulty of selenides (R-Se-R) and/or multiselenides (R-Sen-R; n ≥ 2), we aimed to optimize the reaction condition for the tolerable preparation of sodium selenide (Na2Se) by reducing Se with NaBH4, and then to achieve selective syntheses of dialkyl selenides 1 by subsequently treating the obtained sodium selenide with alkyl halides (RX). Consequently, various dialkyl selenides 1 were efficiently synthesized in good-to-moderate yields. The investigations on reaction pathways and solvent studies were also described.


Selenium Compounds , Solvents
15.
Eur Radiol ; 32(1): 56-66, 2022 Jan.
Article En | MEDLINE | ID: mdl-34170366

OBJECTIVES: To investigate clinical and CT factors associated with local resectability in patients with nonmetastatic pancreatic cancers after neoadjuvant chemotherapy ± radiation therapy (CRT). METHODS: This retrospective study included consecutive patients with nonmetastatic pancreatic cancers who underwent neoadjuvant CRT between June 2009 and June 2019. Tumor size, tumor-vascular contact with artery/vein, and local resectability categories (resectable, borderline resectable, or locally advanced) were assessed at baseline and post-CRT CT. Baseline and post-CRT carbohydrate antigen (CA) 19-9 levels were also assessed. Clinical or imaging features related to R0 resection were determined using logistic regression analysis. RESULTS: A total of 179 patients (mean age, 62.4 ± 9.3 years; 92 men) were included. After neoadjuvant CRT, 105 (58.7%) patients received R0 resection, while 74 (41.3%) did not. R0 resection rates were significantly different according to post-CRT CT resectability categories (p < 0.001): 82.8% (48/58), 70.1% (47/67), and 18.5% (10/54) for resectable, borderline resectable, and locally advanced disease, respectively. For post-CRT borderline resectable disease, ≥ 50% decrease in CA 19-9 was significantly associated with R0 resection (odds ratio (OR), 3.160; p = 0.02). For post-CRT locally advanced disease, small post-CRT tumor size ≤ 2 cm (OR, 9.668; p = 0.026) and decreased tumor-arterial contact (OR, 24.213; p = 0.022) were significantly associated with R0 resection. CONCLUSION: Post-CRT CT resectability categorization may be useful for the assessment of R0 resectability in patients with pancreatic cancer following neoadjuvant CRT. Additionally, ≥ 50% decrease in CA 19-9 was associated with R0 resection in post-CRT borderline resectable disease, while small post-CRT tumor size and decreased tumor-arterial contact were with locally advanced disease. KEY POINTS: • R0 resection rates following neoadjuvant chemotherapy ± radiation therapy (CRT) were 82.8%, 70.1%, and 18.5% in resectable, borderline resectable, and locally advanced disease, respectively, at post-CRT CT (p < 0.001). • For post-CRT borderline resectable disease, ≥ 50% decrease in carbohydrate antigen (CA) 19-9 was significantly associated with R0 resection. • For post-CRT locally advanced disease, small post-CRT tumor size ≤ 2 cm and decreased tumor-arterial contact were significantly associated with R0 resection.


Neoadjuvant Therapy , Pancreatic Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols , Biomarkers, Tumor , Humans , Male , Middle Aged , Multidetector Computed Tomography , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/therapy , Retrospective Studies
16.
Eur Radiol ; 31(12): 9664-9674, 2021 Dec.
Article En | MEDLINE | ID: mdl-34089072

OBJECTIVE: Assess if deep learning-based artificial intelligence (AI) algorithm improves reader performance for lung cancer detection on chest X-rays (CXRs). METHODS: This reader study included 173 images from cancer-positive patients (n = 98) and 346 images from cancer-negative patients (n = 196) selected from National Lung Screening Trial (NLST). Eight readers, including three radiology residents, and five board-certified radiologists, participated in the observer performance test. AI algorithm provided image-level probability of pulmonary nodule or mass on CXRs and a heatmap of detected lesions. Reader performance was compared with AUC, sensitivity, specificity, false-positives per image (FPPI), and rates of chest CT recommendations. RESULTS: With AI, the average sensitivity of readers for the detection of visible lung cancer increased for residents, but was similar for radiologists compared to that without AI (0.61 [95% CI, 0.55-0.67] vs. 0.72 [95% CI, 0.66-0.77], p = 0.016 for residents, and 0.76 [95% CI, 0.72-0.81] vs. 0.76 [95% CI, 0.72-0.81, p = 1.00 for radiologists), while false-positive findings per image (FPPI) was similar for residents, but decreased for radiologists (0.15 [95% CI, 0.11-0.18] vs. 0.12 [95% CI, 0.09-0.16], p = 0.13 for residents, and 0.24 [95% CI, 0.20-0.29] vs. 0.17 [95% CI, 0.13-0.20], p < 0.001 for radiologists). With AI, the average rate of chest CT recommendation in patients positive for visible cancer increased for residents, but was similar for radiologists (54.7% [95% CI, 48.2-61.2%] vs. 70.2% [95% CI, 64.2-76.2%], p < 0.001 for residents and 72.5% [95% CI, 68.0-77.1%] vs. 73.9% [95% CI, 69.4-78.3%], p = 0.68 for radiologists), while that in cancer-negative patients was similar for residents, but decreased for radiologists (11.2% [95% CI, 9.6-13.1%] vs. 9.8% [95% CI, 8.0-11.6%], p = 0.32 for residents and 16.4% [95% CI, 14.7-18.2%] vs. 11.7% [95% CI, 10.2-13.3%], p < 0.001 for radiologists). CONCLUSIONS: AI algorithm can enhance the performance of readers for the detection of lung cancers on chest radiographs when used as second reader. KEY POINTS: • Reader study in the NLST dataset shows that AI algorithm had sensitivity benefit for residents and specificity benefit for radiologists for the detection of visible lung cancer. • With AI, radiology residents were able to recommend more chest CT examinations (54.7% vs 70.2%, p < 0.001) for patients with visible lung cancer. • With AI, radiologists recommended significantly less proportion of unnecessary chest CT examinations (16.4% vs. 11.7%, p < 0.001) in cancer-negative patients.


Artificial Intelligence , Lung Neoplasms , Algorithms , Humans , Lung , Lung Neoplasms/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted , Radiography , Radiography, Thoracic , Sensitivity and Specificity
17.
Sci Rep ; 11(1): 10522, 2021 05 18.
Article En | MEDLINE | ID: mdl-34006918

This study aimed to investigate the effect of intraoperative fluid volume on the postoperative ileus (POI) recovery period. A retrospective review of the Korean robot-assisted radical cystectomy database identified 718 patients who underwent robot-assisted radical cystectomy (RARC). Regression analyses were performed to identify the associations between the amount of intraoperative fluid administration (crystalloid/colloid/total), POI period (time to flatus/bowel movements), and length of hospital stay (LOS) after adjusting for covariates. In addition, we analyzed the risk factors for gastrointestinal complications and prolonged POI using a logistic regression model. An increasing volume of the administered crystalloid/total fluid was associated with prolonged POI (crystalloid R2 = 0.0725 and P < 0.0001; total amount R2 = 0.0812 and P < 0.0001), and the total fluid volume was positively associated with the LOS (R2 = 0.099 and P < 0.0001). The crystalloid amount was a risk factor for prolonged POI (P < 0.001; odds ratio, 1.361; 95% confidence interval, 1.133-1.641; P < 0.001). In the context of RARC, increased intravenous fluids are associated with prolonged POI and longer LOS.


Body Fluids , Cystectomy/adverse effects , Ileus/etiology , Postoperative Complications/etiology , Robotic Surgical Procedures/adverse effects , Aged , Female , Humans , Intraoperative Period , Length of Stay , Male , Middle Aged , Retrospective Studies , Treatment Outcome
18.
Molecules ; 26(5)2021 Mar 08.
Article En | MEDLINE | ID: mdl-33800380

Studies on a one-pot synthesis of novel multisubstituted 1-alkoxyindoles 1 and their mechanistic investigations are presented. The synthesis of 1 was successfully achieved through consecutive four step reactions from substrates 2. The substrates 2, prepared through a two-step synthetic sequence, underwent three consecutive reactions of nitro reduction, intramolecular condensation, and nucleophilic 1,5-addition to provide the intermediates, 1-hydroxyindoles 8, which then were alkylated in situ with alkyl halide to afford the novel target products 1. We optimized the reaction conditions for 1 focusing on the alkylation step, along with the consideration of formation of intermediates 8. The optimized condition was SnCl2·2H2O (3.3 eq) and alcohols (R1OH, 2.0 eq) for 1-2 h at 40 °C and then, base (10 eq) and alkyl halides (R2Y, 2.0 eq) for 1-4 h at 25-50 °C. Notably, all four step reactions were performed in one-pot to give 1 in good to modest yields. Furthermore, the mechanistic aspects were also discussed regarding the reaction pathways and the formation of side products. The significance lies in development of efficient one-pot reactions and in generation of new 1-alkoxyindoles.


Alcohols/chemical synthesis , Indoles/chemical synthesis , Alcohols/chemistry , Alkylation , Cyclization , Molecular Structure , Stereoisomerism , Tin Compounds
19.
J Endourol ; 35(10): 1490-1497, 2021 10.
Article En | MEDLINE | ID: mdl-33678003

Background: We aimed to compare the oncologic outcomes of intracorporeal urinary diversion (ICUD) and extracorporeal urinary diversion (ECUD) following robot-assisted radical cystectomy (RARC) in patients diagnosed with bladder cancer. Materials and Methods: Medical records of 730 patients who underwent RARC between April 2007 and May 2019 in 11 tertiary referral centers were retrospectively reviewed. We assessed recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in the two groups using the Kaplan-Meier method. Cox regression models were used to identify factors associated with RFS, CSS, and OS. Results: Among 591 patients, neobladder diversion was performed more frequently in the ICUD group (70.8% vs 52.5%, p = 0.001). The median follow-up duration was shorter in the ICUD group than in the ECUD group (16 vs 26 months, p < 0.001). The rates of overall recurrence (36.5% vs 25.5%, p = 0.013) and pelvic recurrence (12.1% vs 5.9%, p = 0.031) were higher in the ECUD group. However, no differences in 5-year RFS (43.2% vs 58.4%, p = 0.516), CSS (79.3% vs 89.7%, p = 0.392), and OS (74.3% vs 81.4%, p = 0.411) were noted between the two groups. Multivariable analysis revealed that when compared to ICUD, ECUD was not associated with RFS (hazard ratio [HR], 0.982; p = 0.920), CSS (HR, 0.568; p = 0.126), and OS (HR, 0.642; p = 0.124). Conclusion: Although there was a difference in recurrence rate between the two groups, multivariable analysis indicated that the diversion technique after RARC did not affect the oncologic outcomes. Large prospective studies with long-term follow-up are warranted to verify the oncologic outcomes of ICUD and ECUD following RARC.


Robotic Surgical Procedures , Robotics , Urinary Bladder Neoplasms , Urinary Diversion , Cystectomy , Humans , Neoplasm Recurrence, Local , Postoperative Complications , Prospective Studies , Republic of Korea , Retrospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/surgery
20.
Taehan Yongsang Uihakhoe Chi ; 82(1): 12-28, 2021 Jan.
Article Ko | MEDLINE | ID: mdl-36237466

Mammography is the primary imaging modality for breast cancer detection; however, a high level of expertise is needed for its interpretation. To overcome this difficulty, artificial intelligence (AI) algorithms for breast cancer detection have recently been investigated. In this review, we describe the characteristics of AI algorithms compared to conventional computer-aided diagnosis software and share our thoughts on the best methods to develop and validate the algorithms. Additionally, several AI algorithms have introduced for triaging screening mammograms, breast density assessment, and prediction of breast cancer risk have been introduced. Finally, we emphasize the need for interest and guidance from radiologists regarding AI research in mammography, considering the possibility that AI will be introduced shortly into clinical practice.

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